Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity

Abstract

Allogeneic stem-cell transplantation (SCT) with both myeloablative and reduced-intensity conditioning (RIC) is an effective therapy in AML/MDS. However, the relative merits of each may differ in different settings. To define the role of dose intensity, we analyzed SCT outcomes of 112 consecutive patients with AML/MDS. A total of 45 patients met eligibility criteria for standard myeloablative conditioning and were given intravenous-busulfan (12.8 mg/kg) and cyclophosphamide (ivBuCy). A total of 67 noneligible patients were given RIC with fludarabine and intravenous-busulfan (6.4 mg/kg, FB2, n ¼ 41) or a modified myeloablative regimen with fludarabine and myeloablative doses of intravenous-busulfan (12.8 mg/kg, FB4, n ¼ 26). The overall survival (OS) at 2 years was 50, 49 and 47% after ivBuCy, FB4 and FB2, respectively (P ¼ NS). Nonrelapse mortality was higher after ivBuCy, 22 vs 8% (P ¼ 0.05), but relapse rates were lower. Active disease at SCT was the most significant predictor of reduced survival in multivariable analysis (HR 4.5, P ¼ 0.0001). Myeloablative and RIC regimens had similar outcomes when leukemia was in remission at SCT; however, patients with active disease could only be salvaged by myeloablative conditioning. Among the latter, OS was 45% after ivBuCy but no FB2 recipient survived (P ¼ 0.02). Patients with active disease, ineligible for standard myeloablation, could tolerate modified myeloablation well; however, long-term outcome cannot be determined yet.

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

“…Unrelated umbilical cord blood (UCB) HSCT had similarly successful outcomes as volunteer unrelated donors (URD) transplants using RI conditioning [18]. These data add to an increasing body of evidence [19][20][21][22] that RI HSCT can be clinically potent with an antileukemia effect capable of inducing and maintaining a long term remission in these aggressive myeloid malignancies. The preferred intensity within the spectrum of RI or non-MA conditioning regimens for myeloid leukemia continues to be a subject of study [16,23].…”

“…RI regimens have been reported to reduce the cytokine release and damage to mucosal tissues and result in less aGVHD compared with MA, which can contribute to a lower TRM. The TRM using RI regimens has been reported from 5% [25] to nearly 20% [20,22,26]. TRM varies with the patient population, the time point at which it is assessed following HSCT, and the intensity of the RI regimen.…”

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

“…Similar effects of dose intensity were seen in acute leukemia and in other hematologic malignancies, especially when the malignancy is not in a good remission. 30,31 However, there is an inherent bias in studies with this methodology related to the difference in patient characteristics between patients allocated to myeloablative conditioning and RIC.…”

The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach

“…(86)(87)(88)(89)(90)(91)(92)(93)(94)(95). During the prospective German-Austrian study (76), a growing number of patients received RIC-regimens.…”