Bone Marrow Transplantation最新文献

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and rare hematological malignancy with poor clinical outcomes. Stem cell transplantation helps to achieve long-term survival in adults. However, the benefit of haploidentical stem cell transplantation (HID-SCT) versus chemotherapy is unclear with BPDCN. We retrospectively analyzed 32 patients diagnosed with BPDCN including 15 who underwent HID-SCT and 17 who only received chemotherapy. The median age was 52 (range, 19-78) years. The ratio of male/female was 2.2. Skin, bone marrow and lymph node were the most three common sites of disease involvement. Compared with the chemotherapy group, patients in the HID-SCT group had significantly better progression-free survival (PFS; median, 7 months versus not reached, P < 0.001) and overall survival (OS; median, 13 months versus not reached, P < 0.001). The 4-year rates for PFS and OS in transplant patients were 74% (95% Confidence Interval [CI], 47, 100%) and 93% (79, 100%), respectively, compared to 0 in non-transplant patients. In conclusion, our results demonstrated HID-SCT could provide long-term remissions in BPDCN patients.

We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.

In 2023, 47,731 HCT (20,485 (42.9%) allogeneic and 27,246 (57.1%) autologous) in 43,902 patients were reported by 696 European centers. 6042 patients received advanced cellular therapies, 4888 of which were CAR-T. Compared to the previous year there was an increase in CAR-T (+52.5%), in allogeneic HCT (+7.8%) but none in autologous HCT (+0.4%). Main indications for allogeneic HCT were myeloid (11,748; 60.7%), lymphoid malignancies (4,850; 25.0%), and non-malignant disorders (2558; 13.2%). Use of allogeneic HCT increased for AML (+12.1%) and for NHL (+11.0%), particularly in T-NHL (+25.6%). Main indications for autologous HCT were lymphomas (7890; 32.2%), PCD (14,271; 58.2%), and solid tumors (1608; 6.6%) with recovering numbers for autoimmune diseases. In patients with allogeneic HCT, the use of sibling donors increased by +1.0%, haploidentical donors by +11.7%, and unrelated donors by +11.1%. Cord blood HCT decreased again by -5.4%. Pediatric HCT activity increased slightly (5455; +0.1%) with differences between allogeneic (4111; -0.5%) and autologous HCT (1344: +1.7%). Use of CAR-T increased to a cumulative total of 13,927 patients including patients treated for autoimmune diseases. Overall, numbers show a complete recovery from the pandemic dip with increased cellular therapy at the expense of autologous HCT. Allogeneic HCT activity focuses on myeloid malignancies.

Long-term survivors after allogeneic cell transplantation (HCT) have unique needs. We performed a cross-sectional case-control study to describe the survivorship profile of 244 adult allogeneic transplantation recipients at a median of 8.4 years post-HCT and compared it to controls from the general population (matched 1:3 based on age, gender, and province of residence). The most prevalent medical complications were graft versus host disease (46.7%), impaired kidney function (63.9%), and the presence of a metabolic syndrome (33.6%). Survivors were significantly more likely to report a sub-optimal perceived health status than controls (82.0% versus 52.1% respectively, OR 4.57, p < 0.0001). They also reported significantly lower employment rates (42.6% versus 55.6% respectively, OR 0.389, p < 0.0001) and more polypharmacy (32.0% versus 9.6% respectively, OR 5.0, p < 0.0001) than matched counterparts. Social support and mental health were generally preserved. Apart for a concerning tendency to medication non-adherence, low physical activity (54.5%), and inappropriate exposition to UV (44.7%), health-related behavior was adequate. Many survivors have a health status comparable to chronically ill patients and, if so, should be managed as such. Novel patient-centered initiatives based on chronic care models could support survivors in preventing and dealing with long-term complications, regaining functionality, and returning to their role in society.

Post-transplant cyclophosphamide (PTCY) is increasingly used as effective graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic-cell transplantation (allo-HCT). However, PTCY is associated with toxicities. Whether patients with specific comorbidities are more vulnerable to cyclophosphamide-induced toxicity is unclear. We retrospectively evaluated the impact of individual organ dysfunctions for non-relapse mortality (NRM) risk and overall survival (OS) among 5888 adults who underwent PTCY-based allo-HCT for acute myeloid leukemia between 2010 and 2023. In multivariable analyses 5 of the comorbidities (renal, moderate/severe hepatic, cardiac including arrhythmia/valvular disease, severe pulmonary, infection) were independently associated with adverse NRM and OS without influencing relapse rate. A simplified model using the absence (n = 4390), presence of 1 (n = 1229) or presence of 2 or 3 (n = 269) of the comorbidities which were determined individually to contribute to NRM stratified patients into 3 NRM risk (16.2% vs. 21.6% vs. 36%, retrospectively) and OS categories (64% vs. 56% vs. 36.4%, retrospectively). In Cox model, recipients with 2 or 3 comorbidities had an increased hazard ratio for NRM of 2.38 (95% confidence interval [CI], 1.89-3) and for OS of 1.96 (95% CI 1.64-2.33). Whether patients with concomitant diagnoses, as determined here, may benefit from a reduced PTCY dose remains to be evaluated in prospective clinical trials.

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72-93] vs. 71% [95% CI 66-77], p = 0.048). However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24-50] vs. 43% [95% CI 37-49], p = 0.2), as were 1-year progression-free survival probabilities (62% [95% CI 50-76] vs. 50% [95% CI 44-57], p = 0.14). The early group exhibited a favorable toxicity profile, with lower rate of grade ≥2 cytokine release syndrome (26% vs. 39%, p = 0.031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30-52] vs. 55% [95% CI 49-60], p = 0.027). Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy.