The Lynx Group

Myeloablative Conditioning Remains Standard of Care in Patients with Myelodysplastic Sydrome

March 2016, Vol 7, No 2

Traditional myeloablative conditioning remains the standard of care for preparing patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) for transplant, according to a randomized trial from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The study, presented as a late-breaker at ASH 2015, was halted after a reduced-­intensity conditioning (RIC) regimen proved less effective.

The phase 3 randomized BMT CTN 0901 study included 54 patients with MDS and 218 with AML who had <5% marrow myeloblasts before transplant.

At 18 months, patients had a greater chance of relapse after RIC, and there were no differences in overall survival. The investigators concluded that myeloablative conditioning remains the treatment choice over RIC for patients who are eligible to receive high-intensity–based regimens, according to Bart L. Scott, MD, Assistant Member, Transplantation Program, Fred Hutchinson Cancer Research Center, Seattle.

The investigators did a head-to-head comparison of the 2 conditioning approaches. RIC has been shown to produce less toxicity and less treatment-related mortality; however, relapse rates have been higher than those seen with myeloablative conditioning, according to some studies. The 2 approaches have yielded similar overall survival times.

BMT CTN 0901 Study Details

The principal conditioning myeloablative regimen was 4-day busulfan (Myleran) with cyclophosphamide (Cytoxan) or fludarabine (Fludara). The RIC regimens included fludarabine plus busulfan for 2 days or fludarabine plus melphalan (Alkeran). The principal myeloablative conditioning regimens were 4-day busulfan plus fludarabine or 4-day busulfan plus cyclophosphamide; a few patients received cyclophosphamide plus total body irradiation. The 2 arms were balanced in terms of patient and disease characteristics.

The investigators planned to enroll 356 patients; however, the study was stopped early after investigators concluded that myeloablative conditioning more effectively reduced relapses.

The relapse-free survival at 18 months was superior for myeloablative conditioning, at 68.8% versus 47.3% for RIC (P <.01). The difference was observed among patients with MDS and patients with AML alike. Relapses were observed in 16.5% of patients with AML receiving myeloablative conditioning and in 50% receiving RIC; in patients with MDS, relapses occurred in 3.7% and 37%, respectively.

The overall survival rates were 77.4% with myeloablative conditioning and 67.7% with RIC, not significantly different. Survival among the MDS subset was 81.5% with myeloablative conditioning and 85.2% with RIC, again not significantly different; however, in the AML subset of patients, myeloablative conditioning yielded a significant difference in survival—76.8% versus 63.0% for RIC (P = .027), Dr Scott reported.

Transplant-related mortality was significantly higher with myeloablative conditioning than with RIC (15.8% vs 4.4%, respectively). “Novel, less toxic myeloablative conditioning regimens or more effective posttransplant maintenance regimens are needed to improve disease control in patients requiring RIC,” Dr Scott suggested.

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