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 hematopoietic cell transplantation.


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 (1320 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 25000/microL, extramedullary disease, need for more than 4 weeks of induction chemotherapy to achieve CR, or high-risk chromosomal translocations. Most patients transplanted in CR1 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 CR1 (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.


CONCLUSIONS
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.
Jamieson
Catriona H M
CH
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5623, USA.
Amylon
Michael D
MD
Wong
Ruby M
RM
Blume
Karl G
KG
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D017211:Treatment Failure; D014916:Whole-Body Irradiation
D005047:Etoposide