Fludarabine/Busulfan versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma

Abstract

There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis

“…Seven studies [13][14][15][16][17][18][19] comprising a total 1955 patients with various hematologic malignancies met the criteria for inclusion in the meta-analysis after the screening process (Supplementary Figure 1). Study descriptions and patient characteristics are elaborated in Table 1.…”

“…Two studies included AML/MDS patients [13,14], another 2 included lymphoid malignancies [16,19], 1 included myelofibrosis patients [17], and 2 studies included patients with multiple hematologic malignancies [15,18]. Some patients from the study by Yerushalmi et al [19] (lymphoma patients only) were already included in a prior publication by Shimoni et al [18] (all hematologic diagnosis); hence, the data from the study by Yerushalmi et al [19] were not included in the analysis of all studies to avoid repetition but were included in the subgroup analysis for lymphoma studies, along with the study by Kekre et al [16]. Additionally, the study by Kawamura et al [15] elaborated the results of patients with AML and MDS separately along with reporting results for all hematologic malignancies, and these data on AML/MDS patients were only included in the subgroup analysis for AML/MDS studies in addition to the inclusion of data for pooled analysis of all studies.…”

“…All studies reported OS; 3 studies reported it at 3 years [15,16,19], 3 at 2 years [13,14,18], and 1 at 7 years [17]. Using the reported survival curve, we report OS at 3 years for all studies.…”

“…Using the reported survival curve, we report OS at 3 years for all studies. PFS was reported in 5 studies [13][14][15][16][17].…”

Pre- and posttransplant use of mogamulizumab in patients with aggressive adult T-cell leukemia-lymphoma: A statement from key opinion leaders in Japan

“…In terms of conditioning regimens, the combination of fludarabine plus busulfan was reported to be associated with a lower incidence of GVHD in comparison to fludarabine plus melphalan . Thus, fludarabine plus busulfan might be preferable in patients who receive Moga before allo‐HSCT.…”