Reduced Intensity Conditioning Compared With Myeloablative Conditioning Using Unrelated Donor Transplants in Patients With Acute Myeloid Leukemia

Abstract

Patients receiving RIC were older, received transplants more recently, received peripheral blood stem cells more frequently, and were treated with total-body irradiation less often. In multivariable analysis, in patients younger than 50 years of age, nonrelapse mortality (NRM) was similar using RIC (hazard ratio [HR], 0.85; P = .41), relapse was increased (HR, 1.46; P = .02) and leukemia-free survival (LFS) was the same (HR, 0.88; P = .28), as compared with MAC. In patients > or = 50 years of age, NRM was decreased in the RIC group (HR, 0.64; P = .04), relapse probability was not significantly different (HR, 1.34; P = .16) and LFS was similar (HR, 1.04; P = .79) compared with MAC. CONCLUSION RIC-UD transplants are associated with higher relapse in AML patients younger than 50 years of age and decreased NRM in those > or = 50 years compared with MAC-UD. LFS was similar after both conditioning regimens, regardless of age. Therefore, RIC-UD extend the use of allotransplants for elderly patients and strategies that decrease relapse should be considered mainly in younger patients with AML.

Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML

“…16 As relapse has been reported more frequently after RIC allo-HCT compared with myeloablative conditioning (MAC) allo-HCT in patients with AML, this suggests heterogeneity in the interpretation of a CR, which may be more important after RIC allo-HCT. [17][18][19][20][21][22][23] The CR definition updated in 2003 24 clearly requires no evidence of leukemia by flow cytometry in addition to the morphologic remission as reported: 'The presence of a unique phenotype (by flow cytometry) identical to what was found in the pretreatment specimen (for example, CD34, CD7 coexpression) should be viewed as persistence of leukemia'. Given that relapse occurs in only some patients, though all were in a putative CR at the time of allo-HCT, we evaluated our patients receiving RIC allo-HCT in CR to determine whether the CR criteria were strictly applied at the time of allo-HCT and to determine whether patients with immunophenotypic persistent leukemia had a significantly increased risk of relapse.…”

Impact of intensity of conditioning therapy in patients aged 40–60 years with AML/myelodysplastic syndrome undergoing allogeneic transplantation

“…28 A survival advantage for RIC allogeneic BMT vs the CIC approach has not been shown yet except for in one study 29 similar in size to ours. Most of the other studies 30,31 did not show any difference in survival. Possible reasons for failure to show a survival difference in these studies include a higher relapse rate using RIC regimens, 32 In our study, the reduced intensity regimen used falls within the higher spectrum of intensity of RIC regimens and may explain the relatively higher TRM.…”

Equivalent outcomes using reduced intensity or conventional myeloablative conditioning transplantation for patients aged 35 years and over with AML

“…26 However, some retrospective studies suggest that despite lower TRM, the risk of relapse may increase due to the reduced dose intensity of the conditioning regimen, especially in patients with uncontrolled disease. [8][9][10] More recently, a retrospective study in a heterogeneous population of AML and myelodysplastic syndrome suggested that a RIC regimen may contribute to optimal survival, as no difference in disease-free survival and less toxicity was observed after RIC. 27 In our study, adjusted NRM was significantly higher with MAC than with RIC (P = 0.027).…”

“…9 Using unrelated donors (URDs), another retrospective study reported a higher relapse rate in AML patients younger than 50 years after RIC regimen, with a similar leukemia-free survival between the two regimens. 10 However, the use of RIC regimens has not been extensively studied in younger patients with AML. This population is classically treated with conventional high-intensity regimens in the absence of comorbidities or a history of severe fungal infections.…”