ABSTRACT Prophylaxis strategies for Graft versus host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo‐HCT) frequently encompass a combination of a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). The aim of this retrospective, EBMT registry‐based study was to determine outcome differences for chronic myeloid malignancies and secondary acute myeloid leukemia (sAML) between MTX‐ and MMF‐based prophylaxis regimens while taking potential heterogeneity between subgroups into consideration. Eligible were patients transplanted between 2007 and 2017 who received either MTX‐ or MMF prophylaxis in combination with a CNI. Endpoints after allo‐HCT were overall survival, relapse‐free survival (RFS), relapse incidence, non‐relapse mortality (NRM), and Grades 2–4 acute GVHD (aGvHD). Overall, 13 699 patients from 321 centers were included. Median follow‐up was 42.8 months (IQR 19.8–74.5 months). MTX prophylaxis was associated with reduced overall mortality (HR 0.87, 95% CI 0.81–0.95, p = 0.001) and NRM (HR 0.86, 95% CI 0.78–0.96, p = 0.006) compared with MMF in multivariable Cox regression models in the whole cohort without significant interaction between prophylaxis and subgroups. In contrast, there was no significant association of prophylaxis with risk of relapse (HR 1.03 MTX vs. MMF, 95% CI 0.94–1.14, p = 0.53) or RFS (HR 0.95, 95% CI 0.88–1.01, p = 0.12). There was a reduced risk of Grades 2–4 acute GVHD and reduced mortality after acute GVHD with MTX prophylaxis but no association with outcome in a landmark analysis in patients without aGvHD at 3 months after allo‐HCT. In conclusion, MTX‐complemented CNI prophylaxis was associated with favorable survival, and with favorable survival after aGVHD compared with MMF.
ABSTRACT According to the European LeukemiaNet (ELN) 2022 classification, acute myeloid leukemia (AML) patients with intermediate or adverse risk are offered allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in first remission. In this EBMT study, we included 1735 adult AML patients with ELN‐2022 adverse‐risk cytogenetics allografted between 2010 and 2022 in first remission (67% de novo AML, median age 56 years). Eleven non‐overlapping adverse‐risk cytogenetics groups were defined. The five most frequent were: Group 1 [ n = 394; monosomy 17 or abn(17p); 2‐year leukemia‐free survival (LFS) 22%, and overall survival (OS) 25%]; Group 2 [ n = 313; complex karyotype (CK) involving monosomy 5, monosomy 7, or del(5q) without monosomy 17 or abn(17p); LFS 27%, OS 37%]; Group 3 [ n = 201; monosomy 5, monosomy 7, or del(5q) without CK and without monosomy 17 or abn(17p); LFS: 55%, OS: 63%]; Group 4 [ n = 256; CK without monosomal karyotype (MK) or adverse additional cytogenetic abnormalities (ACA); LFS 50%, OS 61%]; Group 5 [ n = 213; t(v, 11q23) without adverse ACA; LFS 50%, OS 59%]. In multivariable analysis, compared to CK without adverse ACA, LFS was negatively affected by monosomy 17 or 17p abnormalities, monosomy 5, 7, or del(5q) in the presence of CK, and t(8;16). In conclusion, this study revealed a very poor outcome of allografted AML patients with monosomy 17 or 17p abnormalities or CK involving monosomy 5, monosomy 7, and del5q. Outcomes were relatively favorable for most other ELN 2022 adverse categories, including CK with or without MK other than 5, 7, and 17, indicating that allo‐HSCT can overcome their poor outcome.
ABSTRACT Donor preference for acute myeloid leukemia (AML) patients transplanted in second complete remission (CR2) remains unclear, and hematopoietic cell transplantation (HCT) with post‐transplant cyclophosphamide (PTCy) from a haploidentical donor (HAPLO) merits attention. Data of 3878 adult AML patients receiving a first allo‐HCT in CR2 from the European Society of Blood and Marrow Transplantation registry between 2010 and 2022 were analyzed. Univariate analyses and Cox regression models were used. Results of HCTs from 803 HAPLO PTCy, 1271 matched sibling donor (MSD), and 1804 matched unrelated donor (MUD) were analyzed. A higher proportion (80.7%) of patients with European LeukemiaNet (ELN2022) intermediate−/adverse‐risk cytogenetics received an allo‐HCT from HAPLO PTCy than from either MUD (79.6%) or MSD (70.2%). On multivariate analysis, HAPLO PTCy grafts (hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.51–0.82; p < 0.001) were associated with a lower relapse incidence (RI) compared with MSD HCTs, although non‐relapse mortality was higher (HR = 1.77, 95% CI 1.34–2.34; p < 0.001). No difference was observed with respect to leukemia‐free survival and graft‐versus‐host disease (GVHD)‐free, relapse‐free survival (GRFS) for HAPLO PTCy compared to MSD grafts. Notably, HAPLO PTCy HCT was associated with significantly lower RI (HR = 0.64, 95% CI 0.48–0.82; p < 0.001), chronic GVHD (cGVHD) (HR = 0.64, 95% CI 0.51–0.81; p < 0.001) and extensive cGVHD (HR = 0.47, 95% CI 0.34–0.66; p < 0.001) incidences compared to MUD HCTs. Collectively, HAPLO PTCy HCT was associated with superior GRFS (HR = 0.81, 95% CI 0.68–0.95; p = 0.013) than MUD HCT. For AML patients in CR2, HAPLO PTCy HCT is associated with lower RI and cGVHD, leading to superior GRFS compared with MUD HCTs.
ABSTRACT Selecting the optimal donor is crucial for optimizing results of allogeneic hematopoietic cell transplantation (allo‐HCT). We analyzed outcomes based on donor type in 2809 myelofibrosis (MF) patients undergoing first allo‐HCT between 2015 and 2021 at EBMT centers. Study outcomes included overall survival (OS), progression‐free survival (PFS), relapse, non‐relapse mortality (NRM), engraftment, and graft‐versus‐host disease (GvHD). Four groups were compared: matched sibling donor (MSD, n = 742), matched unrelated donor (MUD, n = 1401), mismatched unrelated donor (MMUD, n = 379) and haploidentical donor (HD, n = 287). After a median follow‐up of 33.5 months, 3‐year OS rates were 65.8%, 61.5%, 53.2%, and 57.7% for MSD, MUD, MMUD, and HD, respectively. Multivariable analyses (MSD as reference) showed that donor type significantly correlated with OS (HR: 1.63 for MMUD, HR: 1.42 for HD), PFS (HR: 1.38 for MMUD), NRM (HR: 1.73 for MMUD, HR: 1.47 for HD), engraftment (HR: 0.72 for MMUD, HR: 0.40 for HD), grade 2–4 acute GvHD (HR: 1.53 for MUD, HR: 1.69 for MMUD, HR: 1.49 for HD), and extensive chronic GvHD (HR: 0.77 for MUD, HR: 0.65 for HD). Donor type was not associated with relapse risk. In patients over 60 years, correlations between donor type and outcomes were consistent with those in the overall study population. In summary, with current practices, MF patients receiving MSD or MUD grafts achieve comparable outcomes. In contrast, MMUD and HD transplants have worse OS due to increased NRM. MMUD transplants have a higher risk of GvHD than HD transplants, but this difference seems to disappear with post‐transplant cyclophosphamide.
ABSTRACT Blinatumomab is approved for the treatment of relapsed or refractory (R/R) B‐cell acute lymphoblastic leukemia (B‐ALL). Studies have correlated pre‐blinatumomab high disease burden (HDB) [> 50% bone marrow blasts (BMB)] with lower response rates and increased risk for toxicities, including cytokine release syndrome (CRS) and neurotoxicity (NT). While the administration of pre‐blinatumomab cytoreductive therapy is an appealing approach, larger studies validating the beneficial effect of this strategy in patients with HDB are lacking. We retrospectively analyzed 148 adult patients with R/R B‐ALL treated with blinatumomab. Patients were grouped as low disease burden (LDB, n = 55), HDB without cytoreduction ( n = 41), and HDB with cytoreduction ( n = 52). The median age for the cohort was 40 years; the majority were males (63%) and Hispanic (73%), and the most common ALL subtype was Ph‐like (40%). Patients with HDB with cytoreduction had a significantly higher rate of prior alloHCT ( p = 0.041) and more lines of prior therapy ( p = 0.006) compared to the other cohorts. Compared to patients with HDB, those with LDB had significantly higher response rates to blinatumomab ( p < 0.0001), while rates of CRS and NT were not significantly different. Among patients with HDB, cytoreductive therapy was associated with a significantly lower rate of CRS compared to those who did not receive cytoreduction ( p = 0.038). However, cytoreduction had no significant impact on treatment response, MRD negativity, or NT. Patients with B‐ALL and HDB remain a challenging population for blinatumomab therapy; while cytoreduction may improve safety by reducing CRS, novel strategies are needed to enhance treatment efficacy.
ABSTRACT Given the dismal prognosis for patients with TP53 ‐mutated acute myeloid leukemia (AML), the optimal donor for those undergoing allogeneic hematopoietic cell transplantation (allo‐HCT) remains unclear. We retrospectively analyzed adult patients with TP53 ‐mutated AML who underwent first allo‐HCT in CR1 between 2010 and 2021. Outcomes were compared among using a haploidentical donor (Haplo), a matched sibling donor (MSD), and a 10/10 matched unrelated donor (MUD). The analysis comprised 451 patients, including 86 Haplo, 117 MSD, and 248 MUD. Patients in the three groups were transplanted during a similar period. Haplo, MSD, and MUD groups experienced similar incidences of Day 180 Grades II–IV aGVHD (30.9% vs. 23.6% vs. 28.3%), Grades III–IV aGVHD (13.6% vs. 10.1% vs. 9.1%), 2‐year cGVHD (28.9.% vs. 30.9% vs. 25.6%) and extensive cGVHD (10.9% vs. 16.1% vs. 13.3%). By multivariate analysis, the outcomes were similar in the three groups. The MSD group was associated with a similar 2‐year overall survival (OS: 33.9%; p = 0.799), leukemia‐free survival (LFS: 30.5%; p = 0.956), relapse incidence (RI: 54.2%; p = 0.497), non‐relapse mortality (NRM: 15.3%; p = 0.368), and GVHD‐free, relapse‐free survival (GRFS: 21.8%, p = 0.957) when compared with the Haplo group (2‐year OS: 46.7%, LFS: 37.4%, RI: 40.8%, NRM: 21.7%, GRFS: 25.7%). The MUD group also experienced a similar 2‐year OS (36.9%; p = 0.892), LFS (31%; p = 0.904), RI (50.8%; p = 0.521), NRM (18.2%; p = 0.368) and GRFS (21.9%; p = 0.383) when compared with the Haplo group. In conclusion, outcomes of patients with TP53 ‐mutated AML undergoing allo‐HCT from a haploidentical donor were comparable to those from an MSD or 10/10 MUD HCT.