1. Van Hoef, Marlies MD, PHD, MBA

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Regarding the article in the December 10 issue about autologous and allogeneic transplantation for multiple myeloma: In standard practice allogeneic, stem cell transplants were recommended for high-risk disease or for younger patients with standard-risk disease who are highly motivated and well informed.

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Moreover, allogeneic stem cell transplants in first complete remission should preferably occur in the context of a clinical trial. Autologous transplants were mentioned as being the most reasonable method to consolidate response. The article further addressed the favorable-risk profile of reduced-intensity conditioning compared with ablative-conditioning allogeneic transplantation.


The question arises about what to accomplish by autologous and allogeneic transplantation.


Autologous transplants offer the opportunity to administer more cytotoxic treatment to enhance response rates from partial to very good partial or from the latter to complete remission. The benefit of autologous transplants is in consolidation of complete response rather than in enhancement of partial response. In metastatic breast cancer, no survival benefit was shown by an autologous transplant in partial remission; the reason these studies were not started at the time transplantation for breast cancer was a hot topic.


Allogeneic transplants are intended to eradicate the disease and cure. Ablative allogeneic transplants are more cytotoxic than in reduced-intensity conditioning; an allogeneic transplant is preferably administered in complete remission. An allogeneic transplant administered in incomplete remission has a lower probability for long-term disease-free survival. Disease outcome of allogeneic transplantation in first complete remission is better than in later complete remission.


Upfront treatment by allogeneic transplantation, in particular for stage I and II, is not common. The disease may be indolent and patients can be kept on new treatments for years. However, stage I and II disease, and even smoldering multiple myeloma, is a bone marrow disease, and the opportunity to cure is a successful reduced-intensity conditioning allogeneic transplant or a different strategy to eradicate the disease. Double autologous transplants were recommended.


The article's title ("Allogeneic Transplant Remains Justified for High-Risk Multiple Myeloma") suggests that transplantation for multiple myeloma is under fire. Transplantation for multiple myeloma has a broader context than is presented in the article. However, patient, disease, and transplant-related factors have to be taken into account.


The voice of the patient counts: the eligible patient should be offered the opportunity to be cured upfront versus the prospective of years of treatment and finally progression.


Preferably, induction treatment should be of such strength that optimal response is achieved; autologous transplantation can be used to consolidate, and the reduced-intensity conditioning used to eradicate. The protocol we recommend has a four-step approach that has been designed according to an approach (OT, 9/10/09 issue) used in transplantation to prevent unnecessary treatment. We invite interested investigators to call; meanwhile, we are working on new strategies.