DOI QR코드

DOI QR Code

Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

  • Lee, Eun-Jung (Department of Pediatrics, The Catholic University of Korea, School of Medicine) ;
  • Han, Ji-Yoon (Department of Pediatrics, The Catholic University of Korea, School of Medicine) ;
  • Lee, Jae-Wook (Department of Pediatrics, The Catholic University of Korea, School of Medicine) ;
  • Jang, Pil-Sang (Department of Pediatrics, The Catholic University of Korea, School of Medicine) ;
  • Chung, Nack-Gyun (Department of Pediatrics, The Catholic University of Korea, School of Medicine) ;
  • Jeong, Dae-Chul (Department of Pediatrics, The Catholic University of Korea, School of Medicine) ;
  • Cho, Bin (Department of Pediatrics, The Catholic University of Korea, School of Medicine) ;
  • Kim, Hack-Ki (Department of Pediatrics, The Catholic University of Korea, School of Medicine)
  • Received : 2011.09.15
  • Accepted : 2011.11.14
  • Published : 2012.03.15

Abstract

Purpose: The survival rate for childhood acute lymphoblastic leukemia (ALL) has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR). Methods: Fifty-three ALL patients (42 men, 79%) who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%). Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD), relapse, 1-year transplant-related mortality (TRM), disease-free survival (DFS), and overall survival (OS). Results: Cumulative incidences of acute GVHD (grade 2 or above) and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was $45.2{\pm}6.8%$ and $48.3{\pm}7%$, respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis ($p$=0.010). The rates of relapse and 1 year TRM were $28.9{\pm}6.4%$ and $26.4{\pm}6.1%$, respectively, and unrelated donor HSCT ($p$=0.002) and HLA mismatch ($p$=0.022) were significantly correlated with increased TRM in univariate analysis. Conclusion: In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

Keywords

References

  1. Gaynon PS. Treatment of pediatric acute lymphoblastic leukemia: progress achieved and challenges remaining. Curr Hematol Malig Rep 2007; 2:193-201. https://doi.org/10.1007/s11899-007-0026-y
  2. Barrett AJ, Horowitz MM, Pollock BH, Zhang MJ, Bortin MM, Buchanan GR, et al. Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. N Engl J Med 1994;331:1253-8. https://doi.org/10.1056/NEJM199411103311902
  3. Boulad F, Steinherz P, Reyes B, Heller G, Gillio AP, Small TN, et al. Allogeneic bone marrow transplantation versus chemotherapy for the treatment of childhood acute lymphoblastic leukemia in second remission: a singleinstitution study. J Clin Oncol 1999;17:197-207. https://doi.org/10.1200/JCO.1999.17.1.197
  4. Matsuzaki A, Nagatoshi Y, Inada H, Nakayama H, Yanai F, Ayukawa H, et al. Prognostic factors for relapsed childhood acute lymphoblastic leukemia: impact of allogeneic stem cell transplantation--a report from the Kyushu-Yamaguchi Children's Cancer Study Group. Pediatr Blood Cancer 2005;45:111-20. https://doi.org/10.1002/pbc.20363
  5. Locatelli F, Zecca M, Messina C, Rondelli R, Lanino E, Sacchi N, et al. Improvement over time in outcome for children with acute lymphoblastic leukemia in second remission given hematopoietic stem cell transplantation from unrelated donors. Leukemia 2002;16:2228-37. https://doi.org/10.1038/sj.leu.2402690
  6. Kennedy-Nasser AA, Bollard CM, Myers GD, Leung KS, Gottschalk S, Zhang Y, et al. Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. Biol Blood Marrow Transplant 2008;14:1245-52. https://doi.org/10.1016/j.bbmt.2008.08.010
  7. Smith AR, Baker KS, Defor TE, Verneris MR, Wagner JE, Macmillan ML. Hematopoietic cell transplantation for children with acute lymphoblastic leukemia in second complete remission: similar outcomes in recipients of unrelated marrow and umbilical cord blood versus marrow from HLA matched sibling donors. Biol Blood Marrow Transplant 2009; 15:1086-93. https://doi.org/10.1016/j.bbmt.2009.05.005
  8. 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;107:4961-7. https://doi.org/10.1182/blood-2005-12-4942
  9. Goulden N, Bader P, Van Der Velden V, Moppett J, Schilham M, Masden HO, et al. Minimal residual disease prior to stem cell transplant for childhood acute lymphoblastic leukaemia. Br J Haematol 2003;122:24-9. https://doi.org/10.1046/j.1365-2141.2003.04394.x
  10. Lee JW, Lee KH, Kwon YJ, Lee DH, Chung NG, Jeong DC, et al. The effects of shortened dexamethasone administration on remission rate and potential complications during remission induction treatment for pediatric acute lymphoblastic leukemia. Korean J Pediatr 2007;50:1217-24. https://doi.org/10.3345/kjp.2007.50.12.1217
  11. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995;15:825-8.
  12. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005;11: 945-56. https://doi.org/10.1016/j.bbmt.2005.09.004
  13. Zecca M, Prete A, Rondelli R, Lanino E, Balduzzi A, Messina C, et al. Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome. Blood 2002;100:1192-200. https://doi.org/10.1182/blood-2001-11-0059
  14. Kondo M, Kojima S, Horibe K, Kato K, Matsuyama T. Risk factors for chronic graft-versus-host disease after allogeneic stem cell transplantation in children. Bone Marrow Transplant 2001;27:727-30. https://doi.org/10.1038/sj.bmt.1702868
  15. Muñoz A, Diaz-Heredia C, Diaz MA, Badell I, Verdeguer A, Martinez A, et al. Allogeneic hemopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission-similar outcomes after matched related and unrelated donor transplant: a study of the Spanish Working Party for Blood and Marrow Transplantation in Children (Getmon). Pediatr Hematol Oncol 2008;25:245-59. https://doi.org/10.1080/08880010802016557
  16. Borgmann A, Baumgarten E, Schmid H, Dopfer R, Ebell W, Göbel U, et al. Allogeneic bone marrow transplantation for a subset of children with acute lymphoblastic leukemia in third remission: a conceivable alternative? Bone Marrow Transplant 1997;20:939-44. https://doi.org/10.1038/sj.bmt.1701013
  17. Gassas A, Sung L, Saunders EF, Doyle J. Graft-versus-leukemia effect in hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia: significantly lower relapse rate in unrelated transplantations. Bone Marrow Transplant 2007;40:951-5. https://doi.org/10.1038/sj.bmt.1705853
  18. Sramkova L, Muzikova K, Fronkova E, Krejci O, Sedlacek P, Formankova R, et al. Detectable minimal residual disease before allogeneic hematopoietic stem cell transplantation predicts extremely poor prognosis in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2007;48:93-100. https://doi.org/10.1002/pbc.20794
  19. Ishida Y, Honda M, Ozono S, Okamura J, Asami K, Maeda N, et al. Late effects and quality of life of childhood cancer survivors: part 1. Impact of stem cell transplantation. Int J Hematol 2010;91:865-76. https://doi.org/10.1007/s12185-010-0584-y

Cited by

  1. Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies vol.121, pp.11, 2012, https://doi.org/10.1002/cncr.29271
  2. Prognostic factors and treatment of pediatric acute lymphoblastic leukemia vol.60, pp.5, 2017, https://doi.org/10.3345/kjp.2017.60.5.129