Original Article
Leukemia (2008) 22, 281–286; doi:10.1038/sj.leu.2405037; published online 22 November 2007
Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research
M Eapen1,2, M-J Zhang1, M Devidas3,4, E Raetz5, J C Barredo6, A K Ritchey7, K Godder8, S Grupp9, V A Lewis10, K Malloy1, W L Carroll5, S M Davies11 and B M Camitta2
- 1Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA
- 2Department of Pediatrics, Hematology, Oncology and Transplantation, Medical College of Wisconsin, Milwaukee, WI, USA
- 3Statistical Center, The Children's Oncology Group, National Childhood Cancer Foundation, Arcadia, CA, USA
- 4Department of Statistics, University of Florida, Gainsville, FL, USA
- 5Department of Pediatrics, Hematology and Oncology, New York University Medical Center, New York, NY, USA
- 6Department of Pediatrics, Hematology, Oncology and Stem Cell Transplantation, University of Miami Miller School of Medicine, Miami, FL, USA
- 7Department of Hematology and Oncology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA
- 8Department of Pediatrics, Hematology and Oncology, Medical College of Virginia Hospital, Richmond, VA, USA
- 9Department of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- 10Department of Pediatrics, Southern Alberta Children's Cancer Center, Calgary, AB, Canada
- 11Department of Hematology and Oncology, Children's Hospital Medical Center, Cincinnati, OH, USA
Correspondence: Dr M Eapen, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. E-mail: meapen@mcw.edu
Received 30 August 2007; Revised 8 October 2007; Accepted 17 October 2007; Published online 22 November 2007.
Abstract
In children with acute lymphoblastic leukemia (ALL) with isolated central nervous system (CNS) relapse and a human leucocyte antigen (HLA)-matched sibling, the optimal treatment after attaining second remission is unknown. We compared outcomes in 149 patients enrolled on chemotherapy trials and 60 HLA-matched sibling transplants, treated in 1990–2000. All patients achieved a second complete remission. Groups were similar, except the chemotherapy recipients were younger at diagnosis, less likely to have T-cell ALL and had longer duration (
18 months) first remission. To adjust for time-to-transplant bias, left-truncated Cox's regression models were constructed. Relapse rates were similar after chemotherapy and transplantation. In both treatment groups, relapse rates were higher in older children (11–17 years; RR 2.81, P=0.002) and shorter first remission (<18 months; RR 3.89, P<0.001). Treatment-related mortality rates were higher after transplantation (RR 4.28, P=0.001). The 8-year probabilities of leukemia-free survival adjusted for age and duration of first remission were similar after chemotherapy with irradiation and transplantation (66 and 58%, respectively). In the absence of an advantage for one treatment option over another, the data support use of either intensive chemotherapy with irradiation or HLA-matched sibling transplantation with total body irradiation containing conditioning regimen for children with ALL in second remission after an isolated CNS relapse.
Keywords:
central nervous system relapse, acute lymphoblastic leukemia, chemotherapy, bone marrow transplantation, leukemia-free survival
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