RARE DISEASE
T-cell prolymphocytic leukemia
T-cell prolymphocytic leukemia
T-cell prolymphocytic leukemia
Synonyms: T-PLL, T-cell chronic lymphocytic leukemia
Synonyms: T-PLL, T-cell chronic lymphocytic leukemia
Synonyms: T-PLL, T-cell chronic lymphocytic leukemia
Drug discovery
3
drugs
With orphan designations
Overview
T-cell prolymphocytic leukemia (T-PLL) is an aggressive mature T-cell malignancy characterized by rapid proliferation of post-thymic lymphocytes. It typically presents with hepatosplenomegaly, lymphadenopathy, marked leukocytosis (>100 × 10⁹/L), and cytopenias. Genetic drivers include TCL1 overexpression (80-90% of cases) and ATM mutations [1][4][10]. Median survival is 1–2 years despite alemtuzumab-based therapy, with relapse rates exceeding 80% [2][3][12].
Therapies
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
282 drug discovery papers about T-cell prolymphocytic leukemia, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
282 drug discovery papers about T-cell prolymphocytic leukemia, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2026-03-16 | UMG1 Defines a Targetable Subset of T-Cell Lymphomas and Enables Precision Immunotherapy With a First-in-Class CD3ε Bispecific Engager.
T-cell lymphomas (TCLs) account for a relatively small fraction of lymphoid malignancies and are characterized by highly aggressive course often refractory to current available therapies. We previously reported potent in vitro and in vivo antitumor activity of a Bispecific T-Cell Engager (UMG1/CD3ε-BTCE) directed against UMG1, a unique CD43 epitope that is abundantly expressed on T-cell acute lymphoblastic leukemia (T-ALL) and diffuse large B-cell lymphoma (DLBCL) cells, while absent in most normal tissues, except thymocytes and a small fraction of peripheral blood T lymphocytes (< 5%). Here, we investigated the in vitro efficacy of UMG1/CD3ε-BTCE against TCLs. IHC analysis of Tissue Micro Arrays (TMAs) revealed high UMG1 expression in 62.3% of TCL samples, including peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and ALK-negative anaplastic large cell lymphoma (ALCL). Notably, all T-PLL primary specimens (27/27) were positive, and 3 of 4 TCL cell lines also expressed UMG1 by flow cytometry. The asymmetric UMG1/CD3ε-BTCE induced robust redirected cytotoxicity against UMG1-expressing TCL cells. Moreover, this activity was strengthened by cell exposure to the HDAC inhibitor SAHA. We observed a dose-dependent engaged T-cell-mediated cytotoxicity and inflammatory cytokine release, resulting in lysis of UMG1-expressing cells, with no significant effect on UMG1-not expressing cells. Our findings suggest that the UMG1/CD3ε-BTCE selectively exerts potent anti-tumor activity against a relevant subset of TCLs. These findings support the development of a precision immunotherapy approach for patients with UMG1-expressing aggressive hematologic malignancies.
2026-01-15 | Phase 1B pilot study of itacitinib with alemtuzumab in patients with T-cell prolymphocytic leukemia.
T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and platelet >30 × 103/μL. Cycle 1 included a lead-in phase with itacitinib monotherapy days 1-14. Beginning day 15, patients also received alemtuzumab 30mg IV 3 times weekly for up to 4 (28-day) cycles or until best response. At best response, up to 8 cycles of maintenance with single-agent itacitinib was allowed. Median age was 65 years (range, 39-83). Ten patients (67%) had complex cytogenetics, 11 (73%) had chromosome 14 abnormality, and 13 (87%) were TCL1A positive by fluorescence in situ hybridization. Among frontline patients, overall response rate (ORR) was 88% (complete remission [CR]: 75%), median event-free survival (EFS) and overall survival (OS) were 11.6 and 19.5 months, respectively. Three frontline patients proceeded to allogeneic stem cell transplantation. The ORR in the relapsed/refractory cohort was 57% (CR: 43%), whereas median EFS and OS were 11.1 months. Most (85%) adverse events were grade 1 to 2 and none were attributed to itacitinib. Continued studies evaluating JAK inhibitors in patients with T-PLL are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03989466.
2026-01-03 | CD47 blockade-driven necroptosis complements BCL-2 inhibition-driven apoptosis in lymphoid malignancies
BACKGROUND: Immune checkpoint blockade of CD47 has shown promising results in lymphoid malignancies, with its effects attributed to enabling tumor-cell phagocytosis. However, alternate cytotoxic cell death mechanisms have been reported, potentially contributing to the overall anti-tumor activity. Although previous studies have highlighted a mechanism of caspase-independent cell death, this mechanism has yet to be well-characterized, thereby warranting further investigation to comprehensively understand the anti-tumor mechanism of CD47 blockade to facilitate optimal drug partner selection for combination therapy. METHODS: The fully humanized anti-CD47 monoclonal antibodies, SRF231, magrolimab, as well as a mouse monoclonal anti-CD47 antibody, B6H12, were used. Multiple cell death mechanisms were evaluated including apoptosis, autophagy and necroptosis by using customized Hoechst/Annexin V, the precision medicine technique BH3 profiling, as well as standard experimental techniques – flow cytometry, siRNA and CRISPR Cas9 genetic manipulation, Western blotting, and immunohistochemistry. These techniques were used on a comprehensive range of lymphoid malignant models including diffuse large B-cell lymphoma, Burkitt lymphoma, and T-acute lymphoblastic leukemia cell lines, patient primary chronic lymphocytic leukemia cells, as well as lymphoid cell-line derived and patient-derived xenograft mice, to elucidate the mechanism of cell death by CD47 blockade and to identify the optimal drug partners for treatment combination. RESULTS: We demonstrate that the anti-CD47 antibodies SRF231, magrolimab, and B6H12 eliminated tumor cells from various in vitro and in vivo lymphoid malignant models via the activation of the RIPK1/MLKL/necroptotic pathway. Moreover, the BH3 profiling technique distinguished two different lymphoid malignant models that respond differently to the BCL-2 inhibitor venetoclax when combined with SRF231; one highlighting the effective yet distinct mechanisms of SRF231-induced necroptosis and venetoclax-induced apoptosis in models that were specifically and/or highly dependent on BCL-2 for survival, while the other implicating venetoclax as a counterproductive partner with SRF231 in models that were not dependent on BCL-2 for survival or were not responsive to venetoclax treatment. CONCLUSION: Collectively, this study unravels a novel, non-canonical cell death mechanism of targeting CD47 by activating necroptosis, and provides evidence and rationale for further evaluation of a therapeutic strategy of combining CD47 blockade with and without apoptotic inducers for suitable patients with lymphoid malignancies.
2025-09-08 | A Rare Case of Renal Failure Caused by T-Cell Prolymphocytic Leukaemia Infiltration.
T-cell prolymphocytic leukaemia (T-PLL) is an aggressive and rare post-thymic T cell malignancy, highly refractory to conventional cytotoxic chemotherapeutics. While extranodal involvement is common, solid organ invasion is rare. We present the case of a 76-year-old man who developed acute renal failure secondary to T-PLL renal infiltration. On day four of his admission, prior to commencing alemtuzumab, his creatinine rose from 133 μmol/L to 390 μmol/L, with anuria. Renal biopsy demonstrated an infiltrate of monomorphic, mononuclear cells positive for a STAT5B mutation, consistent with T-PLL infiltration. He required haemodialysis, but was treated with pulsed methylprednisolone and alemtuzumab, with excellent renal recovery, although remission was not achieved. This case demonstrates that renal leukaemic infiltration must be considered in T-PLL patients with rapidly progressive renal failure, and that solid organ invasion should not contraindicate timely commencement of T-PLL-directed therapy with alemtuzumab.
2025-08-23 | Exploring SLAMF5/CD84 in Cancer: Advancing the Frontiers of Tumor Immunology
The Signaling Lymphocytic Activation Molecule (SLAM) family receptors play essential roles in regulating immune cell activation, differentiation, and communication. SLAMF5, also known as CD84, has drawn increasing attention in cancer immunology due to its involvement in both tumor progression and immune modulation. This review explores the expression patterns, signaling mechanisms, and functional roles of SLAMF5/CD84 within the tumor microenvironment. SLAMF5/CD84 is expressed on multiple immune cell types and contributes to immune evasion by enhancing regulatory B cell function, promoting myeloid-derived suppressor cell expansion, and upregulating immune checkpoint molecules such as PD-L1. Its expression has been implicated in various hematologic malignancies and solid tumors, including chronic lymphocytic leukemia, multiple myeloma, and triple-negative breast cancer. Emerging therapeutic approaches targeting SLAMF5/CD84-such as monoclonal antibodies and CAR T-cell therapies-offer promising strategies to counteract immunosuppression and improve treatment outcomes. By highlighting recent findings and therapeutic developments, this review underscores the significance of SLAMF5/CD84 as both a prognostic biomarker and a novel target in cancer immunotherapy. Understanding SLAMF5/CD84's multifaceted roles in the tumor immune landscape could support the development of more effective and personalized cancer treatment strategies.
small molecules
2026-04-09 | A case of T-prolymphocytic leukemia harboring RAS mutation.
The text reports the clinical case of a 61-year-old woman with a long history of generalized pruritus who was eventually diagnosed with T-cell prolymphocytic leukemia (T-PLL), a rare and aggressive T-cell lymphoproliferative disorder. At presentation, the patient had fever, skin lesions, lymphocytosis, thrombocytopenia, coagulation abnormalities, and marked splenomegaly without lymphadenopathy. Morphological, immunophenotypic, and histological analyses of peripheral blood and bone marrow revealed diffuse infiltration by mature T lymphocytes with strong TCL1 expression, and T-cell receptor gene rearrangement confirmed clonality, supporting the diagnosis of T-PLL. The patient initially received bendamustine chemotherapy, which failed to induce a response. Second-line treatment with the anti-CD52 monoclonal antibody alemtuzumab was subsequently initiated, but the disease proved refractory, with persistent bone marrow involvement, worsening cytopenias, disease progression, and clinical deterioration. As a result, alemtuzumab was discontinued and the patient was transitioned to palliative care. A particularly notable finding was the detection, by next-generation sequencing, of a pathogenic KRAS G12A mutation, which has not previously been reported in T-PLL. This mutation was identified incidentally using a myeloid-targeted NGS panel. The finding broadens the known mutational spectrum of T-PLL and suggests that activation of the RAS signaling pathway may represent an alternative oncogenic mechanism beyond the canonical TCL1 and JAK–STAT pathways. We suggest that investigating for KRAS mutations in additional T-PLL cases may be beneficial to explore this pathogenetic pathway and could open new avenues for future targeted therapeutic strategies.
2025-12-04 | Invasive Talaromyces marneffei Fungemia in an HIV-Negative Patient with T-Prolymphocytic Leukaemia: A Case Report and Review of Emerging Risks.
Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus traditionally associated with HIV-related immunosuppression. However, increasing reports have described infections in HIV-negative patients with hematologic malignancies, particularly those receiving novel immunosuppressive therapies. We report a case of disseminated T. marneffei in an HIV-negative 55-year-old woman with T-prolymphocytic leukaemia (T-PLL) undergoing chemotherapy and targeted therapy with chidamide and golidocitinib. The patient presented with fever, pancytopenia, and signs of systemic infection. Blood cultures confirmed T. marneffei, with identification supported by dual-phase morphology and internal transcribed spacer (ITS) sequencing. Due to unavailability of amphotericin B, the patient was treated successfully with voriconazole, achieving rapid clinical improvement and negative follow-up cultures. This case adds to the growing evidence that T. marneffei can cause invasive infections in non-HIV immunocompromised hosts. Through a review of 10 published cases, we identify common features such as neutropenia, kinase inhibitor use, and diagnostic delays. We emphasize the importance of early fungal culture and phase-specific morphology for diagnosis, and highlight voriconazole as a viable alternative therapy when amphotericin B is inaccessible. Clinicians should maintain high suspicion for talaromycosis in immunosuppressed hematologic patients in endemic regions, regardless of HIV status. Prompt recognition and appropriate antifungal therapy are essential to improve outcomes.
2025-11-24 | Epidemiology and survival of patients with T-cell prolymphocytic leukemia
T-prolymphocytic leukemia (T-PLL) is a very rare but aggressive T-cell neoplasm affecting mainly elderly patients [ 1 ]. Clinical presentation typically involves progressive lymphocytosis, hepatosplenomegaly, lymphadenopathy, and extramedullary symptoms, although up to 20% of patients might initially present with a stable disease course [ 2 ]. Consensus criteria for diagnosis and treatment have only recently been defined and clinical trials remain sparse. Consequently, treatment options for patients with T-PLL are limited and reported outcomes in small single institution studies remain poor with a median overall survival of 7.5 to 19 months [ 1 , 2 , 3 ]. Currently, the IgG1 monoclonal CD52 antibody alemtuzumab is recommended as first-line treatment, achieving high initial response rates in newly diagnosed patients [ 4 ]. Alternatively, the combination of Fludarabine, Mitoxantrone and Cyclophosphamide (FMC) has been used. Subsequent autologous or allogenic hematopoietic stem cell transplant (HCT) in complete remission (CR) should follow in fit patients and can induce long-term disease-free survival. However, due to the disease demographics, only 30–50% of patients are eligible for intensive HCT regimens [ 5 , 6 ]. In refractory cases, Pentostatin and Bendamustine have shown limited efficacy, whereas newer options such as Ruxolitinib are being explored with promising early results [ 3 , 4 , 7 ].
2025-11-03 | MYC/GSPT1 protein degradation in refractory/relapsed T-cell prolymphocytic leukemias
Abstract Background: T-cell prolymphocytic leukemia (T-PLLs) is a rare, mature T-cell-derived, aggressive hematologic malignancy. T-PLLs are one of the most challenging hematologic malignancies based on refractoriness to conventional chemotherapy and targeted therapies, including alemtuzumab. Chromosome rearrangement and overexpression of TCL-1 are hallmarks of T-PLL, accounting for approximately 95% of cases. Nearly 50% of cases carry chromosome 8 gains, leading to upregulation of the oncogene c-Myc. Recently, we discovered a feedforward loop of c-Myc and GSPT1 (eRF3a), a key translation termination factor that promotes translation in leukemias, and established highly effective anti-leukemia/lymphoma activities of GT19630, the first-in-class MYC/GSPT1 proteolysis targeting chimera in MYC-driven hematologic malignancies (Nishida et al. biorxiv 2025 650490, under revision). We hypothesized that c-Myc/GSPT1 translation is activated in T-PLL cells and targeting c-Myc/GSPT1 by protein degradation is effective in relapsed/refractory T-PLLs. Method: We evaluated single-cell levels of baseline protein translation using the O-propargyl-puromycin (OPP) nascent protein synthesis assay and multicolor flow cytometry in T-PLL and normal peripheral blood mononuclear cells (PBMCs). We investigated the activity of GT19715 in T-PLL patient-derived xenograft (PDX) models established from relapsed/refractory T-PLL patients in vitro and in vivo. Single-cell mass cytometry (CyTOF) was applied to determine distinct surface and intracellular molecular features of primary and PDX T-PLL cells. Results: c-Myc and GSPT1 protein levels were increased in T-PLL cells compared to PBMCs. Compared to CD3+ normal T-cells from healthy donors (N = 3), CD7+ T-PLL cells in primary T-PLL samples (N = 5) exhibited significantly increased baseline protein translation levels determined by OPP protein synthesis flow cytometry (Mean fluorescence intensity: 532.3 ± 88.1 vs 7,090 ± 1,193 for CD3+ T-cells vs CD7+ T-PLL cells, respectively, P = 0.0062), suggesting increased c-Myc/GSPT1 protein translation in T-PLL cells compared to normal PBMCs. GT19715 degraded c-Myc and GSPT1 proteins at 1 nM and induced cell death in PDX T-PLL cells (IC50 < 1 nM). GT19715 dramatically reduced circulating T-PLL cells and significantly prolonged survival in mice carrying PDX T-PLL cells (median OS 1.0 vs 9.3 weeks for vehicle- and GT19715-treated groups, respectively, P < 0.0001). After euthanizing mice, we found spleen and liver packed with T-PLL cells in vehicle control mice while only minimal remaining tumor cells in liver peri-centrolobular regions, suggesting sustained tumor suppression in vivo. CyTOF analysis revealed high levels of CD2, CD4, CD7, TCL1 and ZAP70 in primary and PDX T-PLL cells compared to normal bone marrow T cells. Primary and PDX T-PLL samples share a distinct cell population with elevated levels of CD26, CD28, CD69, and CD45RA. Interestingly, these cells exhibit elevated TCL-1, ZAP70, BCL-2, MCL-1, p-AKT, p-NFkB and p-STAT5 levels with partially high Ki-67, features that suggest identification of a clone driving propagation and therapy resistance. Conclusion: We identified increased protein translation of c-Myc and GSPT1 in T-PLL cells compared to normal PBMCs. Targeted protein degradation of c-Myc and GSPT1 is highly effective in relapsed/refractory T-PLL in vitro and in vivo, with over 900% extension of survival in a clinically relevant, PDX T-PLL model, providing rationale for clinical investigations.
2025-10-28 | Comparative preclinical drug response analyses of T-prolymphocytic leukemia reveal no differences between known gene expression subgroups.
T-prolymphocytic leukemia (T-PLL) is a rare mature T-cell neoplasm with poor prognosis that mainly affects elderly people. Alemtuzumab is widely considered as first-line therapy, but almost all patients relapse within one year, if not consolidated by an allogeneic stem cell transplantation. The improved understanding of T-PLL-specific molecular pathomechanisms gained over the last years suggested new potential therapeutic targets (epigenetic dysregulation, defective DNA damage response, aberrant cell cycle regulation, dysregulated prosurvival pathways), which were recently evaluated in a preclinical drug response study. In addition, existing genomewide T-PLL gene expression profiles enabled the identification of three robust T-PLL gene expression subgroups differing in cellular processes like immune response, cellular respiration, cell proliferation, apoptosis, or migration. So far, these T-PLL gene expression subgroups were not considered in preclinical drug response analyses, but recently published drug response screens and corresponding already publicly available gene expression profiles offer the great opportunity to integrate both data types. Therefore, we computationally analyzed samples from 34 T-PLL patients of two comparable cohorts for their response to in total 11 drugs. No T-PLL subgroup-specific differences or sex differences in response to the tested drugs were found. With respect to the underlying drug dosage schemes, venetoclax and cladribine were most effective in erasing T-PLL cancer cells among both cohorts. Also dinaciclib, idasanutlin, romidepsin, and KRT-232, which were only tested in one of both cohorts, were very effective for all or most of the T-PLL patient samples. For the three drugs bendamustine, cladribine, and fludarabine, which were only effective in a subset of the T-PLL samples, an exploratory differential gene expression analysis predicted drug-specific genes that distinguished between strongly and not strongly responding samples. In-depth annotation and literature analyses showed that many of these genes are known to play a role in leukemias or other types of cancer. Many of these genes were also confirmed by a direct correlation analysis between gene expression levels and drug responses. The absence of T-PLL gene expression subgroup-specific drug responses across the tested drugs can be important for the design of future drug screens and may ease potential clinical trials. Genes associated with drug-specific responses could be useful for improved patient stratification and may help to characterize molecular settings associated with effective responses. Not applicable. The online version contains supplementary material available at 10.1186/s13062-025-00701-3.
oligonucleotides
2023-04-28 | The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL
T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease.
2023-03-31 | Data from Noncanonical Function of AGO2 Augments T-cell Receptor Signaling in T-cell Prolymphocytic Leukemia
<div>Abstract<p>T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-refractory T-cell malignancy with limited therapeutic options and a poor prognosis. Current disease concepts implicate TCL1A oncogene-mediated enhanced T-cell receptor (TCR) signaling and aberrant DNA repair as central perturbed pathways. We discovered that recurrent gains on chromosome 8q more frequently involve the <i>argonaute RISC catalytic component 2 (AGO2)</i> gene than the adjacent <i>MYC</i> locus as the affected minimally amplified genomic region. AGO2 has been understood as a protumorigenic key regulator of miRNA (miR) processing. Here, in primary tumor material and cell line models, AGO2 overrepresentation associated (i) with higher disease burden, (ii) with enhanced <i>in vitro</i> viability and growth of leukemic T cells, and (iii) with miR-omes and transcriptomes that highlight altered survival signaling, abrogated cell-cycle control, and defective DNA damage responses. However, AGO2 elicited also immediate, rather non–RNA-mediated, effects in leukemic T cells. Systems of genetically modulated AGO2 revealed that it enhances TCR signaling, particularly at the level of ZAP70, PLCγ1, and LAT kinase phosphoactivation. In global mass spectrometric analyses, AGO2 interacted with a unique set of partners in a TCR-stimulated context, including the TCR kinases LCK and ZAP70, forming membranous protein complexes. Models of their three-dimensional structure also suggested that AGO2 undergoes posttranscriptional modifications by ZAP70. This novel TCR-associated noncanonical function of AGO2 represents, in addition to TCL1A-mediated TCR signal augmentation, another enhancer mechanism of this important deregulated growth pathway in T-PLL. These findings further emphasize TCR signaling intermediates as candidates for therapeutic targeting.</p>Significance:<p>The identification of AGO2-mediated activation of oncogenic T cells through signal amplifying protein–protein interactions advances the understanding of leukemogenic AGO2 functions and underlines the role of aberrant TCR signaling in T-PLL.</p></div>
2022-03-31 | Micro-RNA networks in T-cell prolymphocytic leukemia reflect T-cell activation and shape DNA damage response and survival pathways.
T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic mature T-cell malignancy. It typically presents with exponentially rising lymphocyte counts, splenomegaly, and bone marrow infiltration. Effective treatment options are scarce and a better understanding of TPLL's pathogenesis is desirable. Activation of the TCL1 proto-oncogene and loss-of-function perturbations of the tumor suppressor ATM are TPLL's genomic hallmarks. The leukemic cell reveals a phenotype of active T-cell receptor (TCR) signaling and aberrant DNA damage responses. Regulatory networks based on the profile of microRNA (miR) have not been described for T-PLL. In a combined approach of small-RNA and transcriptome sequencing in 46 clinically and moleculary well-characterized T-PLL, we identified a global T-PLL-specific miR expression profile that involves 34 significantly deregulated miR species. This pattern strikingly resembled miR-ome signatures of TCR-activated T cells. By integrating these T-PLL miR profiles with transcriptome data, we uncovered regulatory networks associated with cell survival signaling and DNA damage response pathways. Despite a miR-ome that discerned leukemic from normal T cells, there were also robust subsets of T-PLL defined by a small set of specific miR. Most prominently, miR-141 and the miR- 200c-cluster separated cases into two major subgroups. Furthermore, increased expression of miR-223-3p as well as reduced expression of miR-21 and the miR-29 cluster were associated with more activated Tcell phenotypes and more aggressive disease presentations. Based on the implicated pathobiological role of these miR deregulations, targeting strategies around their effectors appear worth pursuing. We also established a combinatorial miR-based overall survival score for T-PLL (miROS-T-PLL), that might improve current clinical stratifications.
2022-03-08 | Noncanonical Function of AGO2 Augments T-cell Receptor Signaling in T-cell Prolymphocytic Leukemia
Abstract T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-refractory T-cell malignancy with limited therapeutic options and a poor prognosis. Current disease concepts implicate TCL1A oncogene-mediated enhanced T-cell receptor (TCR) signaling and aberrant DNA repair as central perturbed pathways. We discovered that recurrent gains on chromosome 8q more frequently involve the argonaute RISC catalytic component 2 (AGO2) gene than the adjacent MYC locus as the affected minimally amplified genomic region. AGO2 has been understood as a protumorigenic key regulator of miRNA (miR) processing. Here, in primary tumor material and cell line models, AGO2 overrepresentation associated (i) with higher disease burden, (ii) with enhanced in vitro viability and growth of leukemic T cells, and (iii) with miR-omes and transcriptomes that highlight altered survival signaling, abrogated cell-cycle control, and defective DNA damage responses. However, AGO2 elicited also immediate, rather non–RNA-mediated, effects in leukemic T cells. Systems of genetically modulated AGO2 revealed that it enhances TCR signaling, particularly at the level of ZAP70, PLCγ1, and LAT kinase phosphoactivation. In global mass spectrometric analyses, AGO2 interacted with a unique set of partners in a TCR-stimulated context, including the TCR kinases LCK and ZAP70, forming membranous protein complexes. Models of their three-dimensional structure also suggested that AGO2 undergoes posttranscriptional modifications by ZAP70. This novel TCR-associated noncanonical function of AGO2 represents, in addition to TCL1A-mediated TCR signal augmentation, another enhancer mechanism of this important deregulated growth pathway in T-PLL. These findings further emphasize TCR signaling intermediates as candidates for therapeutic targeting. Significance: The identification of AGO2-mediated activation of oncogenic T cells through signal amplifying protein–protein interactions advances the understanding of leukemogenic AGO2 functions and underlines the role of aberrant TCR signaling in T-PLL.
2021-02-18 | The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia
T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and/or genotypic subgroups that may explain the heterogeneity of the disease. Multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups, and no clear T-cell receptor a or β CDR3 skewing was observed between different T-PLL cases. We revealed that the expression of microRNA (miRNA) is aberrant and often heterogeneous in T-PLL. We identified 35 miRNA that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR- 200c/141 and miR-181a/181b expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 correlated with downregulation of their targets ZEB2 and TGFβR3 and aberrant TGFβ1- induced phosphorylated SMAD2 (p-SMAD2) and p-SMAD3, indicating that the TGFβ pathway is affected in T-PLL. Our results thus highlight the potential role for aberrantly expressed oncogenic miRNA in T-PLL and pave the way for new therapeutic targets in this disease.
cell therapies
2026-05-28 | Allogeneic stem cell transplantation in T-cell prolymphocytic leukemia: final disappointment or a chance for cure?
Not available.
2026-03-30 | Allogeneic transplant outcomes in T-cell prolymphocytic leukemia: a single-center retrospective study.
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive malignancy with a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HCT) is often used for treatment, but its effectiveness remains unclear. In this study of 33 adult patients with T-PLL who underwent HCT, 5-year progression-free survival (PFS) was 29% (95% confidence interval [CI], 14-45) and 5-year overall survival (OS) was 41% (95% CI, 24-57). Five-year cumulative incidence of non-relapse mortality was 18%, while 5-year cumulative incidence of relapse was 53%. Univariable analysis revealed that a longer time from diagnosis to HCT was significantly associated with improved PFS (hazard ratio, 0.36; 95% CI, 0.15-0.87). Analysis of immune reconstitution in 22 patients showed a relatively slow recovery of immune cells post-HCT. A higher recovery of CD3 T cells was also associated with increased risk of relapse, which may have prognostic significance and warrants further investigation as a risk factor for disease recurrence.
2026-03-28 | How We Evaluate and Treat Leukemic Presentations of Mature T-Cell Lymphomas.
T-cell non-Hodgkin lymphomas, which arise from post-thymic mature T cells, constitute approximately 10-15% of all non-Hodgkin lymphomas. Their leukemic presentations, referred to here as mature T-cell leukemias, are relatively uncommon and present significant diagnostic and therapeutic challenges requiring an informed approach to diagnosis and management. The initial presentation is often persistent T-cell lymphocytosis that must be distinguished from reactive (non-malignant) causes. Unlike B-cell lymphocytosis, where clonality usually indicates malignancy, T-cell clonality can be detected in benign conditions such as autoimmune disorders and viral infections. Thus, establishing clonality is helpful but not sufficient, and a systematic diagnostic approach integrating clinical features, morphology, immunophenotype, and molecular findings is critical. This review outlines our approach to the diagnosis and treatment of four major subtypes of mature T-cell leukemias: T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), T-large granular lymphocytic leukemia (T-LGL), and Sézary syndrome (SS). Each section includes a discussion of clinical features, workup, and treatment options.
2026-03-09 | Cutaneous‐Only Relapse in T‐Cell Prolymphocytic Leukemia With JAK2 Rearrangement
The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
2026-02-20 | A Unique Case of Concomitant T-Prolymphocytic Leukemia and B-Cell Acute Lymphoblastic Leukemia.
T-prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with a poor prognosis. B-cell acute lymphoblastic leukemia (B-ALL) also confers a poor prognosis, especially in patients with high-risk features without an option for transplant. Here, we present a case of a patient with T-PLL initially treated with multi-agent chemotherapy who then developed B-ALL, the management strategies, and possible pathogenesis of two concurrent rare malignancies. One proposed mechanism for the development of both hematologic malignancies in this patient is the acquisition of a KMT2A rearrangement, raising the possibility of clonal evolution resulting in therapy-related or secondary leukemia. Another explanation is the presence of a common clonal stem cell progenitor harboring a JAK3 mutation.
other
2024-02-12 | [Durable remission of T-cell prolymphocytic leukemia with CLEC16A::IL2 after allogeneic hematopoietic stem cell transplantation].
A 64-year-old woman presented with fine motor impairment in both hands. MRI revealed a contrast-enhanced lesion in the medulla oblongata. Lymphoid cells with abnormal blebs were observed and a CD4+/CD8+ double positive (DP) T cell population was detected by flow cytometry (FCM) in the bone marrow (BM) and the peripheral blood (PB). CLEC16A::IL2 fusion gene was identified by whole exome sequencing with DNA prepared from DP T cells. Clonal rearrangement of the T-cell receptor gene and expression of TCL1A protein were detected. This led to a diagnosis of T-cell prolymphocytic leukemia (T-PLL) with central nervous system (CNS) infiltration. Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab. Meanwhile, the CLEC16A::IL2 fusion mRNA remained detectable in PB. Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.
2018-10-04 | T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1
T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when over-expressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/- adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e. the secondary hair germ) and in the stem cell niche (i.e. the bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative–differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/- and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/- mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KCs.
2016-02-12 | Resimmune, an anti-CD3ε recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma.
Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 - 11.25 μg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%-57%) including four complete remissions (16%, 95% CI, 5%-36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208.
1998-09-22 | Granulocyte colony-stimulating factor in the combination chemotherapy for adult T-cell leukemia (ATL).
We evaluated the effect of granulocyte colony-stimulating factor (G-CSF) on the median survival of 17 patients with Adult T-cell leukemia (ATL). Standard-dose combination chemotherapy using the response-oriented cyclic multidrug (RCM) protocol with G-CSF (lenograstim 2 microg/kg/day or filgrastim 50 microg/m2/day) was administered between October 1990 and December 1994. Complete responses (CR) were achieved in 11 (64.7%) patients, and partial responses (PR) in 4 (23.5%) patients. The median duration of survival was 7.4 months, compared with 6.0 months in ATL patients treated with the RCM protocol alone (historical controls) (n.s.). Infectious complications were the cause of death in 4 (26.7%) of the 15 patients who died. The median duration of neutropenia (absolute neutrophil count < 1.0 x 10(9)/L) was 6 days. G-CSF, in the doses and schedules used here, may have shortened the duration of neutropenia and reduced the incidence of fatal infectious complications. However, concomitant use of G-CSF did not prolong the median duration of survival in patients with ATL treated according to the RCM protocol.
antibodies
2026-03-16 | UMG1 Defines a Targetable Subset of T-Cell Lymphomas and Enables Precision Immunotherapy With a First-in-Class CD3ε Bispecific Engager.
T-cell lymphomas (TCLs) account for a relatively small fraction of lymphoid malignancies and are characterized by highly aggressive course often refractory to current available therapies. We previously reported potent in vitro and in vivo antitumor activity of a Bispecific T-Cell Engager (UMG1/CD3ε-BTCE) directed against UMG1, a unique CD43 epitope that is abundantly expressed on T-cell acute lymphoblastic leukemia (T-ALL) and diffuse large B-cell lymphoma (DLBCL) cells, while absent in most normal tissues, except thymocytes and a small fraction of peripheral blood T lymphocytes (< 5%). Here, we investigated the in vitro efficacy of UMG1/CD3ε-BTCE against TCLs. IHC analysis of Tissue Micro Arrays (TMAs) revealed high UMG1 expression in 62.3% of TCL samples, including peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and ALK-negative anaplastic large cell lymphoma (ALCL). Notably, all T-PLL primary specimens (27/27) were positive, and 3 of 4 TCL cell lines also expressed UMG1 by flow cytometry. The asymmetric UMG1/CD3ε-BTCE induced robust redirected cytotoxicity against UMG1-expressing TCL cells. Moreover, this activity was strengthened by cell exposure to the HDAC inhibitor SAHA. We observed a dose-dependent engaged T-cell-mediated cytotoxicity and inflammatory cytokine release, resulting in lysis of UMG1-expressing cells, with no significant effect on UMG1-not expressing cells. Our findings suggest that the UMG1/CD3ε-BTCE selectively exerts potent anti-tumor activity against a relevant subset of TCLs. These findings support the development of a precision immunotherapy approach for patients with UMG1-expressing aggressive hematologic malignancies.
2026-01-15 | Phase 1B pilot study of itacitinib with alemtuzumab in patients with T-cell prolymphocytic leukemia.
T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and platelet >30 × 103/μL. Cycle 1 included a lead-in phase with itacitinib monotherapy days 1-14. Beginning day 15, patients also received alemtuzumab 30mg IV 3 times weekly for up to 4 (28-day) cycles or until best response. At best response, up to 8 cycles of maintenance with single-agent itacitinib was allowed. Median age was 65 years (range, 39-83). Ten patients (67%) had complex cytogenetics, 11 (73%) had chromosome 14 abnormality, and 13 (87%) were TCL1A positive by fluorescence in situ hybridization. Among frontline patients, overall response rate (ORR) was 88% (complete remission [CR]: 75%), median event-free survival (EFS) and overall survival (OS) were 11.6 and 19.5 months, respectively. Three frontline patients proceeded to allogeneic stem cell transplantation. The ORR in the relapsed/refractory cohort was 57% (CR: 43%), whereas median EFS and OS were 11.1 months. Most (85%) adverse events were grade 1 to 2 and none were attributed to itacitinib. Continued studies evaluating JAK inhibitors in patients with T-PLL are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03989466.
2026-01-03 | CD47 blockade-driven necroptosis complements BCL-2 inhibition-driven apoptosis in lymphoid malignancies
BACKGROUND: Immune checkpoint blockade of CD47 has shown promising results in lymphoid malignancies, with its effects attributed to enabling tumor-cell phagocytosis. However, alternate cytotoxic cell death mechanisms have been reported, potentially contributing to the overall anti-tumor activity. Although previous studies have highlighted a mechanism of caspase-independent cell death, this mechanism has yet to be well-characterized, thereby warranting further investigation to comprehensively understand the anti-tumor mechanism of CD47 blockade to facilitate optimal drug partner selection for combination therapy. METHODS: The fully humanized anti-CD47 monoclonal antibodies, SRF231, magrolimab, as well as a mouse monoclonal anti-CD47 antibody, B6H12, were used. Multiple cell death mechanisms were evaluated including apoptosis, autophagy and necroptosis by using customized Hoechst/Annexin V, the precision medicine technique BH3 profiling, as well as standard experimental techniques – flow cytometry, siRNA and CRISPR Cas9 genetic manipulation, Western blotting, and immunohistochemistry. These techniques were used on a comprehensive range of lymphoid malignant models including diffuse large B-cell lymphoma, Burkitt lymphoma, and T-acute lymphoblastic leukemia cell lines, patient primary chronic lymphocytic leukemia cells, as well as lymphoid cell-line derived and patient-derived xenograft mice, to elucidate the mechanism of cell death by CD47 blockade and to identify the optimal drug partners for treatment combination. RESULTS: We demonstrate that the anti-CD47 antibodies SRF231, magrolimab, and B6H12 eliminated tumor cells from various in vitro and in vivo lymphoid malignant models via the activation of the RIPK1/MLKL/necroptotic pathway. Moreover, the BH3 profiling technique distinguished two different lymphoid malignant models that respond differently to the BCL-2 inhibitor venetoclax when combined with SRF231; one highlighting the effective yet distinct mechanisms of SRF231-induced necroptosis and venetoclax-induced apoptosis in models that were specifically and/or highly dependent on BCL-2 for survival, while the other implicating venetoclax as a counterproductive partner with SRF231 in models that were not dependent on BCL-2 for survival or were not responsive to venetoclax treatment. CONCLUSION: Collectively, this study unravels a novel, non-canonical cell death mechanism of targeting CD47 by activating necroptosis, and provides evidence and rationale for further evaluation of a therapeutic strategy of combining CD47 blockade with and without apoptotic inducers for suitable patients with lymphoid malignancies.
2025-09-08 | A Rare Case of Renal Failure Caused by T-Cell Prolymphocytic Leukaemia Infiltration.
T-cell prolymphocytic leukaemia (T-PLL) is an aggressive and rare post-thymic T cell malignancy, highly refractory to conventional cytotoxic chemotherapeutics. While extranodal involvement is common, solid organ invasion is rare. We present the case of a 76-year-old man who developed acute renal failure secondary to T-PLL renal infiltration. On day four of his admission, prior to commencing alemtuzumab, his creatinine rose from 133 μmol/L to 390 μmol/L, with anuria. Renal biopsy demonstrated an infiltrate of monomorphic, mononuclear cells positive for a STAT5B mutation, consistent with T-PLL infiltration. He required haemodialysis, but was treated with pulsed methylprednisolone and alemtuzumab, with excellent renal recovery, although remission was not achieved. This case demonstrates that renal leukaemic infiltration must be considered in T-PLL patients with rapidly progressive renal failure, and that solid organ invasion should not contraindicate timely commencement of T-PLL-directed therapy with alemtuzumab.
2025-08-23 | Exploring SLAMF5/CD84 in Cancer: Advancing the Frontiers of Tumor Immunology
The Signaling Lymphocytic Activation Molecule (SLAM) family receptors play essential roles in regulating immune cell activation, differentiation, and communication. SLAMF5, also known as CD84, has drawn increasing attention in cancer immunology due to its involvement in both tumor progression and immune modulation. This review explores the expression patterns, signaling mechanisms, and functional roles of SLAMF5/CD84 within the tumor microenvironment. SLAMF5/CD84 is expressed on multiple immune cell types and contributes to immune evasion by enhancing regulatory B cell function, promoting myeloid-derived suppressor cell expansion, and upregulating immune checkpoint molecules such as PD-L1. Its expression has been implicated in various hematologic malignancies and solid tumors, including chronic lymphocytic leukemia, multiple myeloma, and triple-negative breast cancer. Emerging therapeutic approaches targeting SLAMF5/CD84-such as monoclonal antibodies and CAR T-cell therapies-offer promising strategies to counteract immunosuppression and improve treatment outcomes. By highlighting recent findings and therapeutic developments, this review underscores the significance of SLAMF5/CD84 as both a prognostic biomarker and a novel target in cancer immunotherapy. Understanding SLAMF5/CD84's multifaceted roles in the tumor immune landscape could support the development of more effective and personalized cancer treatment strategies.
small molecules
2026-04-09 | A case of T-prolymphocytic leukemia harboring RAS mutation.
The text reports the clinical case of a 61-year-old woman with a long history of generalized pruritus who was eventually diagnosed with T-cell prolymphocytic leukemia (T-PLL), a rare and aggressive T-cell lymphoproliferative disorder. At presentation, the patient had fever, skin lesions, lymphocytosis, thrombocytopenia, coagulation abnormalities, and marked splenomegaly without lymphadenopathy. Morphological, immunophenotypic, and histological analyses of peripheral blood and bone marrow revealed diffuse infiltration by mature T lymphocytes with strong TCL1 expression, and T-cell receptor gene rearrangement confirmed clonality, supporting the diagnosis of T-PLL. The patient initially received bendamustine chemotherapy, which failed to induce a response. Second-line treatment with the anti-CD52 monoclonal antibody alemtuzumab was subsequently initiated, but the disease proved refractory, with persistent bone marrow involvement, worsening cytopenias, disease progression, and clinical deterioration. As a result, alemtuzumab was discontinued and the patient was transitioned to palliative care. A particularly notable finding was the detection, by next-generation sequencing, of a pathogenic KRAS G12A mutation, which has not previously been reported in T-PLL. This mutation was identified incidentally using a myeloid-targeted NGS panel. The finding broadens the known mutational spectrum of T-PLL and suggests that activation of the RAS signaling pathway may represent an alternative oncogenic mechanism beyond the canonical TCL1 and JAK–STAT pathways. We suggest that investigating for KRAS mutations in additional T-PLL cases may be beneficial to explore this pathogenetic pathway and could open new avenues for future targeted therapeutic strategies.
2025-12-04 | Invasive Talaromyces marneffei Fungemia in an HIV-Negative Patient with T-Prolymphocytic Leukaemia: A Case Report and Review of Emerging Risks.
Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus traditionally associated with HIV-related immunosuppression. However, increasing reports have described infections in HIV-negative patients with hematologic malignancies, particularly those receiving novel immunosuppressive therapies. We report a case of disseminated T. marneffei in an HIV-negative 55-year-old woman with T-prolymphocytic leukaemia (T-PLL) undergoing chemotherapy and targeted therapy with chidamide and golidocitinib. The patient presented with fever, pancytopenia, and signs of systemic infection. Blood cultures confirmed T. marneffei, with identification supported by dual-phase morphology and internal transcribed spacer (ITS) sequencing. Due to unavailability of amphotericin B, the patient was treated successfully with voriconazole, achieving rapid clinical improvement and negative follow-up cultures. This case adds to the growing evidence that T. marneffei can cause invasive infections in non-HIV immunocompromised hosts. Through a review of 10 published cases, we identify common features such as neutropenia, kinase inhibitor use, and diagnostic delays. We emphasize the importance of early fungal culture and phase-specific morphology for diagnosis, and highlight voriconazole as a viable alternative therapy when amphotericin B is inaccessible. Clinicians should maintain high suspicion for talaromycosis in immunosuppressed hematologic patients in endemic regions, regardless of HIV status. Prompt recognition and appropriate antifungal therapy are essential to improve outcomes.
2025-11-24 | Epidemiology and survival of patients with T-cell prolymphocytic leukemia
T-prolymphocytic leukemia (T-PLL) is a very rare but aggressive T-cell neoplasm affecting mainly elderly patients [ 1 ]. Clinical presentation typically involves progressive lymphocytosis, hepatosplenomegaly, lymphadenopathy, and extramedullary symptoms, although up to 20% of patients might initially present with a stable disease course [ 2 ]. Consensus criteria for diagnosis and treatment have only recently been defined and clinical trials remain sparse. Consequently, treatment options for patients with T-PLL are limited and reported outcomes in small single institution studies remain poor with a median overall survival of 7.5 to 19 months [ 1 , 2 , 3 ]. Currently, the IgG1 monoclonal CD52 antibody alemtuzumab is recommended as first-line treatment, achieving high initial response rates in newly diagnosed patients [ 4 ]. Alternatively, the combination of Fludarabine, Mitoxantrone and Cyclophosphamide (FMC) has been used. Subsequent autologous or allogenic hematopoietic stem cell transplant (HCT) in complete remission (CR) should follow in fit patients and can induce long-term disease-free survival. However, due to the disease demographics, only 30–50% of patients are eligible for intensive HCT regimens [ 5 , 6 ]. In refractory cases, Pentostatin and Bendamustine have shown limited efficacy, whereas newer options such as Ruxolitinib are being explored with promising early results [ 3 , 4 , 7 ].
2025-11-03 | MYC/GSPT1 protein degradation in refractory/relapsed T-cell prolymphocytic leukemias
Abstract Background: T-cell prolymphocytic leukemia (T-PLLs) is a rare, mature T-cell-derived, aggressive hematologic malignancy. T-PLLs are one of the most challenging hematologic malignancies based on refractoriness to conventional chemotherapy and targeted therapies, including alemtuzumab. Chromosome rearrangement and overexpression of TCL-1 are hallmarks of T-PLL, accounting for approximately 95% of cases. Nearly 50% of cases carry chromosome 8 gains, leading to upregulation of the oncogene c-Myc. Recently, we discovered a feedforward loop of c-Myc and GSPT1 (eRF3a), a key translation termination factor that promotes translation in leukemias, and established highly effective anti-leukemia/lymphoma activities of GT19630, the first-in-class MYC/GSPT1 proteolysis targeting chimera in MYC-driven hematologic malignancies (Nishida et al. biorxiv 2025 650490, under revision). We hypothesized that c-Myc/GSPT1 translation is activated in T-PLL cells and targeting c-Myc/GSPT1 by protein degradation is effective in relapsed/refractory T-PLLs. Method: We evaluated single-cell levels of baseline protein translation using the O-propargyl-puromycin (OPP) nascent protein synthesis assay and multicolor flow cytometry in T-PLL and normal peripheral blood mononuclear cells (PBMCs). We investigated the activity of GT19715 in T-PLL patient-derived xenograft (PDX) models established from relapsed/refractory T-PLL patients in vitro and in vivo. Single-cell mass cytometry (CyTOF) was applied to determine distinct surface and intracellular molecular features of primary and PDX T-PLL cells. Results: c-Myc and GSPT1 protein levels were increased in T-PLL cells compared to PBMCs. Compared to CD3+ normal T-cells from healthy donors (N = 3), CD7+ T-PLL cells in primary T-PLL samples (N = 5) exhibited significantly increased baseline protein translation levels determined by OPP protein synthesis flow cytometry (Mean fluorescence intensity: 532.3 ± 88.1 vs 7,090 ± 1,193 for CD3+ T-cells vs CD7+ T-PLL cells, respectively, P = 0.0062), suggesting increased c-Myc/GSPT1 protein translation in T-PLL cells compared to normal PBMCs. GT19715 degraded c-Myc and GSPT1 proteins at 1 nM and induced cell death in PDX T-PLL cells (IC50 < 1 nM). GT19715 dramatically reduced circulating T-PLL cells and significantly prolonged survival in mice carrying PDX T-PLL cells (median OS 1.0 vs 9.3 weeks for vehicle- and GT19715-treated groups, respectively, P < 0.0001). After euthanizing mice, we found spleen and liver packed with T-PLL cells in vehicle control mice while only minimal remaining tumor cells in liver peri-centrolobular regions, suggesting sustained tumor suppression in vivo. CyTOF analysis revealed high levels of CD2, CD4, CD7, TCL1 and ZAP70 in primary and PDX T-PLL cells compared to normal bone marrow T cells. Primary and PDX T-PLL samples share a distinct cell population with elevated levels of CD26, CD28, CD69, and CD45RA. Interestingly, these cells exhibit elevated TCL-1, ZAP70, BCL-2, MCL-1, p-AKT, p-NFkB and p-STAT5 levels with partially high Ki-67, features that suggest identification of a clone driving propagation and therapy resistance. Conclusion: We identified increased protein translation of c-Myc and GSPT1 in T-PLL cells compared to normal PBMCs. Targeted protein degradation of c-Myc and GSPT1 is highly effective in relapsed/refractory T-PLL in vitro and in vivo, with over 900% extension of survival in a clinically relevant, PDX T-PLL model, providing rationale for clinical investigations.
2025-10-28 | Comparative preclinical drug response analyses of T-prolymphocytic leukemia reveal no differences between known gene expression subgroups.
T-prolymphocytic leukemia (T-PLL) is a rare mature T-cell neoplasm with poor prognosis that mainly affects elderly people. Alemtuzumab is widely considered as first-line therapy, but almost all patients relapse within one year, if not consolidated by an allogeneic stem cell transplantation. The improved understanding of T-PLL-specific molecular pathomechanisms gained over the last years suggested new potential therapeutic targets (epigenetic dysregulation, defective DNA damage response, aberrant cell cycle regulation, dysregulated prosurvival pathways), which were recently evaluated in a preclinical drug response study. In addition, existing genomewide T-PLL gene expression profiles enabled the identification of three robust T-PLL gene expression subgroups differing in cellular processes like immune response, cellular respiration, cell proliferation, apoptosis, or migration. So far, these T-PLL gene expression subgroups were not considered in preclinical drug response analyses, but recently published drug response screens and corresponding already publicly available gene expression profiles offer the great opportunity to integrate both data types. Therefore, we computationally analyzed samples from 34 T-PLL patients of two comparable cohorts for their response to in total 11 drugs. No T-PLL subgroup-specific differences or sex differences in response to the tested drugs were found. With respect to the underlying drug dosage schemes, venetoclax and cladribine were most effective in erasing T-PLL cancer cells among both cohorts. Also dinaciclib, idasanutlin, romidepsin, and KRT-232, which were only tested in one of both cohorts, were very effective for all or most of the T-PLL patient samples. For the three drugs bendamustine, cladribine, and fludarabine, which were only effective in a subset of the T-PLL samples, an exploratory differential gene expression analysis predicted drug-specific genes that distinguished between strongly and not strongly responding samples. In-depth annotation and literature analyses showed that many of these genes are known to play a role in leukemias or other types of cancer. Many of these genes were also confirmed by a direct correlation analysis between gene expression levels and drug responses. The absence of T-PLL gene expression subgroup-specific drug responses across the tested drugs can be important for the design of future drug screens and may ease potential clinical trials. Genes associated with drug-specific responses could be useful for improved patient stratification and may help to characterize molecular settings associated with effective responses. Not applicable. The online version contains supplementary material available at 10.1186/s13062-025-00701-3.
oligonucleotides
2023-04-28 | The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL
T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease.
2023-03-31 | Data from Noncanonical Function of AGO2 Augments T-cell Receptor Signaling in T-cell Prolymphocytic Leukemia
<div>Abstract<p>T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-refractory T-cell malignancy with limited therapeutic options and a poor prognosis. Current disease concepts implicate TCL1A oncogene-mediated enhanced T-cell receptor (TCR) signaling and aberrant DNA repair as central perturbed pathways. We discovered that recurrent gains on chromosome 8q more frequently involve the <i>argonaute RISC catalytic component 2 (AGO2)</i> gene than the adjacent <i>MYC</i> locus as the affected minimally amplified genomic region. AGO2 has been understood as a protumorigenic key regulator of miRNA (miR) processing. Here, in primary tumor material and cell line models, AGO2 overrepresentation associated (i) with higher disease burden, (ii) with enhanced <i>in vitro</i> viability and growth of leukemic T cells, and (iii) with miR-omes and transcriptomes that highlight altered survival signaling, abrogated cell-cycle control, and defective DNA damage responses. However, AGO2 elicited also immediate, rather non–RNA-mediated, effects in leukemic T cells. Systems of genetically modulated AGO2 revealed that it enhances TCR signaling, particularly at the level of ZAP70, PLCγ1, and LAT kinase phosphoactivation. In global mass spectrometric analyses, AGO2 interacted with a unique set of partners in a TCR-stimulated context, including the TCR kinases LCK and ZAP70, forming membranous protein complexes. Models of their three-dimensional structure also suggested that AGO2 undergoes posttranscriptional modifications by ZAP70. This novel TCR-associated noncanonical function of AGO2 represents, in addition to TCL1A-mediated TCR signal augmentation, another enhancer mechanism of this important deregulated growth pathway in T-PLL. These findings further emphasize TCR signaling intermediates as candidates for therapeutic targeting.</p>Significance:<p>The identification of AGO2-mediated activation of oncogenic T cells through signal amplifying protein–protein interactions advances the understanding of leukemogenic AGO2 functions and underlines the role of aberrant TCR signaling in T-PLL.</p></div>
2022-03-31 | Micro-RNA networks in T-cell prolymphocytic leukemia reflect T-cell activation and shape DNA damage response and survival pathways.
T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic mature T-cell malignancy. It typically presents with exponentially rising lymphocyte counts, splenomegaly, and bone marrow infiltration. Effective treatment options are scarce and a better understanding of TPLL's pathogenesis is desirable. Activation of the TCL1 proto-oncogene and loss-of-function perturbations of the tumor suppressor ATM are TPLL's genomic hallmarks. The leukemic cell reveals a phenotype of active T-cell receptor (TCR) signaling and aberrant DNA damage responses. Regulatory networks based on the profile of microRNA (miR) have not been described for T-PLL. In a combined approach of small-RNA and transcriptome sequencing in 46 clinically and moleculary well-characterized T-PLL, we identified a global T-PLL-specific miR expression profile that involves 34 significantly deregulated miR species. This pattern strikingly resembled miR-ome signatures of TCR-activated T cells. By integrating these T-PLL miR profiles with transcriptome data, we uncovered regulatory networks associated with cell survival signaling and DNA damage response pathways. Despite a miR-ome that discerned leukemic from normal T cells, there were also robust subsets of T-PLL defined by a small set of specific miR. Most prominently, miR-141 and the miR- 200c-cluster separated cases into two major subgroups. Furthermore, increased expression of miR-223-3p as well as reduced expression of miR-21 and the miR-29 cluster were associated with more activated Tcell phenotypes and more aggressive disease presentations. Based on the implicated pathobiological role of these miR deregulations, targeting strategies around their effectors appear worth pursuing. We also established a combinatorial miR-based overall survival score for T-PLL (miROS-T-PLL), that might improve current clinical stratifications.
2022-03-08 | Noncanonical Function of AGO2 Augments T-cell Receptor Signaling in T-cell Prolymphocytic Leukemia
Abstract T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-refractory T-cell malignancy with limited therapeutic options and a poor prognosis. Current disease concepts implicate TCL1A oncogene-mediated enhanced T-cell receptor (TCR) signaling and aberrant DNA repair as central perturbed pathways. We discovered that recurrent gains on chromosome 8q more frequently involve the argonaute RISC catalytic component 2 (AGO2) gene than the adjacent MYC locus as the affected minimally amplified genomic region. AGO2 has been understood as a protumorigenic key regulator of miRNA (miR) processing. Here, in primary tumor material and cell line models, AGO2 overrepresentation associated (i) with higher disease burden, (ii) with enhanced in vitro viability and growth of leukemic T cells, and (iii) with miR-omes and transcriptomes that highlight altered survival signaling, abrogated cell-cycle control, and defective DNA damage responses. However, AGO2 elicited also immediate, rather non–RNA-mediated, effects in leukemic T cells. Systems of genetically modulated AGO2 revealed that it enhances TCR signaling, particularly at the level of ZAP70, PLCγ1, and LAT kinase phosphoactivation. In global mass spectrometric analyses, AGO2 interacted with a unique set of partners in a TCR-stimulated context, including the TCR kinases LCK and ZAP70, forming membranous protein complexes. Models of their three-dimensional structure also suggested that AGO2 undergoes posttranscriptional modifications by ZAP70. This novel TCR-associated noncanonical function of AGO2 represents, in addition to TCL1A-mediated TCR signal augmentation, another enhancer mechanism of this important deregulated growth pathway in T-PLL. These findings further emphasize TCR signaling intermediates as candidates for therapeutic targeting. Significance: The identification of AGO2-mediated activation of oncogenic T cells through signal amplifying protein–protein interactions advances the understanding of leukemogenic AGO2 functions and underlines the role of aberrant TCR signaling in T-PLL.
2021-02-18 | The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia
T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and/or genotypic subgroups that may explain the heterogeneity of the disease. Multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups, and no clear T-cell receptor a or β CDR3 skewing was observed between different T-PLL cases. We revealed that the expression of microRNA (miRNA) is aberrant and often heterogeneous in T-PLL. We identified 35 miRNA that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR- 200c/141 and miR-181a/181b expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 correlated with downregulation of their targets ZEB2 and TGFβR3 and aberrant TGFβ1- induced phosphorylated SMAD2 (p-SMAD2) and p-SMAD3, indicating that the TGFβ pathway is affected in T-PLL. Our results thus highlight the potential role for aberrantly expressed oncogenic miRNA in T-PLL and pave the way for new therapeutic targets in this disease.
cell therapies
2026-05-28 | Allogeneic stem cell transplantation in T-cell prolymphocytic leukemia: final disappointment or a chance for cure?
Not available.
2026-03-30 | Allogeneic transplant outcomes in T-cell prolymphocytic leukemia: a single-center retrospective study.
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive malignancy with a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HCT) is often used for treatment, but its effectiveness remains unclear. In this study of 33 adult patients with T-PLL who underwent HCT, 5-year progression-free survival (PFS) was 29% (95% confidence interval [CI], 14-45) and 5-year overall survival (OS) was 41% (95% CI, 24-57). Five-year cumulative incidence of non-relapse mortality was 18%, while 5-year cumulative incidence of relapse was 53%. Univariable analysis revealed that a longer time from diagnosis to HCT was significantly associated with improved PFS (hazard ratio, 0.36; 95% CI, 0.15-0.87). Analysis of immune reconstitution in 22 patients showed a relatively slow recovery of immune cells post-HCT. A higher recovery of CD3 T cells was also associated with increased risk of relapse, which may have prognostic significance and warrants further investigation as a risk factor for disease recurrence.
2026-03-28 | How We Evaluate and Treat Leukemic Presentations of Mature T-Cell Lymphomas.
T-cell non-Hodgkin lymphomas, which arise from post-thymic mature T cells, constitute approximately 10-15% of all non-Hodgkin lymphomas. Their leukemic presentations, referred to here as mature T-cell leukemias, are relatively uncommon and present significant diagnostic and therapeutic challenges requiring an informed approach to diagnosis and management. The initial presentation is often persistent T-cell lymphocytosis that must be distinguished from reactive (non-malignant) causes. Unlike B-cell lymphocytosis, where clonality usually indicates malignancy, T-cell clonality can be detected in benign conditions such as autoimmune disorders and viral infections. Thus, establishing clonality is helpful but not sufficient, and a systematic diagnostic approach integrating clinical features, morphology, immunophenotype, and molecular findings is critical. This review outlines our approach to the diagnosis and treatment of four major subtypes of mature T-cell leukemias: T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), T-large granular lymphocytic leukemia (T-LGL), and Sézary syndrome (SS). Each section includes a discussion of clinical features, workup, and treatment options.
2026-03-09 | Cutaneous‐Only Relapse in T‐Cell Prolymphocytic Leukemia With JAK2 Rearrangement
The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
2026-02-20 | A Unique Case of Concomitant T-Prolymphocytic Leukemia and B-Cell Acute Lymphoblastic Leukemia.
T-prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with a poor prognosis. B-cell acute lymphoblastic leukemia (B-ALL) also confers a poor prognosis, especially in patients with high-risk features without an option for transplant. Here, we present a case of a patient with T-PLL initially treated with multi-agent chemotherapy who then developed B-ALL, the management strategies, and possible pathogenesis of two concurrent rare malignancies. One proposed mechanism for the development of both hematologic malignancies in this patient is the acquisition of a KMT2A rearrangement, raising the possibility of clonal evolution resulting in therapy-related or secondary leukemia. Another explanation is the presence of a common clonal stem cell progenitor harboring a JAK3 mutation.
other
2024-02-12 | [Durable remission of T-cell prolymphocytic leukemia with CLEC16A::IL2 after allogeneic hematopoietic stem cell transplantation].
A 64-year-old woman presented with fine motor impairment in both hands. MRI revealed a contrast-enhanced lesion in the medulla oblongata. Lymphoid cells with abnormal blebs were observed and a CD4+/CD8+ double positive (DP) T cell population was detected by flow cytometry (FCM) in the bone marrow (BM) and the peripheral blood (PB). CLEC16A::IL2 fusion gene was identified by whole exome sequencing with DNA prepared from DP T cells. Clonal rearrangement of the T-cell receptor gene and expression of TCL1A protein were detected. This led to a diagnosis of T-cell prolymphocytic leukemia (T-PLL) with central nervous system (CNS) infiltration. Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab. Meanwhile, the CLEC16A::IL2 fusion mRNA remained detectable in PB. Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.
2018-10-04 | T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1
T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when over-expressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/- adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e. the secondary hair germ) and in the stem cell niche (i.e. the bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative–differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/- and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/- mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KCs.
2016-02-12 | Resimmune, an anti-CD3ε recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma.
Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 - 11.25 μg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%-57%) including four complete remissions (16%, 95% CI, 5%-36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208.
1998-09-22 | Granulocyte colony-stimulating factor in the combination chemotherapy for adult T-cell leukemia (ATL).
We evaluated the effect of granulocyte colony-stimulating factor (G-CSF) on the median survival of 17 patients with Adult T-cell leukemia (ATL). Standard-dose combination chemotherapy using the response-oriented cyclic multidrug (RCM) protocol with G-CSF (lenograstim 2 microg/kg/day or filgrastim 50 microg/m2/day) was administered between October 1990 and December 1994. Complete responses (CR) were achieved in 11 (64.7%) patients, and partial responses (PR) in 4 (23.5%) patients. The median duration of survival was 7.4 months, compared with 6.0 months in ATL patients treated with the RCM protocol alone (historical controls) (n.s.). Infectious complications were the cause of death in 4 (26.7%) of the 15 patients who died. The median duration of neutropenia (absolute neutrophil count < 1.0 x 10(9)/L) was 6 days. G-CSF, in the doses and schedules used here, may have shortened the duration of neutropenia and reduced the incidence of fatal infectious complications. However, concomitant use of G-CSF did not prolong the median duration of survival in patients with ATL treated according to the RCM protocol.
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Drug Discovery Landscape
3 orphan drug designations for T-cell prolymphocytic leukemia.
3 orphan drug designations for T-cell prolymphocytic leukemia.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Tinostamustine | small molecules | EMA | 2020-07-27 | — | Mundipharma Corporation (Ireland) Limited |
tinostamustine hydrochloride | small molecules | FDA | 2019-03-15 | — | Knoa Pharma LLC |
(1S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol-hydrochloride | small molecules | FDA | 2004-08-10 | — | Mundipharma Research Ltd. |
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