DDX41 germline variants causing donor cell leukemia indicate a need for further genetic workup in the context of hematopoietic stem cell transplantation

Blood Cancer Journal, vol. 13, pp. 73

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 ].

Authors 9

1. Benjamin Rolles corresponding Aachen Department of Hematology, Oncology Medical Faculty

   Brigham and Women's Hospital · Harvard University · RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany. brolles@bwh.harvard.edu

   Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany. brolles@bwh.harvard.edu

   Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. brolles@bwh.harvard.edu

2. Robert Meyer Aachen Institute for Human Genetics and Genomic Medicine Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany

   Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany

3. Matthias Begemann Aachen Institute for Human Genetics and Genomic Medicine Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany

   Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany

4. Miriam Elbracht Aachen Institute for Human Genetics and Genomic Medicine Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany

   Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany

5. Edgar Jost Aachen Department of Hematology, Oncology Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany

   Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany

6. Matthias Stelljes

   University of Münster

   Affiliation as printed

   Department of Medicine A, Hematology and Oncology, University of Muenster, Münster, Germany

7. Ingo Kurth Aachen Institute for Human Genetics and Genomic Medicine Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany

   Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany

8. Tim H. Brümmendorf Aachen Department of Hematology, Oncology Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany

   Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany

9. Gerda Silling Aachen Department of Hematology, Oncology Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany

   Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany