The spectrum of myelodysplastic syndromes post-solid organ transplantation: A single institutional experience

Abstract

An increased incidence of acute myeloid leukemia (AML) has recently been documented in patients post-solid organ transplantation but the incidence and types of myelodysplastic syndromes (MDS) occurring in this patient population are not known. We identified 5 patients (3M, 2F, age 48-64 years) who developed MDS ranging from 1.8 to 25 years (median 4.2 years) post-solid organ transplantation, only 2 patients had received azathioprine. The cumulative incidence of MDS in heart and lung transplant recipients at 15 years was 0.5% and 1.8%, respectively, which is markedly higher compared to the general population. Low-risk types of MDS predominated, 3 of 5 patients are alive (median 3.9 years) since diagnosis. Deletions of chromosome 20q, which have not been previously reported in post-transplant MDS/AML, were identified in 3 cases. Our findings expand the morphologic and cytogenetic spectrum of MDS occurring post-solid organ transplantation and suggest that mechanisms beside azathioprine toxicity might be important in disease pathogenesis.

Increased Risk for Lymphoid and Myeloid Neoplasms in Elderly Solid-Organ Transplant Recipients

“…The increased risk that we observed for myeloid neoplasms as a group is somewhat supported by prior research pointing to elevated risk for myelodysplastic syndrome and acute myeloid leukemia following transplantation (37-39). DNA damage resulting from prolonged exposure to azathioprine has been implicated (11, 37), which would be consistent with our observation that risk is greatest more than 10 years after the transplantation.…”

“…DNA damage resulting from prolonged exposure to azathioprine has been implicated (11, 37), which would be consistent with our observation that risk is greatest more than 10 years after the transplantation. Nonetheless, we also observed increased risk earlier following transplantation, and cases of myeloid neoplasms have also been reported in transplant recipients not receiving azathioprine (39). …”

Myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: Diagnostic and therapeutic challenges

“…Proposed mechanisms leading to donor-cell MDS include occult leukemia in the donor, abnormal or defective stroma and/or bone marrow microenvironment, genetic susceptibility, immune-mediated phenomenon, infection, transmission of an oncogene from the host’s original disease into donor cells, toxicity of post-transplant therapies, and possibly GVHD. (7, 35, 38, 43, 45, 50, 53, 54, 59, 65–69) In this reported case of MDS developing in a patient transplanted for a solid tumor, exposure of donor cells to the effects of the chemotherapy and radiation used to manage recurrent Ewing sarcoma is the most plausible etiology of donor-cell MDS. Consistent with this, 36 of 74 (49%) of previously reported cases of DCL had cytogenetic abnormalities typical of therapy-related disease, including abnormalities involving 11q23, 21q22, and chromosomes 5, 7, 8 and 21, and three of these cases were known to have had a history of post-transplant radiation or pre-transplant exposure to chemotherapy in the donor.…”

Adjuvant therapy for pancreatic cancer

“…In contrast, MDS is more likely to be of donor origin in patients transplanted for other conditions, although recipient‐derived t‐MDS may be related to pretransplant exposure to chemotherapy and/or radiation. Proposed mechanisms leading to donor‐cell MDS include occult leukemia in the donor, abnormal or defective stroma and/or bone marrow microenvironment, genetic susceptibility, immune‐mediated phenomenon, infection, transmission of an oncogene from the host's original disease into donor cells, toxicity of post‐transplant therapies, and possibly graft‐versus‐host disease (GVHD) [7, 35, 38, 43, 45, 50, 53, 54, 59, 65–69]. In this reported case of MDS developing in a patient transplanted for a solid tumor, the exposure of donor cells to the effects of the chemotherapy and radiation used to manage recurrent Ewing sarcoma is the most plausible etiology of donor‐cell MDS.…”