Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical outcomes of hematopoietic stem cell transplantation from HLA-matched parental donor in childhood acute leukemia

소아 급성 백혈병 환자에서 주조직적합항원 일치 부모자식간 조혈모세포 이식 후 임상경과

  • Cha, Eun Young (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lee, Moon Hee (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lee, Jae Wook (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kwon, Young Joo (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lee, Dae Hyoung (Department of Pediatrics, College of Medicine, Hallym University) ;
  • Park, Young-Shil (Department of Pediatrics, College of Medicine, Kyung Hee University) ;
  • Chung, Nak Gyun (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Jeong, Dae Chul (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Cho, Bin (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kim, Hack Ki (Department of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 차은영 (가톨릭대학교 의과대학 소아과학교실) ;
  • 이문희 (가톨릭대학교 의과대학 소아과학교실) ;
  • 이재욱 (가톨릭대학교 의과대학 소아과학교실) ;
  • 권영주 (가톨릭대학교 의과대학 소아과학교실) ;
  • 이대형 (한림대학교 의과대학 소아과학교실) ;
  • 박영실 (경희대학교 의과대학 소아과학 교실) ;
  • 정낙균 (가톨릭대학교 의과대학 소아과학교실) ;
  • 정대철 (가톨릭대학교 의과대학 소아과학교실) ;
  • 조빈 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김학기 (가톨릭대학교 의과대학 소아과학교실)
  • Received : 2007.09.10
  • Accepted : 2007.10.10
  • Published : 2008.01.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : In this study, we retrospectively analyzed the clinical outcomes of patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) grafted from HLA-matched parents. Methods : Seven children with acute leukemia (4 acute lymphoblastic leukemia, 3 acute myeloid leukemia) in first complete remission received allogeneic HSCT from their respective parents at the St. Marys Hospital between April, 1999 and October, 2005. The median age of patients at transplantation was 5 years (range, 1-11 years; 2 male, 5 female) and the median age of donors was 35 years (range, 30-41 years; 5 male, 2 female). We investigated the clinical outcomes such as engraftment, acute and chronic graft-versus-host disease (GVHD), transplant-related morbidity and mortality, relapse and survival. Results : Median time from transplantation to last follow-up was 69.5 months (range, 18.8-96.5 months). All patients were successfully engrafted, with a median time of 11 days (range, 10-16 days) and 26 days (range, 13-39 days) for neutrophil and platelet recovery, respectively. Grade II acute GVHD occurred in 3, and grade III acute GVHD in 1 of 7 recipients. Extensive chronic GVHD developed in 2, and limited chronic GVHD in 1 of 7 recipients. Death from transplant-related complications occurred in 1, and relapse occurred in 1 of 7 recipients. Estimated 5-year overall survival was $83{\pm}15%$. Conclusion : The clinical outcomes of recipients who underwent HSCT from HLA-matched parents were comparable to those of patients who received HSCT grafted from HLA-matched sibling donors in childhood leukemia. HLA typing of parents, as well as siblings will increase the likelihood of finding an HLA-matched family donor for patients who need HSCT.

목 적 : 본 연구는 HLA가 일치하는 부모로부터 동종조혈모세포이식을 시행받은 소아의 이식 결과를 분석하고자 하였다. 방 법 : 1999년 4월부터 2005년 10월까지 성모병원 조혈모세포이식센터에서 급성 백혈병으로 1차 관해 후 HLA가 일치된 부모로부터 조혈모세포이식을 시행받은 환아 7명(급성 림프모구성백혈병 4명, 급성 골수성백혈병 3명)을 대상으로 하였다. 이식 시 중앙연령은 5세(범위, 1-11세; 남아 2명, 여아 5명), 공여자의 중앙연령은 35세(범위, 30-41세; 남자 5명, 여자 2명)이었다. 이식 후 대상 환아의 생착, 급성이식편대숙주병, 만성이식편대숙주병, 이식관련 사망, 재발, 이식관련 합병증과 생존율 등을 분석하였다. 결 과 : 이식부터 마지막 추적관찰까지 중앙기간이 69.5개월(범위, 18.8-96.5개월)이었다. 이식을 받은 7명의 환아들은 모두 생착이 되었고 호중구와 혈소판의 생착은 이식 후 각각 11일(범위, 10-16일)과 26일(범위, 13-39일)이었다. Grade II의 급성 이식편대숙주병은 3명(43%), grade III의 급성 이식편대숙주병은 1명(14%)에서 발생하였다. 광범위 만성이식편대숙주병은 2명(28%), 제한적 만성이식편대숙주병은 1명(14%)에서 발생하였다. 이식 후 재발은 1명(14%)이었고 이식관련 사망은 1명(14%)이었다. 대상 환아의 이식 후 5년 전체 생존율은 $83{\pm}15%$이었다. 결 론 : 소아 급성 백혈병에서 HLA가 일치하는 부모자식간 동종조혈모세포이식의 결과는 HLA가 일치하는 형제간 조혈모세포이식의 결과와 비견할 수 있으며 동종조혈모세포이식이 필요한 환아에서 형제뿐만이 아니라 부모의 HLA를 검사하면 조혈모세포 공여자 선정의 가능성이 높아진다.

Keywords

References

  1. Alonzo TA, Wells RJ, Woods WG, Lange B, Gerbing RB, Buxton AB, et al. Postremission therapy for children with acute myeloid leukemia: the childrens cancer group experience in the transplant era. Leukemia 2005;19:965-70 https://doi.org/10.1038/sj.leu.2403763
  2. Woods WG, Neudorf S, Gold S, Sanders J, Buckley JD, Barnard DR, et al. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood 2001;97:56-62 https://doi.org/10.1182/blood.V97.1.56
  3. Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol 1997;15:1767-77 https://doi.org/10.1200/JCO.1997.15.5.1767
  4. 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
  5. Uderzo C, Rondelli R, Dini G, Dallorso S, Messina C, Miniero R, et al. High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study. Br J Haematol 1995;89:790-7 https://doi.org/10.1111/j.1365-2141.1995.tb08416.x
  6. Kim HK, Cho B, Chung NG, Jeong DC, Kim SY, Lee HJ, et al. One hundred cases of HLA-matched sibling allogeneic bone marrow transplantation in children : Single center study. J Korean Pediatr Soc 1999;43:402-10
  7. Kim HK, Cho B, Chung NG, Jeong DC, Jang PS, Kim SY, et al. Two hundred cases of allogeneic hematopoietic stem cell transplantation in children: single center study. Korean J Hemato Stem Cell Trans 2002;7:63-71
  8. Oudshoorn M, Lie JLWT, Bakker JNA, Van Der Zanden HGM, Claas FHJ. Finding the most suitable allogeneic he-matopoietic stem cell donor. In : Atkinson K, Champlin R, Ritz J, Fibbe WE, Ljungman P, Brenner ML, editors. Clinical Bone Marrow And Blood Stem Cell Transplantation. 3rd ed. Cambridge : Cambridge University Press, 2004:369-82
  9. Marks DI, Khattry N, Cummins M, Goulden N, Green A, Harvey J, et al. Haploidentical stem cell transplantation for children with acute leukaemia. Br J Haematol 2006;134:196-201 https://doi.org/10.1111/j.1365-2141.2006.06140.x
  10. Klingebiel T, Handgretinger R, Lang P, Bader P, Niethammer D. Haploidentical transplantation for acute lymphoblastic leukemia in childhood. Blood Rev 2004;18:181-92 https://doi.org/10.1016/S0268-960X(03)00063-8
  11. Mehta J, Singhal S, Gee AP, Chiang KY, Godder K, Rhee Fv F, et al. Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: singlecenter experience of 201 patients. Bone Marrow Transplant 2004;33:389-96 https://doi.org/10.1038/sj.bmt.1704391
  12. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974;18:295-304 https://doi.org/10.1097/00007890-197410000-00001
  13. Zecca M, Pession A, Messina C, Bonetti F, Favre C, Prete A, et al. Total body irradiation, thiotepa, and cyclophosphamide as a conditioning regimen for children with acute lymphoblastic leukemia in first or second remission undergoing bone marrow transplantation with HLA-identical siblings. J Clin Oncol 1999;17:1838-46 https://doi.org/10.1200/JCO.1999.17.6.1838
  14. Hongeng S, Krance RA, Bowman LC, Srivastava DK, Cunningham JM, Horwitz EM, et al. Outcomes of transplantation with matched-sibling and unrelated-donor bone marrow in children with leukaemia. Lancet 1997;350:767-71 https://doi.org/10.1016/S0140-6736(97)03098-5
  15. Eapen M, Rubinstein P, Zhang MJ, Camitta BM, Stevens C, Cairo MS, et al. Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months. J Clin Oncol 2006;24:145-51 https://doi.org/10.1200/JCO.2005.02.4612
  16. Meyers JD. Prevention and treatment of cytomegalovirus infection after marrow transplantation. Bone Marrow Transplant 1988;3:95-104
  17. Miller W, Flynn P, McCullough J, Balfour HH Jr, Goldman A, Haake R, et al. Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-vhost disease. Blood 1986;67:1162-7
  18. Cho EY, Park YS, Lee DH, Park JK, Choi SR, Kim SY, et al. CMV antigenemia following pediatric hematopoietic stem cell transplantation : risk factors and outcomes. Korean J Pediatr 2006;49:173-80 https://doi.org/10.3345/kjp.2006.49.2.173
  19. Mrtelli MF, Aversa F, Velardi A, Reisner Y. HLA-mismatched family member hematopoietic stem cell transplantation. In : Atkinson K, Champlin R, Ritz J, Fibbe WE, Ljungman P, Brenner ML, editors. Clinical Bone Marrow And Blood Stem Cell Transplantation. 3rd ed. Cambridge : Cambridge University Press, 2004:1011-26
  20. Keever-Taylor CA, Bredeson C, Loberiza FR, Casper JT, Lawton C, Rizzo D, et al. Analysis of risk factors for the development of GVHD after T celldepleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T-cell depletion. Biol Blood Marrow transplant 2001;7:620-30 https://doi.org/10.1053/bbmt.2001.v7.pm11760150
  21. Henslee-Downey PJ, Parrish RS, MacDonald JS, Romond EH, Marciniak E, Coffey C, et al. Combined in vitro and in vivo T lymphocyte depletion for the control of graft-versushost disease following haploidentical marrow transplant. Transplantation 1996;61:738-45 https://doi.org/10.1097/00007890-199603150-00012
  22. Petersdorf EW. Risk assessment in haematopoietic stem cell transplantation: histocompatibility. Best Pract Res Clin Haematol 2007;20:155-70 https://doi.org/10.1016/j.beha.2006.09.001
  23. Lee KW, Oh DH, Lee C, Yang SY. Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens 2005;65:437-47 https://doi.org/10.1111/j.1399-0039.2005.00386.x
  24. Flomenberg N, Baxter-Lowe LA, Confer D, Fernandez-Vina M, Filipovich A, Horowitz M, et al. 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;104:1923-30 https://doi.org/10.1182/blood-2004-03-0803
  25. Greinix HT, Fae I, Schneider B, Rosenmayr A, Mitterschiffthaler A, Pelzmann B, et al. Impact of HLA class I highresolution mismatches on chronic graft-versus-host disease and survival of patients given hematopoietic stem cell grafts from unrelated donors. Bone Marrow Transplant 2005;35:57-62 https://doi.org/10.1038/sj.bmt.1704741
  26. Chalandon Y, Tiercy JM, Schanz U, Gungor T, Seger R, Halter J, et al. Impact of high-resolution matching in allogeneic unrelated donor stem cell transplantation in Switzerland. Bone Marrow Transplant 2006;37:909-16 https://doi.org/10.1038/sj.bmt.1705353