Volunteer unrelated donor cell‐derived acute myeloid leukemia with RUNX1‐RUNX1T1

Abstract

A 15-year-old male was diagnosed with acute myeloid leukemia with t(6;9)(p23;q34), a chimeric DEK-NUP214 fusion gene. He underwent allogeneic bone marrow transplantation (allo-BMT) from an unrelated volunteer donor at first molecular remission. Approximately 5 years after allo-BMT, multiple bone marrow aspirations showed increased blasts to 63%, which were positive for myeloperoxidase, CD13, CD33, CD56, and CD34. Surprisingly, t(8;21)(q22;q22.1), a chimeric RUNX1-RUNX1T1 (not DEK-NUP214) fusion gene, was detected with full donor chimerism. To our best knowledge, this is the first case of a volunteer unrelated donor cell-derived acute myeloid leukemia harboring a chimeric RUNX1-RUNX1T1 fusion gene. K E Y W O R D S allogeneic transplantation, donor cell-derived leukemia, volunteer unrelated donor 1 INTRODUCTION Donor cell-derived leukemia (DCL), defined as the development of leukemia from donor cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT), is extremely rare [1-5]; limited evidence exists on the etiology of DCL, associated genetic aberrations, risk factors for its development, and prognosis. A standard treatment for DCL has not been established as yet. Herein, we report a case of RUNX1-RUNX1T1-positive DCL that developed after unrelated allo-Abbreviations: allo-BMT, allogeneic bone marrow transplantation; AML, acute myeloid leukemia; CR, complete remission; DCL, donor cell-derived leukemia; GVHD, graft-versus-host-disease; STR, short tandem repeat; TAC, tacrolimusThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Management of patients with germline predisposition to haematological malignancies considered for allogeneic blood and marrow transplantation: Best practice consensus guidelines from the UK Cancer Genetics Group (UKCGG), CanGene‐CanVar, NHS England Genomic Laboratory Hub (GLH) Haematological Malignancies Working Group and the British Society of Blood and Marrow Transplantation and cellular therapy (BSBMTCT)

“…Although rare, DDL is a specific concern for the patient if they receive HSC donation from a related donor with a germline predisposition. 14,15 A recent survey from the European Society for Blood and Marrow Transplantation (EBMT) estimated a DDL prevalence of 80.5 cases per 100 000 transplants and a cumulative incidence at 5, 10, and 25 years after HSC transplantation of 0.067%, 0.132%, and 0.363% respectively, although this is likely to be an underestimate as, historically lack of awareness has almost certainly led to under reporting. Some studies have also suggested that when affected family members are used as donors, the likelihood of de novo leukaemia appears to be increased in the recipient compared to the donor, suggesting that the microenvironment and cytokine milieu in the recipient can drive the process.…”

“…For the patient there is a risk of DDL and the fact that certain germline variants are associated with non‐malignant phenotypes (e.g., thrombocytopenia [ RUNX1 ], lymphoedema and respiratory disease [ GATA2 ], autoimmune disease [ DDX41 ]), 4 which often have implications peri‐transplant and for long‐term follow‐up. Although rare, DDL is a specific concern for the patient if they receive HSC donation from a related donor with a germline predisposition 14,15 . A recent survey from the European Society for Blood and Marrow Transplantation (EBMT) estimated a DDL prevalence of 80.5 cases per 100 000 transplants and a cumulative incidence at 5, 10, and 25 years after HSC transplantation of 0.067%, 0.132%, and 0.363% respectively, although this is likely to be an underestimate as, historically lack of awareness has almost certainly led to under reporting.…”