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Ǵм Vol.24_No.2 Suppl. P.S569-579, Dec. 2007

Original Article

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Etiology of Treatment Related Mortality after Hematopoietic Stem Cell Transplantation

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åڣ, 뱸 5 317-1, к Ҿưб
Tel: (053) 620-3530, Fax: (053) 629-2252
E-mail: johah@med.yu.ac.kr

December 30, 2007

Abstract

BactgroundThe etiologies of treatment related mortality (TRM) after hematopoietic stem cell transplantation (HSCT) have been variable according to the disease status or the centers. We evlauated the etiologies of TRM for the pediatric patients at Yeungnam University Hospital (YNUH).
Materials and MethodsThe records of 66 patients, 19 years of age or younger, who had HSCT at YNUH from September 1995 to August 2007 were reviewed.
ResultsAmong 66 patients, allogeneic bone marrow transplantation (Allo-BMT) was done in 21 (19 related, 2 unrelated), allogeneic peripheral blood stem cell transplantation (Allo- PBSCT) in 1, cord blood transplantation (CBT) in 12 (1 related, 11 unrelated), autologous peripheral blood stem cell transplantation (Auto-PBSCT) in 32 patients. The TRM rates of Allo-BMT, CBT, and Auto-PBSCT were 19%, 33.3%, and 12.5%, respectively. Among four patients who had TRM after Allo-BMT, two were related transplantation and the others were unrelated. All four patients developed severe acute GVHD of at least grade . Sepsis developed in three patients, acute renal failure (ARF) in two, veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA) in one patient each. All four patients who had TRM after CBT had two mismatches in HLA-A, B, DR, and engraftment syndrome developed in three. Sepsis developed in all four patients, VOD in two, encephalopathy in two, TMA and ARF in one patient each. All four patients who had TRM after Auto-PBSCT developed sepsis and ARF in two, VOD and TMA in one patient each.
ConclusionAlthough the number of cases were not large enough for firm conclusion, sepsis was the most common TRM after HSCT. Therefore, prevention and control of sepsis are very important in reducing TRM after HSCT. Outcomes of severe acute GVHD after Allo-BMT and engraftment syndrome after CBT are very poor and contribute for TRM. Continuous effort to reduce the incidence of GVHD and engraftment syndrome are needed.

Key Words: Hematopoietic stem cell transplantation, Treatment related mortality, Etiology

References

1. Thomas ED, Lochte HL Jr, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med 1957 Sep 12;257(11):491-6.

2. Champlin RE, Gale RP. The early complications of bone marrow transplantation. Semin Hematol 1984 Apr;21(2):101-8.

3. Santos GW, Kaizer H. Bone marrow transplan- tation in acute leukemia. Semin Hematol 1982 Jul;19(3):227-39.

4. Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, et al. Bone marrow transplantation (first of two parts). N Engl J Med 1975 Apr 17;292(16):832-43.

5. McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M, et al. Veno- occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993 Feb 15;118(4):255-67.

6. Lorenz E, Congdon C, Uphoff D. Modification of acute irradiation injury in mice and guinea- pigs by bone marrow injections. Radiology 1952 Jun;58(6):863-77.

7. Bach FH, Albertini RJ, Joo P, Anderson JL, Bortin MM. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Lancet 1968 Dec 28;2(7583):1364-6.

8. Gluckman E, Rocha V, Chevret S. Results of unrelated umbilical cord blood hematopoietic stem cell transplant. Transfus Clin Biol 2001 Jun;8(3):146-54.

9. Eapen M, Horowitz MM, Klein JP, Champlin RE, Loberiza FR Jr, Ringden O, et al. Higher mortality after allogeneic peripheral-blood transplantation compared with bone marrow in children and adolescents: the Histocompa- tibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry. J Clin Oncol 2004 Dec 15;22(24):4872-80.

10. 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 May 15;97 (10):2962-71.

11. Cho B. Pediatric Allogeneic Hematopoietic Stem Cell Transplantation in Korea: April 2000: The Korean Society of Pediatric Hematology- Oncology. Korean J Pediatr Hematol-Oncol 2001 Apr;8(1):1-8.

12. 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 Jan 1;24(1):145-51.

13. Karen KB Haley R, Kurtzberg J. Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a lage cord blood bank. Transfusion 2006 Dec 46:2063-70.

14. Jones RJ, Sharkis SJ, Celano P, Colvin OM, Rowley SD, Sensenbrenner LL. Progenitor cell assays predict hematopoietic reconstitution after syngeneic transplantation in mice. Blood 1987 Oct;70(4):1186-92.

15. Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997 Aug 7;337(6):373-81.

16. Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant 2001 May;27(9):893-98.

17. Foncillas MA, Diaz MA, Sevilla J, Gonzalez Vicent M, Fernandez-Plaza S, Perez A, et al. Engraftment syndrome emerges as the main cause of transplant-related mortality in pediatric patients receiving autologous peripheral blood progenitor cell transplantation. J Pediatr Hematol Oncol 2004 Aug;26(8):492-6.

18. Bradley MB, Cairo MS. Cord blood immunology and stem cell transplantation. Hum Immunol 2005 May;66(5):431-46.

19. Schonberger S, Niehues T, Meisel R, Bernbeck B, Laws HJ, Kogler G, et al. Transplantation of haematopoietic stem cells derived from cord blood, bone marrow or peripheral blood: a single centre matched-pair analysis in a heterogeneous risk population. Klin Padiatr 2004 Nov-Dec;216(6):356-63.

20. van der Meer A, Allebes WA, Paardekooper J, Ruiter J, Joosten I. HLA-C mismatches induce strong cytotoxic T-cell reactivity in the presence of an additional DRB/DQB mismatch and affect NK cell-mediated alloreactivity. Transplantation 2001 Sep 15;72(5):923-9.

21. Martinez C, Salamero O, Arenillas L, Duque J, Lopez-Guillermo A, Rovira M, et al. Autologous stem cell transplantation for patients with active Hodgkins lymphoma: long-term outcome of 61 patients from a single institution. Leuk Lymphoma 2007 Oct;48(10):1968-75.

22. Christensen MS, Heyman M, Mottonen M, Zeller B, Jonmundsson G, Hasle H. Nordic Society of Paediatric Haematology and Oncology (NOPHO). Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992-2001. Br J Haematol 2005 Oct;131(1):50-8.

23. Tomaske M, Bosk A, Eyrich M, Bader P, Niethammer D. Risks of mortality in children admitted to the paediatric intensive care unit after haematopoietic stem cell transplantation. Br J Haematol 2003 Jun;121(6):886-91.

24. Auner HW, Sill H, Mulabecirovic A, Linkesch W, Krause R. Infectious complications after autologous hematopoietic stem cell transplan- tation: comparison of patients with acute myeloid leukemia, malignant lymphoma, and multiple myeloma. Ann Hematol 2002 Jul;81 (7):374-7.

25. Reich G, Mapara MY, Reichardt P, Dorken B, Maschmeyer G. Infectious complications after high-dose chemotherapy and autologous stem cell transplantation: comparison between patients with lymphoma or multiple myeloma and patients with solid tumors. Bone Marrow Transplant 2001 Mar;27(5):525-9.

26. Gil L, Styczynski J, Komarnicki M. Infectious Complication in 314 Patients after High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation: Risk Factors Analysis and Outcome. Infection 2007 Oct 9 [Epub ahead of print].