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

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.

Reduced-intensity conditioning allogeneic hematopoietic cell transplantation using oral fludarabine as part of the conditioning regimen.

BACKGROUND: In 2003, oral fludarabine was introduced for the treatment of patients with hematologic malignancies as an alternative to its intravenous (i.v.) formulation. In an attempt to simplify the management of patients undergoing reduced intensity allogeneic hematopoietic transplantation, we have incorporated oral fludarabine in the conditioning regimen. METHODS: We present a non-randomized retrospective analysis of 37 patients conditioned with oral fludarabine compared with 144 patients conditioned with the i.v. formulation. In addition to fludarabine, the conditioning regimens also included melphalan or busulfan depending on the underlying disease. Donors were HLA-matched siblings in 75% of cases and unrelated donors in the remaining 25%. RESULTS: Eight patients (22%) receiving oral fludarabine were switched to the i.v. route because of gastrointestinal toxicity (three patients), patient preference (two patients) and physician preference (three patients). There were no statistical differences in terms of hospital admission (P=0.16), time to neutrophil engraftment (P=0.35), time to platelet engraftment (P=0.38), acute graft versus host disease rate (P=0.71) and non-relapse mortality at days +30 (P=1.0) and +100 (P=0.43). DISCUSSION: This preliminary analysis confirms that oral fludarabine can replace its i.v. formulation as part of reduced-intensity conditioning regimens with no deleterious effect on any of the early transplantation outcomes. In addition, oral fludarabine can be more convenient for patients and caregivers, facilitating its implementation.