Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Hematopoietic stem cell transplantation in children with acute leukemia: similar outcomes in recipients of umbilical cord blood versus marrow or peripheral blood stem cells from related or unrelated donors

  • Yi, Eun-Sang (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Soo-Hyun (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Son, Meong-Hi (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Ju-Youn (Children's Cancer Center, Samsung Medical Center) ;
  • Cho, Eun-Joo (Children's Cancer Center, Samsung Medical Center) ;
  • Lim, Su-Jin (Department of Nursing, Gangneung Youngdong College) ;
  • Cheuh, Hee-Won (Department of Pediatrics, Dong-A Medical Center, Dong-A University College of Medicine) ;
  • Yoo, Keon-Hee (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Sung, Ki-Woong (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koo, Hong-Hoe (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2011.09.14
  • Accepted : 2011.11.22
  • Published : 2012.03.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: This study compared outcomes in children with acute leukemia who underwent transplantations with umbilical cord blood (UCB), bone marrow, or peripheral blood stem cells from a human leukocyte antigen (HLA)-matched related donor (MRD) or an unrelated donor (URD). Methods: This retrospective study included consecutive acute leukemia patients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) at Samsung Medical Center between 2005 and 2010. Patients received stem cells from MRD (n=33), URD (n=46), or UCB (n=41). Results: Neutrophil and platelet recovery were significantly longer after HSCT with UCB than with MRD or URD ($p$ <0.01 for both). In multivariate analysis using the MRD group as a reference, the URD group had a significantly higher risk of grade III to IV acute graft-versus-host disease (GVHD; relative risk [RR], 15.2; 95% confidence interval [CI], 1.2 to 186.2; $p$=0.03) and extensive chronic GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; $p$ <0.01). For all 3 donor types, 5-year event-free survival (EFS) and overall survival were similar. Extensive chronic GVHD was associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; $p$ <0.01). Multivariate analysis showed that lower EFS was associated with advanced disease at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; $p$ <0.01) and total body irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; $p$=0.04). Conclusion: Survival after UCB transplantation was similar to survival after MRD and URD transplantation. For patients lacking an HLA matched donor, the use of UCB is a suitable alternative.

Keywords

References

  1. Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M, et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999;93:3662-71.
  2. Hows JM, Passweg JR, Tichelli A, Locasciulli A, Szydlo R, Bacigalupo A, et al. Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors. Bone Marrow Transplant 2006;38:799-805. https://doi.org/10.1038/sj.bmt.1705531
  3. Moore J, Nivison-Smith I, Goh K, Ma D, Bradstock K, Szer J, et al. Equivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant 2007;13:601-7. https://doi.org/10.1016/j.bbmt.2007.01.073
  4. Yakoub-Agha I, Mesnil F, Kuentz M, Boiron JM, Ifrah N, Milpied N, et al. Allogeneic marrow stem-cell transplantation from human leukocyte antigen-identical siblings versus human leukocyte antigen-allelic-matched unrelated donors (10/10) in patients with standard-risk hematologic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy. J Clin Oncol 2006;24:5695-702. https://doi.org/10.1200/JCO.2006.08.0952
  5. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007;369:1947-54. https://doi.org/10.1016/S0140-6736(07)60915-5
  6. Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001;97:2962-71. https://doi.org/10.1182/blood.V97.10.2962
  7. 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.
  8. Horwitz ME, Sullivan KM. Chronic graft-versus-host disease. Blood Rev 2006;20:15-27. https://doi.org/10.1016/j.blre.2005.01.007
  9. Yoo KH, Lee SH, Sung KW, Koo HH, Chung NG, Cho B, et al. Current status of pediatric umbilical cord blood transplantation in Korea: a multicenter retrospective analysis of 236 cases. Am J Hematol 2011;86:12-7. https://doi.org/10.1002/ajh.21886
  10. 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
  11. Tomblyn MB, Arora M, Baker KS, Blazar BR, Brunstein CG, Burns LJ, et al. Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. J Clin Oncol 2009;27:3634-41. https://doi.org/10.1200/JCO.2008.20.2960
  12. Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M, et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood 2007;109:1322-30.
  13. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004;351:2265-75. https://doi.org/10.1056/NEJMoa041276
  14. Kumar P, Defor TE, Brunstein C, Barker JN, Wagner JE, Weisdorf DJ, et al. Allogeneic hematopoietic stem cell transplantation in adult acute lymphocytic leukemia: impact of donor source on survival. Biol Blood Marrow Transplant 2008;14:1394-400. https://doi.org/10.1016/j.bbmt.2008.09.021
  15. Szabolcs P, Niedzwiecki D. Immune reconstitution after unrelated cord blood transplantation. Cytotherapy 2007;9:111-22. https://doi.org/10.1080/14653240701231014
  16. Verneris MR, Brunstein CG, Barker J, MacMillan ML, DeFor T, McKenna DH, et al. Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood 2009;114:4293-9. https://doi.org/10.1182/blood-2009-05-220525
  17. Shpall EJ, Quinones R, Giller R, Zeng C, Baron AE, Jones RB, et al. Transplantation of ex vivo expanded cord blood. Biol Blood Marrow Transplant 2002;8:368-76. https://doi.org/10.1053/bbmt.2002.v8.pm12171483
  18. Jaroscak J, Goltry K, Smith A, Waters-Pick B, Martin PL, Driscoll TA, et al. Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System. Blood 2003;101:5061-7. https://doi.org/10.1182/blood-2001-12-0290
  19. Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, et al. Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 2007;21:1733-8. https://doi.org/10.1038/sj.leu.2404777
  20. Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, et al. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood 2007;110: 2764-7. https://doi.org/10.1182/blood-2007-04-087056
  21. Kim DH, Yoo KH, Yim YS, Choi J, Lee SH, Jung HL, et al. Cotransplanted bone marrow derived mesenchymal stem cells (MSC) enhanced engraftment of hematopoietic stem cells in a MSC-dose dependent manner in NOD/SCID mice. J Korean Med Sci 2006;21:1000-4. https://doi.org/10.3346/jkms.2006.21.6.1000

Cited by

  1. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells vol.7, pp.None, 2013, https://doi.org/10.3389/fnins.2013.00194
  2. Stem cell transplantation and lung dysfunction vol.25, pp.3, 2013, https://doi.org/10.1097/mop.0b013e328360c317
  3. Partially CD3+-Depleted Unrelated and Haploidentical Donor Peripheral Stem Cell Transplantation Has Favorable Graft-versus-Host Disease and Survival Rates in Pediatric Hematologic Malignanc vol.26, pp.3, 2012, https://doi.org/10.1016/j.bbmt.2019.11.022