Is there an optimal conditioning for older patients with AML receiving allogeneic hematopoietic cell transplantation?

Abstract

The optimal conditioning regimen for older patients with acute myeloid leukemia (AML) remains unclear. In this study, we compared outcomes of AML patients >60 years of age undergoing allogenic hematopoietic stem cell transplantation at our institution. All 404 consecutively treated patients received 1 of the following conditioning regimens: (1) fludarabine+melphalan 100 mg/m2 (FM100), (2) fludarabine+melphalan 140 mg/m2 (FM140), (3) fludarabine+IV busulfan AUC ≥ 5000/d × 4 d (Bu≥20000), and (4) fludarabine+IV busulfan AUC 4000/d × 4 d (Bu16000). A propensity score analysis (PSA) was used to compare outcomes between these 4 groups. Among the 4 conditioning regimens, the FM100 group had a significantly better long-term survival with 5-year progression-free survival of 49% vs 30%, 34%, and 23%, respectively. The benefit of the FM100 regimen resulted primarily from the lower nonrelapse mortality associated with this regimen, an effect more pronounced in patients with lower performance status. The PSA confirmed that FM100 was associated with better posttransplantation survival, whereas no significant differences were seen between the other regimen groups. In summary, older patients with AML benefited from a reduced-intensity conditioning regimen with lower melphalan doses (FM100), which was associated with better survival, even though it was primarily used in patients who could not receive a more intense conditioning regimen.

Predictors of increased melphalan exposure correlate with overall survival, nonrelapse mortality, and toxicities in patients undergoing reduced-intensity allogeneic stem cell transplantation with fludarabine and melphalan

“…In one recent study of 414 patients ≥60 years of age comparing four RIC regimens (FM100; FM140; fludarabine/busulfan AUC of at least 20,000 μg*h/L/day (Bu ≥ 20000), and Bu16000), FM100 was associated with the longest five-year PFS due to a low NRM compared to the other RIC regimens. 6 This benefit of FM100 regimen was more pronounced in patients with low performance status, in age group of >65 years as well as those without active disease before transplant. The FM140 regimen has been shown to be superior to other RIC regimens such as fludarabine and busulfan 6.4 mg/kg (FB2) in terms of decreasing relapse; however, OS remains similar, mainly due to the fact that the relapse benefit was offset by an increase in NRM.…”

“…HSCT is a potential curative therapy for various hematologic malignancies. 6 However, regimen-related toxicity and NRM preclude the use of conventional MAC regimens in patients who are older or have a poorer functional status. 1,2,5,6,31 RIC regimens have extended the use of HSCT in older and less fit patients who are not able to tolerate MAC regimens.…”

“…6 However, regimen-related toxicity and NRM preclude the use of conventional MAC regimens in patients who are older or have a poorer functional status. 1,2,5,6,31 RIC regimens have extended the use of HSCT in older and less fit patients who are not able to tolerate MAC regimens. 1,3–5,7,10,11,32–35 During the last decade, several RIC regimens have been developed combining purine analogue, primarily fludarabine, with an alkylating agent.…”

“…These RIC regimens have provided long-term survival ranging between 30% and 60%; however, the optimal RIC regimen based upon survival and toxicities for older patients remains unclear. 5,6,9…”

“…4,5 Specifically, fludarabine and melphalan 100 or 140 mg/m 2 (FM100 and FM140) prior to HSCT has been widely adopted in clinical practice as the reduced intensity regimen of choice and is considered to offer improved disease control but variability in outcomes still exist with toxicity still being a major challenge in some patients. 1,2,6–11…”