Allogeneic hematopoietic cell transplantation for patients with high-risk acute lymphoblastic leukemia in first or second complete remission using fractionated total-body irradiation and high-dose etoposide: A 15-year experience

Objective. The rationale for this retrospective study was to identify the long-term overall and event-free survival, relapse, and treatment-related mortality rates of high-risk pediatric and adult first (CR1) and second remission (CR2) patients with acute lymphoblastic leukemia (ALL) who were treated with a single preparatory regimen consisting of fractionated total-body irradiation (FTBI) and high-dose etoposide (VP-16) prior to allogeneic hernatopoietic cell transplantation. Patients and Methods. Over a 15-year period at Stanford University Medical Center, 85 consecutive high-risk pediatric (up to age 17 years; n = 41) and adult (age 18-55 years; n = 44); patients with leukemia (ALL) in CR1 (n = 55) and CR2 (n = 30) received HLA-matched sibling allogeneic bone marrow or peripheral blood progenitor grafts after being treated with FTBI (1,320 cGy) and high-dose VP-16 (60 mg/kg) as their preparatory regimen. The majority of patients transplanted in CR1 (n = 45) had high-risk features, including age above 30 years, white blood cell count at presentation exceeding 25,000/muL, extramedullary disease, need for more than 4 weeks of induction chemotherapy to achieve CR, or high-risk chromosomal translocations. Most patients transplanted in CRI were adults (n = 39), whereas patients in CR2 were primarily children or adolescents (n = 25). Results. The 10-year Kaplan-Meier estimates of relapse were significantly (p = 0.05) lower in CR1 patients (15% +/- 10%) than in CR2 patients (33% +/- 20%). Relapse was the most common cause of treatment failure in patients transplanted in CR2. There was a significantly (p = 0.05) higher rate of chronic graft-vs-host disease in CRI (32 % +/- 14 %) compared with CR2 (9% +/- 11 %) patients; however, overall survival for patients transplanted in CR1 (66% +/- 14%) was comparable (p = 0.67) to that of patients transplanted in CR2 (62% +/- 19%). Event-free survival rates also were similar (p = 0.53) between CR1 (64 % 14 %) and CR2 (61 % +/- 18 %) patients. Treatment-related mortality rates were equivalent (p = 0.51) between CR1 and CR2, as well as between Philadelphia chromosome (Ph) positive (Ph+) and Ph- (p = 0.23) ALL patients. Conclusion. Overall, FTBI/VP-16 is a highly effective preparatory regimen that provides durable remissions for patients receiving allogeneic hematopoietic cell transplantation for high-risk ALL in CR1 or CR2. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc.