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Blood, 1 August 2008, Vol. 112, No. 3, pp. 903-909.
Prepublished online as a Blood First Edition Paper on June 2, 2008; DOI 10.1182/blood-2008-03-143115.
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Submitted March 5, 2008
Accepted May 5, 2008
Long-term remission of Philadelphia chromosome positive acute lymphoblastic leukemia following allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation-etoposide regimen
Ginna G. Laport*, Joseph C. Alvarnas, Joycelynne M. Palmer, David S. Snyder, Marilyn L. Slovak, Athena M. Cherry, Ruby M. Wong, Robert S. Negrin, Karl G. Blume, and Stephen J. Forman
Division of Blood and Marrow Transplantation and Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
Hematology/Hematopoietic Cell Transplantation, Biostatistics and Pathology, City of Hope National Medical Center, Duarte, CA, United States
* Corresponding author; email: glaport{at}stanford.edu.
Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome positive acute lymphoblastic leukemia(Ph+ ALL). Seventy nine with patients with HLA-matched sibling donors received either fractionated total body irradiation(FTBI) and high dose VP16(n=67) while 11 patients received FTBI/VP16/cyclophosphamide and one patient received FTBI/V16/busulfan. The median age was 36 years. At the time of HCT, forty-nine patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1(>CR1). The median followup was 75 months(range, 14-245). The 10 year overall survival for the CR1 and >CR1 patients was 54% and 29%(p=0.01), respectively, and eventfree survival was 48% and 26%(p=0.02), respectively. There was no significant difference in relapse incidence (28% vs 41%, p=0.28) but nonrelapse mortality was significantly higher in the >CR1 patients, (31% vs 54%,p=0.03, respectively). By univariate analysis, factors affecting eventfree(EFS) and overall survival(OS) were white blood cell count at diagnosis (< 30,000µl vs >30,000µl) and disease status (CR1 vs >CR1). By multivariate analysis, WBC at diagnosis and disease status remained significant for both OS and EFS while grade 2-4 acute graft vs host disease was significant for EFS. The median time to relapse for CR1 and for >CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 +/- cyclophosphamide confers long term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome.
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