1.
Clinical relevance of MYC/BCL2 expression and cell of origin in patients with diffuse large b-cell lymphoma treated with autologous transplant
Al-Juhaishi, T., Wang, Y., Milton, D. R., Xu-Monette, Z. Y., Jabbour, E., Daher, M., Im, J. S., Bashir, Q., Iyer, S. P., Marin, D., et al
Bone marrow transplantation. 2023
Abstract
Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall survival. On multivariable analysis, DEL/DHL, age >60 years, and >2 prior therapies, but not COO, were important prognostic factors for overall survival. When we explored the interaction of COO and BCL2 expression, patients with germinal center B-cell (GCB)/BCL2 (+) had inferior progression-free survival (PFS) compared to GCB/BCL2 (-) patients (HR, 4.97; Pā=ā0.027). We conclude that the DEL/non-DHL and non-DEL/non-DHL subtypes of DLBCL have similar survival after ASCT. The negative impact of GCB/BCL2 (+) on PFS warrants future trials targeting BCL2 after ASCT. The inferior outcomes in DEL/DHL need to be verified in a larger number of patients.
2.
9-year follow-up of patients with relapsed follicular lymphoma after nonmyeloablative allogeneic stem cell transplant and autologous transplant
Khouri, I. F., Milton, D. R., Gulbis, A. M., Jabbour, E. J., Nastoupil, L., Ledesma, C., Anderlini, P., Bashir, Q., Daher, M., Im, J. S., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021
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Editor's Choice
Abstract
PURPOSE To compare outcomes between patients with relapsed follicular lymphoma (FL) who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT). EXPERIMENTAL DESIGN We evaluated 194 patients with FL who received an alloSCT (n = 98) or autoSCT (n = 96) at MD Anderson Cancer Center. The transplant type used was based on donor availability and by Medicare reimbursement guidelines. AlloSCT patients were enrolled in 4 consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. AutoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan). RESULTS The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for alloSCT patients compared with autoSCT patients (62% vs. 46%; P = .048). Similarly, progression-free survival rates were 52% in alloSCT patients and 31% in autoSCT patients (P < .001), and the 8-year relapse rates were 11% and 43%, respectively (P < .0001). Only 3 patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2-4 acute graft-versus-host disease (GVHD), grade 3-4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Non-relapse mortality was similar between the 2 groups (15% vs. 11% at 8 years; P = .27). CONCLUSIONS This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with FL.
PICO Summary
Population
Patients with follicular lymphoma at a single US centre (n=194)
Intervention
Nonmyeloablative allogeneic stem cell transplant, receiving fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning (alloSCT, n=98)
Comparison
Autologous transplant with R-BEAM conditioning: rituximab, carmustine, etoposide, cytarabine, and melphalan (autoSCT, n=96)
Outcome
The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for alloSCT patients compared with autoSCT patients (62% vs. 46%). Similarly, progression-free survival rates were 52% in alloSCT patients and 31% in autoSCT patients, and the 8-year relapse rates were 11% and 43%, respectively. Only 3 patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2-4 acute graft-versus-host disease (GVHD), grade 3-4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Non-relapse mortality was similar between the 2 groups (15% vs. 11% at 8 years).
3.
Allogeneic Transplantation after Myeloablative Rituximab/BEAM +/- Bortezomib for Patients with Relapsed/Refractory Lymphoid Malignancies: 5-Year Follow-up Results
Chamoun, K., Milton, D. R., Ledesma, C., Young, K. H., Jabbour, E. J., Alatrash, G., Anderlini, P., Bashir, Q., Ciurea, S. O., Marin, D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Editor's Choice
Abstract
Although bortezomib and rituximab have synergistic activity in patients with lymphoma, and can both attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem-cell transplantation (alloSCT). In this phase 1/2 trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 - 1.3 mg/m(2) per dose) was administered intravenously on days -13, -6, -1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results to a historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B-cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and unrelated matched donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m(2). The weighted cumulative incidences of grade II-IV and grade III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival has not been reached in patients age ≤50 years and who had a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.
PICO Summary
Population
Patients with relapsed lymphoma undergoing allo-SCT
Intervention
Bortezomib added to the rituximab plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen (n=39)
Comparison
Historical control group that received R-BEAM without bortezomib.
Outcome
The R-BEAM regimen has a survival benefit in lymphoma patients age </=50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.