Bone Marrow Transplantation最新文献

NPM1 mutated acute myeloid leukemia (AML) comprises roughly 30% of all AML cases and is mainly classified as favorable or intermediate-risk according to the European Leukemia Net stratification. Some patients, however, either have a poor response to initial intensive chemotherapy or ultimately relapse. NPM1 mutations are common, generally stable at early relapse and AML specific, features which make them ideal targets for measurable residual disease (MRD) monitoring. MRD monitoring via molecular analysis during the course of treatment can inform the role of allogeneic stem cell transplantation (HCT) in first remission in patients with NPM1 mutated AML with high-risk co-occurring mutations, particularly FLT3-ITD, and in favorable risk patients who do not achieve defined molecular milestones. In this review, we evaluate the prognostic role of MRD monitoring in NPM1 mutated AML and its use as a predictive biomarker to refine risk stratification and inform decision making regarding treatment. We explore the impact of pre-HCT MRD positivity on post-HCT outcomes in this AML subset, and how HCT-related factors such as conditioning intensity may influence this risk.

Several CD19 CAR-T-cell drugs are approved for safety and efficacy in advanced B-cell cancers with encouraging results. However, primary refractory and relapse are common. We critically analyze long-term data on efficacy of CD19 CAR-T-cell therapies in B-cell non-Hodgkin lymphomas from clinical trials with those of so-called real world data. We identify co-variates associated with efficacy, discuss mechanisms of relapse, summarize the data on the results of post-failure therapy including allotransplants, monoclonal and bi-specific antibodies, antibody-drug conjugates, immune checkpoint-inhibitors and repeat infusions of CAR-T-cells. We conclude, save for allotransplants, there are few data strongly supporting any of these interventions. Most trial are with few heterogeneously-treated subjects with diverse interventions and brief follow-up. Interventions need to be tailored to the cause(s) of CAR-T-cell failure. Prestly, there is not a convincingly safe and effective therapy of people failing initial CAR-T-cell therapy of B-cell non-Hodgkin lymphoma.

Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM). We compared the baseline characteristics and outcomes of 61 PMs and 816 non-PM patients who underwent a second auto-HCT and who were enrolled in the non-interventional CALM study (NCT01362972). Only patients who collected CD34+ prior to auto-HCT1 were included. Auto-HCT2 comprised both tandem and salvage transplants. PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%). There were no significant differences in engraftment, progression-free survival (PFS) or overall survival (OS) after the second auto-HCT between PM and non-PM patients. There was a trend to shorter PFS in PM patients undergoing salvage auto-HCT (median 9.6 vs. 12.9 months; p = 0.08) but no significant difference in OS. The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT.

Therapy-related myeloid neoplasms (t-MN) are a complication of multiple myeloma (MM) treatment. Our retrospective, EBMT registry study included 157 such patients allografted (allo-HCT) between 2006 and 2018. Most patients (130) had a prior autologous HCT. Fifty-seven (36.4%) were transplanted for t-AML and 100 (63.6%) for t-MDS. Median times from MM and t-MN diagnoses to allo-HCT were 72.6 (interquartile range (IQR), 46.1-102.9) and 6.4 (IQR, 3.9-9.4) months. Fifty-eight (38.4%) t-MN patients were in complete remission (CR) at allo-HCT predominantly conditioned with reduced intensity (70.3%). With a median follow-up of 64.9 (95% CI: 39-76) months, relapse incidence (RI) from MM at 1 and 5 years was 4% (0-10%) and 12% (2-22%), respectively, with few deaths (n = 3) only due to MM disease progression, whereas t-MN RI and non-relapse mortality (NRM) at 1 and 5 years were 35% (95% CI 28-43%) and 45% (95% CI: 36-53%) and 20% (95% CI 13-26%) and 31% (95% CI: 23-39%). Overall survival (OS) and progression-free survival (PFS) estimates at 1 and 5 years were 55% (95% CI: 47-63%) and 27% (95% CI: 19-35%) and 45% (95% CI 36-53%) and 24% (95% CI 16-32%). Older (>65 years) t-MN patients with high-risk cytogenetics do not benefit from allo-HCT.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) utilizing mismatched unrelated donors (MMUD) present a vital option for patients with hematologic malignancies without human leukocyte antigen (HLA)-matched donors. This multicenter retrospective study encompassed 211 adults with hematological malignancies receiving allo-HSCT with antithymocyte globulin (ATG) from ≥1 HLA locus MMUD. The findings revealed cumulative incidences of II-IV acute graft-versus-host disease (GVHD) at 180 days at 26.5%, and III-IV acute GVHD at 12.3%, with 3-year cumulative incidences for total and moderate-severe chronic GVHD at 37.0% and 21.0%. The 3-year non-relapse mortality (NRM) and relapse rates were 19.7% and 25.8%. The study reported a 3-year overall survival (OS) rate of 63.1%, a disease-free survival (DFS) rate of 54.5%, and a GVHD-free, relapse-free survival (GRFS) rate of 40.8%. Administration of a lower-dose ATG-Genzyme (ATG-G, ≤ 6 mg/kg) correlated with improved engraftment without significantly affecting survival, relapse, or viral reactivation rates. The quantity of HLA mismatches did not impact engraftment, GVHD, viral reactivation, OS, DFS, GRFS, relapse, or NRM. In conclusion, MMUD allo-HSCT with ATG demonstrates favorable outcomes for patients with hematological malignancies, with no evident correlation between the degree of mismatch and post-transplantation results. Utilizing a lower dose of ATG-G ( ≤ 6 mg/kg) proved efficacious, delivering comparable clinical advantage.

Observational studies using registry-based data have become indispensable in our management of patients receiving hematopoietic cell transplantation (HCT) or cellular therapies (CT) for hematologic malignancies. These registries support studies that describe the natural history of disease, evaluate clinical effectiveness, or measure safety and quality of patient care. To complement registries, biobanks exist as an essential partner to provide insight on genetic, molecular, and cellular processes. In this review, we discuss and provide examples of several biobank and registry collaborations that have advanced our knowledge in the field of HCT and CT, using the Center for International Blood and Marrow Transplantation Research (CIBMTR) as a highlighted example. The CIBMTR has collected data on over 650,000 patients and has over 60,000 paired donor recipient banked samples available for research. Biospecimens and clinical data from the CIBMTR have led to advancements in our knowledge and care of conditions such as acute myeloid leukemia and myelodysplastic syndrome (MDS), as well as our understanding of the roles of HLA typing and social determinants of health. Despite the utility in advancing research, registries and biobanks do not exist without challenges which are briefly reviewed. Nevertheless, the contributions of these resources in supporting HCT/CT research are noteworthy.