Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has evolved from traditional myeloablative conditioning toward reduced-intensity conditioning (RIC) and strategies using donor-derived immune effector cells. This review summarizes trends in RIC, proposes a practical classification of regimens, and underscores personalized risk stratification and disease-specific conditioning.

The optimal conditioning strategy for adult acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains undefined, particularly in older or medically vulnerable patients. Reduced-intensity regimens lower non-relapse mortality (NRM) but increase relapse risk. Treosulfan-based conditioning may represent an intermediate-intensity alternative, though comparative data in ALL are limited. We conducted a retrospective registry-based study including 967 adult patients with B- or T-ALL undergoing first allo-HSCT in complete remission (CR1 or CR2+) between 2012 and 2024. Patients received fludarabine-melphalan (Flu/Mel, n=778) or fludarabine-treosulfan (Flu/Treo, n=189). The primary endpoint was leukemia-free survival (LFS); secondary endpoints included overall survival (OS), relapse incidence (RI), NRM, and graft-versus-host disease. Outcomes were censored at 2 years. Multivariable Cox models adjusted for clinical and transplant-related variables. Flu/Treo recipients were transplanted more recently, more often received haploidentical donors, and were more frequently beyond CR1. Median age was slightly higher in the Flu/Treo group. At 2 years, OS was 65.6% with Flu/Treo versus 60.5% with Flu/Mel, and LFS 57.2% versus 49.7%. RI was lower with Flu/Treo (24.1% vs 31.5%), while NRM was similar (18.6% vs 18.8%). In multivariable analysis, conditioning regimen did not significantly affect OS or LFS, but Flu/Treo was associated with reduced RI (HR 0.61, p=0.011) without differences in NRM. Similar results were observed in B-ALL, while no differences emerged in T-ALL. Flu/Treo was associated with a lower relapse incidence compared with Flu/Mel, particularly in patients with B-cell ALL, without an increase in non-relapse mortality. However, no significant differences were observed in overall survival or leukemia-free survival. These findings support Flu/Treo as a reasonable alternative conditioning platform for adult patients with ALL and warrant prospective validation.

This is a multi-center, single-arm, phase-II, trial (NCT03263559) of haploidentical bone marrow transplant (BMT) for children with severe sickle cell disease (SCD). Eligible participants were children 5.00 - 14.99 years of age with stroke (silent or overt), abnormal transcranial Doppler cerebral arterial velocity > 200 cm/sec with intracranial vasculopathy, severe acute chest syndrome (ACS) or recurrent vaso-occlusive pain. The primary outcome was 2-year event-free survival (EFS; alive and disease-free). The transplant regimen included hydroxyurea 30mg/kg/day (Day-60 to Day-10), followed by thymoglobulin, thiotepa, fludarabine, cyclophosphamide, and total body irradiation (200 cGy). Graft-versus-host disease (GVHD) prophylaxis included post-transplant cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil. Forty-one participants were enrolled from 18 sites and 95% (39/41) proceeded to BMT. The median age at enrollment was 12.5 years; 98% (38/39) had hemoglobin SS disease, and 82.1% (32/39) had donors mismatched at 4 HLA-loci. The most common indication for BMT was a qualifying neurological event in 69% (27/39), including 15 with overt stroke. Nine participants had recurrent vaso-occlusive pain and 5, severe ACS. The 2-year EFS and overall survival were 79.3% (95% CI: 62.8%, 89.1) and 94.5% (95% CI: 79.7%, 98.6%), respectively. FEV1% predicted increased from 79.5 to 95.7 at 2 years (p=0.014), and eGFR declined from 174 to 127 mL/min/1.73m2 (p<0.001), indicating resolved hyperfiltration. No new or progressive cerebral infacts were detected by serial brain MRI per central adjudication (n=22). While graft failure and GVHD negatively impacted EFS, reduced-intensity haploidentical BMT with PTCy is a promising therapy for children who lack a matched sibling donor.

Standard management guidelines generally recommend immunosuppressive therapy (IST) as first-line treatment for older patients with severe aplastic anemia (SAA), whereas the role of upfront haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in this population remains uncertain, particularly in patients with complex comorbidities. We report a 62-year-old woman with SAA, a history of surgically resected stage IA lung adenocarcinoma, and previous left lower extremity deep vein thrombosis treated with venous stent implantation and long-term aspirin therapy. Because no matched sibling or unrelated donor was available, and following individualized counseling regarding IST and transplantation, the patient underwent upfront haplo-HSCT combined with umbilical cord-derived mesenchymal stem cells after a conditioning regimen including fludarabine, busulfan, cyclophosphamide, antithymocyte globulin, and thiotepa. Neutrophil engraftment occurred on post-transplant day +12, and platelet independence was achieved on day +13. Donor chimerism reached 99.6% by day +14 and remained within the complete-chimerism range through the latest available assessment in January 2026. In late December 2025 and January 2026, the patient developed cytomegalovirus infection accompanied by transient trilineage cytopenia; after anti-CMV treatment with maribavir, the infection was controlled and peripheral blood counts subsequently recovered. At the most recent clinical follow-up on August 6, 2026, approximately 17 months after transplantation, no chronic graft-versus-host disease had developed, the previous lung adenocarcinoma remained in remission, and the thrombotic condition remained clinically stable. This case suggests that upfront haplo-HSCT combined with UC-MSCs may represent a feasible individualized treatment option for carefully selected older patients with SAA who lack matched donors, although broader conclusions require larger studies and longer follow-up.

Objective: To evaluate the efficacy and prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in children. Methods: In this case series study, clinical characteristics, laboratory tests, transplantation protocols, post-transplant disease remission, and survival status of 9 children with IPEX syndrome who underwent allo-HSCT at the Children's Hospital of Fudan University from July 2020 to December 2025 were collected. The transplantation experiences were summarized and the efficacy and safety of allo-HSCT for IPEX children were evaluated. Results: All 9 children were males. Eight children developed symptoms within the first month of age, and 1 at 5 years of age. The initial presentations were diarrhea in 4 children, diabetes mellitus in 2 children, and rash in 3 children. FOXP3 gene variants were maternally inherited in 8 children and de novo in 1 child. A total of 11 HSCT were performed in 9 children, with an overall engraftment of 9 times. Two children who experienced primary graft failure achieved successful engraftment after second HSCT at intervals of 3 and 4 months, respectively. Donor sources included 4 haploidentical donors, 3 unrelated cord blood and 2 matched unrelated donors. All conditioning regimens were based on fludarabine and busulfan. The age at transplantation was 37.5 (12.4, 70.3) months, with a follow-up of 17.4 (9.7, 26.8) months. All 9 children survived. Eight children achieved complete donor chimerism, and 1 had mixed chimerism. The times to neutrophil and platelet engraftment were 13 (11, 18) and 9 (9, 29) d, respectively. The times for absolute CD19[+]and CD4[+] cell counts exceed 2×10[8] cells/L were 165 (94, 270) and 165 (100, 183) d, respectively. Five children developed grade Ⅰ-Ⅱ acute graft versus host disease (GVHD), all presenting as skin involvement and resolved following glucocorticoid-based immunosuppressive therapy. No grade Ⅲ-Ⅳ acute GVHD or chronic GVHD occurred. Recurrent diarrhea, anemia, severe infection, eczema, and nephropathy all achieved complete remission through allo-HSCT. Among the 5 children with hypothyroidism and 2 children with diabetes mellitus, levothyroxine and insulin replacement therapy were still required, with well-controlled conditions. No new autoimmune diseases developed. Conclusions: allo-HSCT is an effective curative approach for IPEX syndrome, capable of halting disease progression, but cannot reverse pre-existing endocrine damage. No severe infections and GVHD occurred post-transplantation. Early diagnosis and early transplantation are crucial for improving outcomes.

IntroductionEvidence on cancer drug wastage comes largely from high-income countries and generally excludes the pediatric setting. This study quantified consumption, leftover reuse and wastage in a chemotherapy compounding unit of the Brazilian public health system.MethodsProspective, observational, descriptive study covering every compounding episode performed between October and December 2024 in a public hospital serving adult oncology and adult and pediatric onco-hematology. Of 32 formulary injectable cytotoxic drugs, the 29 with activity were analyzed by quantity and cost. The daily balance was classified as reusable leftover or wastage by a 24-h stability threshold. Relative wastage (quantity discarded divided by quantity compounded) was calculated per drug.Results1298 patients were treated in 2030 compounding episodes. Compounded doses totaled 612,192 mg or IU (BRL 657,724.73), of which 5.5% by quantity came from reused leftovers. Wastage reached 53,996.45 mg or IU (BRL 30,391.78; USD 5206.84), equivalent to 8.8% of the compounded quantity, 4.6% of its value and 13.9 mg or IU per patient treated per month. Fluorouracil led both compounded quantity (29.5%) and wastage (27.1%), yet relative wastage was highest in low-volume drugs with short stability: fludarabine (158.9%), etoposide (134.0%) and azacitidine (95.5%). Pegaspargase, used predominantly in children, combined 57.5% relative wastage with the largest discard cost (BRL 15,402.00). Pertuzumab, the costliest drug compounded, generated none.ConclusionsWastage concentrated in drugs with short stability and vial sizes poorly matched to prescribed doses, whereas the greatest financial impact fell on high unit-cost biologics. Relative wastage reveals intervention targets that absolute volume does not.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for malignant and non-malignant diseases; however, primary graft failure (GF) is a life-threatening complication, particularly with the increasing use of alternative donors and reduced-intensity conditioning (RIC) strategies. Data on outcomes and optimal management-especially in the pediatric population-remain limited and heterogeneous. The primary endpoint was overall survival (OS) in patients with primary GF. Secondary endpoints included OS in patients with primary GF after salvage HSCT and the evaluation of risk factors associated with engraftment and survival. We conducted a multicenter, retrospective, observational study including pediatric patients (<18 years) diagnosed with primary GF after a first allogeneic HSCT between January 2011 and July 2022 across 10 Spanish pediatric transplant centers. A total of 1561 allogeneic HSCTs were performed. Fifty-seven patients developed primary GF, yielding an overall incidence of 3.65%, which was higher among transplants with donors with HLA disparities. One-year OS for patients with primary GF was 73%. Over 90% of patients underwent salvage HSCT, with 74% achieving engraftment. No risk factors for engraftment were identified. One-year OS after the second HSCT was 71%. Achieving engraftment after the second transplant was the only factor significantly associated with survival (1-year OS, 81% [95% CI, 65-90] vs. 43% [95% CI, 17-66]; P < .001). No other clinical or transplant-related variables showed significant associations with survival. GF remains a major challenge and continues to limit the overall success of HSCT. The majority of patients underwent a second transplant, with engraftment achieved in 74% of patients. Overall survival was 68% at 2 years after the first transplant. The frequent use of RIC regimens including fludarabine and serotherapy in patients undergoing retransplantation reflects a commonly adopted clinical practice, although no specific conditioning regimen was significantly associated with engraftment or survival.

Adult T-cell leukemia/lymphoma (ATL) is associated with a dismal prognosis in aggressive subtypes, with a median overall survival (OS) of less than one year. In Japan, first line chemotherapy followed by allogeneic stem cell transplantation (allo-SCT) is recommended for eligible patients, yet this strategy is scarcely reported elsewhere, especially among ethnic minorities. We prospectively evaluated the feasibility and outcome of allo-SCT in this setting. Between 2016 and 2024, 80 ATL patients were enrolled; 74 (median age 50 years) received frontline chemotherapy (CHO(E)P regimen +/-Brentuximab Vedotin in CD30 positive cases). Of these, 39 subsequently proceeded to allo-SCT using a Thiotepa-Busulfan-Fludarabine conditioning regimen after at least one line of chemotherapy. Two-year OS from first line therapy was 45 %. Time-dependent analysis demonstrated a significant survival benefit for allo-SCT (hazard ratio, 0.32). Uncontrolled disease was the primary reason for transplant ineligibility. At transplantation, 27 patients were in complete remission (CR,) 5 in partial response (PR) and 7 had stable/progressive disease. Donor sources included haploidentical (56%), matched sibling (26%), and unrelated donors (18%). Three-year OS and progression-free survival were both 52%, while one-year non-relapse mortality and cumulative relapse incidence were 15% and 35%, respectively. Absence of CR/PR at allo-SCT was the main risk factor for poor outcomes. Tailored HTLV-1/ATL molecular and flow-cytometric monitoring of assessable patients in remission, revealed that tumor clones became undetectable after allo-SCT, suggesting a potent graft-versus-ATL effect. Overall, our findings support the benefit of allo-SCT in eligible ATL patients. Clinical Trial Identifier: NCT05237245.