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Chemoimmunotherapy followed by autologous stem cell transplantation ( ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma ( MCL). The achievement of complete remission ( CR) and minimal residual disease ( MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine ( RB/ RC). This phase 2 study ( NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD -evaluable patients who completed treatment, 93% achieved MRD negativity after RB/ RC. In conclusion, RB/ RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/ RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population. [ABSTRACT FROM AUTHOR]

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]

Optimal treatment for limited stage diffuse large B-cell lymphoma (DLBCL) in the elderly is controversial. Using the Surveillance, Epidemiology and End Results-Medicare database, we compared overall survival (OS), time to second-line therapy (surrogate for recurrence) and adverse events in elderly patients diagnosed with stage I or II DLBCL in 1999-2009, who received either abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) plus radiation or 6-8 cycles of RCHOP alone. Of 874 patients, 359 received abbreviated RCHOP with radiation, and 515 received a full course of RCHOP. In propensity score-adjusted analyses, OS was similar in both groups (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.76, 1.38). Abbreviated RCHOP with radiation was associated with lower risk of second-line therapy (HR 0.71, 95% CI 0.53, 0.94) and lower odds of febrile neutropenia (odds ratio [OR] 0.27, 95% CI 0.15, 0.50). While the two treatments resulted in similar survival, our data suggest that abbreviated RCHOP with radiation may be better tolerated than a full course of RCHOP. [ABSTRACT FROM AUTHOR]

BACKGROUND High-dose thiotepa, busulfan, and cyclophosphamide (TBC) with autologous stem cell transplantation (ASCT) has been used in patients with central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL). Despite limited penetration into the CNS, rituximab is active in primary CNS NHL. Therefore, high-dose rituximab was combined with TBC for ASCT in patients with CNS NHL. METHODS A single-arm phase 2 trial using high-dose rituximab with cytarabine for stem cell mobilization followed by high-dose rituximab combined with thiotepa, busulfan, and cyclophosphamide (R-TBC) for ASCT was conducted. Doses of rituximab at 1000 mg/m2 were given on days 1 and 8 of mobilization and on days −9 and −2 of TBC. The primary endpoint was efficacy. RESULTS Thirty patients were enrolled. Eighteen patients had primary CNS NHL (12 with complete remission (CR)/first partial remission (PR1) and 6 with CR/PR2), and 12 patients had secondary CNS lymphoma (5 with CR/PR1 and 7 with CR/PR2 or beyond). All patients were in partial or complete remission. Twenty-nine patients proceeded to R-TBC ASCT. Two patients developed significant neurotoxicity. The 100-day nonrelapse mortality rate was 0%, and 1 patient died because of nonrelapse causes 5 months after ASCT. For all patients, at a median follow-up of 24 months (range, 12-40 months), the estimated 2-year progression-free survival rate was 81% (95% confidence interval, 59%-92%), and the 2-year overall survival rate was 93% (95% confidence interval, 76%-98%). There were no relapses or deaths among the 18 patients with primary CNS lymphoma. CONCLUSIONS For patients with CNS involvement by B-cell NHL and especially for patients with primary CNS NHL, R-TBC ASCT shows encouraging activity and merits further study. Cancer 2015;121:226-33. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Pneumonitis is a complication of high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) regimens containing BCNU. Our goal was to define the incidence and risk factors for pneumonitis in patients with lymphoma receiving a uniform conditioning regimen in the modern era. We studied 222 patients who received HDC-ASCT using cyclophosphamide, BCNU and VP-16 (CBV). Pneumonitis incidence was 22%, with 19% receiving systemic corticosteroid treatment and 8% requiring inpatient hospitalization for pneumonitis. Three patients died secondary to pneumonitis-related complications. The following variables were independently associated with pneumonitis: prior mediastinal radiation (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.3-18.9, p = 0.0005), total BCNU dose above 1000 mg (OR 3.4, 95% CI 1.3-8.7, p = 0.012) and age less than 54 (OR 3.0, 95% CI 1.4-6.5, p = 0.0037). Increased vigilance for symptoms of pneumonitis is warranted for patients with prior mediastinal radiation and for younger patients, and dose reduction may be considered for patients who would receive greater than 1000 mg of BCNU. [ABSTRACT FROM AUTHOR]

The article provides information on a study which determined the efficacy and safety of bortezomib in combination with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). A review of the related literature on DLBCL and MCL is offered. It describes the methods utilized in the study. The occurrence of hematologic toxicities are recorded. It observes that bortezomib is feasible to be added to R-CHOP chemotherapy.

Autologous stem cell transplant (ASCT) is the standard of care for patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adding rituximab (R) to the initial therapy has improved outcomes; however, the benefit of ASCT for chemosensitive patients who fail R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, prednisone) is unclear. Patients who underwent ASCT between 1997 and 2006 for DLBCL at two partner institutions were identified. Characteristics and outcomes were compared between patients who received R-CHOP as initial chemotherapy and those who received CHOP. Of the 185 patients evaluated, 137 were initially treated with CHOP and 48 received R-CHOP. Patients who received R-CHOP were older, had shorter remissions, and initially had more advanced stage. With univariate analysis, PFS and OS did not differ; however, multivariable Cox regression analysis suggested a poorer prognosis for patients who underwent ASCT after failing R-CHOP. In conclusion, patients who fail R-CHOP appear to benefit from ASCT, but they may have a worse prognosis compared to patients who fail CHOP alone. [ABSTRACT FROM AUTHOR]

Primary central nervous system non-Hodgkin lymphoma (PCNSL) carries a poor prognosis and, although it responds to chemotherapy, fewer than 20% of patients are long-term disease-free survivors. Secondary CNS non-Hodgkin lymphoma (SCNSL) has an even worse prognosis with a median survival of only months and very few reported long-term survivors. For both of these groups of patients, there has been interest in using high-dose chemotherapy with autologous stem cell transplantation (ASCT) following conditioning with thiotepa, busulfan, and cyclophosphamide (TBC). We performed a retrospective review (from 2006-2010) of 32 patients from the Dana-Farber Cancer Institute and Massachusetts General Hospital with PCNSL or SCNSL who underwent ASCT with TBC conditioning. Of the 32 patients, 56% received TBC/ASCT after achieving brain magnetic resonance imaging (MRI) and/or cerebrospinal fluid complete response in brain, and 44% of patients were treated with TBC/ASCT in the setting of measurable CNS disease. The 100-day transplant-related mortality rate was only 3%. The most common nonhematologic grade 3 or 4 toxicity was mucositis, which occurred in 73% of patients. Notably, there was only 1 patient with prolonged significant neurologic toxicity that manifested as ataxia and dysphagia. The 1-year OS estimate is 93% (95% confidence interval [CI]: 75%-98%), and the 1-year progression-free survival (PFS) estimate is 90% (95% CI: 72%-96%) from the date of transplantation. Although these outcomes are encouraging, longer follow-up is required and comparison with other traditional ASCT regimens used for patients with non-Hodgkin lymphoma (NHL) is warranted. [ABSTRACT FROM AUTHOR]