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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2213-2214.
Allo attack on amyloidosisMAYO CLINIC
In this issue of Blood, the European Cooperative Group for Blood and Marrow Transplantation reports the largest series of allogeneic transplantation in patients with amyloidosis. This technique is feasible, but should remain investigational in application.
Thirty years ago, melphalan/prednisone was introduced for the treatment of amyloidosis, and prospective randomized studies demonstrated survival benefit. Unfortunately, response rates were in the 15% range, and median survival was only 17 months. Following the demonstration of the activity of dexamethasone in the treatment of myeloma, it was introduced for the treatment of amyloidosis. A large Southwest Oncology Group (SWOG) trial demonstrated that dexamethasone produces both complete hematologic (24%) and organ (45%) responses.
Once autologous transplantation was demonstrated to be feasible and effective in the management of multiple myeloma, it was successfully applied to patients with amyloidosis.1 Stem cell transplantation is not proven superior therapy. The patients eligible for autologous transplantation are selected and are a favorable subgroup of patients by virtue of younger age and better cardiac and renal functions. Autologous transplantation also carries a treatment-related mortality rate from 10% to 40% (see figure). Less toxic alternatives have been reported in the management of amyloidosis. Recently, melphalan combined with dexamethasone2 has been reported to produce 67% hematologic responses. A phase 3 trial has raised serious questions about the value of autologous transplantation and its ability to prolong survival.3 Therefore, the optimal therapy for amyloidosis remains uncertain.
In myeloma, allogeneic transplantation remains the only therapy capable of curing the disease.4 With the introduction of reduced-intensity conditioning, early mortality rates have been halved. In this issue of Blood, a report from Schonland and colleagues on behalf of the European Cooperative Group for Blood and Marrow Transplantation describes 19 patients receiving allogeneic transplants for amyloidosis. The group is heterogeneous since it includes 4 syngeneic, 8 reduced-intensity conditioning, and 7 full-dose allogeneic transplants; 10 were T-cell–depleted grafts. The follow-ups are short, and only 4 patients are currently alive after 36 months. Complete responses were seen in 10 patients. The treatment-related mortality was 40%. As in all registry studies, it suffers from the fact that there are 11 centers reporting on 19 patients. In amyloidosis, the natural history of the disease may vary among centers.5 The patient selection and the total number of patients evaluated at these centers as potential allogeneic transplant recipients cannot be known. Nonetheless, it represents the largest number of patients reported, and it is important for the scientific community to be aware of the feasibility of allogeneic transplant and its potential for graft versus tumor, as 5 of 7 patients with complete remission (CR) had chronic graft-versus-host disease (cGvHD). The data are of insufficient power to justify the use of this technique in clinical practice, and it must remain the subject of scientifically conducted clinical trials. Current protocols are under way with combinations containing lenalidomide or bortezomib. Whether these agents will impact on the decision to administer myeloablative chemotherapy is, as yet, unknown. References
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| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
