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Molecular and Clinical Remissions in Multiple Myeloma: Role of Autologous and Allogeneic Transplantation of Hematopoietic Cells

From the Dipartimento di Medicina ed Oncologia Sperimentale, Azienda Ospedaliera San Giovanni Battista-Divisione Universitaria di Ematologia, Torino; Divisione di Ematologia II, Ospedale San Martino, Genova; Unità Trapianto Midollo Osseo, Ospedale Cervello Palermo; and Divisione Universitaria di Ematologia, Palermo, Italy.

Address reprint requests to Paolo Corradini, MD, BMT Unit, Istituto Scientifico H.S. Raffaele, Via Olgettina 60, 20132 Milan, Italy; Email paolo.corradini{at}hsr.it

PURPOSE: To describe molecular monitoring of minimal residual disease in patients with myeloma who have achieved complete remission (CR) after autologous or allogeneic transplantation of hematopoietic cells.

MATERIALS AND METHODS: Clonal markers based upon the rearrangement of immunoglobulin heavy-chain genes were generated for each patient and used for polymerase chain reaction (PCR) detection of residual myeloma cells. Fifty-one patients entered the program and 36 achieved CR. After transplantation, molecular monitoring was performed on 29 patients (15 autologous and 14 allogeneic transplants) who had molecular markers.

RESULTS: Our data show that molecular remissions are rarely achieved (7%) with high-dose chemotherapy followed by single or double autografting. In addition, virtually all peripheral blood progenitor cell and bone marrow samples contained residual myeloma cells, even when sample collection was scheduled after repeated courses of high-dose chemotherapy. All patients autografted with PCR-positive cells remain positive, and eight of 15 have relapsed. Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive group and one in the PCR-negative group.

CONCLUSION: This is the first large study of molecular remissions in myeloma patients to use a PCR-based approach utilizing patient-specific tumor markers. The sizeable fraction of patients who achieved molecular remission after allografting with peripheral blood progenitor cells represents a promising finding in an incurable disease.

Present affiliation of Dr. Corradini: Bone Marrow Transplantation Unit, Istituto Scientifico H.S. Raffaele, Milan, Italy.

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