TY - JOUR
T1 - Autotransplantation in multiple myeloma
AU - Vesole, D. H.
AU - Jagannath, S.
AU - Glenn, L.
AU - Barlogie, B.
PY - 1993
Y1 - 1993
N2 - More than 500 autologous transplants have been reported in myeloma patients, demonstrating the feasibility of high-dose therapy even in advanced and refractory disease. Once a preparative regimen with superior tumor cytoreduction is identified (using single or double transplantation) and the tolerance of such therapy further improved (e.g., by bone marrow and peripheral blood stem cell with hematopoietic growth factor support), comparative trials will be required to determine whether high-dose therapy early in the disease course is justified by marked prolongation of relapse- free and overall survival. From a safety point of view, low mortality in the 1% to 2% range can be anticipated using high-dose melphalan when hematopoietic stem cell function is preserved. This is the case when prior therapy and exposure to alkylating agents is limited to less than 1 year. Among the available preparative regimens, melphalan at maximum tolerated doses (200 mg/m2) can be administered twice with relatively limited extramedullary toxicity even in heavily pretreated patients. Autologous transplantation, however, should not be used as a last resort for refractory myeloma patients because of limited antitumor effect and hematopoietic stem cell damage sustained by prolonged exposures to alkylating agents. Available data are insufficient to make specific recommendations as to which patients are most likely to benefit from high-dose therapy. As with other malignancies, the greatest benefit is likely to be seen among those patients at lowest risk, who in multiple myeloma still have no prospect of cure. Therefore, ongoing clinical trials evaluating early response consolidation with myeloablative therapy and autologous transplantation are anxiously awaited. Several important trials are currently underway that deserve comment. Our group is testing whether more intensive remission induction with sequential non-cross-resistant chemotherapy utilized prior to tandem autologous transplantation with subsequent interferon maintenance will augment the incidence and duration of complete remissions in previously untreated patients. Consistent with the study objective, there was a progressive increase in the incidence of tumor regression by at least 75% during the successive phases of induction therapy, but complete responses depended upon transplant doses of melphalan, reaching about 20% after the first and 50% after the second transplant. Of note is the low treatment- related mortality and the high study compliance. The current Royal Marsden study addresses the role of post-transplant interferon therapy in a randomized trial; early results favor interferon maintenance. The European Bone Marrow Transplant (EBMT) group together with the European Organization for Research and Treatment of Cancer (EORTC) has launched a trial of melphalan 140 mg/m2 and TBI 800 cGy for remission consolidation after VMCP- VBAP to be compared with standard-dose chemotherapy. As additional autologous transplantation trials get underway, the overall benefit of autologous bone marrow transplantation in relationship to standard dose therapies has to be addressed in comparative trials, which are already in the planning or early accrual stage. In relationship to allogeneic transplants, autologous transplants offer several advantages, including their applicability to patients up to the age of 70, low mortality (less than 5%), and relatively short hospitalization, even to the point of outpatient treatment, resulting in significant cost reduction. By comparison, allogeneic transplants can be offered to about 10% of autologous transplant candidates. To date, fewer than 200 allogeneic transplants have been undertaken; complete remissions have been reported in approximately 30% to 40% of patients, usually observed in those patients with less prior therapy and in remission at the time of transplantation. Although the post-transplant morbidity and mortality are quite high, this approach may provide true cures in younger patients with good prognostic factors. As with other hematologic malignancies, the question of 'graft-versus-myeloma' effect may be important, especially when considering myeloma as a malignancy involving an early hematopoietic stem cell. The potential of cyclosporine to induce self-limited autologous graft- versus-host disease deserves clinical investigation in multiple myeloma.
AB - More than 500 autologous transplants have been reported in myeloma patients, demonstrating the feasibility of high-dose therapy even in advanced and refractory disease. Once a preparative regimen with superior tumor cytoreduction is identified (using single or double transplantation) and the tolerance of such therapy further improved (e.g., by bone marrow and peripheral blood stem cell with hematopoietic growth factor support), comparative trials will be required to determine whether high-dose therapy early in the disease course is justified by marked prolongation of relapse- free and overall survival. From a safety point of view, low mortality in the 1% to 2% range can be anticipated using high-dose melphalan when hematopoietic stem cell function is preserved. This is the case when prior therapy and exposure to alkylating agents is limited to less than 1 year. Among the available preparative regimens, melphalan at maximum tolerated doses (200 mg/m2) can be administered twice with relatively limited extramedullary toxicity even in heavily pretreated patients. Autologous transplantation, however, should not be used as a last resort for refractory myeloma patients because of limited antitumor effect and hematopoietic stem cell damage sustained by prolonged exposures to alkylating agents. Available data are insufficient to make specific recommendations as to which patients are most likely to benefit from high-dose therapy. As with other malignancies, the greatest benefit is likely to be seen among those patients at lowest risk, who in multiple myeloma still have no prospect of cure. Therefore, ongoing clinical trials evaluating early response consolidation with myeloablative therapy and autologous transplantation are anxiously awaited. Several important trials are currently underway that deserve comment. Our group is testing whether more intensive remission induction with sequential non-cross-resistant chemotherapy utilized prior to tandem autologous transplantation with subsequent interferon maintenance will augment the incidence and duration of complete remissions in previously untreated patients. Consistent with the study objective, there was a progressive increase in the incidence of tumor regression by at least 75% during the successive phases of induction therapy, but complete responses depended upon transplant doses of melphalan, reaching about 20% after the first and 50% after the second transplant. Of note is the low treatment- related mortality and the high study compliance. The current Royal Marsden study addresses the role of post-transplant interferon therapy in a randomized trial; early results favor interferon maintenance. The European Bone Marrow Transplant (EBMT) group together with the European Organization for Research and Treatment of Cancer (EORTC) has launched a trial of melphalan 140 mg/m2 and TBI 800 cGy for remission consolidation after VMCP- VBAP to be compared with standard-dose chemotherapy. As additional autologous transplantation trials get underway, the overall benefit of autologous bone marrow transplantation in relationship to standard dose therapies has to be addressed in comparative trials, which are already in the planning or early accrual stage. In relationship to allogeneic transplants, autologous transplants offer several advantages, including their applicability to patients up to the age of 70, low mortality (less than 5%), and relatively short hospitalization, even to the point of outpatient treatment, resulting in significant cost reduction. By comparison, allogeneic transplants can be offered to about 10% of autologous transplant candidates. To date, fewer than 200 allogeneic transplants have been undertaken; complete remissions have been reported in approximately 30% to 40% of patients, usually observed in those patients with less prior therapy and in remission at the time of transplantation. Although the post-transplant morbidity and mortality are quite high, this approach may provide true cures in younger patients with good prognostic factors. As with other hematologic malignancies, the question of 'graft-versus-myeloma' effect may be important, especially when considering myeloma as a malignancy involving an early hematopoietic stem cell. The potential of cyclosporine to induce self-limited autologous graft- versus-host disease deserves clinical investigation in multiple myeloma.
UR - http://www.scopus.com/inward/record.url?scp=0027256008&partnerID=8YFLogxK
U2 - 10.1016/s0889-8588(18)30234-x
DO - 10.1016/s0889-8588(18)30234-x
M3 - Article
C2 - 8102136
AN - SCOPUS:0027256008
SN - 0889-8588
VL - 7
SP - 613
EP - 630
JO - Hematology/Oncology Clinics of North America
JF - Hematology/Oncology Clinics of North America
IS - 3
ER -