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• The incidence of AML relapse is reduced with CMV reactivation. • NK cells are involved in CMV-associated protection from AML relapse. • CMV infection trigger/enhance a response by NK expressing activating KIRs. Multiple retrospective studies have demonstrated an association between cytomegalovirus (CMV) reactivation and reduced risk of AML relapse. However, the potential mechanism explaining this association remains elusive. We investigated a homogeneous cohort of 288 adult patients with AML in remission who received allogeneic hematopoietic stem cell transplantation (HCT) from matched sibling/unrelated donors between 1995 and 2011. The 5-year cumulative incidence of relapse was greater in patients without CMV reactivation compared with those with reactivation (30.2% vs. 12.1%, p = 0.001) in a landmark analysis. In multivariate analyses CMV reactivation was independently associated with reduced relapse risk (HR: 0.49 [0.25-0.95], p = 0.036) and increased non-relapse mortality (26.5% vs. 13.1%, p = 0.002) resulting in similar 5-year overall survival (64.5% vs. 59.1%, p = 0.8). In further subgroup analyses the protective effect of CMV reactivation was significant in patients who received HCT from donors with KIR Bx compared to KIR AA (11.7% vs. 29.5%, p = 0.01). Likewise, the protective effect of CMV reactivation was more significant when the donors had 2DS1 activating KIR (11.5% vs. 30.7%, p = 0.05) compared with those without 2DS1 (14.3% vs. 27.5%, p = 0.12). Our data independently confirmed the association between CMV reactivation and AML relapse, suggesting the involvement of donor KIR genotypes and NK cell-mediated graft-versus-leukemia effect. [ABSTRACT FROM AUTHOR]

Abstract: In systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD), mast cell infiltration of the bone marrow coexists with a hematologic neoplasm, usually of myeloid origin. Activating KIT gene mutations are universally present in these neoplastic mast cells. When SM is associated with AML, the leukemic cells commonly carry the t(8;21)(q22;q22) core binding factor translocation. The precise relationship between neoplastic mast cells and the leukemic clone has remained unclear. By target FISH analysis, we demonstrate t(8;21) in the bone marrow mast cells of a patient with systemic mastocytosis associated with t(8;21) AML, thus, proving the origin of these neoplastic mast cells from the leukemic clone. We also show that after successful allogeneic hematopoietic stem cell transplantation, these neoplastic bone marrow mast cells can persist without adverse consequences and gradually decline with time. [Copyright &y& Elsevier]