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Background: Mantle cell lymphoma (MCL) is an aggressive and incurable lymphoma. Standard of care for younger patients with MCL is induction chemotherapy followed by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after auto-HCT has been shown to improve progression-free survival (PFS) and overall survival (OS) in MCL. Bortezomib maintenance therapy has also been shown to be tolerable and feasible in this setting. However, the combination of bortezomib and rituximab as maintenance therapy post-auto-HCT has not been studied., Methods: We conducted a multicenter, phase II trial of bortezomib given in combination with rituximab as maintenance in MCL patients after consolidative auto-HCT. Enrolled patients (n = 23) received bortezomib 1.3 mg/m 2 subcutaneously weekly for 4 weeks every 3 months (up to 24 months) and rituximab 375 mg/m 2 intravenously weekly for 4 weeks every 6 months (up to 24 months) for a total duration of 2 years. The primary study endpoint was disease-free survival (DFS)., Results: With a median follow-up of 35.9 months, the 2-year DFS probability was 90.2% (95% CI 66-97), and 2-year OS was 94.7% (95% CI 68-99). The most frequent grade 3/4 toxic events were neutropenia (in 74% of patients) and lymphopenia (in 35%). The incidence of peripheral neuropathy was 48% for grade 1, 9% for grade 2, and 0% for grade 3/4. We also examined the role of quantitative cyclin D1 (CCND1) mRNA in monitoring minimal residual disease., Conclusion: Combined bortezomib and rituximab as maintenance therapy in MCL patients following auto-HCT is an active and well-tolerated regimen., Trial Registration: ClinicalTrials.gov NCT01267812 , registered Dec 29, 2010.

High-dose therapy followed by autologous stem cell transplantation (ASCT) can improve outcomes for mantle cell lymphoma (MCL) but is associated with a high incidence of relapse. A retrospective study of 191 MCL patients who underwent ASCT at City of Hope was performed to examine prognostic factors for outcomes after ASCT. For all patients the 5-year overall survival (OS) was 71% (95% confidence interval [CI], 63% to 77%) and progression-free survival (PFS) was 53% (95% CI, 45% to 60%). The 5-year cumulative incidence of relapse was 41% (95% CI, 34% to 48%) with a continuous pattern of relapse events occurring at a median of 2.1 years (range, .2 to 13.4) after ASCT. In multivariate analysis, post-transplant maintenance rituximab was the factor most significantly associated with both OS (relative risk [RR], .17; 95% CI, .07 to .38) and PFS (RR, .25; 95% CI, .14 to .44). For the subset of patients who had positron emission tomography (PET) data available and were in a PET-negative first complete remission at ASCT (n = 105), maintenance rituximab was significantly associated with superior OS (RR, .17; 95% CI, .05 to .59) and PFS (RR, .20; 95% CI, .09 to .43). These results support a benefit with maintenance rituximab for all MCL patients treated with ASCT., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The impact of patient body habitus and sex on outcomes in diffuse large B-cell lymphoma (DLBCL) remains controversial. We investigated the impact of body mass index (BMI), body surface area (BSA), age, and sex on clinical outcomes in patients with DLBCL treated in the rituximab era., Patients and Methods: Patients with de novo DLBCL (n=1,386) diagnosed between June 2000 and December 2010 treated with rituximab-containing chemotherapy were identified from the NCCN Oncology Outcomes Database for Non-Hodgkin's Lymphoma. Progression-free survival (PFS) and overall survival (OS) at 3 years were analyzed based on sex, age, and baseline BMI/BSA., Results: High BMI was associated with a lower risk of disease progression or death than low or normal BMI, whereas male sex was associated with poor clinical outcomes, especially among elderly patients (age >60 years). Compared with elderly women, elderly men experienced worse PFS (3-year hazard ratio [HR], 1.5) and OS (3-year HR, 1.6), but these differences diminished with increases in BMI and BSA. In multivariable analysis, normal BMI compared with high BMI was independently associated with poor outcomes (3-year PFS HR, 1.5; OS HR, 1.6) after adjusting for sex. Notably, only 13% of elderly men had BMI less than 25 kg/m 2 and only 26% had BSA less than 2 m 2 CONCLUSIONS: Analysis of unselected patients with DLBCL treated with rituximab-containing chemotherapy confirmed an age-dependent disadvantage to male sex in treatment outcomes, but this effect is abrogated by higher levels of BMI and BSA in most North American men., (Copyright © 2016 by the National Comprehensive Cancer Network.)

Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.

BACKGROUND The role of consolidation radiotherapy was examined for patients with diffuse large B-cell lymphoma who were treated at institutions of the National Comprehensive Cancer Network during the rituximab era. METHODS Failure-free survival (FFS) and overall survival (OS) were analyzed in terms of patient and treatment characteristics. Potential associations were investigated with univariate and multivariate survival analysis and matched pair analysis. RESULTS There were 841 patients, and most (710 or 84%) received 6 to 8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); 293 (35%) received consolidation radiation therapy (RT). Failure occurred for 181 patients: 126 patients (70%) who did not receive RT and 55 patients (30%) who did. At 5 years, both OS and FFS rates were better for patients who had received RT versus those who did not (OS, 91% vs 83% [ P = .01]; FFS, 83% vs 76% [ P = .05]). A matched pair analysis (217 pairs matched by age, stage, International Prognostic Index [IPI] score, B symptoms, disease bulk, and response to chemotherapy) showed that the receipt of RT improved OS (hazard ratio [HR], 0.53 [ P = .07]) and FFS (HR, 0.77 [ P = .34]) for patients with stage III/IV disease, but too few events took place among those with stage I/II disease for meaningful comparisons (HR for OS, 0.94 [ P = .89]; HR for FFS, 1.81 [ P = .15]). A multivariate analysis suggested that the IPI score and the response to chemotherapy had the greatest influence on outcomes. CONCLUSIONS There was a trend of higher OS and FFS rates for patients who had received consolidation RT after R-CHOP (especially for patients with stage III/IV disease), but the difference did not reach statistical significance. Cancer 2014. © 2014 American Cancer Society. Cancer 2015;121:1032-1039. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Histological transformation (HT) is a major cause of morbidity and mortality in patients with indolent non-Hodgkin lymphoma (NHL). The multicentre National Cancer Comprehensive Network database for NHL provides a unique opportunity to investigate the natural history of HT in the rituximab era. 118 patients with biopsy-confirmed indolent lymphoma and subsequent biopsy-confirmed HT were identified. Treatments for HT included autologous stem-cell transplant (auto-SCT) (n = 50), allogeneic SCT (allo-SCT) (n = 18), and treatment without transplant (n = 50). The 2-year overall survival (OS) for the entire cohort was 68%. For auto-SCT patients aged ≼60 years (n = 24), the 2-year OS was 74%. For non-transplanted patients aged ≼60 years (n = 19), the 2-year OS was 59%. The 2-year OS of patients naïve to chemotherapy prior to HT was superior to patients who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0.03). In this largest prospective cohort of patients of strictly defined HT in the rituximab era, the natural history of HT appears more favourable than historical studies. Younger patients who were not exposed to chemotherapy prior to HT experienced a prolonged survival even without transplantation. This study serves as a benchmark for future trials of novel approaches for HT in the Rituximab era. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stem cell transplant (SCT)-related outcomes and prognostication for relapsed/refractory follicular lymphoma (FL) are not well-defined in the post-rituximab era. METHODS: Through the National Comprehensive Cancer Network (NCCN) lymphoma outcomes study, 184 patients with relapsed/refractory FL who underwent autologous SCT (autoSCT) or allogenic SCT (alloSCT) fol-lowing disease relapse after prior rituximab-based therapy were examined. RESULTS: Patients who underwent autoSCT (N = 136) were older compared with patients who underwent alloSCT (N = 48) (54 versus 51 years, respectively, P = .01) and more frequently had grade 3 FL (35% versus 8%, respectively, P = .006). Patients who underwent alloSCT received more prior therapies (4 versus 3, respectively, P<.0001) and more often had resistant disease at SCT (19% versus 6%, respectively, P = .008). Cumulative 100-day non-relapse mortality (NRM) for autoSCT and alloSCT were 1% and 6%, respectively (Pc.0001), whereas 3-year NRM rates were 3% versus 24%, respectively (P<,0001). For autoSCT and alloSCT, cumulative rates of relapse, progression, and/or transformation were 32% ver-sus 16%, respectively (P = .03), whereas 3-year overall survival rates were 87% versus 61% (Pc.0001); there were no differences in failure-free survival. AlloSCT was associated with increased risk of death on multivariate analysis (hazard ratio = 2.77, 95% confidence interval =1.46-5.26, P = .002). This finding persisted on propensity scoring/matching. Multivariate analysis for autoSCT patients identi-fied age >60 years and >3 prior therapies as adverse factors. Furthermore, a survival model was created for the autoSCT cohort based on number of factors present (0,1, 2); 3-year failure-free survival was 72%, 47%, and 20%, respectively (P = .0003), and 3-year overall survival was 96%, 82%, and 62%, respectively (P<.0001). CONCLUSIONS: AutoSCT remains an effective therapy for patients with FL. For alloSCT, continued strategies to reduce NRM are needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Little is known about the utility of central nervous system (CNS) prophylaxis for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. The objective of this study was to characterize patterns of CNS prophylaxis for patients who received combined rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy using the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes Database, a prospective cohort study that collects clinical and outcomes data for patients at 7 participating centers. METHODS: Patients who were eligible for this analysis presented with newly diagnosed DLBCL between January 2001 and July 2008, had no evidence of baseline CNS disease, and had received R-CHOP within 180 days of diagnosis. The authors assessed incidence and covariates of prophylaxis, prophylaxis modality, and, using propensity score analysis, outcomes such as overall survival. RESULTS: Of 989 eligible patients, 117 received CNS prophylaxis (11.8%), most intrathecally (71.8%). Involvement of bone marrow, other high-risk site, >1 extranodal site, higher International Prognostic Index score, and higher stage were associated individually with the receipt of prophylaxis (all P < .0001). At a median follow-up of 2.5 years, there were 20 CNS recurrences (2% [95% confidence interval, 1.1%-2.9%]) among all patients, and overall survival was not affected by prophylaxis. CONCLUSIONS: Given the overall low rate of CNS recurrence and lack of prophylaxis-associated survival benefit, the current data called into question the practice of CNS prophylaxis in the rituximab era. Cancer 2011. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

• Allogeneic hematopoietic stem cell transplantation (HSCT) yielded durable remissions in a subset of patients with relapsed/refractory primary mediastinal large B-cell lymphoma. • Patients with refractory disease at HSCT had a dismal outcome (2-year progression-free survival [PFS] and overall survival [OS] of 0%). • Patients with sensitive disease at HSCT had a 5-year PFS of 44% and OS of 58%. • The 2-year OS in patients who relapsed after allogeneic HSCT was 33%. Standard therapy for relapsed or refractory (rel/ref) primary mediastinal large B cell lymphoma (PMBCL) is salvage therapy followed by autologous (auto) hematopoietic stem cell transplantation (HSCT). However, many patients have refractory disease and are unable to undergo autoHSCT, and a sizeable proportion of patients will relapse after autoHSCT. By analogy to diffuse large B cell lymphoma, these patients may be treated with allogeneic (allo) HSCT with curative intent, but at the risk of significant morbidity and mortality. Given the advent of effective immunotherapy approaches for rel/ref PMBCL, it is important to better understand the toxicity and efficacy of alloHSCT in these patients, to which these new approaches could be an alternative. Therefore, we retrospectively studied the outcomes of alloHSCT in a multicenter cohort of 28 patients with rel/ref PMBCL who underwent transplantation at 4 centers. Most patients (79%) were sensitive to pretransplantation therapy and 86% received reduced-intensity conditioning. The overall progression-free survival (PFS), overall survival (OS), and cumulative incidences of nonrelapse mortality and relapse in the cohort at 5 years were 34%, 45%, 32%, and 33%, respectively. Outcomes were significantly better in patients with pretransplantation responsive disease (2-year PFS and OS of 50% and 58%, respectively) compared with refractory patients (2-year PFS and OS of 0%). In our multicenter retrospective study, alloHSCT produced durable remissions in a proportion of patients with treatment-sensitive disease before transplantation (5-year PFS of 44%) and should be considered in the treatment of patients with rel/ref PMBCL. [ABSTRACT FROM AUTHOR]

Allogeneic (allo) hematopoietic cell transplantation (HCT) can induce long-term remissions in chemosensitive relapsed follicular lymphoma (FL). The Blood and Marrow Transplant Clinical Trials Network conducted a multicenter phase 2 trial to examine the efficacy of alloHCT using reduced-intensity conditioning with rituximab (RTX) in multiply relapsed, chemosensitive FL. The primary endpoint was 2-year progression-free survival (PFS). The conditioning regimen consisted of fludarabine, cyclophosphamide, and high-dose RTX (FCR), in which 3 of the 4 doses of RTX were administered at a dose of 1 gm/m 2 . Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus and methotrexate. Sixty-five patients were enrolled and 62 were evaluable. Median age was 55 years (range, 29 to 74). This group was heavily pretreated: 77% had received ≥ 3 prior regimens, 32% had received ≥ 5 prior regimens, and 11% had received prior autologous HCT. Donors were HLA-matched siblings (n = 33) or HLA-matched unrelated adults (n = 29). No graft failures occurred. The overall response rate after HCT was 94% with 90% in complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 47 months (range, 30 to 73), 3-year PFS and overall survival rates were 71% (95% confidence interval, 58% to 81%) and 82% (95% confidence interval, 70% to 90%), respectively. Three-year cumulative incidences of relapse/progression and nonrelapse mortality were 13% and 16%, respectively. Two-year cumulative incidences of grades 2 to 4 and grades 3 or 4 acute GVHD were 27% and 10%, respectively, and extensive chronic GVHD incidence was 55%. Serum RTX concentrations peaked at day +28 and remained detectable as late as 1 year in 59% of patients with available data. In conclusion, alloHCT with FCR conditioning confers high CR rates, a low incidence of relapse/progression, and excellent survival probabilities in heavily pretreated FL patients. [ABSTRACT FROM AUTHOR]

The effect of desensitization therapy on patients with Donor-specific Anti-HLA Antibodies (DSA) for patients receiving Haplo transplantation are unknown. Data of all 51 patients with DSA receiving Haplo transplantation between 11/2010-1/2019 at MD Anderson Cancer Center (N=41) and City of Hope (N=10) were included. Patients received desensitization with plasma exchange (PE), rituximab (R), and IVIg +/- buffy coat (BC) infused on day-1, as previously described by us (Ciurea SO. BBMT.2018:53:521). We analyzed transplant outcomes for DSA treated patients vs. those without DSA receiving Haplo transplant in the same period of time (control; N=345). The median age of patients with DSA was 51 years (range 19-69) and 47 years (range 18-72) in control group (p=0.15). There were no significant differences in diagnosis, remission status at transplant, DRI and ABO matching between 2 groups. RIC conditioning was used in 28% and 43% in DSA and control group, respectively (p=0.03) whereas 67% and 82% respectively (p=0.02) received marrow stem cell. Median levels of DSA on single antigen assay before desensitization was 5556 MFI (range 2360-28688). Of 51 patients with DSA, 37 (72.5%) DSA patients received desensitization with PE, R and IVIg, and 27/37 (73%) patients also received BC infusion before transplant. Twenty of 37 (54%) desensitized patients had DSA >5000 MFI and 14 out of them had complement binding DSA suggested by a positive C1q assay. Cumulative incidence (CI) of neutrophil engraftment at 28 days for patients who had DSA>5000 MFI and received desensitization was 75% compared with 91% in those without DSA (p=0.12) (Figure 1A) while 1-year NRM was 32% vs. 29% (p=0.57) (Figure 1B) and 1-year OS was 54% vs. 58%, respectively (p=0.18) (Figure 1C). The engraftment rate is significantly improved with desensitization treatment as our previous study demonstrated that only 46% of patients with DSA>5000 MFI achieved engraftment (Ciurea SO. BBMT.2015;21:1392). Remarkably, patients with DSA 2000-10000 who received treatment had 83% engraftment vs. 91% (p=0.86). Among 14 patients who had C1q+ DSA, 8 patients had persistently positive C1q after desensitization and only 4 engrafted, 2 had primary graft failure and 2 died before engraftment with CI of engraftment at 28 days of 43% (p=0.09 compared with control group). Persistent C1q positivity was associated with significantly higher NRM (37% vs. 29% at 1 year, p=0.01) and lower OS (33% vs. 58% at 1 year, p=0.002) compared with control group (Figure 1D). These significances persisted after adjusting for other factors in multivariable analysis. Treatment with PE, R, IVIg and BC infusion is an effective strategy to desensitize patients with DSA before haploidentical transplantation. Patients who remain C1q+ at transplantation have high risk for engraftment failure and should not proceed to transplantation. [ABSTRACT FROM AUTHOR]