Autotransplants in multiple myeloma: Pushing the envelope

S. Jagannath, G. Tricot, B. Barlogie

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19 Scopus citations


Progress in myeloma therapy has been achieved at least through pursuit of the 'more is better' concept, aiming at more marked tumor cytoreduction to increase the incidence of complete remission, including molecular CR, as a first step toward cure. Because high-dose chemotherapy with autotransplants apparently results in a better outcome than with standard chemotherapy, physicians treating myeloma patients should carefully consider treatment options in these patients, trying to avoid standard-dose alkylating therapy and radiotherapy to bone marrow, because it may jeopardize adequate stem cell collection and the safety of subsequent autotransplants. It may also increase the risk of secondary MDS/AML. Local radiotherapy may limit further treatment options with TBI-containing regimens. The demonstration of certain cytogenetic abnormalities conferring poor outcome along with standard variables such as duration of standard therapy, β2-microglobulin, and C-reactive protein prior to the first autotransplant affords a risk-oriented treatment. Because patients with one or more unfavorable prognostic factors have a lower CR rate and tend to relapse earlier after transplantation, it is unlikely that autograft decontamination of tumor cells will be beneficial in these patients. Post- transplantation manipulations directed toward eradication of disease within the patient will be required. One such approach is the administration, upon hematologic recovery after autotransplantation, of further chemotherapy at specified intervals with agents effective against myeloma cells resistant to high-dose melphalan. We have found that DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has excellent antitumor activity in patients relapsing after autotransplants, with approximately 50% of these patients showing at least a 75% reduction in their myeloma protein. Other manipulations are based on immunologic destruction of tumor cells, accomplished by idiotype vaccination or exposure of dendritic cells to the patient-specific idiotype. Another approach is to explore whether chimeric antibodies targeting the myeloma precursor cell and administered after transplantation can eradicate the clonogenic myeloma cells that survive high-dose chemotherapy. Finally, a marked graft-versus-myeloma effect has been demonstrated by the infusion of donor T cells at the time of relapse after allotransplantation. It may be possible to induce a similar graft- versus-myeloma effect by administration of allogeneic peripheral blood cells without performing an actual full allotransplant, with its high inherent transplant-related mortality. Although it is likely with current high-dose regimens with stem cell support that 10% to 20% of patients will have EFS in excess of 10 years, we hope that the previously outlined post-transplant maneuvers will at least double the 10-year EFS, and that within the next decade myeloma will no longer be considered an incurable disease.

Original languageEnglish
Pages (from-to)363-381
Number of pages19
JournalHematology/Oncology Clinics of North America
Issue number2
StatePublished - 1997
Externally publishedYes


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