Search

We assessed outcomes of allogeneic transplantation (HSCT) in favorable risk AML in CR1 over 3 time periods. 1850 patients were included, 2005 to 2009- 222, 2010 to 2014 -392, and 2015 to 2021-1236; 526 with t (8:21), 625 with inv (16), and 699 with NPM1mutFLT3WT. Patients transplanted in 2015–2021 were older (p< 0.0001) with more patients ≥60 years of age (p< 0.0001). The most frequent diagnosis in 2015–2021 was NPM1mutFLT3WTvs. t (8:21) in the 2 earlier periods, (p< 0001). Haploidentical transplants (Haplo) increased from 5.9% to 14.5% (p< 0.0001). Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) was more frequent in 2015–2021 vs. the other 2 periods (p< 0.0001). On multivariate analysis, incidence of total chronic GVHD was reduced in HSCTs performed ≥2015 vs. those performed in 2005–2009, hazard ratio (HR) = 0.74 (95% CI 0.56–0.99, p= 0.046) and GVHD-free, relapse-free survival (GRFS) improved for patients transplanted from 2010–2014 vs. those transplanted in 2005–2009, HR = 0.74 (95% CI 0.56–0.98, p= 0.037). Other HSCT outcomes did not differ with no improvement ≥2015. LFS, OS, and GRFS were inferior in patients with t (8:21) with HR = 1.32 (95% CI 1.03–1.68, p= 0.026), HR = 1.38 (95% CI 1.04–1.83, p= 0.027) and HR = 01.25 (95% CI 1.02–1.53, p= 0.035), respectively. In conclusion, this retrospective analysis of HSCT in patients with favorable risk AML, transplanted over 16 years showed an increased number of transplants in patients ≥60 years, from Haplo donors with PTCy. Most importantly, 3-year GRFS improved ≥2010 and total chronic GVHD reduced ≥2015, with no significant change in other HSCT outcomes.

Isocitrate dehydrogenase 1 and 2 (IDH1and IDH2) mutations have uncertain prognostic implications in AML. We investigate the impact IDH1and IDH2mutations in AML patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1). In total, 1515 adult patients were included, 15.91% (n= 241) carried IDH1mutation (mIDH1), and 26.27% (n= 398) IDH2mutation (mIDH2) and 57.82% (n= 876) had no-IDH mutation. NPM1was frequently encountered with IDH1mutation (no-IDH group, n= 217, 24.8%, mIDH1, n= 103, 42.7%, mIDH2, n= 111, 27.9%, p< 0.0001). At day 180, the cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was significantly lower in mIDH1and mIDH2compared to no-IDH groups (Hazard ratio [HR] = 0.66 (95% CI 0.47–0.91), p= 0.011; HR = 0.73 (95% CI 0.56–0.96), p= 0.025, respectively). In the mIDH1group, overall survival (OS) was improved compared to no-IDH (HR = 0.68 (95% CI 0.48–0.94), p= 0.021), whereas mIDH2was associated with lower incidence of relapse (HR = 0.49 (95% CI 0.34–0.7), p< 0.001), improved leukemia free survival (LFS) (HR = 0.7 (95% CI 0.55–0.9), p= 0.004) and OS (HR = 0.74 (95% CI 0.56–0.97), p= 0.027). In the subgroup of NPM1wild type, only IDH2was associated with improved outcomes. In conclusion, our data suggest that IDH1and IDH2mutations are associated with improved outcomes in patients with AML undergoing allo-HCT in CR1.

The objective of the study was the analysis of clinical types, outcomes, and risk factors associated with the outcome of adenovirus (ADV) infection, in children and adults after allo-HCT. A total number of 2529 patients (43.9% children; 56.1% adults) transplanted between 2000 and 2022 reported to the EBMT database with diagnosis of ADV infection were analyzed. ADV infection manifested mainly as viremia (62.6%) or gastrointestinal infection (17.9%). The risk of 1-year mortality was higher in adults (p= 0.0001), and in patients with ADV infection developing before day +100 (p< 0.0001). The 100-day overall survival after diagnosis of ADV infections was 79.2% in children and 71.9% in adults (p< 0.0001). Factors contributing to increased risk of death by day +100 in multivariate analysis, in children: CMV seropositivity of donor and/or recipient (p= 0.02), and Lansky/Karnofsky score <90 (p< 0.0001), while in adults: type of ADV infection (viremia or pneumonia vs gastrointestinal infection) (p= 0.0004), second or higher HCT (p= 0.0003), and shorter time from allo-HCT to ADV infection (p= 0.003). In conclusion, we have shown that in patients infected with ADV, short-term survival is better in children than adults. Factors directly related to ADV infection (time, clinical type) contribute to mortality in adults, while pre-transplant factors (CMV serostatus, Lansky/Karnofsky score) contribute to mortality in children.

We aimed to compare outcomes following treosulfan (TREO) or busulfan (BU) conditioning in a large cohort of myelofibrosis (MF) patients from the EBMT registry. A total of 530 patients were included; 73 received TREO and 457 BU (BU ≤ 6.4 mg/kg in 134, considered RIC, BU > 6.4 mg/kg in 323 considered higher dose (HD)). Groups were compared using adjusted Cox models. Cumulative incidences of engraftment and acute GVHD were similar across the 3 groups. The TREO group had significantly better OS than BU-HD (HR:0.61, 95% CI: 0.39–0.93) and a trend towards better OS over BU-RIC (HR: 0.66, 95% CI: 0.41–1.05). Moreover, the TREO cohort had a significantly better Progression-Free-Survival (PFS) than both the BU-HD (HR: 0.57, 95% CI: 0.38–0.84) and BU-RIC (HR: 0.60, 95% CI: 0.39–0.91) cohorts, which had similar PFS estimates. Non-relapse mortality (NRM) was reduced in the TREO and BU-RIC cohorts (HR: 0.44, 95% CI: 0.24–0.80 TREO vs BU-HD; HR: 0.54, 95% CI: 0.28–1.04 TREO vs BU-RIC). Of note, relapse risk did not significantly differ across the three groups. In summary, within the limits of a registry-based study, TREO conditioning may improve PFS in MF HSCT and have lower NRM than BU-HD with a similar relapse risk to BU-RIC. Prospective studies are needed to confirm these findings.

Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n= 1844) or unrelated donor (UD, n= 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality. CI of severe grade III-IV acute GVHD was lower with TAC (6.6% vs. 9.1%, p= 0.02), without difference in grade II-IV acute GVHD or grade III-IV acute GVHD/severe chronic GVHD, relapse-free survival (GRFS). In multivariate analysis, TAC was associated with a lower risk of severe grade III-IV acute GVHD solely with haploidentical donors (HR 0.64 [95% CI, 0.42–0.98], p= 0.04), but not UD (HR 0.49 [95% CI, 0.2–1.21], p= 0.12). There was no significant difference for chronic GVHD. In conclusion, PT-Cy/MMF-based GVHD prophylaxis resulted in favorable OS and GRFS, irrespective of the CNI added. In haploidentical HCT, TAC seemed to prevent severe acute GVHD more effectively than CSA without impact on other outcome parameters.

Graft-versus-host disease (GVHD) and cytomegalovirus (CMV)-related complications are leading causes of mortality after unrelated-donor hematopoietic cell transplantation (UD-HCT). The non-conventional MHC class I gene MICB, alike MICA, encodes a stress-induced polymorphic NKG2D ligand. However, unlike MICA, MICB interacts with the CMV-encoded UL16, which sequestrates MICB intracellularly, leading to immune evasion. Here, we retrospectively analyzed the impact of mismatches in MICB amino acid position 98 (MICB98), a key polymorphic residue involved in UL16 binding, in 943 UD-HCT pairs who were allele-matched at HLA-A, -B, -C, -DRB1, -DQB1and MICAloci. HLA-DPtyping was further available. MICB98mismatches were significantly associated with an increased incidence of acute (grade II–IV: HR, 1.20; 95% CI, 1.15 to 1.24; P< 0.001; grade III–IV: HR, 2.28; 95% CI, 1.56 to 3.34; P< 0.001) and chronic GVHD (HR, 1.21; 95% CI, 1.10 to 1.33; P< 0.001). MICB98matching significantly reduced the effect of CMV status on overall mortality from a hazard ratio of 1.77 to 1.16. MICB98mismatches showed a GVHD-independent association with a higher incidence of CMV infection/reactivation (HR, 1.84; 95% CI, 1.34 to 2.51; P< 0.001). Hence selecting a MICB98-matched donor significantly reduces the GVHD incidence and lowers the impact of CMV status on overall survival.