J Korean Med Sci.  2011 Dec;26(12):1548-1555. 10.3346/jkms.2011.26.12.1548.

Hematopoietic Stem Cell Transplantation in Children with Leukemia: A Single Institution Experience with Respect to Donors

• Baek HJ
• Kook H
• Han DK
• Hwang TJ

• KMID: 1786009
• DOI: http://doi.org/10.3346/jkms.2011.26.12.1548

Abstract

Aim of this study was to compare the outcomes of transplantation by donor source and to help select the best alternative donor in children with leukemia. Donor sources included matched related donor (MRD, n = 35), allele-matched unrelated donor (M-UD, n = 10) or -mismatched (MM)-UD (n = 13) or unrelated umbilical cord blood (UCB, n = 11). UCB group had a significantly higher incidence of grade II-IV acute graft versus host disease (MRD, 11.8%; M-UD, 30.0%; MM-UD, 15.4%, UCB, 54.4%, P = 0.004) but there was no difference in incidence of chronic graft versus host disease between 4 groups. The 5-yr leukemia-free survival (LFS) was 76.7%, 60.0%, 69.2%, and 45.5%, respectively (P = 0.128). MRD group showed higher LFS rate than UCB group (P = 0.022). However, LFS of M-UD and MM-UD together (65.2%) was not different from that of MRD group (76.7%, P = 0.325), or from that of UCB (45.5%, P = 0.190). The relapse incidence at 5 yr was 17.1%, 20.0%, 15.4%, and 0%, respectively (P = 0.460). The 100-day treatment-related mortality was 2.9%, 20.0%, 7.7%, and 36.4%, respectively (P = 0.011). Despite the limitations of small number of patients, unrelated donor transplants including even allele-mismatched ones, seem to be as effective in children with leukemia lacking suitable relative donors. Also, UCB transplant may serve as another possible option in urgent transplants.

Keyword

Allogeneic Hematopoietic Stem Cell Transplantation; Leukemia; Unrelated Donor; Umbilical Cord Blood

MeSH Terms

Adolescent
Child
Child, Preschool
*Cord Blood Stem Cell Transplantation/adverse effects/methods
Disease-Free Survival
Female
Fetal Blood/transplantation
Graft vs Leukemia Effect
*Hematopoietic Stem Cell Transplantation/adverse effects/methods/mortality
Histocompatibility Testing
Humans
Infant
Leukemia/mortality/*therapy
Male
Transplantation, Homologous
Treatment Outcome
Unrelated Donors

Figure

• 

  Fig. 1 Probability of Kaplan-Meier 5-yr overall survival (A) and leukemic-free survival (B) by different donor groups.

Reference

1. Kollman C, Abella E, Baitty RL, Beatty PG, Chakraborty R, Christiansen CL, Hartzman RJ, Hurley CK, Milford E, Nyman JA, Smith TJ, Switzer GE, Wada RK, Setterholm M. Assessment of optimal size and composition of the US National Registry of hematopoietic stem cell donors. Transplantation. 2004. 78:89–95.

2. Rocha V, Gluckman E. Eurocord and European Blood and Marrow Transplant Group. Clinical use of umbilical cord blood hematopoietic stem cells. Biol Blood Marrow Transplant. 2006. 12:34–41.

3. Flomenberg N, Baxter-Lowe LA, Confer D, Fernandez-Vina M, Filipovich A, Horowitz M, Hurley C, Kollman C, Anasetti C, Noreen H, Begovich A, Hildebrand W, Petersdorf E, Schmeckpeper B, Setterholm M, Trachtenberg E, Williams T, Yunis E, Weisdorf D. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood. 2004. 104:1923–1930.

4. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, Fernandez-Vina M, Flomenberg N, Horowitz M, Hurley CK, Noreen H, Oudshoorn M, Petersdorf E, Setterholm M, Spellman S, Weisdorf D, Williams TM, Anasetti C. High resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007. 110:4576–4583.

5. Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K, Ishikawa Y, Kato S, Sao H, Sakamaki H, Kawa K, Hamajima N, Asano S, Kodera Y. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood. 2002. 99:4200–4206.

6. Petersdorf EW, Gooley T, Malkki M, Anasetti C, Martin P, Woolfrey A, Smith A, Mickelson E, Hansen JA. The biological significance of HLA-DP gene variation in haematopoietic cell transplantation. Br J Haematol. 2001. 112:988–994.

7. Bray RA, Hurley CK, Kamani NR, Woolfrey A, Müller C, Spellman S, Setterholm M, Confer DL. National marrow donor program HLA matching guidelines for unrelated adult donor hematopoietic cell transplants. Biol Blood Marrow Transplant. 2008. 14:45–53.

8. Grewal SS, Barker JN, Davies SM, Wagner JE. Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood. 2003. 101:4233–4244.

9. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A, Takahashi TA, Vowels M, Ortega J, Bordigoni P, Shaw PJ, Yaniv I, Machado A, Pimentel P, Fagioli F, Verdeguer A, Jouet JP, Diez B, Ferreira E, Pasquini R, Rosenthal J, Sievers E, Messina C, Iori AP, Garnier F, Ionescu I, Locatelli F, Gluckman E. Eurocord Group. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood. 2003. 102:4290–4297.

10. Rocha V, Locatelli F. Searching for alternative hematopoietic stem cell donors for pediatric patients. Bone Marrow Transplant. 2008. 41:207–214.

11. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C, Goldman A, Kersey J, Krivit W, MacMillan ML, Orchard PJ, Peters C, Weisdorf DJ, Ramsay NK, Davies SM. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood. 2002. 100:1611–1618.

12. Kamani N, Spellman S, Hurley CK, Barker JN, Smith FO, Oudshoorn M, Bray R, Smith A, Williams TM, Logan B, Eapen M, Anasetti C, Setterholm M, Confer DL. National marrow Donor Program. State of the art review: HLA matching and outcome of unrelated donor umbilical cord blood transplants. Biol Blood Marrow Transplant. 2008. 14:1–6.

13. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW, Takahashi TA, Ortega J, Filipovich A, Locatelli F, Asano S, Fagioli F, Vowels M, Sirvent A, Laporte JP, Tiedemann K, Amadori S, Abecassis M, Bordigoni P, Diez B, Shaw PJ, Vora A, Caniglia M, Garnier F, Ionescu I, Garcia J, Koegler G, Rebulla P, Chevret S. Eurocord Group. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol. 2004. 32:397–407.

14. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS, Verfaillie CM, Wagner JE. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005. 105:1343–1347.

15. Rocha V, Cornish J, Sievers E, Filipovich A, Locatelli F, Peters C, Remberger M, Michel G, Arcese W, Dallorso S, Tiedemann K, Busca A, Chan KW, Kato S, Ortega J, Vowels M, Zander A, Souillet G, Oakill A, Woolfrey A, Pay AL, Green A, Garnier F, Ionescu I, Wernet P, Sirchia G, Rubinstein P, Chevret S, Gluckman E. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001. 97:2962–2971.

16. Dalle JH, Duval M, Moghrabi A, Wagner JE, Vachon MF, Barrette S, Bernstein M, Champagne J, David M, Demers J, Rousseau P, Winikoff R, Champagne MA. Results of an unrelated transplant search strategy using partially HLA-mismatched cord blood as an immediate alternative to HLA-matched bone marrow. Bone Marrow Transplant. 2004. 33:605–611.

17. Hwang WY, Samuel M, Tan D, Koh LP, Lim W, Linn YC. A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplant. 2007. 13:444–453.

18. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A, Loberiza FR, Champlin RE, Klein JP, Horowitz MM, Wagner JE. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet. 2007. 369:1947–1954.

19. Lee JH, Yoon HS, Song JS, Choi ES, Moon HN, Seo JJ, Im HJ. Unrelated hematopoietic stem cell transplantation for children with acute leukemia: experience at a single institution. J Korean Med Sci. 2009. 24:904–909.

20. Takahashi S, Iseki T, Ooi J, Tomonari A, Takasugi K, Shimohakamada Y, Yamada T, Uchimaru K, Tojo A, Shirafuji N, Kodo H, Tani K, Takahashi T, Yamaguchi T, Asano S. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood. 2004. 104:3813–3820.

21. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE, Stevens C, Barker JN, Gale RP, Lazarus HM, Marks DI, van Rood JJ, Scaradavou A, Horowitz MM. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med. 2004. 351:2265–2275.

22. Rocha V, Labopin M, Sanz G, Arcess W, Schwerdtfeger R, Bosi A, Jacobsen N, Ruutu T, de Lima M, Finke J, Frassoni F, Gluckman E. Acute Leukemia Working Party of European Blood and marrow Transplant Group. Eurocord-Netcord Registry. Transplants of umbilical cord blood or bone marrow from unrelated donors in adult with acute leukaemia. N Engl J Med. 2004. 351:2276–2285.

23. Rocha V, Wagner JE Jr, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM, Gluckman E. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. N Engl J Med. 2000. 342:1846–1854.

24. Parham P, Otha T. Population biology of antigen presentation by MHC class I molecules. Science. 1996. 272:67–74.

25. Decorte R, Cassiman JJ. Forensic medicine and the polymerase chain reaction technique. J Med Genet. 1993. 30:625–633.

26. Al-Kasim FA, Thornley I, Rolland M, Lau W, Tsang R, Freedman MH, Saunders EF, Calderwood S, Doyle JJ. Single-centre experience with allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in childhood: similar survival after matched-related and matched-unrelated donor transplants. Br J Haematol. 2002. 116:483–490.

27. Rocha V, Kabbara N, Ionescu I, Ruggeri A, Purtill D, Gluckman E. Pediatric related and unrelated cord blood transplantation for malignant diseases. Bone Marrow Transplant. 2009. 44:653–659.

28. Przepiorka D, Weisdorf D, Martin P, Klingemann Hg, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995. 15:825–828.

29. Scrucca L, Santucci A, Aversa F. Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant. 2007. 40:381–387.

30. 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. 15:1086–1093.