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ASCT vs CART for Patients with Relapsed LBCL in PR: Role of TMTV
Strati, P., Pasvolsky, O., Feng, L., Xu, G., Tewari, S., Varghese, J., Ow, K., Santiago, M. S., Al Zaki, A., Jallouk, A., et al
Blood advances. 2023
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High-dose chemotherapy and autologous stem-cell transplant for relapsed or refractory primary mediastinal b-cell lymphoma
Alkhaldi, H., Reinhardt, A., Barnett, M., Kundu, S., Hosing, C., Ramdial, J., Saini, N., Srour, S., Alousi, A., Kebriaei, P., et al
Transplantation and cellular therapy. 2023
Abstract
Primary mediastinal large B cell lymphoma (PMBCL) is an uncommon aggressive type of non-Hodgkin lymphoma. Rituximab-containing chemoimmunotherapy ± radiation therapy (RT) is standard first-line treatment. Relapsed or refractory (R/R) disease has long been treated with salvage chemotherapy followed by high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) in appropriate patients. We retrospectively analyzed all patients with R/R PMBCL treated with HDC/ASCT at our center between January 2000 and August 2022. Sixty patients received rituximab-BEAM (N=37) or rituximab-gemcitabine/busulfan/melphalan (R-GemBuMel) ± vorinostat (N=23), with ASCT. Forty-six patients received mediastinal RT, either as prior consolidation of frontline therapy or following ASCT. At median follow-up of 6 years (range, 0.3-21), the 5-year progression-free survival (PFS) and overall survival (OS) rates of the whole group are 58% and 77%, respectively, 51% and 65%, respectively, for R-BEAM patients, and 69% and 82%, respectively, for R-vorinostat/GemBuMel patients. Multivariable analyses showed that negative PET at ASCT [hazard ratio (HR), 0.28)] and involvement of only 1 organ (HR, 0.33) were independently associated with improved PFS. In addition, receiving R-vorinostat/GemBuMel (HR, 0.23) was an independent favorable predictor of OS. In conclusion, HDC/ASCT is effective in R/R PMBCL, with improved outcomes in patients receiving R-vorinostat/GemBuMel.
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Characteristics and outcomes of children, adolescents and young adults with relapsed/refractory non-hodgkin lymphoma undergoing autologous stem cell transplant
Pasvolsky, O., Bassett, R. L., Ghanem, S., Cuglievan, B., Tewari, P., Hosing, C., Srour, S., Ramdial, J., Mahadeo, K. M., Khazal, S., et al
BMC cancer. 2023;23(1):1258
Abstract
BACKGROUND There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). METHODS Patients aged 0-39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. RESULTS Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6-39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03). Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0-196.6) months after ASCT, and SPM was the cause of death in five (50%) of them. CONCLUSIONS CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.
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Positron emission tomography derived metrics in relapsed or refractory large B-cell lymphoma with residual disease before autologous stem cell transplant
Cherng, H. J., Xu, G., Feng, L., Steiner, R., Fayad, L., Strati, P., Nair, R., Nastoupil, L. J., Lee, H. J., Neelapu, S. S., et al
British journal of haematology. 2022
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Abstract
Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A(18) F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, maximum standardised uptake value (SUV(max) ), total metabolic tumour volume (TMTV), and total lesion glycolysis (TLG) were calculated from the post-salvage/pre-ASCT PET scan. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 40% and 54% respectively. A D-5PS score of 5 (p = 0.0082, hazard ratio [HR] 2.09), high SUV(max) (p = 0.0015, HR 2.48), TMTV (p = 0.035, HR 1.83) and TLG (p = 0.0036, HR 2.27) were associated with inferior PFS. A D-5PS score of 5 (p = 0.030, HR 1.98) and high SUV(max) (p = 0.0025, HR 2.55) were associated with inferior OS. PET-derived parameters may help prognosticate outcomes after ASCT in patients with rrLBCL with residual disease after salvage chemotherapy.
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Impact of Cell of Origin Classification on Survival Outcomes after Autologous Transplantation in Relapsed/Refractory Diffuse Large B Cell Lymphoma
Joseph, J., Ma, J., Hennawy, F., Abdulrazzaq, M. N., Saini, N., Patel, R. D., Hosing, C. M., Alousi, A. M., Anderlini, P., Popat, U. R., et al
Transplantation and cellular therapy. 2021;27(5):404.e1-404.e5
Abstract
The cell of origin (COO) classification into germinal center B cell (GCB) and non-GCB types has been shown to predict survival outcomes in newly diagnosed diffuse large B cell lymphoma (DLBCL). In the relapsed/refractory (R/R) setting, there is building evidence that COO does not predict prognosis after high-dose chemotherapy and autologous stem cell transplantation (auto-SCT). The present analysis aimed to compare survival outcomes based on COO classification in R/R DLBCL patients who underwent auto-SCT. This retrospective study included adult patients with R/R DLBCL who underwent auto-SCT at MD Anderson Cancer Center between January 2007 and December 2016. The Hans algorithm using CD10, BCL6, and MUM1 markers was used to classify patients by COO. A total of 122 patients with DLBCL (71 GCB, 51 non-GCB) were included in the analysis. There were no significant differences in patient characteristics between the 2 groups, except for older median age in the GCB cohort (64 years versus 58 years; P < .004). The median overall survival (OS) time was 68.5 (95% confidence interval [CI], 51.3 to not reached) months for the total population, 68.5 (95% CI, 44.8 to not reached) for GCB, and not reached for non-GCB. The 3-year OS rate was 0.659 (95% CI, 0.575 to 0.755) for the total population, 0.653 (95% CI, 0.547 to 0.779) for GCB, and 0.666 (95% CI, 0.537 to 0.824) for non-GCB. When adjusted for age and other factors of interest, no statistically significant associations for OS or progression-free survival were observed between the 2 cohorts. Our results confirm that COO loses its prognostic potential in patients with R/R DLBCL who receive high-dose chemotherapy followed by auto-SCT and both GCB and non-GCB types of DLBCL derive similar benefit from auto-SCT. Younger age, female sex, and pretransplantation disease status were associated with better OS.
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A randomized phase II study of standard-dose versus high-dose rituximab with BEAM in autologous stem cell transplantation for relapsed aggressive B-cell non-hodgkin lymphomas: long term results
Srour, S. A., Li, S., Popat, U. R., Qazilbash, M. H., Lozano-Cerrada, S., Maadani, F., Alousi, A., Kebriaei, P., Anderlini, P., Nieto, Y., et al
British Journal of Haematology. 2017;178(4):561-570
Abstract
High-dose rituximab (HD-R) combined with carmustine, cytarabine, etoposide and melphalan (BEAM) and autologous stem cell transplant (ASCT) was effective and tolerable in a single-arm prospective study of relapsed aggressive B-cell non-Hodgkin lymphoma (R-NHL). We performed a randomized phase 2 study comparing HD-R versus standard-dose rituximab (SD-R) in R-NHL. Ninety-three patients were randomized to HD-R (1000 mg/m2 ) (n = 42) or SD-R (375 mg/m2 ) (n = 51) administered on post-transplant days +1 and +8, using a Bayesian adaptive algorithm. The 2 treatment arms were balanced in regards to patient demographic and clinical characteristics. At a median follow-up of 7.92 years, the 5-year disease-free survival (DFS) and overall survival (OS) were 40% and 48%, respectively. We found no statistically significant differences between HD-R and SD-R in 5-year DFS (36% vs. 43%; P = 0.205) and OS (43% vs. 52%; P = 0.392). In multivariate analyses, only disease status before ASCT [residual disease versus complete remission (CR)] (hazard ratio [HR] 1.79, 95% confidence interval [CI]: 1.08-2.95) and number of prior treatments received (>2 vs. <=2 lines of treatment) (HR 1.89, 95% CI: 1.13-3.18) were associated with worse DFS and OS. Patients who had SCT while in CR or who received <=2 lines of treatment prior to SCT had better 5-year OS (57% vs. 35%; P = 0.02 and 54% vs. 30%, P = 0.001, respectively) in both arms. No differences in engraftments or adverse events were noted in the 2 arms. When combined with BEAM and ASCT in relapsed aggressive B-cell NHL, HD-R provided no DFS or OS advantage over SD-R. In patients who have been exposed to rituximab in the frontline or salvage setting, the addition of rituximab in the peri-transplant setting remains controversial.