small molecules

2026-09-25 | Case Report: Successful salvage therapy with sulbactam-durlobactam combined with meropenem for carbapenem-resistant Acinetobacter baumannii bloodstream infection in a child after failure of allogeneic hematopoietic stem cell transplantation.

Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) constitute a serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT), with pediatric patients facing particularly formidable therapeutic challenges. The phase III ATTACK trial demonstrates that sulbactam-durlobactam (SUL-DUR), a novel β-lactam-β-lactamase inhibitor combination is non-inferior to colistin and is associated with fewer adverse events in adults. However, evidence for SUL-DUR use in post-transplant pediatric patients remains extremely limited. This article reports the first global case of a pediatric patient who experienced two successive HSCT failures and was successfully salvaged with SUL-DUR combined with meropenem for CRAB associated BSI after failing to respond to high-dose sulbactam (150 mg/kg/day) and tigecycline during persistent severe neutropenia, providing a novel strategy for managing resistant bacterial infections in high-risk transplant populations.

Open article ↗

2026-09-23 | Paeoniflorin prevents acute graft-versus-host disease while preserving graft-versus-tumor effects.

Acute graft-versus-host disease (aGVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study investigated the preventive effects of paeoniflorin (PF), a natural monoterpene glycoside, on aGVHD. Candidate herb-derived compounds against aGVHD were screened using SymMap, HERB, ADMETlab, and InflamNat, followed by molecular docking. The preventive effects of PF were evaluated in major histocompatibility complex (MHC)-mismatched murine aGVHD models. An entire-process paeoniflorin (EP-PF) regimen, involving donor pretreatment before transplantation and recipient treatment after transplantation, was proposed for enhancing the preventive effect. Survival, body weight, clinical score, hematopoietic reconstitution, donor T cell infiltration, cytokine and chemokine levels, gut injury, apoptosis, gut microbiota, transcriptomic changes, and graft-versus-tumor (GVT) activity were assessed. PF was identified as a promising multi-target compound for aGVHD prevention. PF reduced clinical severity, body weight loss, and mortality, while improving hematopoietic recovery and increasing hematopoietic stem/progenitor cell (HSPC) numbers. EP-PF regimen showed stronger protection than recipient-only PF administration. Mechanistically, EP-PF reduced intestinal donor cluster of differentiation 4 (CD4) positive and cluster of differentiation 8 (CD8) positive T cell infiltration, partially restored CD4+/CD8+ T cell balance, and reversed inflammatory transcriptional programs in donor T cells. Moreover, EP-PF balanced serum levels of cytokines and chemokines, preserved gut barrier integrity, reduced intestinal apoptosis, and partially corrected gut microbiota dysbiosis. Importantly, EP-PF preserved donor cell-mediated tumor control in a green fluorescent protein (GFP)-labeled A20 GVT model. PF also directly inhibited the proliferation of hematologic tumor cells and promoted their apoptosis in vitro and in vivo. PF prevents experimental aGVHD through coordinated regulation of donor T cell responses, inflammatory mediators, hematopoietic reconstitution, intestinal barrier injury, apoptosis, and gut microbiota, while preserving GVT activity. These findings support PF as a potential prophylactic candidate for allo-HSCT.

Open article ↗

2026-09-16 | Conversion from calcineurin inhibitor to ruxolitinib as GVHD prophylaxis during patients with transplant-associated thrombotic microangiopathy.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with multifactorial etiology. Existing clinical guidelines recommend discontinuation or tapering of calcineurin inhibitors (CNIs) as the primary intervention after the initial TMA diagnosis; however, data on the options for immunosuppression manipulation (ISM) are limited. Ruxolitinib is an effective option in treatment of steroid refractory graft-versus-host disease (SR-GVHD), which seems promising to replace CNIs as a prophylactic agent with better GVHD control in patients with TA-TMA. We retrospectively analyzed the outcomes of 48 TA-TMA patients who received ISM with steroids (steroid group) or ruxolitinib (ruxolitinib group) as CNI substitutes. The primary endpoint was not met: the ORR at 4 weeks did not differ significantly between the ruxolitinib and steroid groups (65.2% vs. 80.0%, P = 0.250). However, in exploratory secondary analyses, more patients in the ruxolitinib group achieved complete response (CR) than in the steroid group (40% vs. 13%, P=0.036), and first remission was achieved more rapidly (13.5 vs. 25 days, P=0.046). Additionally, the ruxolitinib group demonstrated faster normalization of lactate dehydrogenase (LDH) levels and significantly better overall survival (HR 0.32, 95% CI 0.12-0.84, p=0.025) and relapse-free survival (HR 0.41, 95% CI 0.17-0.99, p=0.048) than the steroid group. Although hematologic recovery was slower in the ruxolitinib group than in the steroid group, we attribute this to ruxolitinib-induced myelosuppression. Infection was a significant risk factor in the ruxolitinib group (P=0.0426). However, there were no significant differences in the incidence of infection following treatment with steroid or ruxolitinib: pneumonia (26.1% vs. 16%, P=0.487), sepsis (17.4% vs. 12%, P=0.696), Epstein-Barr virus (EBV) reactivation (47.8% vs. 36%, P=0.406), or Cytomegalovirus (CMV) reactivation (56.5% vs. 52%, P=0.753). In this pilot study, the primary endpoint (ORR) was not met. Exploratory secondary analyses suggest that replacing CNIs with ruxolitinib during TA-TMA is feasible and may be associated with more rapid LDH normalization and CR, at the cost of slower peripheral count recovery; these observations are hypothesis-generating and require confirmation in adequately powered, prospective, multicenter studies.

Open article ↗

2026-09-13 | Post-Transplant Cyclophosphamide-Based Related Haploidentical Transplantation for Adult Diamond-Blackfan Anemia: Long-Term Survival and Review.

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome (CBMFS) primarily managed with corticosteroids and blood transfusions; however, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option when these therapies fail or relapse occurs. We report the case of a 21-year-old woman diagnosed with DBA caused by an RPS19 mutation shortly after birth. Although she responded well to corticosteroid therapy until 18 years of age, discontinuation led to relapse and subsequent transfusion dependence, necessitating allogeneic transplantation. In the absence of a human leukocyte antigen (HLA)-matched donor, she underwent post-transplantation cyclophosphamide (PT-Cy)-based haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) at 21 years of age, utilizing her father as the donor. Myeloablative conditioning was performed using fludarabine, melphalan, and busulfan. For acute graft-versus-host disease (GVHD) prophylaxis, PT-Cy (50 mg/kg on days 3 and 4), tacrolimus, and mycophenolate mofetil were administered, resulting in successful neutrophil engraftment on day 16 post-transplantation. Although the patient developed acute GVHD (grade II), it resolved with corticosteroid therapy. Post-discharge, she was readmitted due to acute gastrointestinal GVHD (grade II), which improved after methylprednisolone administration. She was discharged on day 92 and achieved complete transfusion independence for the past 5 years, making this the first reported case of long-term survival following PT-Cy-based haplo-PBSCT for this condition. Including our patient, there are only four reported cases of allo-HSCT using PT-Cy for adult patients with DBA; notably, all patients survived without developing severe GVHD or infectious complications. Generally, transplant outcomes for DBA worsen with increasing age due to severe GVHD and organ damage secondary to long-term iron overload. Given that DBA is a non-malignant disease, meticulous attention must be paid to prevent unnecessary GVHD and graft failure. In adult patients with DBA, PT-Cy yielded successful engraftment and safety, with no incidence of severe GVHD, leading to long-term survival and minimal complications. These findings suggest that allo-HSCT utilizing PT-Cy remarkably expands donor options for congenital bone marrow failure syndromes. Consequently, this approach is expected to become a promising therapeutic strategy not only for hematologic malignancies but also for non-malignant disorders.

Open article ↗

2026-08-29 | Peripheral Neuropathy After Allogeneic Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, and Electrophysiologic Features.

Peripheral neuropathy (PN) is an uncommon but clinically significant complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the incidence, clinical features, risk factors, and electrophysiological characteristics of PN remain unclear. To determine the incidence and risk factors of post-transplant PN (PTPN) and characterize its electrophysiological features using nerve conduction studies (NCS). We retrospectively analyzed consecutive patients aged ≥16 years who underwent first allogeneic HSCT at the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital between January 2010 and December 2022. The primary endpoint was cumulative PTPN incidence. The cumulative incidence of PTPN was estimated with death treated as a competing event. Overall survival (OS) after PTPN onset was estimated using the Kaplan-Meier method. Risk factors for PTPN were evaluated using univariate and multivariate analyses using the Fine-Gray hazard model. Acute and chronic graft-versus-host disease (GVHD) were analyzed as time-dependent covariates. NCS findings were reviewed to characterize electrophysiological features and identify factors associated with reduced conduction parameters. Among 1332 patients who underwent HSCT, 57 developed PTPN. The 3-year cumulative incidence was 3.9% (95% confidence interval [CI], 2.9 to 5.1). Median time from HSCT to PTPN onset was 195 days (range, 11 to 1917). At PTPN onset, motor weakness and sensory disturbances were observed in 51 (89.5%) and 53 (93.0%) patients, respectively. Among 20 patients treated with intravenous immunoglobulin and/or methylprednisolone pulse therapy, only 2 (10.0%) showed symptomatic improvement. Multivariable analysis identified re-transplantation (hazard ratio [HR], 1.87; 95% CI, 1.05 to 3.34), grade II to IV acute GVHD (HR, 2.32; 95% CI, 1.34 to 4.00), and extensive chronic GVHD (HR, 4.27; 95% CI, 2.18 to 8.36) as independent risk factors for PTPN. Median survival after PTPN onset was 218 days (range, 5 to 3106), and the 3-year overall survival rate after PTPN onset was 33.0% (95% CI, 20.9 to 45.6). NCS was performed in 55 patients and 53 (96.4%) showed axonal-type neuropathy. Motor and sensory amplitudes were generally lower in the lower extremities than in the upper extremities. Median ulnar motor nerve conduction velocity and compound muscle action potential amplitude were 47.7 m/s and 3.4 mV, respectively, whereas the corresponding tibial values were 37.6 m/s and 2.2 mV. Median ulnar sensory nerve conduction velocity and sensory nerve action potential amplitude were 48.4 m/s and 12.2 μV, respectively, whereas the corresponding sural values were 42.7 m/s and 4.2 μV. Older age (≥50 years), male sex, re-transplantation, and PTPN onset within 200 days after HSCT were associated with reduced nerve conduction velocities or amplitudes. PTPN was associated with GVHD and re-transplantation and was characterized predominantly by axonal neuropathy. The electrophysiological pattern suggests that PTPN may represent a distinct neurological complication rather than classical immune-mediated demyelinating neuropathy. Further studies are needed to clarify its pathophysiology and develop transplant-specific diagnostic and treatment strategies.

Open article ↗

proteins

2026-09-16 | Expanding the spectrum of post-HSCT hemolysis: from passenger lymphocyte syndrome to host- and graft-associated alloimmune hemolytic anemia.

Immune-mediated alloimmunization and hemolytic anemia can complicate ABO-incompatible hematopoietic stem cell transplantation (HSCT). After major ABO-incompatible HSCT, clinical manifestations may include pure red cell aplasia and delayed hemolysis. Passenger lymphocyte syndrome and delayed hemolysis are typical complications of minor ABO-incompatible HSCT. Because delayed hemolysis after major or minor ABO mismatch may be indistinguishable, the terms host-associated alloimmune hemolytic anemia and graft-associated alloimmune hemolytic anemia have been tentatively proposed to distinguish these conditions according to their host or graft origin. However, the rarity of these subgroups may limit the clinical utility of this classification. Management across the clinical spectrum includes transfusion support, plasmapheresis, and therapeutics related to immunomodulatory therapies.

Open article ↗

2026-08-06 | Long-term outcome of sinusoidal obstruction syndrome secondary to hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) is a potentially severe complication of conditioning regimens in hematopoietic stem cell transplantation (HSCT). Its long-term outcome is unknown. The aim of this study was to investigate the long-term liver outcome of patients with SOS. We retrospectively analyzed the outcome of all patients with histologically proven SOS related to HSCT conditioning who survived 6 months or more after HSCT. 22 patients with SOS were included. Median follow-up after SOS was 6.1 years. During this period, 10 patients (45%) developed signs of portal hypertension and 8 (36%) of them liver-related complications (ascites, n=8; spontaneous bacterial peritonitis, n=1; hepatic encephalopathy, n=3; variceal bleeding, n=3). Cumulative incidence of signs of portal hypertension was 27% at 3 years. Patients who developed signs of portal hypertension were less likely to have received defibrotide (hazard ratio:0.096; p<0.001) and had lower mean arterial pressure than those who did not. Of the 10 patients who developed signs of portal hypertension during follow-up, 3 underwent a second liver biopsy; all biopsies showed features of porto-sinusoidal vascular disorder. Cumulative incidence of death, considering non-liver-related death as a competing event, was significantly higher in patients who developed signs of portal hypertension than in those who did not [hazard ratio: 10.7 (1.27-89.9)]. Development of signs of portal hypertension and liver-related complications are common in the long-term after SOS following HSCT, especially when patients did not receive defibrotide, and this affects patients' survival. Features consistent with a porto-sinusoidal vascular disorder may be seen in liver histology in a subset of patients at the long-term follow-up after SOS. Long-term liver outcome of sinusoidal obstruction syndrome (SOS) following conditioning regimens in haematopoietic stem cell transplantation (HSCT) is unknown.This study demonstrates that signs of portal hypertension and liver-related complications are common during long-term follow-up after SOS following HSCT. Treatment of SOS with defibrotide seems to be associated with a lower risk of developing portal hypertension. Liver histology at the long-term follow-up after SOS may show features consistent with PSVD.SOS following HSCT might thus be removed from the PSVD exclusion criteria.

Open article ↗

2026-06-05 | Growth hormone therapy after hematopoietic cell transplantation in childhood: a nationwide survey and longitudinal cohort study.

Growth impairment is a major late effect in survivors of childhood hematopoietic cell transplantation (HCT); however, the long-term effectiveness and response patterns of growth hormone (GH) therapy after HCT remain unclear. Thus, this study aimed to evaluate the effectiveness of GH therapy and clinical factors associated with GH response in patients who underwent HCT during childhood and were diagnosed with short stature and to further examine long-term response patterns among those receiving GH therapy. We conducted a nationwide, multicenter retrospective cohort study of childhood HCT survivors with post-transplant short stature. Height outcomes were evaluated using final adult height standard deviation scores (SDS) and changes in SDS (ΔSDS). Factors associated with height outcomes and GH responsiveness were analyzed using multivariable regression models, and longitudinal growth trajectories after GH initiation were assessed at 1 year, 5 years, and final height. Among 171 patients with available final height data, 58 received GH therapy. GH-treated patients showed significantly greater improvement in final height SDS and ΔSDS than untreated patients, although growth responses were heterogeneous. Total body irradiation (TBI), HCT before 5 years of age, and chronic graft-versus-host disease were independently associated with poorer height outcomes. Factors associated with GH responsiveness differed by transplant type: absence of TBI and female sex were favorable in allogeneic HCT. Regarding complications, GH therapy was not associated with an increased risk of slipped capital femoral epiphysis, secondary malignancies, or relapse of the primary disease. GH therapy improves height outcomes after childhood HCT, but responses vary and are strongly influenced by transplant-related toxicity and long-term complications. To improve height outcomes, optimizing GH therapy and developing strategies for patients expected to respond poorly remain important challenges.

Open article ↗

2026-03-21 | Bone marrow SELENOP+ macrophages support hematopoiesis after transplantation via GAS6-AXL signaling pathway.

Poor hematopoietic reconstitution (PHR), a serious complication after chemotherapy or radiotherapy in patients with hematological or solid malignancies, which lacks effective treatment options because its underlying pathogenesis remains unclear. Bone marrow macrophages (BM MΦs) are multifunctional, plastic cells essential in hematopoiesis though our previous study demonstrated distinct hematopoietic regulatory role between M1 and M2 subtypes. However, the specific phenotype of M2-MΦ and pathways involved in hematopoietic support remain unclear. Here, we identified a novel population of BM-MΦs, SELENOP+ MΦs, that exhibit an M2-biased phenotype with hematopoietic stem cell (HSC)-supporting ability. These cells were markedly impaired in patients with poor graft function (PGF) after allogeneic HSC transplantation, potentially because of defective autocrine GAS6-AXL (ligand-receptor) signaling. Both in vitro and BM MΦ-specific AXL knockdown mouse models confirmed that reduced AXL activity contributed to MΦ dysfunction and the downstream reduction in IGF1 secretion. Notably, treatment with GAS6 partially restored the HSC-supporting ability of impaired BM MΦ from PGF patients in vitro. Overall, our study identified an HSC-supportive SELENOP+ MΦ subset regulated by GAS6-AXL signaling, offering novel therapeutic insights for impaired hematopoiesis.

Open article ↗

2025-10-15 | Real-World Outcome of Defibrotide Treatment for Severe Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation.

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication following hematopoietic cell transplantation (HCT), with a markedly poor prognosis in patients with severe or very severe presentations. Defibrotide (DF) is the sole approved treatment for severe to very severe VOD/SOS, but real-world evidence remains limited, particularly in East Asian populations. We retrospectively analyzed 73 adult patients with severe or very severe VOD/SOS treated with DF between 2016 and 2023 at a single tertiary center in Korea. Diagnosis and grading were based on the revised European Society for Blood and Marrow Transplantation criteria. During the study period, national reimbursement guidelines for DF evolved from requiring ≥4 of 6 severity criteria to ≥2 of 5 severity criteria, allowing earlier initiation of treatment. The median time from HCT to diagnosis of VOD/SOS was 24 days (range, 1 to 843 days), and DF was administered within a median of 1 day after diagnosis. At DF initiation, 40 patients were classified as severe and 33 were classified as very severe; disease progression resulted in 53 patients reaching the very severe category. The overall response rate was 46.5%, and complete resolution was achieved in 39.7% of cases. The 100-day overall survival was 34.2%, significantly higher in the patients receiving DF within 2 days of diagnosis (36.0% versus 17.4%; P = .049). High total bilirubin levels at diagnosis and at the worst disease period were strongly associated with poor long-term survival regardless of severity criteria. These data provide real-world support for the early use of DF and suggest the prognostic utility of total bilirubin level in guiding treatment for VOD/SOS following HCT.

Open article ↗

antibodies

2026-09-29 | Kidney Injury After Hematopoietic Stem Cell Transplantation: Acute Kidney Injury, Transplant-Related Complications, and Long-Term Outcomes

Kidney complications are common after hematopoietic stem cell transplantation (HSCT) and contribute substantially to short- and long-term morbidity and mortality. Acute kidney injury (AKI) affects a large proportion of recipients, particularly after allogeneic transplantation, and reflects the combined effects of baseline patient vulnerability, conditioning intensity, calcineurin inhibitor exposure, infection, hemodynamic disturbances, and transplant-specific complications. This review summarizes the epidemiology, risk factors, and major causes of kidney injury after HSCT, with emphasis on a time-based diagnostic approach. Important etiologies include sepsis, marrow infusion syndrome, sinusoidal obstruction syndrome, graft-versus-host disease–associated kidney injury, transplant-associated thrombotic microangiopathy, and glomerular disease. We also discuss emerging therapeutic approaches, including complement-directed therapy for transplant-associated thrombotic microangiopathy and defibrotide for sinusoidal obstruction syndrome. Beyond the acute transplant period, AKI is increasingly recognized as a major determinant of subsequent chronic kidney disease, cardiovascular risk, and impaired long-term survival. Structured surveillance of kidney function, blood pressure, and proteinuria, together with early recognition of transplant-specific syndromes and closer nephrology follow-up in high-risk patients, is therefore essential. Multidisciplinary collaboration between transplant hematology and nephrology is central to improving kidney and overall outcomes across the HSCT continuum.

Open article ↗

2026-09-21 | Early prophylactic rituximab reduces EBV infection and PTLD in high-risk patients receiving allogeneic hematopoietic stem cell transplantation.

Epstein-Barr virus (EBV) infection is a major complication after allogeneic hematopoietic cell transplantation (allo-HCT) and may progress to post-transplant lymphoproliferative disorder (PTLD). Current management relies on preemptive rituximab guided by EBV DNA monitoring, but this approach is inherently dependent on detectable EBV DNAemia and may not prevent early viral expansion. To evaluate the efficacy and safety of prophylactic rituximab compared with a standard preemptive strategy in preventing EBV infection and PTLD in high-risk patients receiving allo-HCT. In this multicenter retrospective cohort study, patients were stratified according to receipt of prophylactic rituximab (n = 280) or a preemptive rituximab strategy (n = 434). The primary endpoint was the 180-day cumulative incidence of EBV infection. Secondary endpoints included EBV-PTLD, transplant-related outcomes, immune reconstitution, and survival. To account for baseline imbalances, inverse probability of treatment weighting (IPTW) was applied. Additionally, Fine-Gray proportional subdistribution hazards model was utilized to identify independent risk and protective factors. Prophylactic rituximab was associated with a significantly lower 180-day incidence of EBV infection compared with the preemptive strategy (4.74% vs. 36.83%, P < 0.001), and a reduced incidence of PTLD (1.10% vs. 4.52%, P = 0.040). In multivariable analysis, prophylactic rituximab remained an independent protective factor for EBV infection (sHR = 0.12, P < 0.001). No significant differences were observed in overall survival, non-relapse mortality, relapse incidence, or major transplant-related complications. B-cell recovery remained suppressed through 12 months, whereas serum IgG levels and first-year IVIG use were comparable between groups. Prophylactic rituximab markedly reduces EBV infection and PTLD in high-risk patients undergoing allo-HCT, without adversely affecting survival or transplant outcomes. These findings support a risk-adapted prophylactic strategy for patients at high risk of EBV-related complications and warrant prospective evaluation of patient selection and long-term safety.

Open article ↗

2026-07-28 | Sequential Sinusoidal Obstruction Syndrome and TA-TMA After Haploidentical Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Challenges.

Background/Objectives: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has expanded donor availability for patients with acute myeloid leukemia; however, it is associated with a high risk of endothelial complications. Among them, sinusoidal obstruction syndrome (SOS) and transplant-associated thrombotic microangiopathy (TA-TMA) are life-threatening conditions with overlapping clinical features, making early diagnosis and management challenging. Case Presentation: We report the case of a 47-year-old woman with acute myeloid leukemia who underwent haploidentical HSCT and developed sequential endothelial complications. On day +11 post-transplant, she presented with weight gain (>5%), hyperbilirubinemia (44 μmol/L), elevated liver enzymes (ALT 2228 U/L and AST 3477 U/L), and multi-organ dysfunction, consistent with probable SOS according to EBMT criteria. Intensive supportive care, glucocorticosteroids, and hemodiafiltration resulted in partial clinical improvement. Subsequently, on day +22, the patient developed progressive thrombocytopenia, hemolytic anemia (hemoglobin 71 g/L), elevated lactate dehydrogenase (3129 U/L), undetectable haptoglobin, and schistocytosis (up to 3.9%), accompanied by neurological symptoms, leading to the diagnosis of TA-TMA. Results: Management included discontinuation of tacrolimus, initiation of plasma exchange, and complement inhibition with eculizumab, along with ruxolitinib for graft-versus-host disease prophylaxis. This approach resulted in rapid clinical and laboratory improvement, including resolution of hemolysis, reduction in schistocytes (to 1%), normalization of lactate dehydrogenase, and regression of neurological symptoms. The patient was discharged in stable condition, although requiring ongoing renal replacement therapy. Conclusions: This case highlights the complexity of diagnosing and managing sequential endothelial complications after haplo-HSCT. SOS and TA-TMA may reflect overlapping manifestations of endothelial injury rather than entirely isolated complications.

Open article ↗

2026-07-27 | Paraneoplastic Minimal Change Disease Signaling Post-Transplant AML Relapse: Two Cases and a Literature Review.

Membranous nephropathy (MN) and minimal change disease (MCD) are the most common causes of nephrotic syndrome following hematopoietic stem cell transplantation (HSCT), a complication conventionally attributed to chronic graft-versus-host disease (GVHD). Paraneoplastic MCD is well described in lymphoid malignancies but is rarely reported in myeloid neoplasms. We report two cases of biopsy-confirmed MCD presenting as the initial manifestation of acute myeloid leukemia (AML) relapse following allogeneic HSCT. Both patients were White men in their sixties with relapsed/refractory AML who developed nephrotic-range proteinuria and acute kidney injury after matched unrelated donor HSCT without histologic evidence of GVHD. Renal biopsies confirmed MCD in both cases. Corticosteroid therapy was ineffective in halting renal deterioration; renal function improved only after initiation of leukemia-directed therapy, with one patient achieving dialysis independence. These cases highlight a rare paraneoplastic presentation of AML relapse. Nephrotic syndrome due to MCD may signal post-HSCT leukemia recurrence, and evaluation for AML relapse warrants consideration in steroid-refractory cases or those without concurrent GVHD. In such cases, control of the underlying malignancy, rather than escalation of immunosuppression, may be central to renal recovery.

Open article ↗

2026-07-15 | Successful eradication of de novo HLA antibodies with daratumumab in immune-mediated cytopenias after allogeneic stem cell transplantation: a case report.

Refractory immune-mediated cytopenias (IMCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are a challenging complication with limited therapeutic options. Although preexisting human leukocyte antigen (HLA) antibodies, particularly donor-specific antibodies (DSAs), are well-established risk factors for graft failure, the clinical significance and mechanistic role of de novo HLA antibodies emerging after transplantation remain poorly defined. Whether such antibodies are associated with posttransplant IMCs has not been systematically explored. We report two patients with severe aplastic anemia who developed refractory IMCs after allo-HSCT in association with high-titer de novo HLA antibodies and preserved full donor chimerism. In case 1, combined HLA class I and II antibodies were detected in association with trilineage cytopenia. Rituximab, corticosteroids and plasma exchange reduced HLA class II antibodies (including DSAs), whereas persistent HLA class I antibodies were linked to ongoing pancytopenia despite multi-agent treatment. In case 2, isolated high-titer de novo HLA class II antibodies were detected in association with late-onset thrombocytopenia, refractory to corticosteroids and rituximab. In both patients, plasma cell-directed therapy with daratumumab led to definitive clearance of de novo HLA antibodies and was followed by rapid and sustained hematologic recovery, including coordinated trilineage recovery in case 1 and selective platelet recovery in case 2. These cases provide initial hypothesis-generating observations that de novo HLA antibodies are associated with and may contribute to refractory IMCs after allo-HSCT. The concordance across antibody class, lineage-specific or multilineage hematopoietic injury, and lineage-matched recovery after antibody clearance suggests a functional immunophenotype-hematopoietic phenotype coupling that warrants further investigation.

Open article ↗

cell therapies

2026-09-29 | CAR-T Versus Non-CAR-T Bridging Strategies Before Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A Systematic Review.

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) remains a major therapeutic challenge despite recent advances in immunotherapy. Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising bridging strategy to allogeneic hematopoietic stem cell transplantation (allo-HSCT), although its impact on post-transplant outcomes compared with non-CAR-T bridging strategies remains uncertain. This systematic review compared CAR-T-based with non-CAR-T bridging strategies before allo-HSCT in patients with R/R B-ALL or persistent/recurrent measurable residual disease (MRD) during first complete remission (CR1). PubMed/MEDLINE and Scopus were searched from database inception to August 18, 2026. Eligible comparative studies reported post-transplant outcomes according to the pre-transplant bridging strategy. Two reviewers independently screened the studies, extracted data, and assessed methodological quality using the appropriate Joanna Briggs Institute (JBI) critical appraisal tools. Given the substantial clinical and methodological heterogeneity, a narrative synthesis was performed rather than a meta-analysis. Of 1,957 records identified, 10 comparative reports met the eligibility criteria. Potential patient-level overlap could not be excluded between two reports from the same institution, and all included studies were conducted at single-center institutions in China. CAR-T-based bridging produced deep pre-transplant remissions, but no consistent advantage over non-CAR-T strategies in achieving MRD negativity was observed. One study reported a significantly lower cumulative incidence of relapse (CIR) and higher disease-free survival (DFS) after CAR-T bridging (18.9% vs. 42.2%, p = 0.02; 82.5% vs. 53.7%, p = 0.01), with CAR-T remaining independently associated with a reduced risk of relapse in multivariable analysis. A significant unadjusted overall survival (OS) advantage favoring CAR-T was observed in one small pediatric cohort (84.6% vs. 40.0%, p = 0.008), although potential overlap with another included cohort limits the independent interpretation of this finding. In the largest cohort, CAR-T bridging was independently associated with improved OS in multivariable analysis (hazard ratio = 0.365, 95% CI 0.154-0.857, p = 0.025), despite a nonsignificant unadjusted OS comparison and significantly lower leukemia-free survival (LFS). Across the remaining studies, OS did not differ significantly between bridging strategies, including in two studies comparing CAR-T with blinatumomab. Non-relapse mortality (NRM), hematopoietic engraftment, graft-versus-host disease (GVHD), infectious complications, and endothelial toxicity showed no consistent direction of effect across studies, although delayed platelet recovery and increased viral reactivation emerged as potential safety signals in specific cohorts, particularly following dual-target CD19/CD22 CAR-T therapy. Overall, CAR-T-based bridging before allo-HSCT may improve disease control in selected patients with R/R B-ALL, but the expanded evidence base does not demonstrate a consistent survival or safety advantage over non-CAR-T bridging strategies. The choice of bridging strategy should therefore be individualized according to MRD status, disease biology, CAR-T construct, and transplant eligibility. Prospective multicenter comparative studies are needed to define the optimal sequencing of CAR-T therapy, alternative immunotherapies, and allo-HSCT.

Open article ↗

2026-09-19 | [Uterine and ovarian relapse of acute lymphoblastic leukemia after transplantation: A case report].

Acute lymphoblastic leukemia (ALL) is a common type of acute leukemia and is essentially a malignant clonal proliferative disorder of hematopoietic stem cells. Currently, the widespread application of high-dose chemotherapy combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) has significantly improved patient survival and has become the most effective therapeutic strategy for ALL. However, relapse remains a major challenge after transplantation. Most relapses occur in the bone marrow, whereas extramedullary relapse is relatively uncommon, and relapse involving the female reproductive system is extremely rare. Herein, we report a case of ALL with uterine and ovarian relapse after allo-HSCT. Extramedullary relapse was confirmed by pelvic mass biopsy. The patient subsequently received combined treatment with chemotherapy, radiotherapy, and chimeric antigen receptor T‑cell (CAR‑T) immunotherapy, resulting in complete regression of the uterine and ovarian lesions and achieving clinical remission. It should be noted that relapse of acute leukemia in the reproductive system after transplantation can be easily misdiagnosed as a primary malignancy of the reproductive system. Therefore, accurate differentiation between primary and secondary tumors and early initiation of effective treatment are essential. In clinical practice, diagnostic accuracy should be improved by integrating the patient's clinical history with magnetic resonance imaging (MRI) findings, thereby avoiding unnecessary surgical trauma and improving long‑term prognosis.

Open article ↗

2026-09-04 | Graft CD3+/CD4 - CD8- T-cell ratio: a predictor of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in pediatric patients.

Acute graft-versus-host disease (aGVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study investigated the association between the graft CD3+/CD4 - CD8- T-cell ratio and the incidence of aGVHD in pediatric recipients. A total of 112 pediatric patients with high-risk hematologic malignancies undergoing allo-HSCT were enrolled in this retrospective study. Associations between the graft CD3+/CD4 - CD8- T-cell ratio and aGVHD were evaluated using Fine-Gray regression models. Receiver operating characteristic (ROC) analysis was performed to determine the predictive performance and optimal cutoff value of the graft CD3+/CD4 - CD8- T-cell ratio. Spearman's rank correlation coefficient was used to assess correlations among different cellular subsets. The day-100 cumulative incidence of grade II-IV aGVHD was 41.1%. In multivariable analysis, the graft CD3+/CD4 - CD8- T-cell ratio was independently associated with grade II-IV aGVHD. ROC analysis identified 56 as the optimal cutoff value for the graft CD3+/CD4 - CD8- T-cell ratio. Patients with a high ratio had a significantly higher incidence of grade II-IV aGVHD than those with a low ratio (56.3% vs. 20.8%, P < 0.001), whereas no significant differences were observed in disease relapse or cytomegalovirus (CMV) infection. The graft CD4 - CD8- T-cell dose was positively correlated with early peripheral CD4 - CD8- T-cell recovery after transplantation. A higher graft CD3+/CD4 - CD8- T-cell ratio is independently associated with an increased risk of day-100 grade II-IV aGVHD in pediatric allo-HSCT recipients. Optimizing the graft CD3+/CD4 - CD8- T-cell ratio may help mitigate aGVHD, thereby serving as a practical biomarker for individualized aGVHD risk stratification.

Open article ↗

2026-08-26 | Incidence and risk factors of Epstein-Barr virus infection and post-transplant lymphoproliferative disorder in paediatric haploidentical allogeneic hematopoietic stem cell transplantation.

Epstein-Barr virus (EBV) reactivation after haploidentical stem cell transplant (haplo-HSCT) is a serious complication, which sometimes progresses to post-transplant lymphoproliferative disorder (PTLD). We retrospectively analyzed 448 pediatric patients ( ≤ 18 years) undergoing anti-thymocyte globulin (ATG)-based haplo-HSCT with letermovir prophylaxis at Peking University People's Hospital (Oct 2022-Oct 2025), using a 1:3 propensity score-matched design. EBV viremia and PTLD incidences were 12.4% and 4.9%. Multivariate analysis showed prior Chimeric Antigen Receptor (CAR) T-cell therapy (Hazard ratio (HR) = 2.040, 95% CI 1.061-3.920; p = 0.033) and Cytomegalovirus (CMV) viremia preceding EBV viremia (HR = 6.075, 95% CI 3.377-10.928; p < 0.001) were risk factors for EBV viremia. The PTLD risk was higher with a total body irradiation (TBI)-based conditioning regimen (HR = 1.917, 95% CI 0.980-3.750; p = 0.050). Overall survival did not differ between groups (EBV + : 92.9% vs. EBV-: 96.4%; p = 0.10), but event-free survival was inferior in EBV-infected patients (86.6% vs. 94.6%; p = 0.004). Chronic graft-versus-host disease (17.0% vs. 6.5%; p < 0.001) and transplant-related mortality (7.1% vs. 2.1%; p = 0.005) were significantly higher in the EBV viremia cohort. EBV reactivation and PTLD pose serious challenges, and risk factors include TBI conditioning, prior CAR-T therapy, and CMV viremia preceding EBV viremia. Preemptive cytotoxic T lymphocyte therapy may benefit high-risk patients.

Open article ↗

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.

Open article ↗

other

2026-05-19 | Vaccine-Induced Anti-HBs Response is Associated with Protection Against Hepatitis B Virus Reactivation after Allogeneic Hematopoietic Cell Transplantation: A Randomized Trial.

Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients with resolved HBV infection undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Although HBV DNA-guided preemptive nucleos(t)ide analog therapy prevents HBV-related hepatitis, strategies to prevent HBV reactivation itself remain limited. Hepatitis B vaccination after allo-HCT has been suggested as a potential preventive strategy, but prospective randomized evidence is lacking. To evaluate whether hepatitis B (HepB) vaccination reduces HBV reactivation after allo-HCT and to examine the association between vaccination-induced anti-hepatitis B surface antibody (anti-HBs) response and protection against HBV reactivation. In this multicenter randomized controlled trial (UMIN000034113), adults who were hepatitis B surface antigen-negative and anti-hepatitis B core antigen-positive and underwent first allo-HCT were prospectively enrolled. At 140 days post-HCT, patients without HBV reactivation were randomized to receive HepB vaccination or no vaccination. HBV DNA levels and anti-HBs titers were centrally monitored for 2 years after transplantation. The primary endpoint was HBV reactivation, defined as HBV DNA ≥ 1.3 log IU/mL. Vaccine response was defined as anti-HBs response, requiring both an increase in anti-HBs from baseline and a post-vaccination anti-HBs ≥ 10 mIU/mL. Among 109 enrolled patients, 64 were randomized. With a median HBV DNA follow-up of 19.4 months, HBV reactivation occurred in 6 of 33 patients in the vaccination group, including 2 who experienced reactivation before receiving the first vaccine dose, and 9 of 31 patients in the control group. Probabilities of HBV reactivation were 19.8% and 37.9% in the HepB vaccination and control groups, respectively, at 18 months after randomization (P = .205). Baseline anti-HBs <10 mIU/mL was a significant risk factor for HBV reactivation. No HBV-related hepatitis was observed. Vaccine responses were achieved in 9 of 29 patients after the initial series and in 5 of 10 after the additional series. Importantly, HBV reactivation did not occur after patients achieved anti-HBs response, although several reactivation events occurred before vaccination or before anti-HBs response was achieved. No severe vaccine-related adverse events were observed. Although HepB vaccination did not significantly reduce HBV reactivation, it was feasible and induced anti-HBs response in a subset of patients. Achieving vaccine-induced anti-HBs response may provide protective immunity against HBV reactivation after allo-HCT.

Open article ↗

2026-05-11 | Case Report: Short-course defibrotide combined with eculizumab for TA-TMA.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a severe complication following hematopoietic stem cell transplantation, with its pathogenesis not yet fully understood and a lack of highly effective treatment options currently available. This article reports a case of a female patient with acute myeloid leukemia (AML) who was diagnosed with TA-TMA three months after a second allogeneic hematopoietic stem cell transplantation (allo-HSCT). After promptly discontinuing cyclosporine (CSA), and following ineffective treatments with anti-infective therapy, glucocorticoids, and plasma exchange, a short-course combination regimen-defibrotide (10 days) and eculizumab (3 weeks)-was administered. The TA-TMA-related indicators rapidly improved and returned to normal. During follow-up, the patient's primary disease remained in remission, and she remained free of TA-TMA recurrence for five months. At eight months after the second allo-HSCT, TA-TMA recurred due to concurrent pneumonia and sepsis. The same short-course combination regimen-defibrotide (18 days) and eculizumab (3 weeks)-was administered, and the patient showed improvement in clinical and laboratory parameters again. This study is the first to report the use of a short-course combination therapy with defibrotide and eculizumab for TA-TMA. The combination regimen demonstrated good efficacy and tolerability, offering a potential treatment option for refractory TA-TMA, though its broader applicability requires further research and validation.

Open article ↗

2026-04-29 | Clinical burden and healthcare resource utilization after allogeneic hematopoietic stem cell transplant for sickle cell disease or β-thalassemia

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potentially curative treatment for patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or β-thalassemia. Real-world data on post-allo HSCT outcomes are limited among these patients. Patients with SCD with recurrent VOCs or β-thalassemia with allo-HSCT were identified in the Merative MarketScan Research Databases. Clinical outcomes, allo-HSCT complications, and healthcare resource utilization were summarized after allo-HSCT. Eighty-one patients with SCD with recurrent VOCs and 33 with β-thalassemia were included. About one-third of patients with SCD experienced a VOC and one-quarter of patients with β-thalassemia required a red blood cell transfusion, in the year after the first 100 days following allo-HSCT. Approximately 40.7% of patients with SCD and 42.4% of patients with β-thalassemia developed acute graft-versus-host disease (GvHD), while 32.1% and 27.3% developed chronic GvHD, respectively. Patients with SCD had a mean of 74.1 (59.6) outpatient visits per patient per year and patients with β-thalassemia had a mean (SD) of 76.1 (61.3). Due to the lack of International Classification of Diseases, 10th Revision (ICD-10) codes to distinguish between different types of allo-HSCT, this study was unable to assess outcomes of patients with haploidentical hematopoietic stem cell transplantation (haplo-HSCT), which is a type of allo-HSCT. Many patients with SCD with recurrent VOCs or β-thalassemia endure potentially life-threatening transplant-related complications and require substantial healthcare utilization following allo-HSCT. These findings suggest limitations of allo-HSCT and underscore the need for alternative curative treatment options.

Open article ↗

2026-04-10 | Late-phase impact of CMV/EBV reactivation on survival after hematopoietic stem-cell transplantation: a 5-year single-center cohort study.

Whether simultaneous cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation confers additional late mortality beyond isolated CMV remains controversial. We retrospectively analyzed 202 consecutive first-ever hematopoietic stem cell transplantations performed between 2018 and 2019, using twice-weekly PCR surveillance and uniform preemptive therapy. Cox models were used to estimate hazard ratios (HRs) for overall survival (OS) and leukemia-free survival (LFS) at the 1-, 3-, and 5-year landmarks. Although 1-year outcomes were similar, divergence emerged thereafter: 5-year OS was 19.4% with coreactivation, 36.6% with isolated CMV, and 25.1% with no reactivation (p = 0.041); corresponding LFS was 19.4%, 36.6%, and 25.2% (p = 0.060). Multivariate analysis identified sustained CMV replication as the dominant late risk factor (OS HR 5.295, 95% CI 1.5888-17.6464; p = 0.0067), whereas coreactivation lost significance because EBV clearance shortened the overall viral window. Interestingly, viral enteritis was identified as an independent adverse predictor of 1-year LFS (HR 6.2453, 95% CI 1.3245-7.2376; p = 0.0010). Late mortality is driven by persistent CMV-driven endothelial injury rather than transient EBV coreactivation. Extending PCR surveillance from day 100 to year 2 and targeting chronic low-level CMV should be prioritized to improve long-term transplantation success.

Open article ↗

2026-03-16 | Successful Treatment of Primary Poor Graft Function After Haploidentical Hematopoietic Stem Cell Transplantation With Low-Dose Decitabine Followed by Donor Lymphocyte Infusion and Eltrombopag.

Primary poor graft function (PGF) is a common and serious complication after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study retrospectively evaluates the efficacy and safety of a novel combination therapy consisting of low-dose decitabine, donor lymphocyte infusion (DLI), and eltrombopag for the treatment of primary PGF subsequent to haplo-HSCT. In this analysis of ten patients, decitabine was administered at a dose of 7 mg/m2/day for three consecutive days, followed by DLI on the fifth day and eltrombopag, which was started at 50 mg/day and titrated up to 150 mg. The primary endpoints of the study encompassed hematologic recovery. Nine patients (90%) achieved a complete response with normalized blood counts, while one patient (10%) showed a partial response with transfusion independence. Adverse events included manageable graft-versus-host disease (GVHD) in four patients. These findings indicate that this triple therapy represents a promising approach for the management of primary PGF following haplo-HSCT.

Open article ↗