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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4961-4967.
Prepublished online as a Blood First Edition Paper on February 21, 2006; DOI 10.1182/blood-2005-12-4942.
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Submitted December 14, 2005
Accepted February 11, 2006
Outcomes after HLA-matched sibling transplants or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research
Mary Eapen*, Elizabeth Raetz, Mei-Jie Zhang, Catherine Muehlenbein, Meenakshi Devidas, Thomas Abshire, Amy Billett, Alan Homans, Bruce Camitta, William L Carroll, and Stella M Davies
Statistical Center, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA
New York University Medical Center, New York, NY, USA
Statistical Center of the Children's Oncology Group, Arcadia, CA, USA; University of Florida, Gainsville, FL, USA
Emory University, Atlanta, GA, USA
Dana-Farber Cancer Institute, Boston, MA, USA
University of Vermont College of Medicine, Burlington, VT, USA
Medical College of Wisconsin, Milwaukee, WI, USA
Children's Hospital Medical Center, Cincinnati, OH, USA
* Corresponding author; email: meapen{at}mail.mcw.edu.
The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled on chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median: 5 vs. 8 years) and less likely to have combined marrow and extra-medullary relapse (19% vs. 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (< 36 months), risk of a second relapse was significantly lower after total body irradiation (TBI) containing transplant regimens (relative risk [RR] 0.49, 95% confidence interval [CI] 0.33-0.71, p< 0.001) than chemotherapy regimens. For children with a late first relapse ( 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy but significantly higher after non-TBI containing regimens (RR 2.49, 95% CI 1.21-5.10, p=0.01). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.
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