Autologous stem cell transplantation for HIV-infected individuals with relapsed lymphomas: no longer an experimental strategy
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《血液学杂志》
NATIONAL CANCER INSTITUTE, AVIANO, ITALY
High-dose chemotherapy and autologous stem cell transplantation in HIV-infected patients with relapsed lymphomas led to a durable remission with an 85% progression-free survival.
The introduction of highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality of HIV/AIDS with malignancies being the first cause of death. However, HIV-positive patients with relapsed lymphomas have very limited therapeutic options. Autologous stem cell transplantation (ASCT) is the first-choice treatment for HIV-negative patients with relapsed chemosensitive lymphomas. American and European groups, such as ours, have recently explored this approach in HIV patients, and it has been demonstrated that the treatment is feasible and active also in this setting. Previous studies have already shown that it is usually possible to mobilize a sufficient number of stem cells, that HAART can be administrated with high-dose chemotherapy (HDC), and that the rates of infectious complications are similar to the ones occurring in HIV-negative patients when the appropriate prophylaxes are used.1-3
But, up to now, we have little information about the long-term follow-up in these patients, and little is known about the dynamics of immune reconstitution and HIV replication after the ASCT.
Overall survival after ASCT, N = 20. See the complete figure in the article beginning on page 874.
In this issue of Blood, Krishnan and colleagues reported the results of the longest follow-up performed in HIV patients with lymphomas who underwent ASCT. In this series of 20 patients, 17 are still alive and in remission after a median period of observation of 31.8 months. The progression-free survival is 85% and the overall survival (OS) is 85% for the entire group (Figure 1). These results are very impressive and the best reported in literature, but they are affected by a favorable patient selection: 4 patients were in first complete remission (CR). Moreover, the study is not an intention-to-treat analysis as reported by Re et al.3 Therefore, the paper does not completely clarify how many patients with HIV-related lymphomas may really benefit from ASCT.
The authors also demonstrated that the underlying HIV infection did not worsen as a result of the transplantation, and CD4 count returned to baseline within 1 year. This observation is not a surprise; in fact, we have observed that HIV patients with relapsed lymphomas treated with HDC and ASCT with the same program offered to the general population had the same dynamics of immune reconstitution.4 In the Krishnan et al series, the long-term follow-up showed that 10 of 17 patients experienced viral failure and needed HAART changes, nevertheless the CD4 count overcame the baseline level at the second year. All of these observations demonstrated that the iatrogenic immunodepression following ASCT not only does not significantly differ from HIV-negative patients, but it might not enhance HIV progression, if particular attention is taken in the management of HAART and antiretroviral options are still available.
This paper not only confirms the feasibility and the favorable long-term survival of ASCT in HIV patients, but clearly points out that this therapeutic strategy should be offered as a salvage therapy in HIV-related relapsed chemosensitive lymphomas, while it should be considered still experimental for patients in first CR.
References
Gabarre J, Marcelin AG, Azar N, et al. High-dose therapy plus autologous hematopoietic stem cell transplantation for human immunodeficiency virus (HIV)-related lymphoma: results and impact on HIV disease. Haematologica. 2004;89: 1100-1108.
Molina A, Krishnan A, Nademanee A, et al. High-dose therapy and autologous stem cell transplantation for the human immunodeficiency virus-associated non-Hodgkin's lymphoma in the era of highly active antiretroviral therapy. Cancer. 2000;89: 680-689.
Re A, Cattaneo C, Michieli M, et al. High dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for HIV-associated lymphomas in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003;23: 4423-4427.
Simonelli C, Michieli M, Spina M, et al. Immunereconstitution after high dose chemotherapy (HDC) and peripheral blood stem cell transplantation (PBSCT) in HIV+ patients (pts) vs HIV- pts . 8th International Conference on Malignancies in AIDS and Other Immunodeficiencies. April 2004. Abstract 10. Bethesda, MD.(Cecilia Simonelli, and Ma)
High-dose chemotherapy and autologous stem cell transplantation in HIV-infected patients with relapsed lymphomas led to a durable remission with an 85% progression-free survival.
The introduction of highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality of HIV/AIDS with malignancies being the first cause of death. However, HIV-positive patients with relapsed lymphomas have very limited therapeutic options. Autologous stem cell transplantation (ASCT) is the first-choice treatment for HIV-negative patients with relapsed chemosensitive lymphomas. American and European groups, such as ours, have recently explored this approach in HIV patients, and it has been demonstrated that the treatment is feasible and active also in this setting. Previous studies have already shown that it is usually possible to mobilize a sufficient number of stem cells, that HAART can be administrated with high-dose chemotherapy (HDC), and that the rates of infectious complications are similar to the ones occurring in HIV-negative patients when the appropriate prophylaxes are used.1-3
But, up to now, we have little information about the long-term follow-up in these patients, and little is known about the dynamics of immune reconstitution and HIV replication after the ASCT.
Overall survival after ASCT, N = 20. See the complete figure in the article beginning on page 874.
In this issue of Blood, Krishnan and colleagues reported the results of the longest follow-up performed in HIV patients with lymphomas who underwent ASCT. In this series of 20 patients, 17 are still alive and in remission after a median period of observation of 31.8 months. The progression-free survival is 85% and the overall survival (OS) is 85% for the entire group (Figure 1). These results are very impressive and the best reported in literature, but they are affected by a favorable patient selection: 4 patients were in first complete remission (CR). Moreover, the study is not an intention-to-treat analysis as reported by Re et al.3 Therefore, the paper does not completely clarify how many patients with HIV-related lymphomas may really benefit from ASCT.
The authors also demonstrated that the underlying HIV infection did not worsen as a result of the transplantation, and CD4 count returned to baseline within 1 year. This observation is not a surprise; in fact, we have observed that HIV patients with relapsed lymphomas treated with HDC and ASCT with the same program offered to the general population had the same dynamics of immune reconstitution.4 In the Krishnan et al series, the long-term follow-up showed that 10 of 17 patients experienced viral failure and needed HAART changes, nevertheless the CD4 count overcame the baseline level at the second year. All of these observations demonstrated that the iatrogenic immunodepression following ASCT not only does not significantly differ from HIV-negative patients, but it might not enhance HIV progression, if particular attention is taken in the management of HAART and antiretroviral options are still available.
This paper not only confirms the feasibility and the favorable long-term survival of ASCT in HIV patients, but clearly points out that this therapeutic strategy should be offered as a salvage therapy in HIV-related relapsed chemosensitive lymphomas, while it should be considered still experimental for patients in first CR.
References
Gabarre J, Marcelin AG, Azar N, et al. High-dose therapy plus autologous hematopoietic stem cell transplantation for human immunodeficiency virus (HIV)-related lymphoma: results and impact on HIV disease. Haematologica. 2004;89: 1100-1108.
Molina A, Krishnan A, Nademanee A, et al. High-dose therapy and autologous stem cell transplantation for the human immunodeficiency virus-associated non-Hodgkin's lymphoma in the era of highly active antiretroviral therapy. Cancer. 2000;89: 680-689.
Re A, Cattaneo C, Michieli M, et al. High dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for HIV-associated lymphomas in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003;23: 4423-4427.
Simonelli C, Michieli M, Spina M, et al. Immunereconstitution after high dose chemotherapy (HDC) and peripheral blood stem cell transplantation (PBSCT) in HIV+ patients (pts) vs HIV- pts . 8th International Conference on Malignancies in AIDS and Other Immunodeficiencies. April 2004. Abstract 10. Bethesda, MD.(Cecilia Simonelli, and Ma)