The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial
[en] Variable numbers of CD34(+) cells can be harvested from the blood of AML patients in CR after G-CSF supported mobilization following consolidation chemotherapy. We hypothesized that a decreased ability to mobilize stem cells reflects a chemotherapy-induced reduction in the number of normal and leukemic stem cells. We therefore analyzed whether the mobilizing capacity of these patients was of prognostic significance. 342 AML-patients in first CR received daily G-CSF from day 20 of the consolidation course and underwent 1-6 aphereses to obtain a minimum dose of 2 x 10(6) CD34(+) cells/kg. Afterwards they were randomized for autologous bone marrow (M) or blood SCT. As a surrogate marker for the mobilizing capacity, the highest yield of CD34(+) cells of a single apheresis was adopted. Patients could be categorized into four groups: no harvest (n = 76), low yield (<1 x 10(6) CD34(+)/kg; n = 50), intermediate yield (1-6.9 x 10(6) CD34(+) cells/kg; n = 128) and high yield ( :7 x 106 CD34+ cells/kg; n = 88). The median follow-up was 3.4 years; 163 relapses and 16 deaths in CR were reported. Autologous blood or BM SCT was performed in 36%, 64%, 81% and 88%, respectively, of the patients assigned to the no harvest, low, intermediate and high CD34(+) yield group. The 3-year disease-free survival rate was 46.7%, 65.0%, 50.4% and 26.9% (P= 0.0002) and the relapse incidence was 47.5%, 30.1%, 43.1% and 71.9% (P < 0.0001). Multivariate Cox's proportional hazards model showed that the CD34(+) yield was the most important independent prognostic variable (P = 0.005) after cytogenetics. Patients with the highest mobilizing capacity have a poor prognosis due to an increased relapse incidence.
Disciplines :
Oncology Hematology
Author, co-author :
Keating, S.
Suciu, S.
de Witte, T.
Zittoun, R.
Mandelli, F.
Belhabri, A.
Amadori, S.
Fibbe, W.
Gallo, E.
Fillet, Georges ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie - Oncologie médicale
The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial
Reiffers J, Gaspard MH, Maraninchi D, Michallet M, Marit G, Stoppa AM, Corront B, David B, Gastaut JA, Scotto JJ, Broustet A, Carcassonne Y, Hollard D. Comparison of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukemia in first remission: a prospective controlled trial. Br J Haematol 1989; 72: 57-63.
Reiffers J, Stoppa AM, Attal M, Michallet M, Marit G, Blaise D, Huguet F, Corront B, Cony-Makhoul P, Gastaut JA, Laurent G, Molina L, Broustet A, Maraninchi D, Pris J, Hollard D, Faberes C. Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: the BGMT 87 study. Leukemia 1996; 10: 1874-1882.
Harousseau JL, Cahn JY, Pignon B, Witz F, Milpied N, Delain M, Lioure B, Lamy T, Desablens B, Guilhot F, Caillot D, Abgrall JF, Francois S, Briere J, Guyotat D, Casassus P, Audhuy B, Tellier Z, Hurteloup P, Herve P. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM). Blood 1997; 90: 2978-2986.
Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S. for the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell 'Adulto (GIMEMA) Leukemia Cooperative Groups. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med 1995; 332: 217-223.
Burnett AK, Goldstone AH, Stevens R, Hann IM, Rees JK, Gray RG, Wheatley K. Randomised comparison of addition autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet 1998; 351: 700-708.
Martin C, Torres A, Leon A, Rubio V, Alvarez MA, Herrera C, Jean-Paul E, Correa MA, Rojas R, Campos R, Serrano J, Romero R, Roman J, Guzman JL, Flores R, Falcon M, Martinez F, Gomez P. Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission. Role of intensification therapy in outcome. Bone Marrow Transplant 1998; 21: 375-382.
Kessinger A, Armitage JO, Landmark JD, Smith DM, Weisenburger DD. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. Blood 1988; 71: 723-727.
Schwartzberg L, Birch R, Blanco R, Wittlin F, Muscato J, Tauer K, Hazelton B, West W. Rapid and sustained hematopoietic reconstitution by peripheral blood stem cell infusion alone following high-dose therapy. Bone Marrow Transplant 1993; 11: 369-374.
To LB, Roberts MM, Haylock DN, Dyson PG, Branford AL, Thorp D, Ho JQ, Dart GW, Horvath N, Davy ML, Olweny CLM, Adbi E, Juttner CA. Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant 1992; 9: 277-284.
Henon PhR, Liang H, Beck-Wirth G, Eisenmann JC, Lepers M, Wunder E, Kandel G. Comparison of hematopoietic and immune recovery after autologous bone marrow or blood stem cells transplants. Bone Marrow Transplant 1992; 9: 285-291.
de Witte T, Keating S, Suciu S, Zittoun R, Mandelli F, Amadori F, Resegotti L, Varet B, Belhabri A, Fazi P, Rodts P, Willemze R. A randomized comparison of the value of autologous BMT versus autologous PSCT for patients with AML in first CR in the AML 10 trial of the EORTC LCG and GIMEMA. Blood 2001; 98: Abstr. 3565.
de Witte T, Suciu S, Zittoun R, Resegotti L, Liso V, Willemze R, Belhabri A, Amadori S, Giustolisi R, Labar B, Fioritoni G, Rossi-Ferrini G, Leone G, Jehn U, Keating S, Fazi P, Rodts P, Solbu G, Mandelli F. The type of anthacycline administered during remission induction and consolidation therapy of AML has an impact on feasibility of subsequent autologous or allogeneic transplantation and induced marrow toxicity: Preliminary results of the EORTC/GIMEMA AML-10 randomized trial. Blood 2000; 96: Abstr. 2167.
Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H, Levy R, Hoagland C, Henry P, Gottlieb A, Cornell C, Berenberg J, Hutchison JL, Raich P, Nissen N, Ellison RR, Frelick R, James GW, Falkson G, Silver RT, Haurani F, Green M, Henderson E, Leone L, Holland JF. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 1982; 60: 454-462.
Mitelman F. (ed). An International System for Human Cytogenetic Nomenclature. S. Karger: Basel, 1995.
Klein JP, Moeschberger ML. Survival Analysis: Techniques for Censored and Truncated Data. Statistics for Biology and Health. Springer Verlag: New York, 1997.
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. Blood 1998; 92: 2322-2333.
Slovak ML, Kopecky J, Casseleth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 2000; 15: 4075-4083.
