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Acute Leukemias

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

Leukemia volume 22, pages 281–286 (2008)Cite this article

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.

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References

  1. Messina C, Cesaro S, Rondelli R, Rossetti F, Locatelli F, Pession A et al. Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in Italy. AIEOP/FONOP-TMO group. Italian association of paediatric haemato-oncology. Bone Marrow Transplant 1998; 21: 1015–1021.

    Article  CAS  Google Scholar 

  2. Ritchey AK, Pollock BH, Lauer SJ, Andejeski Y, Barredo J, Buchanan GR . Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: a pediatric oncology group study. J Clin Oncol 1999; 17: 3745–3752.

    Article  CAS  Google Scholar 

  3. Silverman LB, Declerck L, Gelber RD, Dalton VK, Asselin BL, Barr RD et al. Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981–1995). Leukemia 2000; 14: 2247–2256.

    Article  CAS  Google Scholar 

  4. Gaynon PS, Trigg ME, Heerema NA, Sensel MG, Sather HN, Hammond GD et al. Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995. Leukemia 2000; 14: 2223–2233.

    Article  CAS  Google Scholar 

  5. Barredo JC, Devidas M, Lauer SJ, Billett A, Marymont M, Pullen J et al. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study. J Clin Oncol 2006; 24: 3142–3149.

    Article  CAS  Google Scholar 

  6. Borgmann A, Hartmann R, Schmid H, Klingebiel T, Ebell W, Gobel U et al. Isolated extramedullary relapse in children with acute lymphoblastic leukemia: a comparison between treatment results of chemotherapy and bone marrow transplantation. BFM Relapse Study Group. Bone Marrow Transplant 1995; 15: 515–521.

    CAS  Google Scholar 

  7. Borgmann A, Schmid H, Hartmann R, Baumgarten E, Hermann K, Klingebiel T et al. Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matched-pair analysis. The Berlin-Frankfurt-Munster Study Group. Lancet 1995; 346: 873–876.

    Article  CAS  Google Scholar 

  8. Borgmann A, von Stackelberg A, Hartmann R, Ebell W, Klingebiel T, Peters C et al. Unrelated donor stem cell transplantation compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission: a matched-pair analysis. Blood 2003; 101: 3835–3839.

    Article  CAS  Google Scholar 

  9. Yoshihara T, Morimoto A, Kuroda H, Imamura T, Ishida H, Tsunamoto K et al. Allogeneic stem cell transplantation in children with acute lymphoblastic leukemia after isolated central nervous system relapse: our experiences and review of the literature. Bone Marrow Transplant 2006; 37: 25–31.

    Article  CAS  Google Scholar 

  10. Klein JP, Moeschberger ML . Survival Analysis: Techniques of Censored and Truncated Data. 2nd edn. Springer-Verlag: New York, NY, 2003, 92–133.

    Google Scholar 

  11. Cox DR . Regression models and life tables. J R Stat Soc B 1972; 34: 187–200.

    Google Scholar 

  12. Andersen PK, Klein JP, Zhang MJ . Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med 1999; 18: 1489–1500.

    Article  CAS  Google Scholar 

  13. Bordigoni P, Esperou H, Souillet G, Pico J, Michel G, Lacour B et al. Total body irradiation-high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation from HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Societe Francaise de Greffe de Moelle study. Br J Haematol 1998; 102: 656–665.

    Article  CAS  Google Scholar 

  14. Eapen M, Raetz E, Zhang MJ, Muehlenbein C, Devidas M, Abshire T et al. Outcomes after HLA-matched sibling transplantation 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. Blood 2006; 107: 4961–4967.

    Article  CAS  Google Scholar 

  15. Davies SM, Ramsay NK, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 2000; 18: 340–347.

    Article  CAS  Google Scholar 

  16. Socie G, Curtis RE, Deeg HJ, Sobocinski KA, Filipovich AH, Travis LB et al. New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. J Clin Oncol 2000; 18: 348–357.

    Article  CAS  Google Scholar 

  17. Socie G, Stone JV, Wingard JR, Weisdorf D, Henslee-Downey PJ, Bredeson C et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late effects working committee of the International Bone Marrow Transplant Registry. N Engl J Med 1999; 341: 14–21.

    Article  CAS  Google Scholar 

  18. Brown RT, Maden-Swain A, Walco GA, Cherrick I, Ievers CE, Conte PM et al. Cognitive and academic late effects among children previously treated for acute lymphoblastic leukemia receiving chemotherapy as CNS prophylaxis. J Pediatr Psychol 1998; 23: 333–340.

    Article  CAS  Google Scholar 

  19. Pui CH, Cheng C, Leung W, Rai SN, Rivera GK, Sandlund JT et al. Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 2003; 349: 640–649.

    Article  Google Scholar 

  20. Goulden N, Langlands K, Steward C, Katz F, Potter M, Chessels J et al. PCR assessment of bone marrow status in isolated extramedullary relapse of childhood B-precursor acute lymphoblastic leukaemia. Brit J Haematol 1994; 87: 282–285.

    Article  CAS  Google Scholar 

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Acknowledgements

The study was supported by Public Health Service Grant U24-CA76518-08 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases and the National Heart, Lung and Blood Institute and U10-CA098543 from the National Cancer Institute and the Department of Health and Human Services.

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Authors and Affiliations

  1. Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA

    M Eapen, M-J Zhang & K Malloy

  2. Department of Pediatrics, Hematology, Oncology and Transplantation, Medical College of Wisconsin, Milwaukee, WI, USA

    M Eapen & B M Camitta

  3. Statistical Center, The Children's Oncology Group, National Childhood Cancer Foundation, Arcadia, CA, USA

    M Devidas

  4. Department of Statistics, University of Florida, Gainsville, FL, USA

    M Devidas

  5. Department of Pediatrics, Hematology and Oncology, New York University Medical Center, New York, NY, USA

    E Raetz & W L Carroll

  6. Department of Pediatrics, Hematology, Oncology and Stem Cell Transplantation, University of Miami Miller School of Medicine, Miami, FL, USA

    J C Barredo

  7. Department of Hematology and Oncology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA

    A K Ritchey

  8. Department of Pediatrics, Hematology and Oncology, Medical College of Virginia Hospital, Richmond, VA, USA

    K Godder

  9. Department of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA

    S Grupp

  10. Department of Pediatrics, Southern Alberta Children's Cancer Center, Calgary, AB, Canada

    V A Lewis

  11. Department of Hematology and Oncology, Children's Hospital Medical Center, Cincinnati, OH, USA

    S M Davies

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  1. M Eapen
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  2. M-J Zhang
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  3. M Devidas
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  4. E Raetz
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  7. K Godder
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  9. V A Lewis
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  10. K Malloy
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  11. W L Carroll
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  12. S M Davies
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  13. B M Camitta
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Correspondence to M Eapen.

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Eapen, M., Zhang, MJ., Devidas, M. et al. 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. Leukemia 22, 281–286 (2008). https://doi.org/10.1038/sj.leu.2405037

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