Journal of Hematology - Supplements - Haematologica

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28 those reported in studies on allograft of bone marrow cells from either a family or an unrelated donor in pediatric leukemia patients. 26-28 These data suggest that UCBT from either a relative or an unrelated donor is a feasible procedure, capable of curing a relevant number of children with acute leukemia, who failed to benefit from conventional chemotherapy or who are at risk of relapse. It is therefore evident that if the aim of UCBT is to achieve a definitive cure in leukemia patients, this transplant should not be considered as a treatment of last resort for patients with end-stage disease, but rather as a well-established and accepted therapy for patients who have achieved a second remission after relapse and for those children who are in first hematologic remission with a high risk of recurrence. Few data have been published on the biological mechanisms of the UCBT-related GVL effect. In particular, while several authors have demonstrated that cytotoxic T-lymphocytes (CTL) directed against allogeneic leukemia blasts can be detected in the peripheral blood of healthy donors, 29-31 no study on a cord blood T-cell specific HLA-restricted activity towards leukemia blasts has been reported. Innate cell-mediated cytotoxic activities, which are promptly activated by cord blood lymphocytes in response to a primary antigenic challenge, 32 might represent the most important mechanism for controlling the re-growth of leukemia blasts in UCBT recipients. In fact, previously published studies indicate that cord blood lymphokine-activated killer (LAK) cells are able to lyse non-cultured fresh leukemia blasts 15 and that their activity towards cell lines, such as Daudi and YAC-1 cells, is greater than that of bone marrow cells. 33 In summary, available evidence indicates that for several disorders amenable to cure by an allograft of haematopoietic stem cells, the overall event-free survival with UCBT is not statistically different from that observed after bone marrow transplants. This finding confirms the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants. Acknowledgments This work was partly supported by grants from the AIRC (Associazione Italiana Ricerca sul Cancro), CNR (Consiglio Nazionale delle Ricerche) and IRCCS Policlinico S. Matteo to F.L. References 1. Gluckman E, Broxmeyer HE, Auerbach AD, et al. Hematopoietic reconstitution in a patient with Fanconi anemia by means of umbilical cord blood from a HLA identical sibling. N Engl J Med 1989; 321:1174- 8. 2. Rebulla P, Lecchi L Poretti L, et al Practical placental blood banking. Transfus Med Rev 1999; 13:205-26. 3. Armitage S, Warwick R, Fehili, D Navarette C, Contreras M. Cord blood banking in London: the first 1000 collections. Bone Marrow Transplantation 1999; 24: 139-45. 4. Sirchia G, Rebulla P. Placental/umbilical cord blood transplantation. Haematologica 1999; 84:738-47. 5. Wagner JE, Kernan NA, Steinbuch M, Broxmeyer HE, Gluckman E. Allogeneic sibling umbilical cord blood transplantation in forty-four children with malignant and non-malignant disease. Lancet 1995; 346:214-9. 6. Kurtzberg J, Laughlin M, Smith J, et al. Placental blood as a source of hemopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 1996; 335:157-66. 7. Gluckman E, Rocha V, Chammard A, 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; 337:373-81. 8. Rubinstein P, Carrier C, Scaradavou A, et al. Outcomes among 562 recipients of placental blood transplants from unrelated donor. N Engl J Med 1998; 339: 1565-77. 9. Locatelli F, Rocha V, Chastang C, et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Blood 1999; 93: 3662-71. 10. Gluckman E, Rocha V, Chevret S. Related and unrelated cord blood transplantation in Cord blood characteristics role in stem cell transplantation. Edited by SBA Cohen, E. Gluckman, A. Madrigal, and P. Rubinstein. Martin Dunitz editor London pp. 215-6, 2000. 11. Rocha V, Wagner JE, Sobocinski KA, et al. 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; 342:1846-54. 12. Rocha V, Cornish J, Sievers E, et al. Comparison of the outcome of unrelated bone marrow or cord blood transplant in children with acute leukemia. Blood 1999; 94 (Suppl. 1):712a. 13. Madrigal JA, Cohen SBA, Gluckman E, Charron DJ. Does cord blood transplantation results in lower graftversus-host disease? It takes more than two to tango. Hum Immunol 1997; 56:1-5. 14. Chalmers I, Janossy G, Contreras M, Navarrete C. Intracellular cytokine profile of cord and adult blood lymphocytes. Blood 1998; 92:11-8. 15. Keever CA, Abu-Hajir M, Graf W, et al. Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells. Bone Marrow Transplant 1995; 15:407-19. 16. Cohen SBA, Perez-Cruz I, Fallen P, et al. Analysis of the cytokine production by cord and adult blood. Hum Immunol 1999; 60:331-6. 17. Risdon G, Gaddy J, Horrie M, et al. Alloantigen priming induces a state of unresponsiveness in human umbilical cord blood T cells. Proc Natl Acad Sci USA 1995; 92:2413-7. 18. Maccario R, Burgio GR. T and NK lymphocyte subpopulations in the neonate. In: Immunology of the neonate. Burgio GR, Hanson L, Ugazio AG, eds. Springer Verlag, Berlin-Heidelberg, 1987. p. 120-9. 19. Lee S, Suen Y, Chang L, et al. Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon-gamma, natural killer and lymphokine-activated killer activity by IL-12 in cord blood mononuclear cells. Blood 1996; 88:945-54. 20. Quian JX, Lee S, Suen Y, et al. Decreased interleukin- haematologica vol. 85(supplement to n. 11):November 2000
29 15 from activated cord versus adult peripheral blood mononuclear cells and the effect of interleukin-15 in upregulating anti-tumour immune activity and cytokine production in cord blood. Blood 1997; 90:3106-7. 21. Sorg RV, Kogler G, Wernet P. Identification of cord blood dendritic cells as an immature CD11c- population. Blood 1999; 93: 2302-7. 22. Barrett AJ, Horowitz MM, Gale RP, et al. Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival. Blood 1989; 74:826-33. 23. Santos GW. Marrow transplantation in acute nonlymphocytic leukemia. Blood 1989; 74:901-14. 24. Gratwohl A, Gahrton G. Allogeneic bone marrow transplantation in leukemia. Acta Oncol 1988; 27: 557. 25. Armitage JO. Bone marrow transplantation. N Engl J Med 1994; 330:827-38. 26. Balduzzi A, Gooley T, Anasetti C, et al. Unrelated donor marrow transplantation in children. Blood 1995; 86:3247-56. 27. Davies SM, Wagner JE, Shu XO, et al. Unrelated donor bone marrow transplantation for children with acute leukemia. J Clin Oncol 1997; 15:557-65. 28. Oakhill A, Pamphilon DH, Potter MN, et al. Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission. Br J Haematol 1996; 94:574- 81. 29. Faber LM, van Luxemburg-Heijs SAP, Willemze R, Falkenburg JHF. Generation of leukemia-reactive cytotoxic T lymphocyte clones from the HLA-identical bone marrow donor of a patient with leukemia. J Exp Med 1992; 176:1283-9. 30. Sosman JA, Oettel KR, Hank JA, Fisch P, Sondel PM. Specific recognition of human leukemic cells by allogeneic T cell lines. Transplantation 1989; 48:486-95. 31. Salomo M, Steinmann J, Glass B, et al. Leukemia-specific allogeneic donor T cells: quantification by limiting dilution assay. Bone Marrow Transplant 1995; 15:179-86. 32. Moretta A, Comoli P, Montagna D, et al. High frequency of Epstein-Barr virus (EBV) lymphoblastoid cell line-reactive lymphocytes in cord blood: evaluation of cytolytic activity and IL-2 production. Clin Exp Immunol 1997; 107:312-8. 33. Gardiner CM, O'Meara A, Reen DJ. Differential cytotoxicity of cord-blood and bone marrow-derived natural killer cells. Blood 1998; 91:207-13. haematologica vol. 85(supplement to n. 11):November 2000
Page 1 and 2: Haematologica established in 1920 e
Page 3 and 4: haematologica Journal of Hematology
Page 5 and 6: 3 Table 1. Indications for allogene
Page 7 and 8: 5 ease-free survival for childhood
Page 9 and 10: 7 Allogeneic bone marrow transplant
Page 11 and 12: haematologica 2000; 85(supplement t
Page 13 and 14: 11 achieved. However the relapse ra
Page 15 and 16: 13 ease. This observation is confir
Page 17 and 18: 15 plant failure. The role of DLI i
Page 19 and 20: 17 non-myeloablative regimen. Blood
Page 21 and 22: apheretic products obtained after m
Page 23 and 24: 21 Kinetics of activation of CFC in
Page 25 and 26: 23 according to the flow cytometric
Page 27 and 28: 25 mal cell activators and inhibito
Page 29: 27 reduced responsiveness to alloge
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Page 35 and 36: 33 Table 5. Timing and causes of tr
Page 37 and 38: 35 of children with storage disorde
Page 41 and 42: 39 parents wishes (the patient was
Page 45 and 46: 43 washing the cell suspension and
Page 47 and 48: 45 tive selection is usually around
Page 51 and 52: 49 chemotherapy blocks has been adm
Page 53 and 54: 51 Recently some clinical studies h
Page 55 and 56: 53 lymphoblastic leukaemia in Italy
Page 57 and 58: 55 Table 1. Summary of clinical dat
Page 59 and 60: 57 HLA-restricted cytomegalovirus (
Page 61 and 62: 59 that short-term artificial nutri
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Page 67 and 68: 65 References 1. Clarke DE, Raffin
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Page 71 and 72: 69 platin-thiotepa-etoposide is 34%
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Page 77 and 78: 75 Special Issues Conditioning The
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79 treatment of poor risk systemic
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haematologica 2000; 85(supplement t
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83 Table 1. Rheumatologic disorders
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85 ly in terms of steroid-sparing a
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87 the same buffer was added to all
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haematologica 2000; 85(supplement t
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91 patients, 10 with a systemic for
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I index of authors Albertini A 41 A
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