Risk factors for tMDSAML after autologous stem cell transplantation

Because t-MDS/AML is frequently a fatal complication, there is a need to better understand the risk factors and to identify individuals at risk prior to ASCT. There are three contributors to the risk of t-MDS/AML in this context that have been

Time to MDS after SCT

Time to MDS after SCT

Years after BMT

Fig. 5.1 Actuarial probability of development of t-MDS/AML after ASCT

Years after BMT

Fig. 5.1 Actuarial probability of development of t-MDS/AML after ASCT

identified: pretransplant therapy, the method of stem cell mobilization, and the transplant conditioning regimens.

The data implicating pretransplant therapy as a risk factor include the demonstration that patients who do not undergo ASCT have a risk of development of t-MDS/AML, although there is a relatively longer latency of development of t-MDS/ AML in patients who have undergone ASCT. In patients who have undergone ASCT, there is increased risk with increased cumulative exposure to alkylating agents and with prior external beam irradiation. Specific cytogenetic abnormalities and clonal hematopoiesis have been identified at the time of stem cell harvest in patients who subsequently develop t-MDS/AML.

The method of stem cell collection may influence the risk of developing t-MDS/AML. For example, patients undergoing ASCT using peripheral blood stem cells (PBSC) have a higher risk of developing t-MDS/AML than those receiving bone marrow stem cells. There may be several explanations for this observation, including the possibility that previously only those patients who had inadequate marrow harvests had PBSC collected. It has also been reported that patients primed by receiving etoposide as part of their mobilization regimen had a higher risk of developing t-MDS/AML; this included patients with 11q23 and 21q22 chromosomal abnormalities.

The use of total body irradiation (TBI) in the conditioning regimen is associated with an increased risk of t-MDS/AML after ASCT, although a randomized trial to determine the contribution of TBI to the risk of t-MDS/AML has not been done. Only one study has compared patients who did and did not receive TBI at a single institution, and this did not demonstrate increased incidence in patients who received a TBI containing regimen.

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