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Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia.
Biol Blood Marrow Transplant. 2009 Nov; 15(11):1376-85.BB

Abstract

For patients with advanced leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), a major obstacle to success, especially in those with a high leukemia cell burden, is relapse of the underlying disease. To improve the outcome of allo-HSCT for refractory leukemia, we investigated the strategy of sequential intensified conditioning and early rapid tapering of prophylactic immunosuppressants therapy for graft-versus-host disease (GVHD) during the early stage after transplantation. A total of 51 patients with refractory leukemia (median age, 30.0 years; unfavorable karyotypes, 49%) received fludarabine (Flu) 30 mg/m(2)/day and cytarabine 2 g/m(2)/day (on days -10 to -6), 4.5 Gy total body irradiation (TBI)/day (on days -5 and -4), and cyclophosphamide (Cy) 60 mg/kg/day and etoposide 600 mg/day (on days -3 and -2) for conditioning. Cyclosporine A (CsA) was withdrawn rapidly in a stepwise fashion to avoid overwhelming GVHD reactions if acute GVHD (aGVHD) did not develop at day +30. All 51 patients developed regimen-related toxicities (13 with grade III-IV); 93.9% of them achieved complete remission by day +30. Median follow-up was 41 months (range, 6.6 to 92.2 months); 5-year overall survival (OS) and disease-free survival (DFS) were 44.6% +/- 8.1% and 38.2% +/- 7.7%, respectively. Thirteen patients relapsed; the 3-year cumulative incidence of leukemia relapse was 33.3%. On multivariate analysis, cytogenetic status was the only significant pretransplantation factor. Survival was better in patients with grade I or II aGVHD than in those without aGVHD. Our data indicate that the sequential strategy of cytoreductive chemotherapy followed immediately by intensified myeloablative (MA) conditioning for allo-HSCT and rapid tapering of prophylactic immunosuppressants for GVHD in the early stage after transplantation has an acceptable toxicity profile and may be a better approach to treating refractory leukemia.

Authors+Show Affiliations

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. liuqifa@fimmu.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

19822296

Citation

Liu, Qi-Fa, et al. "Sequential Intensified Conditioning and Tapering of Prophylactic Immunosuppressants for Graft-versus-host Disease in Allogeneic Hematopoietic Stem Cell Transplantation for Refractory Leukemia." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 15, no. 11, 2009, pp. 1376-85.
Liu QF, Fan ZP, Zhang Y, et al. Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia. Biol Blood Marrow Transplant. 2009;15(11):1376-85.
Liu, Q. F., Fan, Z. P., Zhang, Y., Jiang, Z. J., Wang, C. Y., Xu, D., Sun, J., Xiao, Y., & Tan, H. (2009). Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 15(11), 1376-85. https://doi.org/10.1016/j.bbmt.2009.06.017
Liu QF, et al. Sequential Intensified Conditioning and Tapering of Prophylactic Immunosuppressants for Graft-versus-host Disease in Allogeneic Hematopoietic Stem Cell Transplantation for Refractory Leukemia. Biol Blood Marrow Transplant. 2009;15(11):1376-85. PubMed PMID: 19822296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia. AU - Liu,Qi-Fa, AU - Fan,Zhi-Ping, AU - Zhang,Yu, AU - Jiang,Zu-Jun, AU - Wang,Chun-Yan, AU - Xu,Dan, AU - Sun,Jing, AU - Xiao,Yang, AU - Tan,Huo, Y1 - 2009/08/19/ PY - 2009/05/12/received PY - 2009/06/26/accepted PY - 2009/10/14/entrez PY - 2009/10/14/pubmed PY - 2009/12/16/medline SP - 1376 EP - 85 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 15 IS - 11 N2 - For patients with advanced leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), a major obstacle to success, especially in those with a high leukemia cell burden, is relapse of the underlying disease. To improve the outcome of allo-HSCT for refractory leukemia, we investigated the strategy of sequential intensified conditioning and early rapid tapering of prophylactic immunosuppressants therapy for graft-versus-host disease (GVHD) during the early stage after transplantation. A total of 51 patients with refractory leukemia (median age, 30.0 years; unfavorable karyotypes, 49%) received fludarabine (Flu) 30 mg/m(2)/day and cytarabine 2 g/m(2)/day (on days -10 to -6), 4.5 Gy total body irradiation (TBI)/day (on days -5 and -4), and cyclophosphamide (Cy) 60 mg/kg/day and etoposide 600 mg/day (on days -3 and -2) for conditioning. Cyclosporine A (CsA) was withdrawn rapidly in a stepwise fashion to avoid overwhelming GVHD reactions if acute GVHD (aGVHD) did not develop at day +30. All 51 patients developed regimen-related toxicities (13 with grade III-IV); 93.9% of them achieved complete remission by day +30. Median follow-up was 41 months (range, 6.6 to 92.2 months); 5-year overall survival (OS) and disease-free survival (DFS) were 44.6% +/- 8.1% and 38.2% +/- 7.7%, respectively. Thirteen patients relapsed; the 3-year cumulative incidence of leukemia relapse was 33.3%. On multivariate analysis, cytogenetic status was the only significant pretransplantation factor. Survival was better in patients with grade I or II aGVHD than in those without aGVHD. Our data indicate that the sequential strategy of cytoreductive chemotherapy followed immediately by intensified myeloablative (MA) conditioning for allo-HSCT and rapid tapering of prophylactic immunosuppressants for GVHD in the early stage after transplantation has an acceptable toxicity profile and may be a better approach to treating refractory leukemia. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/19822296/Sequential_intensified_conditioning_and_tapering_of_prophylactic_immunosuppressants_for_graft_versus_host_disease_in_allogeneic_hematopoietic_stem_cell_transplantation_for_refractory_leukemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(09)00303-6 DB - PRIME DP - Unbound Medicine ER -