2026-08-15 | Anti-CD123 CAR-T therapy combined with autologous SCT and venetoclax maintenance in refractory BPDCN ineligible for allogeneic transplantation: a case report and review of the literature.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with limited therapeutic options for patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). While CD123-targeted therapies and CAR T-cell infusion have shown promise, achieving durable remission without consolidative transplantation remains challenging. We report a pioneering "triple-integrated" consolidation strategy in a 55-year-old male with relapsed/refractory BPDCN and central nervous system involvement who lacked a suitable HLA-matched donor. After achieving a complete metabolic response with persistent bone marrow minimal residual disease (MRD) following Hyper-CVAD chemotherapy, the patient underwent high-dose conditioning and autologous stem cell transplantation (ASCT) sequentially followed by autologous CD123 CAR T-cell infusion (1.74×106/kg). The clinical course was complicated by Grade 3 cytokine release syndrome and suspected immune effector cell-associated HLH-like syndrome (IEC-HS), which were successfully managed with glucocorticoid and emapalumab. Notably, ASCT served as a "hematopoietic rescue" for CAR-T-induced prolonged cytopenia. To prevent late clonal escape, maintenance therapy with the BCL-2 inhibitor venetoclax was initiated post-transplant. The patient achieved sustained MRD-negative CR with a disease-free survival exceeding 13 months. This multimodal paradigm-combining intensive cytoreduction, targeted immunotherapy with marrow rescue, and molecular maintenance-provides a feasible and potentially curative alternative for BPDCN patients in the "no-donor" setting.
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2026-08-15 | TA-TMA occurring after sequential CD7 CAR-T cell therapy and allogeneic hematopoietic stem cell transplantation: a case report.
Currently, CAR-T cell therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a pivotal therapeutic strategy for refractory/relapsed hematologic malignancies. Sequential therapy with CD7 chimeric antigen receptor T (CAR-T) cells combined with allo-HSCT provides a novel therapeutic approach for T-lymphoid malignancies, CD7-highly expressed acute myeloid leukemia (AML), and mixed phenotype acute leukemia (MPAL). This strategy circumvents the toxicities of conventional myeloablative conditioning chemotherapy and immunosuppressive agents, while achieving tumor eradication, hematopoietic reconstitution, and prevention of graft-versus-host disease (GVHD). Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but life-threatening complication following allo-HSCT, associated with elevated non-relapse mortality (NRM). This article reports a case of early-onset TA-TMA in a patient with MPAL after CD7 CAR-T bridging to allo-HSCT. This study aims to enhance clinicians' awareness of the diagnosis and management of TA-TMA following CAR-T bridging to allo-HSCT, provide a reference for early identification and timely intervention, and further improve patient outcomes.
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2026-08-14 | Ruxolitinib-Associated Improvement in Post-transplant Air-Leak Syndrome Complicating Steroid-Dependent Organizing Pneumonia: A Case Report.
Air-leak syndrome (ALS), including pneumothorax, pneumomediastinum, and subcutaneous emphysema, is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, no standard treatment has yet been established. Here, we report the case of a 60-year-old man with acute myeloid leukemia who underwent allogeneic HSCT. He developed chronic graft-versus-host disease (GVHD) and cryptogenic organizing pneumonia (COP) on day 126 after transplantation. Although initial corticosteroid therapy improved the COP, the relapse occurred during tapering, and repeated steroid treatment failed to achieve sustained disease control. The patient subsequently developed pneumomediastinum, consistent with ALS. Ruxolitinib treatment was initiated on day 265 for steroid-dependent chronic GVHD and organizing pneumonia. Following treatment, oxygenation improved, pneumomediastinum improved, and corticosteroids were successfully tapered and discontinued without COP recurrence. Serum Krebs von den Lungen-6 (KL-6) levels decreased in parallel with clinical and radiological improvement. The introduction of ruxolitinib is associated with improvements in ALS and enabled the discontinuation of steroids. Adverse events included cytopenia and mild liver dysfunction, consistent with known safety profiles. The patient died of acute respiratory failure after transfusion, which was not considered a direct complication of the ruxolitinib treatment. This case suggests that ruxolitinib may facilitate corticosteroid tapering and radiographic improvement of organizing pneumonia-associated ALS after allogeneic transplantation.
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2026-08-13 | Protective Role of Donor KIR B Haplotype in Cytomegalovirus Reactivation Following T-Cell-Depleted Hematopoietic Stem Cell Transplantation.
Background: Cytomegalovirus (CMV) reactivation is a major complication after hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells help control CMV through killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands, but donor-derived CMV-specific T-cells may confound the interpretation of NK-mediated effects. Methods: We analyzed 276 HLA-matched (10/10) adults receiving ATG-based T-cell-depleted myeloablative HSCT with a known donor and recipient CMV serostatus. The donor and recipient KIR genotypes were scored by the Cooley B-content score (0-4; ≥2 = high). Clinically significant CMV reactivation (plasma viral load > 25,000 IU/mL, the institutional threshold for pre-emptive therapy) was analyzed with Fine-Gray competing-risks regression, stratified by the donor-recipient serostatus. Results: In seronegative-donor/seropositive-recipient (D-R+) pairs (n = 68), a high donor KIR B-content score was associated with a significantly lower reactivation risk (sub-hazard ratio, 0.46; 95% CI, 0.24-0.91; p = 0.024). No effect was seen in D+R+ pairs (n = 82; SHR, 0.65; p = 0.241); D+R- (n = 28) had too few events to model. A donor Tel-AA/recipient Tel-B+ mismatch was independently associated with a higher reactivation risk (adjusted HR, 2.41; 95% CI, 1.33-4.37; p = 0.004). The overall survival was unaffected in either stratum. Conclusions: A high donor KIR B-content score protects against CMV reactivation in D-R+, but not D+R+, HSCT recipients, consistent with NK dominance when CMV-specific donor T-cells are sparse. A specific donor-recipient telomeric mismatch independently modifies the risk. Donor KIR profiling warrants prospective evaluation in donor-selection algorithms.
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2026-08-12 | Total body irradiation-based conditioning in allogeneic transplantation in patients with hematological malignancies: impact in outcomes by stem-cell source.
Total body irradiation is widely used in conditioning regimens before allogeneic hematopoietic stem-cell transplantation (allo-HSCT), most often in high-risk acute lymphoblastic leukemia. This study assessed survival outcomes and treatment-related toxicity in patients who underwent TBI-based myeloablative conditioning. We conducted a retrospective single-center study of patients who underwent allo-HSCT after TBI-based conditioning at a reference TBI-unit serving transplant across the Community of Madrid. Between 2011 and 2020, most patients (n = 52) received 10 Gy in 2 Gy fractions twice daily. Primary endpoints were overall survival (OS), disease-free survival (DFS), and relapse; secondary endpoints included non-relapse mortality (NRM), disease-related mortality (DRM), and toxicity. 58 patients underwent TBI-based conditioning using peripheral blood stem cells (PBSC; n = 37), umbilical cord blood (UCB; n = 19), or bone marrow (BM; n = 1); one patient died before graft infusion. Diagnoses were B-ALL (79.3%), followed by T-ALL (15.5%), non-Hodgkin lymphoma (3.4%), and acute myeloid leukemia (1.7%). Median follow-up was 28 months. At 12 months, OS, DFS, and relapse were 64%, 48%, and 29%, respectively. PBSC transplantation had significantly higher 12-month OS than UCB (78% vs. 37%, p < 0.001). Six-month NRM was 5% and 8% in PBSC recipients vs. 43% and 54% in UCB (p < 0.001). Graft-versus-host disease occurred in 51.7%, pulmonary complications in 32.8%, and neurological toxicity in 25.9%. Secondary malignancies were reported in four patients. TBI-based conditioning achieved acceptable outcomes in PBSC recipients but was associated with markedly higher NRM in UCB recipients. These findings highlight graft source as a critical determinant of survival and support individualized strategies in allo-HSCT.
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