Myeloablative Conditioning Effective in AML Secondary to MDS/MPN Prior to Allogeneic HCT

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Allogeneic hematopoietic cell transplant (HCT) is the only available curative therapy for sAML.
Allogeneic hematopoietic cell transplant (HCT) is the only available curative therapy for sAML.

Myeloablative conditioning (MAC) may improve long-term survival outcomes among patients who developed secondary acute myeloid leukemia (sAML) after myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN), a study published in Blood Advances has shown.

sAML is a difficult-to-treat hematologic disorder that is associated with worse outcomes compared with primary AML, and patients are more likely to have worse prognoses due to factors such as advanced age, high-risk cytogenetics, and more previous lines of treatment. Allogeneic hematopoietic cell transplant (HCT) is the only available curative therapy, but optimal conditioning regimens prior to HCT in this high-risk group has not been determined. 

For the retrospective European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study, researchers identified 802 patients with sAML and prior MDS/MPN who received MAC or reduced-intensity conditioning (RIC). For this study, RICwas defined as regimens that could induce cytopenias and required stem cell support for hematologic recovery, and MAC was defined as regimens that involved total body irradiation and/or alkylating agents at doses that would inhibit autologous hematologic recovery.

Among all patients, the 2-year cumulative incidence of relapse (RI), leukemia-free survival (LFS), overall survival (OS), non-relapse mortality (NRM), and chronic graft-versus-host disease (cGVHD), was 37%, 40%, 46%, 23%, and 39%, respectively. 

A univariate analysis revealed that after 6 months patients in the MAC group had statistically significant improvements in RI, LFS, and OS, but not for NRM. Multivariable analyses further confirmed these findings; RI, LFS, and OS remained significantly improved, but no differences in NRM were observed.

The researchers concluded that these “data demonstrate the utility of MAC in patients with sAML to reduce the risk for post-transplantation relapse without significantly increasing NRM.Further prospective studies are needed to study preemptive strategies to reduce the risk for relapse in high-risk groups.”

Reference

Sengsayadeth S, Gatwood KS, Boumendil A, et al. Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study[published online August 28, 2018]. Blood Adv. doi: 10.1182/bloodadvances.2018019976

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