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PAX5, NOTCH3, CBFB, and ACD drive an activated RAS pathway and monosomy 7 to B-ALL and AML in donor cell leukemia

Bone Marrow Transplantation volume 54, pages 1124–1128 (2019)Cite this article

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Allogeneic stem cell transplantation (SCT) is a successful strategy for the treatment of many hematologic malignancies. Disease relapse, however, may occur at different periods post transplant, usually representing return of the original clone that survived conditioning intensive chemotherapy, radiotherapy, and graft-versus-leukemia effect. Relapses seldom arise in engrafted cells from donor origin. However, when these occur, they are known as donor cell leukemia (DCL) and represent a rare entity with an approximate incidence of 5% of post-transplant leukemia cases.

We herein report on the clinical and molecular features of DCL in two unrelated cases. Table 1 lists the clinical features and findings of both the cases, including their primary leukemia and subsequent DCL. Briefly, Cases 1 and 2 were females with a normal karyotype diagnosed with severe aplastic anemia (SAA) and chronic lymphocytic leukemia (CLL), respectively. Both the cases underwent an allogeneic hematopoietic stem cell transplant (HSCT) from their respective healthy HLA-matched male siblings, which was of bone marrow origin in Case 1 and peripheral blood in Case 2. PCR genotyping of 16 short tandem repeats at 2–3 weeks following transplantation demonstrated 99% engraftment of donor cells in both the cases and a karyotype of 46, XY. Both the cases received prophylactic treatment for graft vs host disease (GVHD) and did not develop any sign of complication and rejection. However, Case 1 evolved to a B-ALL and Case 2 to an AML-M4 at 17 and 89 months post-transplant, respectively. They were both treated with chemotherapy; while Case 2 also received an additional SCT from a matched-unrelated donor, both the cases eventually relapsed and succumbed to the sequelae of their respective DCL.

Table 1 Demographics and disease characteristics of the two DCL cases
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Author notes

  1. These authors contributed equally: Rita Assi, Rami Mahfouz.

Authors and Affiliations

  1. Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Rita Assi

  2. Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Rami Mahfouz

  3. Quest Diagnostics, Nichols Institute, San Juan Capistrano, CA, USA

    Renius Owen

  4. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA

    Martha Gunthorpe & Farid F. Chehab

  5. Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Ali Bazarbachi

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Assi, R., Mahfouz, R., Owen, R. et al. PAX5, NOTCH3, CBFB, and ACD drive an activated RAS pathway and monosomy 7 to B-ALL and AML in donor cell leukemia. Bone Marrow Transplant 54, 1124–1128 (2019). https://doi.org/10.1038/s41409-018-0419-7

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