Since its introduction in 2003, oral fludarabine has gradually replaced the intravenous (IV) formulation as treatment for patients with hematological malignancies. In an attempt to simplify the management of patients undergoing reduced intensity allogeneic transplantation, we have incorporated oral fludarabine to the conditioning regimen. We present a retrospective analysis of 37 patients conditioned with oral fludarabine compared with a historical cohort of 134 patients conditioned with the IV formulation. In addition to fludarabine, the conditioning regimens also included IV melphalan or oral busulfan depending on the underlying disease. Donors were HLA-matched siblings in 76% of cases and unrelated donors in the remaining 24%. Patient characteristics are summarized in Table 1. There were no statistical differences in terms of hospital admission (P = 0.414), time to neutrophil engraftment (P = 0.392), time to platelet engraftment (P = 0.307), acute graft-versus-host disease rate (P = 0.182) or non-relapse mortality at days +30 (P = 1.0) and +100 (P = 0.433). The subgroup of patients conditioned with oral fludarabine plus busulfan had a significantly higher incidence of mixed chimerism by day +100, but this did not translate into a significantly increased relapse rate. Side effects were tolerable and all patients on oral fludarabine were able to commence their conditioning regimen as outpatients. This preliminary analysis confirms that oral fludarabine could replace its IV formulation as part of reduced intensity conditioning regimens with no deleterious effect on any of the early transplantation outcomes. Furthermore, the use of oral fludarabine in combination with oral cyclophosphamide, oral busulfan or low dose total-body irradiation could potentially reduce hospital admission or even allow us to perform reduced-intensity allogeneic transplants as outpatient procedures. Finally, other advantages of oral fludarabine are cheaper costs and a more convenient use for both patients and health care workers.

Patient characteristics according to fludarabine administration route

Oral fludarabine (n = 37)IV fludarabine (n = 134)P value
Age, median (range) 57 (38–69) 52 (18–70) 0.002 
Sex, male/female % 60/40 65/35 0.566 
Underlying diseases, n (%)   0.129 
Acute myeloid leukemia 7 (19) 21 (16)  
Myelodysplastic syndrome 6 (16) 19 (14)  
Acute lymphoid leukemia 0 (0) 4 (3)  
Non-Hodgkin’s lymphoma 10 (27) 26 (18)  
Hodgkin’s lymphoma 0 (0) 30 (22)  
Myeloproliferative disorder 1 (3) 2 (2)  
Multiple myeloma 7 (19) 20 (15)  
Chronic lymphocytic leukemia 4 (11) 9 (7)  
Chronic myeloid leukemia 2 (5) 2 (2)  
Paroxysmal nocturnal hemoglobinuria 0 (0) 1 (1)  
Stem cell source, PB/BM % 100/0 93/7 0.121 
Donor, n (%)   0.821 
Matched related 29 (78) 101 (75)  
Mismatched related 0 (0) 2 (2)  
Matched unrelated 6 (16) 20 (15)  
Mismatched unrelated 2 (6) 11 (8)  
Previous autograft, n (%) 8 (22) 52 (39) 0.055 
Conditioning regimen, n (%)   0.333 
Fludarabine plus melphalan 21 (57) 89 (66)  
Fludarabine plus busulfan 16 (43) 45 (34)  
CD34+ cell dose (x106/kg), median (range) 6.1 (2.9–15) 6.5 (1.29–18.1) 0.787 
Follow-up (days), median (range) 298 (83–631) 847 (80–1925) < 0.001 
Oral fludarabine (n = 37)IV fludarabine (n = 134)P value
Age, median (range) 57 (38–69) 52 (18–70) 0.002 
Sex, male/female % 60/40 65/35 0.566 
Underlying diseases, n (%)   0.129 
Acute myeloid leukemia 7 (19) 21 (16)  
Myelodysplastic syndrome 6 (16) 19 (14)  
Acute lymphoid leukemia 0 (0) 4 (3)  
Non-Hodgkin’s lymphoma 10 (27) 26 (18)  
Hodgkin’s lymphoma 0 (0) 30 (22)  
Myeloproliferative disorder 1 (3) 2 (2)  
Multiple myeloma 7 (19) 20 (15)  
Chronic lymphocytic leukemia 4 (11) 9 (7)  
Chronic myeloid leukemia 2 (5) 2 (2)  
Paroxysmal nocturnal hemoglobinuria 0 (0) 1 (1)  
Stem cell source, PB/BM % 100/0 93/7 0.121 
Donor, n (%)   0.821 
Matched related 29 (78) 101 (75)  
Mismatched related 0 (0) 2 (2)  
Matched unrelated 6 (16) 20 (15)  
Mismatched unrelated 2 (6) 11 (8)  
Previous autograft, n (%) 8 (22) 52 (39) 0.055 
Conditioning regimen, n (%)   0.333 
Fludarabine plus melphalan 21 (57) 89 (66)  
Fludarabine plus busulfan 16 (43) 45 (34)  
CD34+ cell dose (x106/kg), median (range) 6.1 (2.9–15) 6.5 (1.29–18.1) 0.787 
Follow-up (days), median (range) 298 (83–631) 847 (80–1925) < 0.001 

Author notes

Disclosure: No relevant conflicts of interest to declare.

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