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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0131.
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Blood, 1 August 2002, Vol. 100, No. 3, pp. 755-760
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Autologous stem cell transplantation followed by a dose-reduced
allograft induces high complete remission rate in multiple
myeloma
Nicolaus Kröger,
Rainer Schwerdtfeger,
Michael Kiehl,
Herbert Gottfried Sayer,
Helmut Renges,
Tatjana Zabelina,
Boris Fehse,
Florian Tögel,
Georg Wittkowsky,
Rolf Kuse, and
Axel Rolf Zander
From the Bone Marrow Transplantation, University
Hospital Hamburg, Department of Bone Marrow Transplantation, Wiesbaden
and Idar-Oberstein, Department of Oncology and Hematology University
Jena, and Department of Hematology AK St Georg, Hamburg,
Germany.
We evaluated toxicity, engraftment, chimerism,
graft-versus-host disease (GVHD), and response to a dose-reduced
allograft after cytoreductive autografting in 17 patients with advanced stage II/III multiple myeloma (MM). After autografting with melphalan (200 mg/m2) the patients received after a median interval
of 119 days (range 60-210) a dose-reduced regimen consisting of
fludarabine (180 mg/m2), melphalan (100 mg/m2),
and antithymocyte globulin (3 × 10 mg/kg) followed by allografting from related (n = 7), mismatched related (n = 2), or unrelated (n = 8) donors to induce a graft-versus-myeloma effect. After dose-reduced allografting all patients became neutropenic
(< 0.2 × 109/L) for at least 8 days. All patients
engrafted with a median time for leukocyte
(> 1 × 109/L) and platelet
(> 20 × 109/L) counts of 16 (range, 11-24) and 23 days
(range, 12-43), respectively. Complete donor chimerism was detected
after a median of 30 days (range, 19-38). Acute GVHD stage II occurred
in 4 patients (25%) and grade III GVHD in 2 patients (13%).
Chronic GVHD developed in 40% of the patients, but only 1 patient
experienced extensive chronic GVHD requiring further immunosuppressive
therapy. Two patients died of alveolar hemorrhage and pneumonia,
resulting in a day 100 mortality rate of 11%. The rate of complete
remission with negative immunofixation increased from 18% after
autografting to 73% after allografting. After a median follow-up of 17 months after autologous and 13 months after allogeneic transplantation 13 patients are alive and 12 of them free of relapse or progression. The tandem auto-allotransplant protocol is highly active and provides rapid engraftment with complete donor chimerism and tolerable toxicity.
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