Long-Term Survival after Autologous Bone Marrow Transplantation for Follicular Lymphoma in First Remission

Abstract

The role of autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma is still being defined in the era of antibody therapy. Here we report the long-term 12-year clinical outcomes of patients treated with autologous bone marrow transplantation (ABMT) for follicular non-Hodgkin's lymphoma (NHL) in first remission. Between 1988 and 1993, advanced-stage follicular NHL patients in need of initial therapy were enrolled in 2 consecutive prospective treatment trials of either standard-dose CHOP induction (83 patients) or high-dose CHOP plus granulocyte-colony stimulating factor (G-CSF) (20 patients). Patients who achieved an adequate remission with induction therapy underwent conditioning with cyclophosphamide and total body irradiation (TBI) followed by ABMT in first remission using bone marrow (BM) purged in vitro with anti-B cell monoclonal antibodies and rabbit complement (96 patients). At 12-year follow-up, 61% of the patients are alive and 43% remain in continuing complete remission. The only predictors of decreased progression-free survival proved to be histologic BM involvement at time of harvest (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.3-3.9, P<.004) and PCR detectable disease in the BM product after purging (HR 4.18, 95% CI 1.99-8.8, P=.0002). No significant predictors of overall survival were identified. These results at 12-year follow-up suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission.

Antibody-mediated B-cell depletion before adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell receptors facilitates eradication of leukemia in immunocompetent mice

“…16,[35][36][37] However, significant toxicities can be associated with global lymphodepletion-conditioning regimens and autologous stem cell transplantation. [38][39][40][41] Our results show that B-cell depletion alone, which produces few toxicities in patients, 42 is sufficient to allow T cells to eliminate a modest established leukemia burden without producing long-term T cell-mediated B-cell lymphopenia. In contrast to global lymphodepletion, 35 B-cell depletion did not induce homeostatic proliferation of T cells, but it did promote modest antigen-specific proliferation that may contribute to the antileukemic response.…”

Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program

“…Most studies showed that MRD negativity is associated with a superior outcome and acts as an independent predictor. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] However, a few studies failed to confirm this observation. [25][26][27][28] In particular, a recent report by van Oers et al 28 failed to demonstrate any benefit of achieving postinduction PCRnegative status.…”

“…[1][2][3] The risk for recurrence is more pronounced among patients older than 60 years, as they often receive less-intense treatments. 4 Considerable evidence indicates that the persistence of polymerase chain reaction (PCR)-detectable residual tumor cells in the bone marrow (BM) and, to a lesser extent, peripheral blood is an independent predictor of relapse in FL [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ; nevertheless, a few studies have failed to confirm this observation. [25][26][27][28] Concerns about the value of minimal residual disease (MRD) detection as an effective prognostic tool have been raised, particularly when applied to The results of this study were the subject of an oral presentation at the 2012 American Society of Hematology annual meeting.…”

The role of autologous and allogeneic stem cell transplantation in the management of indolent B-cell lymphoma

“…65 An institutional review from the Dana-Farber Cancer Institute with a 12-year follow-up of patients undergoing ASCT as consolidation of primary therapy reported a second malignancy incidence of 28%. 66 In these 27 patients, the malignancies included 10 cases of therapy-related myelodysplastic syndrome (T-MDS) or therapy-related acute myeloid leukemia (T-AML), 2 other hematologic malignancies, 9 solid tumors, and 10 nonmelanoma skin cancers. The cumulative incidence of second malignancy in a competing risk model was estimated to be 38% at 15 years.…”