Tandem Bone Marrow Transplantation in Multiple Myeloma
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Attal et al. (Dec. 25 issue)1 report that double autologous stem-cell transplantation improves overall survival among patients with multiple myeloma, especially those who do not have a very good partial response after a first transplantation. However, these results are potentially misleading, for several reasons: the intention-to-treat analysis showed no difference in overall survival between the two groups; the study end point was not the survival rate, but the rate of complete response; the intervals between the diagnosis and the first transplantation and between the first and second transplantations varied; the different conditioning regimen used after the first transplantation may have biased the selection of patients with a good response or a poor response after the first transplantation; and patients who had a poor response may have received more intense salvage treatments than those with a good response and for this reason may have had improved overall survival.
Naoko Murashige, M.D.
Yukiko Kishi, M.D.
National Cancer Center Hospital
Tokyo 104-0045, Japan
nmurashi@ncc.go.jp
References
Attal M, Harousseau J-L, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003;349:2495-2502.
To the Editor: Attal et al. report the results of a randomized study in which they found significant improvements in relapse-free and overall survival in patients with multiple myeloma after double, as compared with single, autologous stem-cell transplantation. In contrast, they found similar response rates in the two treatment groups in an intention-to-treat analysis. It is also interesting that the response rate was so different between the two groups after the first transplantation (48 percent vs. 26 percent, in favor of single transplantation), when the only difference in treatment was the addition of total-body irradiation in the single-transplantation group. This may suggest some biologic differences between the two groups. Although the groups seemed well matched, no cytogenetic information is reported. Recent studies have shown that certain genetic abnormalities confer a poor prognosis, even in patients who undergo high-dose therapy and autologous transplantation.1,2 I wonder whether differences in the cytogenetic characteristics of the two cohorts account for the difference in survival or explain why the difference in survival was seen only after five years.
Wee J. Chng, M.D.
National University Hospital
Singapore 119074, Singapore
chngwj@nuh.com.sg
References
Facon T, Avet-Loiseau H, Guillerm G, et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta 2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001;97:1566-1571.
Shaughnessy J, Jacobson J, Sawyer J, et al. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression. Blood 2003;101:3849-3856.
To the Editor: In the study conducted by Attal et al., salvage treatments for patients with myeloma who had a relapse after single or double autologous stem-cell transplantation included no therapy, "conventional" chemotherapy, another transplantation, and treatment with thalidomide. It would be of great interest to know whether and how these different approaches affected the clinical outcome. In our experience,1 for instance, the overall survival of 24 patients who had a first relapse after autologous peripheral-blood stem-cell transplantation and who were treated with a combination of thalidomide, dexamethasone, and zoledronate was similar to that in an analogous group of patients who received a new transplant but was significantly better than that of historical controls who were treated with other therapies.
Salvage treatments represent an important aspect of the global therapeutic strategy for patients with multiple myeloma, particularly when relapse occurs after autologous transplantation, considering that this procedure currently represents the front-line therapy of choice for most patients younger than 65 years of age.2 Knowing what strategy may offer the best second chance is mandatory, especially in the care of patients who cannot undergo another transplantation.
Pellegrino Musto, M.D.
Casa Sollievo della Sofferenza
71013 S. Giovanni Rotondo, Italy
p.musto@tin.it
References
Musto P, Bodenizza C, Falcone A, et al. Treatment of myeloma patients relapsed after frontline autologous stem cell transplantation with the association of thalidomide, dexamethasone and zoledronate. Blood 2003;102:382b-382b. abstract.
Stadtmauer EA. Multiple myeloma 2004 -- one or two transplants? N Engl J Med 2003;349:2551-2553.
The author replies: Drs. Murashige and Kishi contend that our results are potentially misleading. However, it is important to note that the intention-to-treat analysis showed that double transplantation conferred a significant survival advantage. In addition, the multivariate analysis of factors influencing the outcome among patients surviving for three months after a first transplantation showed that age, the treatment group, and the degree of response within three months after the first transplantation were the only significant factors, whereas the intervals between the diagnosis and the first transplantation and between the first and second transplantations did not appear to have a significant effect. Finally, the probability of survival after relapse was similar in the two treatment groups, and the nature of the salvage therapy was not found to be related to the magnitude of the initial response.
Dr. Chng correctly points out that the response rate was 48 percent after transplantation preceded by conditioning with melphalan (140 mg per square meter of body-surface area) plus total-body irradiation (8 Gy), as compared with 26 percent after transplantation preceded by conditioning with melphalan alone (140 mg per square meter). Dr. Chng speculates that (despite randomization) some biologic differences between the two cohorts could be responsible for this result. Although cytogenetic analysis was not performed in this study, which was initiated in 1994, we do believe that the different response rate is due to the addition of total-body irradiation.
Dr. Musto comments correctly that salvage therapy represents a major aspect of the global therapeutic strategy for myeloma and addresses the crucial issue of the best treatment option for patients who have a relapse after high-dose therapy. We analyzed survival after relapse among patients treated at the time of relapse with conventional chemotherapy, thalidomide, or another transplantation. We confirm that the outcomes for patients treated with thalidomide and those who underwent another transplantation were similar. However, the different treatment groups were not randomized. Thus we believe that this crucial issue should be addressed in a prospective, randomized trial.
Michel Attal, M.D.
H?pital Purpan
31059 Toulouse, France
attal.m@chu-toulouse.fr
Naoko Murashige, M.D.
Yukiko Kishi, M.D.
National Cancer Center Hospital
Tokyo 104-0045, Japan
nmurashi@ncc.go.jp
References
Attal M, Harousseau J-L, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003;349:2495-2502.
To the Editor: Attal et al. report the results of a randomized study in which they found significant improvements in relapse-free and overall survival in patients with multiple myeloma after double, as compared with single, autologous stem-cell transplantation. In contrast, they found similar response rates in the two treatment groups in an intention-to-treat analysis. It is also interesting that the response rate was so different between the two groups after the first transplantation (48 percent vs. 26 percent, in favor of single transplantation), when the only difference in treatment was the addition of total-body irradiation in the single-transplantation group. This may suggest some biologic differences between the two groups. Although the groups seemed well matched, no cytogenetic information is reported. Recent studies have shown that certain genetic abnormalities confer a poor prognosis, even in patients who undergo high-dose therapy and autologous transplantation.1,2 I wonder whether differences in the cytogenetic characteristics of the two cohorts account for the difference in survival or explain why the difference in survival was seen only after five years.
Wee J. Chng, M.D.
National University Hospital
Singapore 119074, Singapore
chngwj@nuh.com.sg
References
Facon T, Avet-Loiseau H, Guillerm G, et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta 2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001;97:1566-1571.
Shaughnessy J, Jacobson J, Sawyer J, et al. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression. Blood 2003;101:3849-3856.
To the Editor: In the study conducted by Attal et al., salvage treatments for patients with myeloma who had a relapse after single or double autologous stem-cell transplantation included no therapy, "conventional" chemotherapy, another transplantation, and treatment with thalidomide. It would be of great interest to know whether and how these different approaches affected the clinical outcome. In our experience,1 for instance, the overall survival of 24 patients who had a first relapse after autologous peripheral-blood stem-cell transplantation and who were treated with a combination of thalidomide, dexamethasone, and zoledronate was similar to that in an analogous group of patients who received a new transplant but was significantly better than that of historical controls who were treated with other therapies.
Salvage treatments represent an important aspect of the global therapeutic strategy for patients with multiple myeloma, particularly when relapse occurs after autologous transplantation, considering that this procedure currently represents the front-line therapy of choice for most patients younger than 65 years of age.2 Knowing what strategy may offer the best second chance is mandatory, especially in the care of patients who cannot undergo another transplantation.
Pellegrino Musto, M.D.
Casa Sollievo della Sofferenza
71013 S. Giovanni Rotondo, Italy
p.musto@tin.it
References
Musto P, Bodenizza C, Falcone A, et al. Treatment of myeloma patients relapsed after frontline autologous stem cell transplantation with the association of thalidomide, dexamethasone and zoledronate. Blood 2003;102:382b-382b. abstract.
Stadtmauer EA. Multiple myeloma 2004 -- one or two transplants? N Engl J Med 2003;349:2551-2553.
The author replies: Drs. Murashige and Kishi contend that our results are potentially misleading. However, it is important to note that the intention-to-treat analysis showed that double transplantation conferred a significant survival advantage. In addition, the multivariate analysis of factors influencing the outcome among patients surviving for three months after a first transplantation showed that age, the treatment group, and the degree of response within three months after the first transplantation were the only significant factors, whereas the intervals between the diagnosis and the first transplantation and between the first and second transplantations did not appear to have a significant effect. Finally, the probability of survival after relapse was similar in the two treatment groups, and the nature of the salvage therapy was not found to be related to the magnitude of the initial response.
Dr. Chng correctly points out that the response rate was 48 percent after transplantation preceded by conditioning with melphalan (140 mg per square meter of body-surface area) plus total-body irradiation (8 Gy), as compared with 26 percent after transplantation preceded by conditioning with melphalan alone (140 mg per square meter). Dr. Chng speculates that (despite randomization) some biologic differences between the two cohorts could be responsible for this result. Although cytogenetic analysis was not performed in this study, which was initiated in 1994, we do believe that the different response rate is due to the addition of total-body irradiation.
Dr. Musto comments correctly that salvage therapy represents a major aspect of the global therapeutic strategy for myeloma and addresses the crucial issue of the best treatment option for patients who have a relapse after high-dose therapy. We analyzed survival after relapse among patients treated at the time of relapse with conventional chemotherapy, thalidomide, or another transplantation. We confirm that the outcomes for patients treated with thalidomide and those who underwent another transplantation were similar. However, the different treatment groups were not randomized. Thus we believe that this crucial issue should be addressed in a prospective, randomized trial.
Michel Attal, M.D.
H?pital Purpan
31059 Toulouse, France
attal.m@chu-toulouse.fr