GVHD occurrence does not reduce AML relapse following PTCy-based haploidentical transplantation: a study from the ALWP of the EBMT

The association between graft-versus-host disease (GVHD) occurrence and acute myeloid leukemia (AML) relapse in patients treated with HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis has remained debated. Here, we addressed this issue in patients with active AML at transplantation. 2-year cumulative incidences of relapse and leukemia-free survival (LFS) were 49% and 32.3%, respectively. There were no associations between acute nor chronic GVHD of any grade and lower relapse incidence. However, grade I acute GVHD was associated with better LFS (HR = 0.71, 95% CI 0.51–0.99, P = 0.04). In contrast, grade III–IV acute (HR = 3.09, 95% CI 1.87–5.12, P < 0.0001) as well as extensive chronic (HR = 3.3, 95% CI 1.81–6.04, P = 0.0001) GVHD correlated with higher nonrelapse mortality leading to lower LFS (HR = 1.36, 95% CI 0.99–1.86, P = 0.056 and HR = 1.97, 95% CI 1.35–2.89, P = 0.0004, respectively). In conclusion, these data suggest a dissociation of graft-versus-leukemia effects from GVHD in patients with active AML treated with PTCy-based Haplo-HCT

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

\ua9 2021, The Author(s).Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 7 10−8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 7 10−10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)