Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia.

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 Cyclosporine A (CsA) was withdrawn rapidly in a stepwise fashion to avoid overwhelming GVHD reactions if acute GVHD (aGVHD) did not develop at day +30.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: Qi-Fa Liu, Zhi-Ping Fan, Yu Zhang, Zu-Jun Jiang, Chun-Yan Wang, Dan Xu, Jing Sun, Yang Xiao, Huo Tan
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 15 Issue 11 Pg. 1376-85 (Nov 2009) ISSN: 1523-6536 [Electronic] United States
• PMID: 19822296 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Anti-Infective Agents
• Antibodies, Monoclonal
• IL2RA protein, human
• Immunosuppressive Agents
• Interleukin-2 Receptor alpha Subunit
• Myeloablative Agonists

Topics

• Adolescent
• Adult
• Anti-Infective Agents (administration & dosage, therapeutic use)
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Combined Modality Therapy
• Disease-Free Survival
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Female
• Graft vs Host Disease (prevention & control)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Interleukin-2 Receptor alpha Subunit (immunology)
• Leukemia (drug therapy, mortality, surgery)
• Male
• Middle Aged
• Myeloablative Agonists (administration & dosage)
• Premedication
• Prospective Studies
• Retrospective Studies
• Salvage Therapy
• Transplantation Conditioning (methods)
• Treatment Outcome
• Whole-Body Irradiation
• Young Adult