DDX41 germline variants causing donor cell leukemia indicate a need for further genetic workup in the context of hematopoietic stem cell transplantation
Benjamin Rolles, Robert Meyer, Matthias Begemann, Miriam Elbracht, Edgar Jost, Matthias Stelljes, Ingo Kurth, Tim H. Brümmendorf, Gerda Silling
Abstract
Hematopoietic stem cell transplantation (HSCT) represents the standard treatment for patients with high or intermediate-2 risk (IPSS classification) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with intermediate or unfavorable risk (ELN classification) [ 1 ]. Despite recent progress in both induction treatment as well as conditioning regimens before transplantation and immunosuppression thereafter, relapse of MDS and AML occurs in 30–50% of patients and remains the most frequent cause of mortality. Disease relapse originates in almost all cases from residual leukemic stem cells escaping the chemotherapeutic and (allo-) immunological effects of transplantation. Rarely “relapse” actually originates from donor-derived cells. These so-called donor cell leukemias (DCL) reflect approximately 2% of AML or MDS relapses after HSCT [ 1 ].