Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS)

Blood - Tập 109 - Trang 1395-1400 - 2007
Elihu Estey1, Marcos de Lima2, Raoul Tibes1, Sherry Pierce1, Hagop Kantarjian1, Richard Champlin2, Sergio Giralt2
1Departments of Leukemia,
2Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Tóm tắt

Abstract To prospectively assess the applicability of reduced-intensity conditioning hematopoietic stem cell transplantation (RIC-HSCT), we wrote a protocol in which all untreated patients 50 years or older with acute myeloid leukemia (AML) and unfavorable cytogenetics would be evaluated during induction for a possible RIC-HSCT in first complete remission (CR1). Ninety-nine of 259 patients entered CR. Fifty-three of the 99 were seen by the Transplant Service with the remainder not seen because of illness, lack/unavailability of siblings, refusal, or, primarily, unclear reasons (21 patients). A donor was identified for 26 patients (21 sibling, 5 unrelated) with RIC-HSCT performed in 14 (13 sibling). Results in consulted patients suggested that 50% or fewer of the 85 patients who did not undergo transplantation were potential transplant candidates. We attempted to find one or more chemotherapy pair-mates for each patient who underwent transplantation based on cytogenetics, age, and a relapse-free survival (RFS) time that was more than or equal to the time from CR1 to RIC-HSCT in the patient who underwent transplantation. Thirty-two of the 39 matches favored (longer RFS) RIC-HSCT and 7, chemotherapy. The probability that the corresponding beta distribution was different than expected (ie, that RIC-HSCT was superior) was 0.99 (P = .004). Results were similar with respect to survival. While RIC-HSCT thus seems of interest, methods are needed to extend its applicability.

Tài liệu tham khảo

Mrozek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev2004; 18:115–136. Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood2001; 98:1312–1320. Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood2000; 96:4075–4083. Burnett AK, Wheatley K, Goldstone AH, et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol2002; 118:385–400. Cassileth PA, Harrington DP, Appelbaum FR, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med1998; 339:1649–1656. Keating S, de Witte T, Suciu S, et al. The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA: European Organization for Research and Treatment of Cancer: Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Br J Haematol1998; 102:1344–1353. Suciu S, Mandelli F, de Witte T, et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood2003; 102:1232–1240. Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia: European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med1995; 332:217–223. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood1997; 89:4531–4536. de Lima M, Anagnostopoulos A, Munsell M, et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood2004; 104:865–872. Wong R, Giralt SA, Martin T, et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood2003; 102:3052–3059. Shimoni A, Kroger N, Zabelina T, et al. Hematopoietic stem-cell transplantation from unrelated donors in elderly patients (age >55 years) with hematologic malignancies: older age is no longer a contraindication when using reduced intensity conditioning. Leukemia2005; 19:7–12. Niederwieser DW, Hegenbert U, Sandmaier BM, et al. Treatment for acute myelogenous leukemia by low dose irradiation based conditioning and hematopoietic cell transplantation from related and unrelated donors [abstract]. Blood2004; 104:840a. Sayer HG, Kroger M, Beyer J, et al. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor. Bone Marrow Transplant2003; 31:1089–1095. Ho A, Pagliuca A, Kenyon M, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood2004; 104:1616–1623. Diaconescu R, Flowers CR, Storer B, et al. Morbidity and mortality with nonmyeloablative compared to myeloablative conditioning before hematopoietic cell transplantation from HLA matched donors. Blood2004; 104:1550–1558. Valcarcel D, Martino R, Sureda A, et al. Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematologic malignancies. Eur J Haematol2005; 74:144–151. Sorror ML, Maris MB, Stover B, et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplant comorbidities. Blood2004; 104:961–968. Berry D. Densities for proportions. Statistics: a Bayesian Perspective1996;Belmont CA Wadsworth Publishing Company pp. 200–205. Mohty M, de Lavallade H, Ladaique P, et al. The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs. no donor comparison. Leukemia2005; 19:916–920. Gray R and Wheatley K. How to avoid bias when comparing bone marrow transplantation with chemotherapy. Bone Marrow Transplant1991; 7:suppl 3, 9–12. Goldstone A, Burnett A, Wheatley K, et al. Attempts to improve treatment outcomes in acute myeloid leukemia in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood2001; 98:1302–1311. Estey E and Thall P. New designs for phase 2 clinical trials. Blood2003; 102:442–448. Schmid C, Schleuning M, Schwerdtfeger R, et al. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood2006; 108:1092–1099. Estey E, Wang X-M, Tahll P, et al. Plausibility of delaying induction therapy in untreated AML [abstract]. Blood2004; 104:251a Abstract 879.
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Blood

Tập 109

1395-1400

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