Bone Marrow Transplantation最新文献

Graft failure (GF) is a barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelofibrosis (MF). We investigated the incidence, risk factors, and prognosis for GF after allo-HSCT for MF. Two hundred and eleven patients with MF who underwent allo-HSCT across 32 hematology centers in China between December 2008 and December 2024 were retrospectively analyzed. Among them, 66 underwent matched sibling donor HSCT, 127 haploidentical HSCT, and 18 unrelated donor HSCT. The overall GF incidence was 12.5%. GF incidence was significantly associated with donor type (matched sibling, 4.8%; alternative, 13.3%; P = 0.024). Pretransplant massive splenomegaly increased GF incidence (non-massive splenomegaly, 8.5%; massive, 18.5%; P = 0.034). In multivariate analysis, massive splenomegaly (HR = 3.047; P = 0.007) and alternative donors (HR = 3.528; P = 0.041) increased GF risk. With median follow-up of 734 days, 3-year OS, DFS, relapse rate and NRM was 65.5%, 60.8%, 10.1% and 27.8%, respectively. Multivariate analysis showed pretransplant splenomegaly reduced 3-year DFS (HR = 1.671; P = 0.025), and alternative donors reduced 3-year OS (HR = 2.033; P = 0.015). In conclusion, Allo-HSCT provides curative outcomes for MF patients. However, GF remains a significant challenge, particularly in haploidentical HSCT and those with massive pretransplant splenomegaly.

Haploidentical hematopoietic cell transplantation (HCT) is widely used in high-risk acute lymphoblastic leukemia (ALL), yet optimal donor selection remains unclear. We retrospectively analyzed 933 ALL patients receiving post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis to evaluate the impact of donor characteristics on outcomes. Donors had a median age of 36 years; 38% were female, including 23% who donated to male recipients. Peripheral blood (PB) was the graft source in 69%, and CMV-seronegative donors were used in 16% of CMV-negative recipients. Multivariate analysis showed that PB grafts were associated with inferior overall survival (OS) and GVHD-free/relapse-free survival. CMV-matched seronegative pairs had reduced non-relapse mortality and improved OS. Chronic GVHD was more frequent with older donors and in male recipients of female donor grafts, the latter also increasing extensive cGVHD risk. In conclusion, donor and graft selection significantly influence outcomes after haplo-HCT with PTCy. When feasible, bone marrow should be favored over PB grafts, and CMV-seronegative donors prioritized for CMV-seronegative recipients. Older donor age and female-to-male sex mismatch were associated with increased chronic GVHD risk.

Primary refractory acute myeloid leukemia (prAML) is a poor prognosis disease, with allogeneic hematopoietic stem cell transplantation (allo-HSCT) being the only potentially curative option. We retrospectively evaluated outcomes in 1574 adult prAML patients who underwent allo-HSCT from matched sibling donors (MSD), 10/10 or 9/10 unrelated donors (UD), or haploidentical donors between 2015 and 2020. Median follow-up was 24, 30, 38, and 24 months for MSD, UD 10/10, UD 9/10, and haploidentical transplants, respectively. MSD recipients were younger (median age 53 vs. 58-59 years in other groups, p < 0.001), had better performance status, and proceeded to transplant more quickly (3.8 months vs. >4 months in other groups, p = 0.004). In multivariate analysis, haploidentical HSCT was associated with inferior leukemia-free survival (LFS) and overall survival (OS) compared to other donor types. Additional negative predictors included adverse cytogenetics and longer time from diagnosis to transplant. Conversely, reduced-intensity conditioning and good performance status of the patient were associated with improved LFS. Disease progression remained the leading cause of transplant failure, underscoring the urgent need for more effective early post-transplant strategies.

Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly offered as a consolidation strategy for older/infirm patients with acute myeloid leukemia (AML). Fludarabine/melphalan (Flu/Mel) conditioning is associated with effective disease control but results in significant toxicity and non-relapse mortality (NRM) when combined with calcineurin-inhibitors plus methotrexate or mycophenolate mofetil. Flu/Mel with alternative graft-versus-host disease (GVHD) prophylaxis may be better tolerated and result in superior outcomes in patients with AML. In this single-center retrospective analysis, we analyzed long-term outcomes of patients with AML (n = 342) who underwent allo-HCT with Flu/Mel conditioning and tacrolimus/sirolimus (Tac/Sir)-based GVHD prophylaxis from 2008-2019 at City of Hope. Patient median age was 63 years (range: 23-78), with 37% having high-very high Disease Risk Index (DRI) and 42% with HCT-Comorbidity Index (CI) ≥ 3. Five-year overall survival (OS: primary objective) was 55% (95% CI: 49-61%) among all patients and 70% (95% CI: 55-81%) in patients ≥70 years old. Only presence of active disease correlated with lower 5-year OS on multivariate analysis (HR = 1.95; p < .001). Five-year NRM was 24% (95% CI: 19-29%) among all patients and 21% (95% CI: 11-34%) in those ≥70 years old. In conclusion, Flu/Mel conditioning with Tac/Sir GVHD prophylaxis is associated with favorable OS and acceptable NRM, even in older/infirm patients with AML.

Late Immune Effector Cell-Associated HematoToxicity (ICAHT) is a recognized complication following CAR T therapy, yet their incidence and clinical consequences remain poorly defined. We assessed early and late hematotoxicity in 290 patients with large B-cell lymphoma receiving CAR T therapy. Early ICAHT ( ≤ 30 days post-infusion) occurred in 78% of patients (grade 1: 22%, grade 2: 26%, grade 3: 22%, grade 4: 8.1%). Cumulative incidence of late ICAHT ( > 30 days post-infusion) by day 100 was 45% (95% CI 39-51) for any grade, 40% (95% CI 34-46) for grade≥2, 22% (95% CI 17-27) for grade ≥3, and 7.2% (95% CI 4.4-11) for grade 4. Cumulative incidences of late moderate-severe thrombocytopenia ( < 50 × 10³/μL) and anemia ( < 8 g/dL) at day 100 were 20% (95% CI 15-25) and 14% (95% CI 10-19), respectively. Early severe ICAHT (grade ≥3) was independently associated with late severe ICAHT (p < 0.001), late severe thrombocytopenia (p < 0.001), and late moderate-severe anemia (p = 0.037). Late severe ICAHT was associated with an increased hazard of late infections (HR 2.85 [95% CI 1.18-6.88], p = 0.032). These findings highlight late hematologic toxicity as a frequent and clinically relevant complication of CAR T therapy. Incorporating ICAHT grading into post-infusion monitoring may inform preventive strategies to mitigate long-term complications.