This study investigates early cardiac events (ECEs) occurring during the first 180 days after allogeneic hematopoietic cell transplant (allo-HCT) in 416 adults receiving posttransplant cyclophosphamide (PTCY) (n = 258) or not receiving PTCY (n = 158). Total body irradiation (TBI) was given to 133 (31.9%) patients, of whom 111 (83.4%) received TBI combined with PTCY. The day +180 cumulative incidence function (CIF) of ECEs was 8.4%, with heart failure (n = 13) and pericardial complications (n = 11) being the most prevalent complications. The incidence of ECEs was higher in patients receiving PTCY, and receiving TBI. ECEs were more prevalent in haploidentical HCTs than in matched sibling donor, 10/10 HLA-matched unrelated donor, and 9/10 HLA-mismatched unrelated donor allo-HCTs. As for the ECE risk from the combination of PTCY and TBI, the multivariate analysis reported that patients receiving PTCY without TBI, TBI without PTCY, and TBI with PTCY were at higher risk for ECEs compared with patients receiving neither PTCY nor TBI. Pre-existing cardiac morbidity predicted ECEs. However, using high-dose CY-containing preparative regimens did not increase the risk for cardiac toxicity at +180 days after allo-HCT. ECEs were associated with higher nonrelapse mortality and lower overall survival. Considering that PTCY and TBI were predictors for ECEs, and the impact of this complication on transplant mortality, the implementation of cardiac monitoring plans could be appropriate in patients receiving these medications.

Clinical trials have shown that nivolumab has remarkable activity against relapsed/refractory classical Hodgkin lymphoma (cHL). However, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as consolidation therapy in these patients remains controversial. We performed a retrospective analysis of data from 74 patients treated with nivolumab. The overall response rate was 58% (including 30.6% with complete responses). Treatment-related adverse events were reported in 56.8% of patients (grade ≥3 in 9.4%). The main reasons for nivolumab discontinuation were referral for transplantation (41.7% patients) and disease progression (37.5%). The 2-year overall survival (OS) rate was 52% for the entire series. Ultimately, 39 patients underwent allo-HSCT. The cumulative incidence of grade II-IV acute graft-versus-host disease was 33.3% (grade III-IV in 2 patients). The cumulative incidence of nonrelapse mortality was 13.2%. Among the patients who responded to nivolumab, the 2-year OS and progression-free survival (PFS) were higher in patients who underwent consolidation with allo-HSCT (77.5% versus 42.6% [P = .126] and 73.9% versus 27.2% [P = .025], respectively). Thus, the efficacy and safety of nivolumab were comparable to values reported in previous clinical trials. The percentage of patients who bridged to transplantation was high, indicating a preference for Spanish physicians. These results suggest that consolidation allo-HSCT increases OS and PFS.

The optimal prophylaxis regimen for graft-versus-host disease (GVHD) in the setting of single-locus mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation (alloHSCT) is unclear. The use of high-dose post-transplant cyclophosphamide (PTCy) after haploidentical transplantation is effective at overcoming the negative impact of HLA disparity on survival. Limited information is available regarding the efficacy of this strategy in alloHSCT from MMUDs. Most of the published studies have used the triple immunosuppressant model of haploidentical transplant combining PTCy with calcineurin inhibitors and mycophenolate mofetil or methotrexate. In our study, we propose the use of a simpler GVHD prophylaxis protocol comprising PTCy in combination with tacrolimus for MMUD and matched unrelated donor (MUD) alloHSCT. We performed a retrospective analysis of 109 consecutive recipients of alloHSCT from unrelated donors (MMUD, n = 55; MUD, n = 54) in a single center. Graft source was primarily peripheral blood (98%). No differences were observed between the MMUD and MUD groups with respect to 100-day cumulative incidence of grade II to IV acute GVHD (aGVHD; 31% versus 32%, respectively, P = .9), grade III to IV aGVHD (9% versus 7%, P = .7), and moderate/severe chronic GVHD (cGVHD) at 2 years (18% versus 14%, P = .6). Both groups showed similar cumulative incidence of 1 year nonrelapse mortality (13% versus 9%; P = .5) and 3-year relapse rates (24% versus 25%, P = .7). Progression-free survival and overall survival at 3 years for MMUD and MUD were 56% and 57% (P = .9) and 64% and 65% (P = .6), respectively. The 3-year probability of survival free of moderate/severe cGVHD and relapse was 56% and 55%, respectively. GVHD prophylaxis with PTCy and tacrolimus achieves low rates of severe aGVHD and cGVHD, as well as good survival outcomes, in recipients of both MMUD and MUD peripheral blood alloHSCT. This strategy overcomes the negative impact of single-locus HLA disparity.

Checkpoint inhibitors (CPIs) have shown remarkable efficacy in Hodgkin lymphoma (HL), and are now used routinely. While allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for HL, there are concerns prior CPIs may exacerbate post–allo-HCT complications, particularly graft-versus-host disease (GVHD), and lead to worse outcomes. Given the relative paucity of data, we performed a Center for International Blood and Marrow Transplant Research/European Society for Blood and Marrow Transplantation study to examine the impact of prior CPIs in allo-HCT. We included 2186 adult patients aged >18 years who received a first allo-HCT using a matched related, unrelated, or haploidentical donor from 2008 to 2023. Twenty-seven percent of patients received prior CPIs. GVHD prophylaxis was posttransplant cyclophosphamide (PTCy) in 55.8% of patients in the CPI cohort, and 35% in the non-CPI cohort. Median follow-up among survivors was longer for the non-CPI (39 months) than CPI cohort (16.5 months). In multivariate analysis, prior CPI exposure did not affect overall survival (OS) or nonrelapse mortality, but resulted in improved progression-free survival (non-CPI vs CPI hazard ratio [HR], 0.81; 0.67-0.98; P = .03) and lower relapse incidence (HR, 0.58; 0.45-0.76; P < 001). While grade 2 to 4 (HR, 1.26; 1.04-1.53; P = .02) and 3 to 4 (HR, 1.41; 1.04-1.92; P = .03) acute GVHD (aGVHD) were increased, differences in chronic GVHD (cGVHD) were not significant. PTCy–based GVHD prophylaxis resulted in improved OS, lower grade 2 to 4 aGVHD, and cGVHD in patients with prior CPI exposure. In summary, allo-HCT should still be considered a curative option for patients with HL in the era of CPIs.