Among patients with myelofibrosis, the use of 2 alkylating agents in conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) appeared to confer better disease control compared with the use of a single alkylating agent, according to a retrospective analysis published in the American Journal of Hematology.

In this study based in Italy, outcomes were examined for 120 patients with myelofibrosis and available chimerism data. Patients were stratified by type of conditioning regimen prior to alloHSCT, with 1 group including 42 patients who were treated with fludarabine and a single alkylating agent (thiotepa, busulfan, or melphalan). The other group included 78 patients who were treated with 2 alkylating agents, thiotepa and busulfan, in addition to fludarabine.

Baseline characteristics differed between the 2 groups. Patients who received both thiotepa and busulfan were slightly older, were less likely to have undergone splenectomy, and more often had higher risk scores compared with patients receiving a single alkylating agent. Patients who received 2 alkylating agents also more often received grafts from alternative donors, rather than from human leukocyte antigen-identical siblings, and these patients were more often treated with ruxolitinib prior to alloHSCT.

The group receiving thiotepa and busulfan achieved a higher rate of full donor chimerism (87%) on day 30 after alloHSCT, compared with 45% for those given a single alkylating agent (P <.0001).


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The use of 2 alkylating agents was also associated with a lower 5-year cumulative incidence of relapse (9%), compared with a single alkylating agent (43%; P <.00001). The 5-year cumulative incidence of relapse was also lower with full donor chimerism compared with mixed donor chimerism (14% vs 40%; P =.01).

The group using 2 alkylating agents showed a higher 5-year disease-free survival (63%) than did the group using a single alkylating agent (43%; P =.004). The 5-year overall survival was 71% for patients given 2 alkylating agents, compared with 43% with 1 alkylating agent (P =.002). The 5-year graft-vs-host disease-free, relapse-free survival was also higher with 2 alkylating agents (51% vs 24%; P =.002).

Based on these results, the study investigators concluded that conditioning using 2 alkylating agents was linked to improved disease control in these patients with myelofibrosis. They indicated that this appeared to be enabled through a higher rate of full donor chimerism provided with 2 alkylating agents.

Reference

Chiusolo P, Bregante S, Giammarco S, et al. Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: the role of the conditioning regimen. Am J Hematol. Published online November 4, 2020. doi:10.1002/ajh.26042