The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1%) were males and 454 (39.9%) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8%) candidates had full match donors; 352/1138 (30.8%) were eligible for alloBMT. Only 235 of 352 (66.7%) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%); monthly family income ranged from US$60 (7$400 (36%). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil.31532

Correlation of mixed lymphocyte culture with chronic graft-versus-host disease following allogeneic stem cell transplantation

The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3%) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6%). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7%, with a median of 0.5%. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5% than in those with RR 4.5%), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5% associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication.56757

Cronic Myeloid Leukemia - Bone Marrow Transplantation [leucemia Mielóide Crônica - Transplante De Medula óssea]

Although the only curative therapy for chronic myeloid leukemia remains allogeneic stem cell transplantation (allo-SCT), the results of imatinib in newly diagnosed patients are sufficiently impressive to have displaced allo-SCT to second or third-line treatment. Patients now arrive at a decision for transplantation in a variety of disease situations: failing to achieve certain hematological, cytogenetic and molecular remission by some pre-determined timepoint, having lost a previous best response or due to progression to an advanced phase. The decision is also how to transplant. In this review article, the evidence supporting some of these decisions and current controversies are discussed.30SUPPL. 14146How, G.J., I treat chronic myeloid leukemia in the imatinib era (2007) Blood, 110 (8), pp. 2828-2837Silver RT, Woolf SH, Hehlmann R, et al. An Evidence-Based Analysis of the Effect of Busulfan, Hydroxyurea, Interferon, and Allogeneic Bone Marrow Transplantation in Treating the Chronic Phase of Chronic Myeloid Leukemia: Developed for the American Society of Hematology. Blood. 1999;94(5):1517-36Goldman, J., Management of chronic myeloid leukemia (2003) Semin Hematol, 40, pp. 1-103Druker, B.J., Talpaz, M., Resta, D.J., Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia (2001) New Engl J Med, 344, pp. 1031-1037Gratwohl, A., Baldomero, H., HorisbergerB, Current trends in hematopoietic stem cell transplantation in Europe. Accreditation Committee of the European Group for Blood and Marrow Transplantation (EBMT) (2002) Blood, 100, pp. 2374-2386Kantarjian, H., Sawyers, C., Hochhaus, Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia (2002) New Engl J Med, 346, pp. 645-652Gratwohl, A., Brand, R., Apperley, J., Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: Transplant activity, long-term data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) (2006) Haematologica, 91, pp. 513-521Olavarria E, Apperley J. Managemente of patients with imatinib resistence. EHA. 2006;1(1):230-38Hughes, T.P., Kaeda, J., Branford, S., Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia (2003) New Engl J Med, 349, pp. 1423-1432Gratwohl, A., Hermans, J., Goldman, J.M., Risk assessment for patients with chronic myeloid leukaemiabefore allogeneic blood or marrow transplantation (1998) Lancet, 352, pp. 1087-1092van Rhee, F., Szydlo, R.M., Hermans, J., Long term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: A report from the chronic leukemia working party of the European Group for Blood and Marrow Transplantation (1997) Bone Marrow Transplant, 20, pp. 553-560Devergie, A., Apperley, J., Labopin, M., European results of matched unrelated bone marrow transplantation for chronic myeloid leukemia: Impact of class II matching (1997) Bone Marrow Transplant, 20, pp. 11-19Hansen, J.A., Gooley, T.A., Martin, P.J., Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia (1998) N Engl J Med, 338, pp. 962-968De Souza, C.A., Vigorito, A.C., Ruiz, M.A., Validation of the EBMT risk score in chronic myeloid leukemia in Brazil and allogeneic transplant outcome (2005) Haematologica, 90, pp. 232-237Passweg JR, Walker I, Sobocinski KA, et al. Validation and extension of the EBMT Risk Score for patients with chronic myeloid leukaemia (CML) receiving allogeneic haematopoietic stem cell transplants. BJH. 2004;125:613-20Petersdorf, E.W., Anasetti, C., Martin, P.J., Limits of HLA mismatching in unrelated hematopoietic cell transplantation (2004) Blood, 104, pp. 2976-2980Guglielmi, C., Arcese, W., Dazzi, F., Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: Prognostic relevance of the initial cell dose (2002) Blood, 100, pp. 397-405Apperley, J., (2006) Managing the patient with chronic myeloid leukemia through and after allogeneic stem cell transplantation, pp. 226-232. , American Society of HematologyGratwohl, A., Baldomero, H., Frauendorfer, K., Urbano-Ispizua, A., EBMT activity survey 2004 and changes in disease indication over the past 15 years (2006) Bone Marrow Transplant. 2006, 37, pp. 1069-1085Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: An individual patient data meta-analysis of nine randomized trials (2005) J Clin Oncol, 23, pp. 5074-5087. , Stem Cell Trialists' Collaborative Grou

Allogeneic Hematopoietic Stem Cell Transplant For Multiple Myeloma [o Transplante Alogênico De Células-tronco Hematopoé Ticas No Tratamento Do Mieloma Múltiplo]

Multiple myeloma (MM) is a incurable hematological malignancy with an average survival of 3 years with conventional therapy. Allogeneic hematopoietic cell transplantation (allo - HCT) may cure some patients, but has been associated with a high transplantation-related-mortality (TRM) of over 40%. The potential advantages of allo - HCT are the ability to collect myeloma free stem cells and the graft - versus - myeloma effect. But, despite these factors, long term cure is rare. Relapse continues at a rate of approximately 7% per year with long term follow-up. The graft-versus-host disease (GVHD) can also be a problem, requiring therapy and impairing quality of life. Approaches to improve the outcome of allo - HCT for MM include consideration of patient status, efficacy and toxicity of induction therapy, source of hematopoietic graft, and conditioning regimens. Recent attempts to improve outcome include autologous hematopoietic cell transplantation (AHCT) followed by non - myeloablative allogeneic transplantation, and allo-HCT with T depletion and subsequent donor lymphocyte infusions. With the use of strategies directed at cell signaling, patients' lives can be prolonged, and the quality of their lives can be improved compared with the current approach that transplantation provides, despite its survival benefit.2914247Gratwohl A, Baldomero H, Frauendorfer K, Urbano-Ispizua A. EBMT activity survey 2004 and changes in disease indication over the past 15 years. Bone Marrow Transplant 2006;37:1.069-85Bjorkstrand, B., European Group for Blood and Marrow Transplantation Registry studies in multiple myeloma (2001) Semin Hematol, 38, pp. 219-225Gahrton G, Tura S, Ljungman P, et al. Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol 1995;13:1.312-22Bensinger WI, Buckner CD, Anasetti C, et al. Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. Blood 1996;88:2.787-93Mehta, J., Tricot, G., Jagannath, S., Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft? (1998) Bone Marrow Transplant, 21, pp. 887-892Gahrton, G., Svensson, H., Cavo, M., Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: A comparison between transplants performed 1983-93 and 1994-8 at European Group for Blood and Marrow Transplantation centres (2001) Br J Haematol, 113, pp. 209-216Catley, L., Anderson, K., Strategies to improve the outcome of stem cell transplantation in multiple myeloma (2004) Hematol J, 5, pp. 9-23Bird, J.M., Russell, N.H., Samson, D., Minimal residual disease after bone marrow transplantation for multiple myeloma: Evidence for cure in long-term survivors (1993) Bone Marrow Transplant, 12, pp. 651-654Corradini, P., Voena, C., Tarella, C., Molecular and clinical remissions in multiple myeloma: Role of autologous and allogeneic transplantation of hematopoietic cells (1999) J Clin Oncol, 17, pp. 208-215Martinelli G, Terragna C, Zamagni E, et al. Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma. J Clin Oncol 2000;18:2.273-81Gahrton, G., Svensson, H., Bjorkstrand, B., Syngeneic transplantation in multiple myeloma - a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation (1999) Bone Marrow Transplant, 24, pp. 741-745Gahrton G, Tura S, Ljungman P, et al. Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation. N Engl J Med 1991;325:1.267-73Bensinger WI, Buckner CD, Clift RA, et al. Phase I study of busulfan and cyclophosphamide in preparation for allogeneic marrow transplant for patients with multiple myeloma. J Clin Oncol 1992;10:1.492-7Cavo, M., Benni, M., Cirio, T.M., Gozzetti, A., Tura, S., Allogeneic bone marrow transplantation for the treatment of multiple myeloma (1995) An overview of published reports. Stem Cells, 13 (SUPPL. 2), pp. 126-131Bensinger, W.I., Buckner, D., Gahrton, G., Allogeneic stem cell transplantation for multiple myeloma (1997) Hematol Oncol Clin North Am, 11, pp. 147-157Bensinger, W.I., Maloney, D., Storb, R., Allogeneic hematopoietic cell transplantation for multiple myeloma (2001) Semin Hematol, 38, pp. 243-249Bjorkstrand BB, Ljungman P, Svensson H, et al. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 1996;88:4.711-8Arora M, McGlave PB, Burns LJ, et al. Results of autologous and allogeneic hematopoietic cell transplant therapy for multiple myeloma. Bone Marrow Transplant 2005;35:1.133-40Bellucci R, Alyea EP, Weller E, et al. Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma. Blood 2002;99:4.610-7Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LL, Verdonck LF. Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997;90:4.206-11Alyea, E., Weller, E., Schlossman, R., T-cell - depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: Induction of graft-versus-myeloma effect (2001) Blood, 98, pp. 934-939Collins Jr., R.H., Shpilberg, O., Drobyski, W.R., Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation (1997) J Clin Oncol, 15, pp. 433-444Majolino, I., Corradini, P., Scime, R., High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors (2003) Bone Marrow Transplant, 31, pp. 767-773Blade J, Vesole DH, Gertz M. High-dose therapy in multiple myeloma. Blood 2003;102:3.469-70Giralt, S., Thall, P.F., Khouri, I., Melphalan and purine analog-containing preparative regimens: Reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation (2001) Blood, 97, pp. 631-637Badros A, Barlogie B, Morris C, et al. High response rate in refractory and poor-risk multiple myeloma after allo transplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood 2001;97:2.574-9Badros A, Barlogie B, Siegel E, et al. Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning. J Clin Oncol 200220:1.295-303Lee, C.K., Badros, A., Barlogie, B., Prognostic factors in allogeneic transplantation for patients with high-risk multiple myeloma after reduced intensity conditioning (2003) Exp Hematol, 31, pp. 73-80Barlogie, B., Shaughnessy, J., Tricot, G., Treatment of multiple myeloma (2004) Blood, 103, pp. 20-32Giralt, S., Aleman, A., Anagnostopoulos, A., Fludarabine/ melphalan conditioning for allogeneic transplantation in patients with multiple myeloma (2002) Bone Marrow Transplant, 30, pp. 367-373Einsele, H., Schafer, H.J., Hebart, H., Follow-up of patients with progressive multiple myeloma undergoing allografts after reduced-intensity conditioning (2003) Br J Haematol, 121, pp. 411-418Crawley C, Lalancette M, Szydlo R, et al. Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. Blood 2005;105:4.532-9Kroger N, Sayer HG, Schwerdtfeger R, et al. Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality. Blood 2002;100:3.919-24Maloney, D.G., Molina, A.J., Sahebi, F., Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma (2003) Blood, 102, pp. 3447-3454Kroger, N., Schwerdtfeger, R., Kiehl, M., Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma (2002) Blood, 100, pp. 755-760Hari, P., Pasquini, M.C., Vesole, D.H., Cure of multiple myeloma - more hype, less reality (2006) Bone Marrow Transplant, 37, pp. 1-18Kroger N, Schilling G, Einsele H, et al. Deletion of chromosome band 13q14 as detected by fluorescence in situ hybridization is a prognostic factor in patients with multiple myeloma who are receiving allogeneic dose-reduced stem cell transplantation. Blood 2004;103:4.056-61Garban F, Attal M, Michallet M, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood 2006;107:3.474-80Badros A, Barlogie B, Morris C, et al. High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood 2001;97:2.574-9Perez-Simon, J.A., Martino, R., Alegre, A., Chronic but not acute graft-versus-host disease improves outcome in multiple myeloma patients after non-myeloablative allogeneic transplantation (2003) Br J Haematol, 121, pp. 104-108Peggs KS, Thomson K, Hart DP, et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. Blood 2004;103:1.548-56Vesole DH. Transplantation for multiple myeloma: who, when, how often? Patient selection and goals. Blood 2003;102:3.471-2Smith, A., Wisloff, F., Samson, D., Guidelines on the diagnosis and management of multiple myeloma 2005 (2006) Br J Haematol, 132, pp. 410-45

The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1%) were males and 454 (39.9%) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8%) candidates had full match donors; 352/1138 (30.8%) were eligible for alloBMT. Only 235 of 352 (66.7%) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%); monthly family income ranged from US$60 (7$400 (36%). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil

Importance Of Killer Immunoglobulin-like Receptors In Allogeneic Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA) compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients) can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.332126130Moretta, A., Marcenaro, E., Parolini, S., Ferlazzo, G., Moretta, L., NK cells at the interface between innate and adaptive immunity (2008) Cell Death Differ, 15 (2), pp. 226-233Andoniou, C.E., Andrews, D.M., Degli-Esposti, M.A., Natural killer cells in viral infection: More than just killers (2006) Immunol Rev, 214, pp. 239-250Gardiner, C.M., Killer cell immunoglobulin-like receptors on NK cells: The how, where and why (2008) Int J Immunogenet, 35 (1), pp. 1-8Rajagopalan, S., Long, E.O., Understanding how combinations of HLA and KIR genes influence disease (2005) J Exp Med, 201 (7), pp. 1025-1029McVicar, D.W., Burshtyn, D.N., Intracellular signaling the killer immunoglobulin-like receptors and Ly49 (2001) Sci STKE, (75). , re1Rajagopalan, S., Long, E.O., A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells (1999) J Exp Med, 189 (7), pp. 1093-1100. , Erratum in: J Exp Med 2000;191(11): following 2027O'Connor, G.M., Hart, O.M., Gardiner, C.M., Putting the natural killer cell in its place (2006) Immunology, 117 (1), pp. 1-10Boyton, R.J., Altmann, D.M., Natural killer cells, killer immunoglobulinlike receptors and human leukocyte antigen class I in disease (2007) Clin Exp Immunol, 149 (1), pp. 1-8Katz, G., Markel, G., Mizrahi, S., Arnon, T.I., Mandelboim, O., Recognition of HLA-Cw4 but not HLA-Cw6 by the NK cell receptor killer cell Ig-like receptor two-domain short tail number 4 (2001) J Immunol, 166 (12), pp. 7260-7267Laguila, V.J.E., Lieber, S.R., Lopes, P.L.B., Dutra, M.S.B., Vigorito, A.C., Penteado, A.F.J., Relationship between cytokine gene polymorphisms and graft-versus-host disease after allogeneic stem cell transplantation in a Brazilian population (2005) Cytokine, 32 (3-4), pp. 171-177Viel, D.O., Tsuneto, L.T., Sossai, C.R., Lieber, S.R., Marques, S.B., Vigorito, A.C., IL2 and TNFA gene polymorphisms and the risk of graft versus host disease after allogeneic stem cell transplantation (2007) Scand J Immunol, 66 (6), pp. 703-710Vizoni, S.L., Lieber, S.R., de Souza, C.A., Sell, A.M., Visentainer, J.E., Papel das citocinas na imunopatogênese da doença do enxerto contra o hospedeiro (2008) Rev Bras Hematol Hemoter, 30 (2), pp. 142-152Koh, L.P., Rizzieri, D.A., Chao, N.J., Allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors (2007) Biol Blood Marrow Transplant, 13 (11), pp. 1249-1267Kärre, K., Immunology. A perfect mismatch (2002) Science, 295 (5562), pp. 2029-2031. , Comment on: Science. 2002;295(5562):2097-100Science. 2002;295(5562):2094-7Ruggeri, L., Capanni, M., Casucci, M., Volpi, I., Tosti, A., Perruccio, K., Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation (1999) Blood, 94 (1), pp. 333-339Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W.D., Tosti, A., Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants (2002) Science, 295 (5562), pp. 2097-2100. , Comment in: Science. 2002;295 (5562):2029-31Bishara, A., de Santis, D., Witt, C.C., Brautbar, C., Christiansen, F.T., Or, R., The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreative T cells causing GVHD (2004) Tissue Antigens, 63 (3), pp. 204-211Miller, J.S., Soignier, Y., Panoskaltsis-Mortari, A., McNearney, S.A., Yun, G.H., Fautsch, S.K., Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer (2005) Blood, 105 (8), pp. 3051-3057Keller, M.D., Chen, D.F., Condron, S.A., Liu, N., Reinsmoen, N.L., Buckey, R.H., The effect of natural killer cell killer Ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID) (2007) J Clin Immunol, 27 (1), pp. 109-116. , Erratum in: J Clin Immunol. 2007;27(6):659Ruggeri, L., Mancusi, A., Capanni, M., Urbani, E., Carotti, A., Aloisi, T., Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: Challenging its predictive value (2007) Blood, 110 (1), pp. 433-440Ruggeri, L., Aversa, F., Martelli, M.F., Velardi, A., Allogeneic hematopoietic transplantation and natural killer cell recognition of missing self (2006) Immunol Rev, 214, pp. 202-218Cook, M.A., Milligan, D.W., Fegan, C.D., Darbyshire, P.J., Mahendra, P., Craddock, C.F., The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia (2004) Blood, 103 (4), pp. 1521-1526Witt, C.S., Christiansen, F.T., The relevance of natural killer cell human leukocyte antigen epitopes and killer cell immunoglobulinlike receptors in bone marrow transplantation (2006) Vox Sang, 90 (1), pp. 10-20Hsu, K.C., Keever-Taylor, C.A., Wilton, A., Pinto, C., Heller, G., Arkun, K., Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes (2005) Blood, 105 (12), pp. 4878-4884Schellekens, J., Rozemuller, E.H., Petersen, E.J., van den Tweel, J.G., Verdonck, L.F., Tilanus, M.G., Activating KIRs exert a crucial role on relapse and overall survival after HLA-identical sibling transplantation (2008) Mol Immunol, 45 (8), pp. 2255-2261(2011) Registro Nacional De Doadores De Medula Óssea (REDOME), , http://www.inca.gov.br/conteudo_view.asp?ID=677, Instituto Nacional de Câncer, Brasília: INCA, [cited 2011 Jan 12]. Available fromDavies, S.M., Ruggieri, L., Defor, T., Wagner, J.E., Weisdorf, D.J., Miller, J.S., Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants (2002) Blood, 100 (10), pp. 3825-3827Giebel, S., Locatelli, F., Lamparelli, T., Velardi, A., Davies, S., Frumento, G., Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors (2003) Blood, 102 (3), pp. 814-819Bornhauser, M., Schwerdtfeger, R., Martin, H., Frank, K.H., Theuser, C., Ehninger, G., Role of KIR ligand incompatibility in hematopoietic stem cell transplantation using unrelated donors (2004) Blood, 103 (7), pp. 2860-2861. , author reply 2862. Comment on: Blood. 2003102(3):814-9Beelen, D.W., Ottinger, H.D., Ferencik, S., Elmaagacli, A.H., Peceny, R., Trenschel, R., Genotypic inhibitory killer immunoglobulinlike receptor ligand incompatibility enhances the long term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias (2005) Blood, 105 (6), pp. 2594-2600de Santis, D., Bishara, A., Witt, C.S., Nagler, A., Brautbar, C., Slavin, S., Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants (2005) Tissue Antigens, 65 (6), pp. 519-528Hsu, K.C., Gooley, T., Malkki, M., Pinto-Agnello, C., Dupont, B., Bignon, J.D., Bornhäuser, M., Petersdorf, E., International Histocompatibility Working Group. KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy (2006) Biol Blood Marrow Transplant, 12 (8), pp. 828-836Farag, S.S., Bacigalupo, A., Eapen, M., Hurley, C., Dupont, B., Caligiuri, M.A., Boudreau, C., Davies, S.M., KIR Study Group, Center for International Blood and Marrow Transplantation Research. The effect of KIR ligand incompatibility on the outcome of unrelated donor transplantation: A report from the center for international blood and marrow transplant research, the European blood and marrow transplant registry, and Dutch registry (2006) Biol Blood Marrow Transplant, 12 (8), pp. 876-884Giebel, S., Nowak, I., Wojnar, J., Markiewicz, M., Dziaczkowska, J., Wylezol, I., Impact of activating killer immunoglobulin-like receptor genotype on outcome of unrelated donor-hematopoietic cell transplantation (2006) Transplant Proc, 38 (1), pp. 287-291Han, M., Fallena, M., Guo, Y., Stastny, P., Natural killer cell crossmatch: Functional analysis of inhibitory killer immunoglobulin-like receptors and their HLA ligands (2007) Hum Immunol, 68 (6), pp. 507-51

The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1%) were males and 454 (39.9%) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8%) candidates had full match donors; 352/1138 (30.8%) were eligible for alloBMT. Only 235 of 352 (66.7%) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%); monthly family income ranged from US$60 (7$400 (36%). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil