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There is limited information concerning the impact of physical activity and obesity on non-Hodgkin lymphoma ( NHL) prognosis. We examined the associations between pre-diagnosis physical activity and body mass index ( BMI) with survival in 238 diffuse large B-cell ( DLBCL) and 175 follicular lymphoma cases, with follow-up from 2000 to 2015. The most physically active DLBCL cases had 41% lower risk of dying in the follow-up period than the least active [Hazard ratio ( HR) = 0·59, 95% confidence interval ( CI) = 0·36-0·96], while obese follicular lymphoma cases had a 2·5-fold risk of dying ( HR = 2·52, 95% CI = 1·27-5·00) compared with cases with normal BMI. NHL-specific survival results were similar. [ABSTRACT FROM AUTHOR]

The National Clinical Trials Network lymphoid malignancies Clinical Trials Planning Meeting (CTPM) occurred in November of 2014. The scope of the CTPM was to prioritize across the lymphoid tumors clinically significant questions and to foster strategies leading to biologically informed and potentially practice changing clinical trials. This review from the Hodgkin lymphoma (HL) subcommittee of the CTPM discusses the ongoing clinical challenges in HL, outlines the current standard of care for HL patients from early to advanced stage, and surveys the current science with respect to biomarkers and the landscape of ongoing clinical trials. Finally, we suggest areas of unmet need in HL and elucidate promising therapeutic strategies to guide future HL clinical trials planning across the NCTN. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the risk of secondary breast cancer (SBC) is reduced in women with Hodgkin lymphoma (HL) treated with smaller field radiation therapy (SFRT) versus mantle field radiation therapy (MRT).Methods and Materials: We used the BC Cancer Agency (BCCA) Lymphoid Cancer Database to identify female patients treated for HL between January 1961 and December 2009. Radiation therapy volumes were categorized as MRT or SFRT, which included involved field, involved site, or involved nodal radiation therapy. SBC risk estimates were compared using competing risk analysis and Fine and Gray multivariable model: MRT ± chemotherapy, SFRT ± chemotherapy, or chemotherapy-only.Results: Of 734 eligible patients, 75% of the living patients have been followed up for more than 10 years, SBC has developed in 54, and 15 have died of breast cancer. The 20-year estimated risks (competing risk cumulative incidence) for SBC differed significantly: MRT 7.5% (95% confidence interval [CI] 4.4%-11.5%), SFRT 3.1% (95% CI 1.0%-7.7%), and chemotherapy-only 2.2% (95% CI 1.0%-4.8%) (P=.01). Using a Fine and Gray model to control for death and patients lost to follow-up, MRT was associated with a higher risk of SBC (hazard ratio [HR] = 2.9; 95% CI 1.4%-6.0%; P=.004) compared with chemotherapy-only and with SFRT (HR = 3.3; 95% CI 1.3%-8.4%; P=.01). SFRT was not associated with a greater risk of SBC compared with chemotherapy-only (HR = 0.87; 95% CI 0.28%-2.66%; P=.80).Conclusion: This study confirms that large-volume MRT is associated with a markedly increased risk of SBC; however, more modern small-volume RT is not associated with a greater risk of SBC than chemotherapy alone. [ABSTRACT FROM AUTHOR]

The impact of treatment delays on outcomes in Hodgkin lymphoma (HL) is currently unknown. Time from definitive histologic diagnosis to first ABVD treatment (TDT) was calculated in 810 adults with HL: 365 (45%) TDT ≤4 weeks, 369 (46%) TDT 5–8 weeks, 76 (9%) TDT >8 weeks. The 5-year overall survival (OS) was 92% TDT ≤4 weeks, 92% TDT 5–8 weeks, and 83% TDT >8 weeks (p = 0.007). The 5-year disease-specific survival (DSS) was 93% TDT ≤4 weeks, 95% TDT 5–8 weeks, and 87% TDT >8 weeks (p = 0.094). The 5-year progression-free survival (PFS) was similar between groups (p = 0.139). In the multivariate analysis, TDT >8 weeks was not associated with worse OS, DSS, or PFS. Despite the univariate association between initiation of ABVD >8 weeks and worse OS, these data do not support such cut-off to improve outcomes. Nevertheless, clinicians should make every effort possible to initiate curative-intent chemotherapy as soon as a diagnosis of HL is established. [ABSTRACT FROM AUTHOR]

Treatment of Hodgkin lymphoma is associated with 2 major types of risk: that the treatment may fail to cure the disease or that the treatment will prove unacceptably toxic. Careful assessment of the amount of the lymphoma (tumor burden), its behavior (extent of invasion or specific organ compromise), and host related factors (age; coincident systemic infection; and organ dysfunction, especially hematopoietic, cardiac, or pulmonary) is essential to optimize outcome. Elaborately assembled prognostic scoring systems, such as the International Prognostic Factors Project score, have lost their accuracy and value as increasingly effective chemotherapy and supportive care have been developed. Identification of specific biomarkers derived from sophisticated exploration of Hodgkin lymphoma biology is bringing promise of further improvement in targeted therapy in which effectiveness is increased at the same time off-target toxicity is diminished. Parallel developments in functional imaging are providing additional potential to evaluate the efficacy of treatment while it is being delivered, allowing dynamic assessment of risk during chemotherapy and adaptation of the therapy in real time. Risk assessment in Hodgkin lymphoma is continuously evolving, promising ever greater precision and clinical relevance. This article explores the past usefulness and the emerging potential of risk assessment for this imminently curable malignancy. [ABSTRACT FROM AUTHOR]

The article discusses brentuximab vedotin treatment combined with chemotherapy for advanced stages of Hodgkin lymphoma. Topics discussed doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), impact of pulmonary toxicity on patients that proved to be fatal, and observations that were based on the bleomycin.

Due to disease rarity, there is limited information regarding the optimal therapy and outcome for patients with advanced-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Forty-two patients with NLPHL by the Revised European-American Lymphoma/World Health Organization classification with advanced-stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) matched by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range, 1.9 to 35.5 years) for NLPHL patients and 10.7 years (range, 1.6 to 26.3 years) for CHL patients. The majority received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-Uke chemotherapy. Although the 10-year overall survival (OS) (P = .579) and HL freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL patients (75% vs 73%; P = .610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10-year, 63% vs 73%; P = .040). Splenic involvement was associated with an inferior 10-year TTP in patients treated with ABVD (48% vs 71 %; P = .049) and an increased cumulative incidence of secondary aggressive lymphoma (P = .014) providing a rationale for further evaluation of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab in NLPHL. [ABSTRACT FROM AUTHOR]

Objective: To compare the TNM and Ann Arbor staging systems in predicting outcome in ocular adnexal lymphoma (OAL). Methods: Retrospective review of the clinical, imaging and histopathologic records of OALs between 1986 and 2009. Outcome measures included local recurrence and progression. Results: One hundred and sixty patients of OAL were included. Mean age was 65 ± 15 years (range 20-97) and 68 (43%) were male. The median follow-up of all OAL patients was 65 months (range 2.5-238). Histopathology identified low-grade, indolent B-cell lymphomas in 140 patients (87.5%) and rest had aggressive grades. Of 134 indolent OAL patients, those with unilateral disease had a 10-year progression free survival of 72% versus 48% in their bilateral counterparts ( p = 0.001). Amongst unilateral OAL patients staged within the T1-2 group, a significantly better outcome was noted for patients without nodal or metastatic involvement compared to those with such involvement ( p = 0.0001). The above observations helped to formulate a simple scoring system to prognosticate OALs based on their laterality and node/metastatic status. Amongst the 3 groups identified, group 1 with a score of 0 (unilateral OALs with no nodes or metastasis) had a 10-year progression free survival of 75%; group 2 with score 1 (either bilateral or positive nodes/metastasis) 50% and group 3 with score 2 (both bilateral OAL with positive nodes/metastasis) zero at 10 years ( p < 0.00001). Conclusions: The TNM-based staging system better predicts outcome in OAL than the Ann Arbor system primarily by delineation of bilateral disease and nodal/metastatic involvement at presentation. [ABSTRACT FROM AUTHOR]

Summary: Background: Roughly 70–80% of patients with advanced stage Hodgkin's lymphoma are cured with various first-line and second-line treatments, including ABVD, BEACOPP, and stem-cell transplantation. Brentuximab vedotin has shown significant clinical activity, with a manageable safety profile, in patients with relapsed or refractory Hodgkin's lymphoma. We aimed to assess the safety and early clinical efficacy of this drug as first-line treatment in combination with standard or modified-standard treatment in patients with previously untreated Hodgkin's lymphoma. Methods: We did a phase 1, open-label, dose-escalation safety study comparing brentuximab vedotin in combination with standard (ABVD) or a modified-standard (AVD) treatment. Patients were enrolled into the groups sequentially. Main entry criteria were newly diagnosed, treatment-naive, CD30-positive patients with Hodgkin's lymphoma who had histologically confirmed stage IIA bulky disease or stage IIB–IV disease and an Eastern Cooperative Oncology Group performance status of two or less. Patients received doses of 0·6, 0·9, or 1·2 mg/kg brentuximab vedotin by intravenous infusion every 2 weeks with either ABVD (25 mg/m2 doxorubicin, 10 units/m2 bleomycin, 6 mg/m2 vinblastine, and 375 mg/m2 dacarbazine) or AVD (ABVD modified regimen without the inclusion of bleomycin) for up to six cycles. Our primary objectives were to assess the safety profile and establish the maximum tolerated dose (MTD) of brentuximab vedotin in combination with ABVD and AVD. The safety profile and MTD was assessed for the safety population. The study has completed and the final analysis is presented. This study was registered with ClinicalTrials.gov, number NCT01060904. Findings: Between Jan 29, 2010, and Sept 17, 2012, 51 patients were enrolled and received at least one dose of brentuximab vedotin. The maximum tolerated dose of brentuximab vedotin when combined with ABVD or AVD was not exceeded at 1·2 mg/kg. 21 (95%) of 22 patients given brentuximab vedotin and ABVD achieved complete remission, as did 24 (96%) of 25 patients given brentuximab vedotin and AVD. Adverse events were generally grade 1 or 2; however, an unacceptable number of patients in the brentuximab vedotin and ABVD groups had pulmonary toxic effects (11 [44%] of 25), which exceeded the historical incidence for ABVD alone. No patients experienced pulmonary toxic effects when treated with brentuximab vedotin plus AVD. The most common grade 3 or worse events were neutropenia (20 [80%] of 25 patients in the brentuximab vedotin and ABVD group vs 20 [77%] of 26 patients in the brentuximab vedotin and AVD group), anaemia (five [20%] vs three [12%]), febrile neutropenia (five [20%] vs two [8%]), pulmonary toxic effects (six [24%] vs 0), syncope (three [12%] vs two [8%]), dyspnoea (three [12%] vs one [4%]), pulmonary embolism (three [12%] vs 0), fatigue (one [4%] each), and leucopenia (one [4%] each). Serious events occured in 41% of all patients (14 [56%] in the brentuximab vedotin and ABVD group and seven [27%] in the brentuximab vedotin and AVD group). Serious events occurring in 10% of patients or more overall were febrile neutropenia (four [16%] in the brentuximab vedotin and ABVD group vs two [8%] in the brentuximab vedotin and AVD group), and, in the brentuximab vedotin and ABVD group only, pulmonary toxic effects (six [24%]). Interpretation: Brentuximab vedotin should not be given with bleomycin in general or specifically as first-line therapy for patients with treatment naive, advanced stage Hodgkin's lymphoma. 1·2 mg/kg brentuximab vedotin combined with AVD given every 2 weeks was generally well tolerated by patients. At present, a phase 3 trial comparing brentuximab vedotin plus AVD to ABVD alone is ongoing (ClinicalTrials.gov, number NCT01712490) and will formally assess whether brentuximab vedotin plus AVD might redefine therapy in treatment-naive patients with Hodgkin's lymphoma. Funding: Seattle Genetics Inc and Takeda Pharmaceuticals International Co. [ABSTRACT FROM AUTHOR]

BACKGROUND: For limited-stage diffuse large B-cell lymphoma (DLBCL), treatment decisions are often influenced by toxicity profiles. One strategy that minimizes chemotherapy-induced toxicities is abbreviated chemotherapy plus consolidation involved-field radiotherapy (IFRT). Involved-node radiotherapy (INRT) is a new concept to DLBCL, aimed to reduce radiotherapy-induced toxicities. We retrospectively review the long-term outcomes of limited-stage DLBCL treated with abbreviated systemic therapy and radiotherapy focusing on field size: IFRT versus INRT. METHODS: The British Columbia Cancer Agency Lymphoid Cancer Database was used to identify patients diagnosed with limited-stage DLBCL (stage I/II, without B-symptoms; bulk < 10 cm) from 1981 to 2007. Patients were prescribed 3 cycles of chemotherapy plus IFRT (1981-1996) or INRT≤5 cm (1996-2007), defined as INRT to the prechemotherapy involved nodes with margins ≤ 5 cm. RESULTS: A total of 288 patients were identified: 56% were aged >60 years, 34% had stage II disease, 55% had extranodal disease, 19% had elevated lactate dehydrogenase levels, and 15% received rituximab. The two radiotherapy groups were IFRT (138 patients; 48%) and INRT≤5cm (150 patients; 52%); median follow-up was 117 and 89 months, respectively. Distant relapse was the most common site of failure in both groups. After INRT≤5 cm, marginal recurrence was infrequent (2%). Time to progression ( P = .823), progression-free survival ( P = .575), and overall survival ( P = .417) were not significantly different between the radiotherapy cohorts. Radiotherapy field size was not a significant prognostic factor on multivariate analyses. CONCLUSIONS: This research is the first known body of work to apply the concept of INRT to limited-stage DLBCL. Reducing the field size from IFRT to INRT≤5 cm maintains a low marginal recurrence risk with no impact on overall outcome. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma typically characterized by cyclin D1 overexpression as result of the t(11;14) translocation. MCL is biologically and clinically heterogeneous and frequently involves extranodal dissemination. Although MCL is incurable with current therapies, with the exception of allogeneic stem cell transplant, recent advances are improving long-term outcomes in MCL. Intensive research has continued to focus on elucidating biological mechanisms of MCL, identifying new molecular targets, and optimizing existing therapies. Most recently, researchers have begun focusing on new areas such as epigenetics and microRNAs and their potential applications to MCL therapy. Advances across a broad spectrum of MCL research were presented at a recent MCL Workshop. This report provides an overview of the scientific highlights from the meeting and a framework for future research. [ABSTRACT FROM AUTHOR]

The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort. [ABSTRACT FROM AUTHOR]

The author addresses the potential of immune checkpoint inhibition in enhancing treatment of lymphomas. Topics discussed include the role of HIV in development of non-Hodgkin lymphoma among senior adults aged at least 60 years old, the approach involves a mix of checkpoint inhibitors and standard agents used in chemotherapy, and the risks of causing autoimmune diseases linked to immune checkpoint inhibition.

Summary. Recurrent chromosomal translocations in malignant lymphomas most commonly involve 18q21 (bcl-2), 8q24 (c-myc) and 3q27 (bcl-6), with an incidence of 27%, 11% and 6%, respectively. Individual cases concurrently harbouring two of these three rearrangements have been previously reported. This report describes four patients with cytogenetic alterations affecting all three loci, which was confirmed by molecular analysis in one case. Clinically, each patient had aggressive B-cell lymphoma with disseminated disease often involving the central nervous system, poor response to chemotherapy and short survival. Activation of c-myc in association with deregulation of bcl-2, bcl-6 or both confers high-grade disease with a poor prognosis. [ABSTRACT FROM AUTHOR]

Focuses on the management problems in lymphomas. Incidence of advanced stage diseases in elderly patients; Difficulty in treating follicular large and diffuse small cleaved cell lymphoma; Complications of gastrointestinal lymphomas.

Evaluates the characteristics and medical intervention of non-hodgskin's lymphoma. Classification of the disease; Prognostic factors for the outcome of the disease; Staging procedures for the disease.

Study Objective: To determine the efficacy and toxicity of brief chemotherapy and involved field radiation therapy for treatment of limited-stage, histologically aggressive malignant lymphoma.Design: Single-arm prospective trial.Setting: Comprehensive cancer treatment center serving the entire population of British Columbia.Patients: Consecutive enrollment of 78 patients ranging in age from 21 to 82 years (median, 64) with limited-stage (no B symptoms, Ann Arbor stage I or II, tumors less than 10 cm in diameter), diffuse large cell, mixed or immunoblastic histologic characteristics of malignant lymphoma seen at our institution between May 1980 and December 1984. All eligible patients were evaluated for response and relapse-free and overall survival.Interventions: Chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for three cycles followed by involved field radiation therapy to the original site of disease in a dose equivalent to 3000 cGy in ten fractions.Main Results: The complete response rate was 99% (77 of 78 patients). With a median follow-up off treatment of 30 months the actuarial relapse-free survival is 84% and the overall survival is 85%. No deaths due to toxicity occurred.Conclusions: Brief chemotherapy and involved field radiation therapy is highly successful treatment for patients with limited-stage, histologically aggressive malignant lymphoma. Toxicity of this approach is acceptable, even in the elderly. Staging laparotomy is not needed to select these patients. Future trials should incorporate more effective chemotherapy programs. [ABSTRACT FROM AUTHOR]

Between April 1981 and May 1984, 61 patients with advanced diffuse large-cell lymphoma completed treatment with MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin), an innovative pilot chemotherapy program emphasizing weekly treatment, antibiotic prophylaxis, daily corticosteroid treatments, and brief duration (12 weeks). Fifty-one patients (84%) achieved a complete response and 10 patients (16%) had a partial response. Over a median follow-up after treatment of 23 months, the actuarial overall survival for the entire group has been 76%; for complete responders the relapse-free survival has been 90%. Toxicity was modest with one treatment-related death and seven episodes of serious infection. The most frequent toxicity was mucositis. Thus, MACOP-B is an effective treatment for large-cell lymphoma that can be delivered in 12 weeks with an acceptable incidence of toxicity. This regimen can achieve results similar and possibly superior to those of other presently used regimens of longer duration. [ABSTRACT FROM AUTHOR]

Background: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.Methods: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.Results: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.Conclusions: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.). [ABSTRACT FROM AUTHOR]

The author comments on the article "Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy" by B. D. Cheson, S. Ansell, and colleagues. She mentions that the treatment of the lymphoid cancer is crucial to its' management in terms of determining the quality, amount, and duration. She also notes the first international accepted criteria for non-Hodgkin lymphoma published by the International Working Group chaired by Bruce Cheson in 1999.

We report on outcomes of 111 patients with treatment naïve Waldenström macroglobulinemia (TN WM) treated with frontline bendamustine–rituximab (BR) (n = 57) or rituximab–cyclophosphamide–vincristine–prednisone (RCVP) (n = 54). Median follow-up was 60.7 months (range 1.9–231.6). Median progression-free survival (PFS) was 60.5 months (95% CI 47.6–73.4) for BR and 79.0 months (95% CI 31.3–126.8) for RCVP (p =.96). Median overall survival (OS) was not reached for BR and 153.4 months (95% CI 114.5–192.4) for RCVP (p =.37). While overall and major response rates did not differ between treatment groups, BR had numerically higher rate of very good partial response or better response (51% vs. 37%, p =.30) and complete response (26% vs. 13%, p =.13). RCVP confers comparable outcomes to BR in a real-world population of TN WM patients and remains an effective regimen, particularly when tolerance or frailty is an issue, or in resource-limited settings. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the use of radiation in treating patients with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL).

The article discusses research on the efficiency of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation in treating Hodgkin's lymphoma. The German Hodgkin Study Group (GHSG) showed in a series of clinical trials of patients with such lymphoma that dose intensification with the use of the escalated regimen involving prednisone and etoposide enhances the cure rate with primary chemotherapy. However, the downside of this treatment is that it has a 3 percent death rate.

A response by Christian Steidl, Joseph M. Connors and Randy D. Gascoyne to a letter to the editor about their article "Tumor-Associated Macrophages and Survival in Classic Hodgkin's Lymphoma" in the March 11, 2010 issue of the "New England Journal of Medicine" is presented.

Three patients with diffuse large B-cell type of post-transplant lymphoproliferative disease after lung transplantation were treated with rituximab, an anti-CD2O monoclonal antibody. Treatment resulted in two complete remissions and one non-response. [ABSTRACT FROM AUTHOR]

Summary: Treatment of Burkitt lymphoma (BL) with intensive, multi‐agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population‐based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high‐dose methotrexate (MTX) (CODOX‐M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX‐M/IVAC) ± rituximab over a 15‐year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus‐associated BL), 5‐year progression‐free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63–83%] and 77% (95% CI: 66–85%), respectively, with no treatment‐related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5‐year PFS 86% (P = 0·04) and OS 92% (P = 0·008), as did those under 60 years with 5‐year PFS 82% (P = 0·005) and OS 86% (P = 0·002), which remained significant in multivariate analysis [PFS: hazard ratio (HR) 3·36, P = 0·018; OS HR 4·03, P = 0·012]. Incorporation of high‐dose systemic methotrexate also significantly affected multivariate survival outcomes (OS HR 0·28, P = 0·025). Stem cell transplant in first remission had no effect on OS or PFS. This large, real‐world analysis of BL patients treated with CODOX‐M/IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice. [ABSTRACT FROM AUTHOR]

Ibrutinib has dramatically changed the treatment landscape for chronic lymphocytic leukemia (CLL) since its availability in British Columbia (BC), Canada in 2014. We analyzed patterns of use and real-world survival outcomes in 370 patients who received ibrutinib for first-line (1 L, n = 35) and relapsed/refractory (R/R, n = 335) CLL between 2014–2018 in BC. Dose reductions and interruptions were frequent in 32% and 27%, respectively. With a median follow-up of 27.6 months, 35% of patients discontinued ibrutinib, primarily for adverse events (AEs) rather than progressive disease. Over the course of treatment, 87% of patients experienced at least one adverse event. The 2-year overall survival (OS) and event-free survival (EFS) were excellent at 83.9% and 76.1%, respectively, with medians not reached. However, patients who discontinued ibrutinib had a median OS of 32.5 months and median EFS of only 3.8 months from time of discontinuation, highlighting the need to minimize toxicity in the real-world. [ABSTRACT FROM AUTHOR]

The article presents information on radioimmunotherapy, a therapeutic process used in the treatment of lymphomas. Follicular lymphoma is one of the two common lymphoid neoplasms in North America and Europe. It has been diagnosed in approximately 15,000 adults in North America in a calendar year. For the treatment of this disorder, researchers have paid attention on targeted agents, such as molecules that interfere with the anti-apoptotic BCL2 oncogene and monoclonal antibodies against CD20, a membrane-spanning protein on B cells. According to them, a radioimmunoconjugate is used for the treatment of follicular lymphoma because of its selectivity for the lymphoma, which consists of malignant B cells that are radiosensitive.

In that study, patients who started treatment more than 8 weeks after diagnosis were older and had other identifiable reasons for treatment delays (ex. comorbidities) that may have contributed to the association between treatment delay and OS. "Refusers" were further refined to patients who had at least a 16-week interval between pathologic diagnosis and treatment, and after chart review had declined to undergo the recommended treatment. With extended follow up, 13% of patients in the refuser cohort (2 of 15 refusers) died from cHL specifically, compared to 4% of patients in the control cohort (2 of 47 controls) though this did not reach statistical significance ( I p i = 0.185, Figure 1(c)). Fortunately, treatment refusal is uncommon, as only 17 (0.6%) patients out of a total of 2640 diagnosed with cHL over 20 years had documented initial treatment refusal. [Extracted from the article]

Mantle cell lymphoma (MCL) is a rare B-cell malignancy that carries a relatively poor prognosis compared to other forms of non-Hodgkin lymphoma. Standardized preclinical tools are desperately required to hasten the discovery and translation of promising new treatments for MCL. Via an initiative organized through the Mantle Cell Lymphoma Consortium and the Lymphoma Research Foundation, we gathered MCL cell lines from laboratories around the world to create a characterized MCL Cell Bank at the American Type Culture Collection (ATCC). Initiated in 2006, this collection now contains eight cell lines, all of which have been rigorously characterized and are now stored and available for distribution to the general scientific community. We believe the awareness and use of these standardized cell lines will decrease variability between investigators, harmonize international research efforts, improve our understanding of the pathogenesis of the disease and hasten the development of novel treatment strategies. [ABSTRACT FROM AUTHOR]

Summary: Hodgkin variant Richter transformation (HvRT) is a rare and challenging complication of chronic lymphocytic leukaemia (CLL) for which information on prognostic factors and treatment approaches remain limited. We analysed characteristics and survival outcomes of a population‐based cohort of 32 patients with HvRT identified in British Columbia over a 40‐year period. Median interval from CLL diagnosis to HvRT was 5.6 years (range, 0–33.6), with five cases diagnosed concurrently. Most patients (80%) had treatment for CLL prior to HvRT. Median age at HvRT was 71 years (range, 51–86) and the majority of patients had high‐risk disease, including stage 3–4 in 87% and International Prognostic Score (IPS) ≥ 4 in 65%. Two‐year progression‐free (PFS) and overall survival (OS) from HvRT were 47% (95% CI: 29%–64%) and 57% (95% CI: 38%–72%), respectively. OS from HvRT was significantly worse in those with anaemia (p = 0.02), elevated lactate dehydrogenase (p = 0.04), high IPS (p = 0.04), and worse performance status (p = 0.001). For those treated with curative‐intent ABVD/ABVD‐like therapy, 2‐year PFS and OS were 70% (95% CI: 45%–85%) and 74% (95% CI: 49%–89%), respectively. In this real‐world population‐based cohort, HvRT was associated with poor clinical outcomes overall; however, those able to tolerate curative‐intent therapy had similar survival to older patients with de novo HL. [ABSTRACT FROM AUTHOR]

Both patients with a partial response subsequently progressed and received EBRT to 24 Gy in 12 fractions, 1 and 3.75 years after RIT, respectively, with complete response in both patients. In 2008, a group from the MD Anderson Cancer Center reported a novel strategy of radioimmunotherapy (RIT), which they used in 12 patients with bilateral orbital extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) [[2]]. Grade 1-2 cytopenia occurred in seven patients, grade 3 in two patients, and one patient experienced grade 4 thrombocytopenia requiring platelet transfusion. If localized, the treatment of choice for orbital adnexal lymphoma is external beam radiotherapy, which leads to local control rates of 86-100% [[1]]. [Extracted from the article]

The purine analogs, pentostatin and cladribine, induce high remission rates when used as first-line monotherapy for hairy cell leukemia (HCL); however, patients continue to relapse. Re-treatment with the same or alternate purine analog produces lower response rates and a shorter duration of response. Fludarabine is another purine analog widely used in indolent lymphoid cancers, often in combination with rituximab, but there are few reports of its use in HCL. We identified 15 patients treated in British Columbia with fludarabine and rituximab (FR) from 2004 to 2010 for relapsed/refractory HCL after first-line cladribine (n = 3) or after multiple lines of therapy (n = 12). All patients with available response data re-sponded to FR. With median follow-up of 35 months, 14 patients remain progression-free, whereas 1 patient has developed progressive leukemia and died. Five-year progression-free and overall survivals are 89% and 83%, respectively. FR is a safe and effective therapeutic option for relapsed/refractory HCL. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths. Methods: We randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival. Results: The median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin's lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkin's lymphoma or early toxic effects from the treatment and 20 were related to another cause. Conclusions: Among patients with Hodgkin's lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.) [ABSTRACT FROM PUBLISHER]

Background: Diffuse large B-cell lymphoma (DLBCL) has primarily been treated with cyclophosphamide, doxorubicin, vincristine, and predisone (CHOP) chemotherapy since the 1970s. Recently, the addition of rituximab to CHOP (CHOP-R) has been found to improve survival and trial-based results have suggested that it is a cost-effective alternative to CHOP. Objectives: The objective in this study was to evaluate the cost-effectiveness of CHOP-R relative to CHOP in first-line treatment of DLBCL in a population-based setting in British Columbia, Canada. Methods: We created a patient-level simulation model describing potential pathways for DLBCL patients initiating treatment with either CHOP or CHOP-R. Model parameters were populated with statistical analyses of individual-level treatment and effectiveness data and published cost estimates. All results were stratified by age at treatment initiation (<60 years vs. ≥60 years). The base-case scenario was based on a 15-year time horizon and a 3% discount rate. Probabilistic sensitivity analysis was performed. All costs are reported as 2006 $CDN. Results: For the base-case scenario, incremental cost-effectiveness ratios (ICERs) for younger individuals ranged from $11,965 per disease-free life-year gained to $19,144 per quality-adjusted life-year gained. For older individuals, estimated ICERs for all health outcomes were below $10,000 per unit outcome gained for a 15-year time horizon. Conclusions: Using population-based data, CHOP-R was found to be a cost-effective alternative to CHOP, particularly for individuals aged 60 years and older. Results from this Canadian observational data source were consistent with international clinical trial-based studies. The use of CHOP-R as a first-line treatment for DLBCL is recommended, with respect to both clinical and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Forty-four patients with relapsed or refractory aggressive histology non-Hodgkin lymphoma (NHL) (diffuse large B cell, n = 23; peripheral T cell, n = 5; transformed B cell, n = 16) proceeded to allogeneic stem cell transplant (allo-SCT) between 1987 and 2003. Median age at transplant was 40 years (range 19–56 years). At the time of transplant, 35 were chemosensitive and nine were chemorefractory. Thirty-three patients had matched sibling donors and 11 had unrelated donors. Forty-two patients (95%) received radiation-based conditioning regimens. Event-free survival (EFS) and overall survival (OS) at 5 years was 43% [95% confidence interval (CI): 27–58%] and 48% (95% CI: 32–63%) respectively. Treatment-related mortality was 25% at 1 year. Grade III–IV acute graft- versus-host disease (GVHD) was the only significant variable affecting OS and EFS, and had a negative impact. Chronic GVHD did not influence survival. Lymphoma relapse <12 months after initial therapy predicted for increased risk of relapse post-transplant ( P = 0·02). Patients with chemorefractory lymphoma were not at increased risk of relapse ( P = 0·20) with four of nine patients remaining alive without disease 12–103 months post-transplant. In conclusion, allo-SCT for relapsed or refractory aggressive histology NHL results in long-term EFS and OS of 40–50%. Patients with chemorefractory disease can have a durable remission post-transplant. [ABSTRACT FROM AUTHOR]

Myeloablative allogeneic bone marrow transplantation (BMT) may be curative in patients with follicular non-Hodgkin's lymphoma, however, the impact of this therapy on long-term survival, disease progression and functional status is less clear. Twenty-nine patients (median age 42 years, range: 20–53) with advanced stage follicular lymphoma proceeded to allogeneic BMT a median of 25 (range: 8–154) months postdiagnosis, between 1985 and 2001, and have been followed for a minimum of 2 years. Eleven of 29 (38%) had refractory disease (n = 5 induction failure,n = 6 resistant relapse). Most (27 of 29, 93%) received total body irradiation-based conditioning; stem cell source was marrow from a related donor (n = 20) or unrelated donor (n = 9). Seventeen of 29 patients (59%) were alive a median of 5 years (range: 2–11) post-BMT with a median Karnofsky Performance Score of 100%. Death occurred because of transplant complications in seven patients (cumulative incidence of non-relapse mortality 24%), and progressive lymphoma in five patients (cumulative incidence of refractory/recurrent lymphoma 23%). The 5-year probability of overall and event-free survival was 58% and 53% respectively. Allogeneic BMT has resulted in long-term disease-free survival for approximately 50% of this cohort of patients with advanced follicular lymphoma and most of them now enjoy robust health. [ABSTRACT FROM AUTHOR]

Determines the treatment of multiply relapsed aggressive non-Hodgkin's lymphoma (NHL). Effects of cancer chemotherapy on bone marrow suppression; Neurotoxicity of vincristine; Myelosuppressive activity of NHL.

Discusses results of clinicopathological analysis of follicular lymphoma (FL) with a polyploid karyotype. Ploidy level as an independent prognostic factor in non-Hodgkin's lymphoma; Pattern of clinical behavior of FL; Observation of polyploidy in different frequencies across the subtypes of FL.

Summary: Nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is a rare entity, with limited data on the outcome in the relapsed/refractory setting. We evaluated the outcome of all patients diagnosed between 04/1979 and 01/2019 with relapsed or progressive NLPHL after initial active therapy at two institutions, refractory disease being defined as lack of response to treatment and/or relapse within three months of treatment. NLPHL patients with histological evidence of transformation at time of first relapse or progression were excluded. In total, 69 patients with recurrent NLPHL were included in the study. After a median follow‐up after initial diagnosis of 14 years (range, 0·5–46 years), median progression‐free survival after front‐line treatment (PFS‐1) was four years. Second‐line therapy included chemotherapy in 28 (41%) patients, biological therapy (rituximab, lenalidomide or brentuximab vedotin) in 14 (20%), high‐dose chemotherapy followed by autologous stem cell transplant in 14 (20%) and radiation therapy (RT) alone in 10 (15%). The five‐year PFS after second‐line therapy (PFS‐2) was 68% [95% confidence interval (CI), 54–79%] but the five‐year overall survival (OS) after second‐line therapy (OS‐2) remained excellent, at 94% (95% CI, 85–99%). Due to excellent outcome in case of recurrence, studies aimed at characterizing its biology to guide therapy de‐escalation are needed. [ABSTRACT FROM AUTHOR]

Motivation: B cells display remarkable diversity in producing B-cell receptors through recombination of immunoglobulin (Ig) V-D-J genes. Somatic hypermutation (SHM) of immunoglobulin heavy chain variable (IGHV) genes are used as a prognostic marker in B-cell malignancies. Clinically, IGHV mutation status is determined by targeted Sanger sequencing which is a resource-intensive and low-throughput procedure. Here, we describe a bioinformatic pipeline, CRIS (Complete Reconstruction of Immunoglobulin IGHV-D-J Sequences) that uses RNA sequencing (RNAseq) datasets to reconstruct IGHV-D-J sequences and determine IGHV SHM status. Results: CRIS extracts RNA-seq reads aligned to Ig gene loci, performs assembly of Ig transcripts and aligns the resulting contigs to reference Ig sequences to enumerate and classify SHMs in the IGHV gene sequence. CRIS improves on existing tools that infer the B-cell receptor repertoire from RNA-seq data using a portion IGHV gene segment by de novo assembly. We show that the SHM status identified by CRIS using the entire IGHV gene segment is highly concordant with clinical classification in three independent chronic lymphocytic leukemia patient cohorts. [ABSTRACT FROM AUTHOR]

Phase I/II experience Despite favorable outcomes in the front-line setting for most patients, 20-30% of patients develop relapsed disease or do not respond to initial therapy [[2]]. Among the 65 patients originally reported, the median age, number of prior therapies, and percentage of patients who received ASCT was 36 years (range, 18-72), 4 (range, 1-12), and 65%, respectively [[6]]. Three patients who did not undergo a consolidative ASCT had relapse of disease after a DOR of 13.5, 14 months and 33 months; two of these patients are alive at the time of this analysis. [Extracted from the article]

Summary: A novel prognostic score (IPS‐3), comprised of only three of the seven IPS‐7 indicators (age ≥45, stage IV, haemoglobin <105 g/l), was recently proposed as a simplified model for advanced‐stage classic Hodgkin lymphoma (cHL). We aimed to validate this model in advanced‐stage cHL patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) in British Columbia. The estimated five‐year freedom from progression (FFP) for scores of 0, 1, 2 and 3 were very similar to the original report at 84%, 76%, 72% and 68% respectively. The IPS‐3 score is highly reproducible in this independent dataset and its simplicity makes it appealing for everyday clinical practice. [ABSTRACT FROM AUTHOR]

Summary: Brentuximab vedotin (BV) is the first approved novel agent for salvage treatment of relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after autologous stem cell transplantation (ASCT). In this study, a literature‐based analysis was undertaken to assess, via an indirect treatment comparison, the comparative efficacy of BV to salvage chemotherapy as treatment for R/R cHL patients following ASCT. This comparative effectiveness research was undertaken to support a reimbursement submission for BV to the Australian Pharmaceutical Benefits Advisory Committee. Retrospective analysis of individual patient data from four data sources demonstrated that the use of BV as first salvage treatment in cHL patients relapsing or progressing post‐ASCT achieved improvements in both clinical response and overall survival. More specifically, BV was associated with an incremental improvement of 22% in overall response rate compared to salvage chemotherapy. Five‐year overall survival and progression‐free survival rates were 92·2% [95% confidence interval (CI): 85·5–99·3%] and 32·2% (95% CI: 19·1–54·6%) respectively for BV, compared to 30·5% (95% CI: 22·2–42·0%) and 3·2% (95% CI: 1·1–8·9%) respectively for salvage chemotherapy. The encouraging results from this conservative analysis have the potential to support informed clinical management and funding decisions for the first salvage of cHL patients demonstrating recurrence after ASCT. [ABSTRACT FROM AUTHOR]