Autologous or Allogeneic Bone Marrow Transplantation Compared with Intensive Chemotherapy in Acute Myelogenous Leukemia
Robert A. Zittoun, M.D., Franco Mandelli, M.D., Roel Willemze, M.D., Theo de Witte, M.D., Boris Labar, M.D., Luigi Resegotti, M.D., Franco Leoni, M.D., Eugenio Damasio, M.D., Giuseppe Visani, M.D., Giuseppe Papa, M.D., Francesco Caronia, M.D., Marcel Hayat, M.D., Pierre Stryckmans, M.D., Bruno Rotoli, M.D., Pietro Leoni, M.D., Marc E. Peetermans, M.D., Murielle Dardenne, B.S., Maria Luce Vegna, M.D., Maria Concetta Petti, M.D., Gabriel Solbu, M.S., Stefan Suciu, M.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
Background Allogeneic or autologous bone marrow transplantationand intensive consolidation chemotherapy are used to treat acutemyelogenous leukemia in a first complete remission.
Methods After induction treatment with daunorubicin and cytarabine,patients who had a complete remission received a first courseof intensive consolidation chemotherapy, combining intermediate-dosecytarabine and amsacrine. Patients with an HLA-identical siblingwere assigned to undergo allogeneic bone marrow transplantation;the others were randomly assigned to undergo autologous bonemarrow transplantation (with unpurged bone marrow) or a secondcourse of intensive chemotherapy, combining high-dose cytarabineand daunorubicin. Comparisons were made on the basis of theintention to treat.
Results A total of 623 patients had a complete remission; 168were assigned to undergo allogeneic bone marrow transplantation,and 254 were randomly assigned to one of the other two groups.Of these patients, 343 completed the treatment assignment: 144in the allogeneic-transplantation group, 95 in the autologous-transplantationgroup, and 104 in the intensive-chemotherapy group. The relapserate was highest in the intensive-chemotherapy group and lowestin the allogeneic-transplantation group, whereas the mortalityrate was highest after allogeneic transplantation and lowestafter intensive chemotherapy. The projected rate of disease-freesurvival at four years was 55 percent for allogeneic transplantation,48 percent for autologous transplantation, and 30 percent forintensive chemotherapy. However, the overall survival aftercomplete remission was similar in the three groups, since morepatients who relapsed after a second course of intensive chemotherapyhad a response to subsequent autologous bone marrow transplantation.Other differences were also observed, especially with regardto hematopoietic recovery (it occurred later after autologoustransplantation) and the duration of hospitalization (it waslonger with bone marrow transplantation).
Conclusions During first complete remission in acute myelogenousleukemia, autologous as well as allogeneic bone marrow transplantationresults in better disease-free survival than intensive consolidationchemotherapy with high-dose cytarabine and daunorubicin. Transplantationsoon after a relapse or during a second complete remission mightalso be appropriate.
Source Information
From the Departments of Hematology of Hôtel-Dieu, Paris (R.A.Z.); Università La Sapienza, Rome (F.M., M.L.V., M.C.P.); Leiden University, Leiden, the Netherlands (R.W.); St. Radboud Hospital, Nijmegen, the Netherlands (T.W.); Hospital Rebro, Zagreb, Croatia (B.L.); Ospedale Maggiore S.G. Battista, Turin, Italy (L.R.); Università di Firenze, Florence, Italy (F.L.); Ospedale San Martino, Genoa, Italy (E.D.); Istituto L.A. Seragnoli, Università di Bologna, Bologna, Italy (G.V.); Università Tor Vergata, Rome (G.P.); Ospedale Cervello, Palermo, Italy (F.C.); Institut Gustave Roussy, Villejuif, France (M.H.); Institut Jules Bordet, Brussels, Belgium (P.S.); II Università di Napoli, Naples, Italy (B.R.); Università di Ancona, Ancona, Italy (P.L.); University of Antwerp, Antwerp, Belgium (M.E.P.); and the EORTC Data Center, Brussels, Belgium (M.D., G.S., S.S.). Presented in part at the 35th annual meeting of the American Society of Hematology, St. Louis, December 3–7, 1993.
Address reprint requests to Dr. Zittoun at Hôtel-Dieu, 1, Place du Parvis Notre Dame, 75181 Paris Cedex 04, France.
Treatment of Acute Myeloid Leukemia
Kanda Y., Miwa A., Togawa A., Perez-Calvo J., Brugarolas A., Suzuki R., Seto M., Morishima Y., Gorin N.-C., Labopin M., Woods W. G., Sanders J. E., Neudorf S., Cassileth P. A., Appelbaum F. R., Wiernik P. H., Burnett A. K.
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N Engl J Med 1999;
340:1436-1439, May 6, 1999.
Correspondence
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