TY - JOUR
T1 - Fludarabine-based reduced toxicity yet myeloablative conditioning is effective and safe particularly in patients with high-risk thalassemia undergoing allogeneic transplantation
AU - Sheth, Vipul
AU - Grisariu, Sigal
AU - Avni, Batia
AU - Stepensky, Polina
AU - Ashkenazi, Maayan
AU - Shapira, Michael Y.
AU - Or, Reuven
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2018/11
Y1 - 2018/11
N2 - Introduction: Thalassemia major (TM) is an inherited disorder caused by ineffective erythropoiesis. At the present time, allogeneic stem cell transplantation (allo-SCT) is a curative option. Conventional busulfan and cyclophosphamide based myeloablative conditioning regimens are limited by increased toxicity, especially in high-risk patients. Replacement of cyclophosphamide with fludarabine has reduced toxicity and nonrelapse mortality (NRM), thus improving outcomes. We analyzed long-term data of our fludarabine-based myeloablative, reduced toxicity protocol, specifically in high-risk patients. Methods: We retrospectively analyzed a cohort of 47 consecutive patients with TM undergoing allo-SCT from matched donors, using the fludarabine-based regimen (reduced toxicity regimen). The median age of the cohort was 10 years. Thirty-eight patients (80%) were in the high-risk and nine patients (20%) were in the low-risk category. The primary aim of this analysis was thalassemia-free survival (TFS). Results: The rejection rate was 11% within high-risk patients with NRM of 2%. With a median follow-up period of 7 years (1–15 years), the 10-year TFS in the entire cohort was 87%, and the overall survival (OS) was 97%. The 10-year TFS and OS among the low-risk and high-risk groups were 90% versus 84%, respectively (P = 0.45) and 100% versus 96%, respectively (P = 0.5), and both subsets of patients did equally well. Conclusion: In conclusion, replacement of high-dose cyclophosphamide with fludarabine is well tolerated with minimal regimen-related toxicity and acceptable rejection rates, especially in high-risk patients.
AB - Introduction: Thalassemia major (TM) is an inherited disorder caused by ineffective erythropoiesis. At the present time, allogeneic stem cell transplantation (allo-SCT) is a curative option. Conventional busulfan and cyclophosphamide based myeloablative conditioning regimens are limited by increased toxicity, especially in high-risk patients. Replacement of cyclophosphamide with fludarabine has reduced toxicity and nonrelapse mortality (NRM), thus improving outcomes. We analyzed long-term data of our fludarabine-based myeloablative, reduced toxicity protocol, specifically in high-risk patients. Methods: We retrospectively analyzed a cohort of 47 consecutive patients with TM undergoing allo-SCT from matched donors, using the fludarabine-based regimen (reduced toxicity regimen). The median age of the cohort was 10 years. Thirty-eight patients (80%) were in the high-risk and nine patients (20%) were in the low-risk category. The primary aim of this analysis was thalassemia-free survival (TFS). Results: The rejection rate was 11% within high-risk patients with NRM of 2%. With a median follow-up period of 7 years (1–15 years), the 10-year TFS in the entire cohort was 87%, and the overall survival (OS) was 97%. The 10-year TFS and OS among the low-risk and high-risk groups were 90% versus 84%, respectively (P = 0.45) and 100% versus 96%, respectively (P = 0.5), and both subsets of patients did equally well. Conclusion: In conclusion, replacement of high-dose cyclophosphamide with fludarabine is well tolerated with minimal regimen-related toxicity and acceptable rejection rates, especially in high-risk patients.
KW - fludarabine conditioning
KW - thalassemia
KW - transplantation
UR - http://www.scopus.com/inward/record.url?scp=85052390952&partnerID=8YFLogxK
U2 - 10.1002/pbc.27312
DO - 10.1002/pbc.27312
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C2 - 30070020
AN - SCOPUS:85052390952
SN - 1545-5009
VL - 65
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 11
M1 - e27312
ER -