Cancer Treatment Today

Standard doxorubicin-based combination chemotherapy, such as CHOP, frequently induces remissions of short duration. In an attempt to obtain durable remissions, high-dose therapy (HDT) with autologous stem-cell support was given in a few centers for patients who were in remission upon CHOP-like induction therapy. In the last decade, several pediatric groups have obtained impressive results for BL- and B-cell acute lymphoblastic leukaemia patients by giving blocks of intensified chemotherapy for five to seven consecutive days with 2- to 3-week interval. Five-year disease-free and overall survival >90% in paediatric patients have been reported. In the German Adult Acute Lymphoblastic Leukaemia (ALL) 05/93 protocol, the BFM-90 protocol was adjusted with dose modifications for adult patients.

There was only one randomized study to my knowledge in aggressive lymphomas that compared standard chemotherapy and ASCT after remission. The long-term outcome for patients with aggressive non-Hodgkin’s lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival. Patients aged 15–65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low–intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results. They concluded that”standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low–intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.”

Since 2000, a number of studies suggested efficacy of ASCT in HIV-related relapsed lymphoma. This includes a French study that reported OS and PFS rates of 30 and 20%, respectively, 3-years post-transplant in 14 HIV-related lymphomas. The largest study to date, involving 68 HIV-related lymphomas, reported that PFS was 56% at a median follow up of 32 months. CR and chemosensitive disease at ASCT were identified as the main favorable prognostic factors for survival, whilst the use of more than two pre-ASCT treatment lines, and failure to achieve CR at transplantation were found at multivariate analysis to be adverse prognostic factors for relapse. On relapse,2017 NCCN recommends a clinical trial, suppotive care or retreatment with high dose chemotherapy and stem cell transplant in selected patients. NCCN recommends transplantation, for relapse. It refers one from  the AIDS Associate Lymphoma page to BCEL-6, where that treatment is listed.

Recent results from a multicenter, phase 2 trial suggest that patients with HIV and aggressive lymphoma should receive autologous stem cell transplant as standard of care. Risk of serious complications after undergoing autologous stem cell transplant in these patients is equal to that of patients who are not HIV infected Recent results from a multicenter, phase 2 trial suggest that patients with HIV and aggressive lymphoma should receive autologous stem cell transplant as standard of care. Risk of serious complications after undergoing autologous stem cell transplant in these patients is equal to that of patients who are not HIV infected

Alvarnas JC, Le Rademacher J, Wang Y, et al. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the (BMT CTN) 0803/(AMC) 071 Trial [published online June 13, 2016]. Blood. doi:10.1182/blood-2015-08-664706.

Betticher, D., Martinelli, G, Radford, J., Kaufmann, M, Dyer, M., Kaiser, U, Aulitzky, W., Beck, J, von Rohr, A, Kovascovics, T, Cogliatti, S., Cina, S, Maibach, R, Cerny, T, Linch, D. (2006). Sequential high dose chemotherapy as initial treatment for aggressive sub-types of Non-Hodgkin Lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol 17: 1546-1552

Stewart, D. A., Bahlis, N., Valentine, K., Balogh, A., Savoie, L., Morris, D. G., Jones, A., Brown, C., Russell, J. A. (2006). Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood 107: 4623-4627

A. Krishnan, A. Molina, J. Zaia, D. Smith, D. Vasquez, N. Kogut, P. M. Falk, J. Rosenthal, J. Alvarnas, and S. J. Forman
Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas
Blood, January 15, 2005; 105(2): 874 – 878.

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 89, 1100–1108 (2004).

Krishnan A, Molina A, Zaia J et al.: Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 105, 874–878 (2005).

Balsalobre P, Diez-Martin JL, Re A et al.: Autologous stem-cell transplantation in patients with HIV-related lymphoma. J. Clin. Oncol. 27, 2192–2198 (2009).

Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2009 Jan 30. 78 p. (Recommendation report; no. 1).  [66 references]

Revised 3/11/2010