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Mantle cell lymphoma (MCL) outcomes have improved over the last two decades; however, late relapses occur. Bortezomib has shown single agent activity of 33% in relapsed MCL and has an additive/synergistic effect in vitro when combined with drugs currently used to treat MCL. We hypothesized that a combination of bortezomib with current intense non-transplant chemoimmunotherapy might prevent late relapses. The toxicity of bortezomib when combined with methotrexate and cytarabine is unknown. Patients aged 18–79 years with untreated aggressive MCL were treated with R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) alternating with rituximab-methotrexate/cytarabine (R-M/A). Bortezomib was added to the R-Hyper-CVAD combination as a fixed dose of 1·3 mg/m2 IV on days 2 and 5 and was added to the R-M/A regimen after rituximab, in increasing doses of 0·7, 1, and 1·3 mg/m2 in cohorts of three patients. Twenty patients were assessed for toxicity of the regimen. The principal toxicity was haematological and did not differ from that observed with a similar regimen without the bortezomib. In particular, there was no pulmonary or neurological dose-limiting toxicity, showing that bortezomib can be safely combined with R-HyperCVAD and R-M/A. [ABSTRACT FROM AUTHOR]

We conducted a retrospective cohort study examining the influence of obesity on treatment outcome and survival among 712 patients with intermediate-grade B-cell NHL receiving frontline therapy between 1988 and 2001. Baseline adiposity was approximated by body mass index categorized according to the World Health Organization schema. Logistic and Cox proportional hazards regression modeling was used to adjust for baseline patient demographic, disease, and treatment variables. Approximately 37% of cohort patients were overweight (BMI 25 to <30 kg/m2) and more than 23% were obese (BMI ≥ 30 kg/m2). Risk factors were similar across groups and treatment intensity did not vary by BMI. Median follow-up was 45.7 and 62.8 months for PFS and OS, respectively. After adjustment for other significant prognostic factors, BMI in the overweight range was associated with significantly reduced hazard for both PFS (OR 0.72, p = 0.011) and OS (OR 0.74, p = 0.030). Increased BMI is associated with significantly improved survival among patients with treatment-naive, intermediate-grade B-cell NHL. Prospective confirmation of these results is warranted given the increasing prevalence of both NHL and obesity. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) has a poor overall survival after treatment with conventional chemotherapy. Intense chemoimmunotherapy without consolidation stem cell transplantation is a potential therapeutic option. We report on a prospective Phase II study with rituximab in combination with fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R-Hyper-CVAD) alternating with rituximab in combination with high-dose methotrexate-cytarabine (R-MA) in untreated patients with diffuse and nodular MCL and their blastoid variants. Ninety-seven patients were treated, of whom 97% responded and 87% achieved a complete remission. At 10 years of follow up (median 8 years), the median overall survival (OS) for all patients had not been reached and the median time to failure (TTF) for all patients was 4.6 years, without a plateau in the curves. For the group of patients aged 65 years or younger, the median OS had not been reached and the median TTF was 5.9 years. Multivariate analysis revealed pre-treatment serum levels of β2 microglobulin, International Prognostic Index (IPI) score and mantle cell IPI (MIPI) score, as predictive of both OS and TTF. We conclude that intense chemoimmunotherapy without stem cell transplantation is effective for untreated aggressive MCL. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder (PCSM‐LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy.Our aim was to characterize treatment options for PCSM‐LPD, with a focus on the role of radiotherapy.This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM‐LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy.All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra‐low‐dose radiotherapy (4 Gy in 1–2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids.Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra‐low‐dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy. [ABSTRACT FROM AUTHOR]

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non‐Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity—rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study. Methods: The authors conducted an open‐label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression‐free survival (PFS) at 24 months. Results: This study included 48 participants with previously untreated FL grade 1–3a (N = 38), or MZL (N = 10). Participants received 12, 28‐day cycles of lenalidomide (15 mg, days 1–21 cycle 1; 20 mg, cycles 2–12), rituximab (375 mg/m2 weekly in cycle 1; day 1 cycles 2‐12), and ibrutinib 560 mg daily. With a median follow‐up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%–91.4%) and 60‐month PFS was 59.7% (95% CI, 46.6%–76.4%). One death occurred unrelated to disease progression. Grade 3–4 adverse events were observed in 64.6%, including 50% with grade 3–4 rash. Conclusions: IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3–4 toxicity, particularly rash. The study was registered with ClinicalTrials.gov (NCT02532257). After 5 years of follow‐up from a phase 2 clinical trial of ibrutinib, lenalidomide, and rituximab in previously untreated patients with follicular and marginal zone lymphoma, the 5‐year progression‐free survival rate was 59.7% and the overall survival rate was 97.9%. [ABSTRACT FROM AUTHOR]

BACKGROUND: B-cell lymphoma, Unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, for convenience referred to here as unclassifiable B-cell lymphoma, is a category in the 2008 World Health Organization system used for a group of histologically aggressive neoplasms that are difficult to classify definitively. Currently, there is no established standard therapy for these neoplasms. METHODS: The authors assessed MYC status and correlated it with treatment response and outcome in a group of 52 patients with unclassifiable B-cell lymphoma treated with either a standard DLBCL regimen (R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone-related therapy]) or more intensive regimens, such as R-hyper-CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). The regimens were selected by the treating clinicians based on the overall clinical and pathological findings. RESULTS: Thirty (58%) unclassifiable B-cell lymphomas had MYC abnormalities ( MYC+) including 27 with rearrangement, 2 with amplification, and 1 with both. The MYC+ and MYC− groups were similar in their age distribution and International Prognostic Index scores. Progression-free survival of patients with MYC+ unclassifiable B-cell lymphoma treated initially with R-CHOP was significantly worse than patients treated with R-hyper-CVAD ( P = .0358). In contrast, for the MYC− unclassifiable B-cell lymphoma group, some patients responded to R-CHOP, and others were refractory to R-hyper-CVAD. CONCLUSIONS: MYC aberrations are common in unclassifiable B-cell lymphoma. The presence of MYC aberrations identifies a patient subset that requires more aggressive therapy than R-CHOP. In contrast, MYC− unclassifiable B-cell lymphoma patients responded variably to either R-CHOP or aggressive therapy, and the latter showed no survival advantage. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article focuses on a study which aims to investigate the activity of gemcitabine in combination with rituximab in individuals with recurring or refractory Hodgkin lymphoma (HL). It cites that the malignant Hodgkin and Reed-Sternberg (HRS) cells of HL express various receptors that belong to the tumor necrosis factor (TNF) receptor family, such as CD40, CD30 and exogenous soluble CD40 ligand. It notes that gemcitabine in combination with rituximab generated an overall response rate of 48% in individuals with recurring or refractory HL.

In 27 patients randomized to receive commercial trivalent influenza vaccine (TIV) containing 15 μg of the hemagglutinin (HA) of influenza A (H3N2 and H1N1) and B virus or a recombinant vaccine (rHAO) containing 15, 45, or 135 μg of each HA, reactogenicity was minor. Among patients with similar prevaccination titers, 40% given 45 μg and 60% given 135 μg of rHAO developed an increase in influenza A/H3 neutralizing antibody levels; there were no increases in 4 given TIV. For each vaccine, the highest frequencies of increases in neutralizing antibody levels and the highest mean titers occurred in those given the 135-μg vaccine. [ABSTRACT FROM AUTHOR]

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 − 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure. [ABSTRACT FROM AUTHOR]

Rosai-Dorfman disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a rare disorder involving lymph nodes, respiratory tract, skin and soft tissues.1 The histiocytes of RDD (S100 SP + sp , CD68 SP + sp , CD1a SP - sp , CD14 SP + sp ) exhibit I emperipolesis i , a histological phenomenon describing engulfment of normal-appearing lymphocytes residing in cytoplasm of pathological histiocytes.1-4 Studies suggest a possible clonal origin of RDD from NRAS proto-oncogene, GTPase ( I NRAS i ), KRAS proto-oncogene, GTPase ( I KRAS i ), mitogen-activated protein kinase kinase 1 ( I MAP2K1 i ) and A-Raf proto-oncogene, serine/threonine kinase ( I ARAF i ) mutations.5 Patients are typically observed clinically; chemotherapy traditionally has not been uniformly successful in management, with variable responses to imatinib,3 cladribine4-7 and clofarabine.8 Recently, histiocytic disorders have been successfully treated with the mitogen-activated protein kinase (MEK)-inhibitor cobimetinib (COBI), suggesting pathological dependence on mitogen-activated protein kinase signalling and MEK-inhibition.9-12 The clinical spectrum of RDD overlaps with other conditions including autoimmune lymphoproliferative syndrome (ALPS) and RAS-associated autoimmune leucoproliferative disorder (RALD).5,13 RALD involves lymphadenopathy, splenomegaly, hypergammaglobulinaemia, B-cell lymphocytosis and activating mutations of I KRAS i or I NRAS i , which have also been found in ~25% of patients with juvenile myelomonocytic leukaemia (JMML).14 Despite the chronic nature of RALD, it has been hypothesised to have rare potential for transformation to myeloid malignancies resembling JMML or chronic myelomonocytic leukaemia (CMML).14 However, given the rarity of RALD there currently is no consensus criteria to define disease progression. [Extracted from the article]

MZL rarely involves the central nervous system (CNS) and accounts for only 1.4% of all CNS lymphomas [[2]]. While activity has been shown for the treatment of CNS involvement of other indolent B-cell NHL, such as chronic lymphocytic leukemia (CLL) [[8]], its efficacy in CNS MZL has not been previously reported. Radiological and pathological findings in a patient with marginal zone lymphoma (MZL) and central nervous system (CNS) involvement (patient 5). In a recent multicenter study, patients with CNS MZL were treated with surgery, methotrexate-based chemotherapy and/or radiation [[12]], the latter in light of the radio-sensitivity typically reported for extra-nodal CNS MZL [[13]]. [Extracted from the article]

Histologic transformation of indolent lymphomas account for 13% of I de novo i presentations of diffuse large B-cell lymphoma (DLBCL) [[1]]. 126 (84%) patients had follicular lymphoma [FL], 10 (7%) low grade B-cell lymphoma not otherwise specified [NOS], 10 (7%) marginal zone lymphoma, 3 (2%) mucosa-associated lymphoid tissue [MALT] lymphoma and 1 (1%) Waldenstrom's macroglobulinemia. A separate retrospective study in Japan identified 52 patients with untreated Tr-iNHL who received R-CHOP or R-CHOP-like induction therapy, of whom 15 patients received MR. [Extracted from the article]

• Human herpesvirus-6 (HV-6) reactivation and myelitis have been reported in cases • Chimeric antigen receptor (CAR) T-cell therapy may also confer risk. • HHV-6 should be evaluated in encephalitis or myelitis after CAR T-cell therapy. This article reports a fatal case of human herpesvirus 6 (HHV-6) myelitis following CD19-targeted chimeric antigen receptor T-cell therapy. Infection from HHV-6 reactivation after haematopoietic stem cell transplant is established, and outside of this population is limited to case reports. The patient developed cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome that responded to corticosteroids both clinically and on imaging. Subsequently, ascending flaccid paralysis developed, leading to neuromuscular respiratory failure and, ultimately, death. Disease progression was refractory to foscarnet and multiple immunomodulating agents. HHV-6 should be considered in patients with encephalitis and myelitis after adoptive T-cell therapy. [ABSTRACT FROM AUTHOR]

In 2 randomized phase 3 trials BR resulted in longer progression-free survival (PFS) than frontline R-CHOP in patients with indolent and mantle cell lymphoma. However, in subset analyses of follicular lymphoma (FL), the results were incongruent. We conducted a retrospective matched-pair analysis to compare the outcome of patients with advanced stage FL, receiving frontline BR (N = 73) or R-CHOP (N = 73), matched by age, gender, stage, and FL International Prognostic Index score. On multivariable analysis, baseline maximum standardized uptake value (SUVmax) >13 was associated with use of R-CHOP (p =.001). After a median follow-up of 69 months for the BR arm and 126 months for the R-CHOP arm, 5-year PFS was 80% and 70%, respectively (p =.07). After adjusting for SUVmax >13, the trend for better PFS in BR was not maintained. Prospective studies are needed to validate the role of pretreatment SUVmax as a stratification factor in future randomized therapeutic trials in FL. [ABSTRACT FROM AUTHOR]

CD5+ diffuse large B-cell lymphoma (DLBCL), NOS represents a distinct subset of DLBCL associated with poorer outcomes and extranodal disease. We analyzed characteristics and outcomes for 102 CD5+ DLBCL patients diagnosed between 2001-2016. The majority had poor-risk disease based on R-IPI scores; 80% had extranodal disease at diagnosis. CNS relapse occurred 23% of the time. Median PFS and OS was 18.9 months and 112 months, respectively. Four-year PFS rates were 100%, 53%, and 41% for patients with R-IPI scores of very good, good, and poor, respectively. CD5+ DLBCL represents a subset of patients with poor outcomes despite rituximab and anthracycline-based regimens. There is a need for novel therapies and clinical trials for this high-risk group of patients. Given high rates of CNS relapse, better CNS prophylaxis with frontline therapy requires more study. [ABSTRACT FROM AUTHOR]

Patients with early-stage nodal follicular lymphoma (FL) may be rendered free of detectable disease by a diagnostic excisional biopsy. We reviewed the management and outcomes of 48 patients with FL, diagnosed from 2003–2013, treated at a single institution. The primary endpoints were local control (LC) and progression-free survival (PFS). Median age at diagnosis was 54.5 years (range 15–74 years). Forty-seven patients were stage I (97.9%); 15 patients (31.3%) had grade 3 disease. Initial management consisted of observation (12 patients; 25.0%), radiation therapy (RT) alone (12 patients; 25.0%), systemic therapy alone (9 cases; 18.8%), or both (15 patients; 31.3%). Median follow-up was 4.92 years (range 0.5–13.83 years). 4-year PFS and OS were 80.9% and 97.1%, respectively. Patients treated with additional therapy experienced significantly better 4-year LC (100% vs. 81.8%; p =.012) and 4-year PFS (86.7% vs. 63.6%; p =.006). Patients with completely resected limited-stage FL would benefit from therapy beyond excisional biopsy alone. [ABSTRACT FROM AUTHOR]

Controversy exists regarding the optimal management of limited stage grade 3 follicular lymphoma (FL3). We assessed the treatment outcomes of 190 consecutive patients with stage I-II FL. Fifty two patients had FL3 disease, in whom the median age was 55 years. At a median follow-up of 65 months, 5-year progression-free survival (PFS) and overall survival (OS) rates were 76.6% and 87.6%, respectively. Patients receiving systemic therapy followed by radiation therapy (RT) had a significantly better PFS (p=.003) than those treated with RT alone, but similar OS (p =.476). Patients treated with RT had 100% local control. Compared to 132 patients with grade 1–2 FL, those with FL3 had similar PFS (p =.493) and OS (p =.330). Patients with FL3 can experience favorable outcomes when treated with a combination of systemic therapy and RT, comparable to low grade FL. [ABSTRACT FROM AUTHOR]

Summary: Lack of consensus for first‐line marginal zone lymphoma (MZL) treatment and toxicities associated with currently available systemic therapies have inspired evaluation of immunotherapeutic agents yielding robust outcomes with improved tolerability. We previously reported durable efficacy with first‐line lenalidomide and rituximab (R2) in follicular lymphoma, MZL and small lymphocytic lymphoma with a subsequent long‐term follow‐up shown here in MZL patients. This phase 2 investigator‐initiated study included previously untreated, stage III/IV MZL patients treated with lenalidomide 20 mg/day on days 1–21 and rituximab 375 mg/m2 on day 1 of each 28‐day cycle, continuing in responders for ≥6–12 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints were complete and partial response (CR, PR), safety, and progression‐free survival (PFS). The ORR was 93% with 70% attaining CR/CR unconfirmed. At median follow‐up of 75·1 months, median PFS was 59·8 months and 5‐year OS was 96%. Most non‐haematological adverse events (AE) were grade 1/2. Grade 3 haematological AEs were neutropenia (33%) and leucopenia (7%), and grade 4 were leucopenia (3%) and thrombocytopenia (3%). Two patients died of secondary malignancies; no treatment‐related fatalities occurred. With extended follow‐up, outcomes for MZL patients receiving R2 were robust with no unexpected late or delayed toxicities. [ABSTRACT FROM AUTHOR]

This study investigated the safety and efficacy of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP) in patients with advanced diffuse large B-cell lymphoma (DLBCL) and explored the impact of cell-of-origin (COO) on patient outcomes. Patients (N = 100) received obinutuzumab (1000 mg on the days 1, 8, and 15 of cycle 1, and day 1 of cycles 2–8) plus CHOP (cycles 1–6). For patients without grade ≥3 infusion-related reactions (IRRs) to standard-rate obinutuzumab infusion, a shorter duration of infusion (SDI) was evaluated. Overall and complete response rates, as determined according to the Cheson et al. criteria by investigators/independent radiological facility, were 82.0/75.0% and 55.0/58.0%, respectively. SDI of 120 minutes and 90 minutes were well tolerated with no grade ≥3 IRRs. Among all patients, IRRs typically occurred during cycle 1, day 1. G-CHOP is active and has an acceptable safety profile in the first-line treatment of patients with advanced DLBCL. Clinical Trials: NCT01414855DLBCL [ABSTRACT FROM AUTHOR]

Treatment strategies and outcomes were assessed in 25 patients with primary breast diffuse large B-cell lymphoma (PB-DLBCL) treated between 1995 and 2016. We specifically investigated the timing of recurrence, and the roles of radiotherapy (RT) and central nervous system prophylaxis (CNS PPX). Fifty-two percent of patients received RT, and 28% received CNS PPX. Fourteen patients (56%) experienced recurrence, with 76% of relapses occurring ≥24 months after diagnosis, in contrast to reports supporting the use of 24-month event-free survival as a surrogate endpoint in the general DLBCL population. Use of RT was associated with a trend toward improved progression-free survival (PFS). Twenty percent of patients experienced CNS relapse, with no clear benefit to CNS PPX. These data emphasize the importance of long-term follow-up for PB-DLBCL patients, suggest a PFS benefit with the addition of RT, and highlight high rates of CNS relapse. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to randomized phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Topics discussed include efficacy and safety of Inotuzumab ozogamicin with rituximab; antitumour activity in patients with R/R aggressive B-NHL; and examination of inotuzumab ozogamicin-containing combination therapies.

Background: Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or synergistic effects in preclinical trials with known effective agents.Methods: This is a report of a prospective phase 2 trial of bortezomib added to rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (BzR-hyperCVAD)/rituximab, high-dose methotrexate, and high-dose cytarabine (BzR-MA) for 95 patients with newly diagnosed MCL.Results: The overall and complete response rates were 100% and 82%, respectively. Hematologic toxicity was high but expected and did not lead to an increased incidence of neutropenic fever or dose reductions in comparison with a similar reported regimen without bortezomib. After a median follow-up of 44 months, the median overall survival had not been reached, and the time to treatment failure (TTF) was 55 months, which is not different from that of historical controls.Conclusions: BzR-hyperCVAD/BzR-MA at the dose and schedule studied produced high rates of response and a TTF similar to that of historical reports without bortezomib. Cancer 2018;124:2561-9. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the efficacy of radiation therapy (RT) in the management of secondary central nervous system (CNS) lymphoma.Methods and Materials: The cohort comprised 44 patients with systemic diffuse large B-cell lymphoma (DLBCL) secondarily involving the brain and/or leptomeninges at initial diagnosis or relapse that was treated with RT.Results: Of these patients, 29 (66%) were in systemic remission when CNS disease was diagnosed. The overall response rate to RT by magnetic resonance imaging was 88% (42% complete, 46% partial). The median overall survival (OS) after RT initiation was 7 months (95% confidence interval 4-10 months). The OS curve plateaued at 31% from 2 to 8 years. OS was superior in patients who achieved a complete or partial response to RT, underwent stem cell transplantation after RT, and had brain parenchymal (vs leptomeningeal) disease. Eight cases of CNS disease progression occurred after RT: 1 involved the brain parenchyma, and 7 involved the spine and/or cerebrospinal fluid and/or meninges.Conclusions: We conclude that RT is associated with high response rates and may contribute to long-term OS. In addition, RT may provide CNS disease control that facilitates successful salvage with stem cell transplantation in patients with chemotherapy-refractory disease. [ABSTRACT FROM AUTHOR]

This phase-I/phase-II study evaluated panobinostat in combination with ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory classical Hodgkin lymphoma. During phase I, panobinostat was given daily on Monday/Wednesday/Friday starting one week prior to Cycle 1 (C1) of ICE and during two weeks of C1-2 of ICE (Schedule A). No DLT was observed at 30 mg. However, frequent (84%) grade-4 thrombocytopenia during second week prompted us to omit the second week of panobinostat 30 mg (Schedule B) for phase II, where this regimen was compared to ICE.In the randomized phase-II study, CR was seen in 9/11 (82%) and 8/12 (67%) for P-ICE and ICE, respectively (p = .64). Grade-4 neutropenia (55% vs. 8%) and thrombocytopenia (100% vs. 33%) were more common in P-ICE. In summary, combination therapy using panobinostat produced high CR rate at the cost of greater bone marrow toxicity. Investigation of panobinostat with less myelosuppressive agents is of interest. [ABSTRACT FROM AUTHOR]

We performed a retrospective analysis to identify risk factors and survival outcome for central nervous system (CNS) relapse of peripheral T-cell lymphoma (PTCL) by histologic type. Records of 600 PTCL patients diagnosed between 1999 and 2014 were analyzed including PTCL not otherwise specified (PTCL-NOS, 174 patients), angoimmunoblastic T-cell lymphoma (AITL, 144), ALK+anaplastic large cell lymphoma (ALCL, 74), ALK-ALCL (103), extranodal NK-cell lymphoma (ENKL, 54), or others (51). With a median follow up of 57 months, 13 patients (4 PTCL-NOS, 1 AITL, 4 ALK+ALCL, 2 ALK-ALCL, 2 ENKL) experienced CNS relapse. One-year and 5-year cumulative incidence of CNS relapse were 1.5% (95%CI: 0.7–2.8%) and 2.1% (95%CI: 1.1–3.5%), respectively. The 5-year cumulative incidence of CNS relapse was 1.8% in PTCL-NOS, 0.7% in AITL, 5.4% in ALK+ALCL, 2.1% in ALK-ALCL and 3.7% in ENKL. Extranodal involvement >1 site was the only significant factor associated with higher chance of CNS relapse (HR: 4.9, 95%CI: 1.6–15.0, p = 0.005). Patients with ALK+ALCL who had extranodal involvement >1 (N = 19) had very high risk of CNS relapse with one year cumulative incidence of 17% (95%CI: 4%-37%), all occurring within six months after diagnosis. All patients with CNS relapse eventually died (median, 1.5 months; range, 0.1–10.1 months). CNS relapse in patients with PTCL is rare event but the risk varies by subtype. ALK+ALCL patients with extranodal involvement >1 site have a very high risk of early CNS relapse, and thus evaluation of CNS involvement at the time of diagnosis and possible CNS-directed prophylaxis may be considered. [ABSTRACT FROM AUTHOR]

The article discusses the treatment of patients with systemic lymphoma who have secondary central nervous system (CNS) involvement using dose-adjusted etoposide, prednisone, vincristine/Oncovin and doxorubicin hydrochloride in combination with rituximab (EPOCH-R) and mid-cycle high dose methotrexate. Topics discussed include survival outcome, complete response (CR) achieved by all patients, and the relapse-free status of patients who did not undergo autologous stem cell transplantation (ASCT).

In 120 Stage I–IV testicular diffuse large B-cell lymphoma (DLBCL) patients treated from 1964 to 2015, we assessed the benefits of prophylactic contralateral testicular radiation (RT) and prophylactic central nervous system (CNS) therapy on overall, progression free, testicular relapse free, and CNS relapse free survival (OS, PFS, TRFS, and CRFS, respectively). Seventy percent of patients received RT, 53% received anthracyclines and rituximab (modern therapy), and 61% received CNS prophylaxis. On univariate analysis RT was associated with improved TRFS, PFS, and trended toward improved OS. On multivariate analysis (MVA), RT was significantly associated with improved OS and PFS; the PFS benefit persisted among patients receiving modern therapy. CNS prophylaxis was associated with improved OS, PFS, and TRFS, but not CRFS on univariate analysis, and was not significant on MVA. RT is associated with improved survival, and should be considered for all testicular DLBCL patients, but additional strategies are needed to prevent CNS relapse. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzed patients diagnosed with gray-zone lymphoma (GZL) at the University of Texas MD Anderson Cancer Center in Houston, Texas. Topics discussed include characteristics of patients with GZL, longer progression-free survival (PFS) found in patients with mediastinal GZL, and indication that dose-adjusted etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (DA-EPOCH-R) may improve outcome for patients with GZL.

Early-stage classical Hodgkin lymphoma (HL) patients are evaluated by an end-of-chemotherapy positron emission tomography-computed tomography (eoc-PET-CT) after doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and before radiation therapy (RT). We determined freedom from progression (FFP) in patients treated with ABVD and RT according to the eoc-PET-CT 5-point score (5PS). Secondarily, we assessed whether patients with a positive eoc-PET-CT (5PS of 4-5) can be cured with RT alone. The cohort comprised 174 patients treated for stage I-II HL with ABVD and RT alone. ABVD was given with a median of four cycles and RT with a median dose of 30·6 Gy. Five-year FFP was 97%. Five-year FFP was 100% (0 relapses/98 patients) for patients with a 5PS of 1-2, 97% (2/65) for a 5PS of 3, 83% (1/8) for a 5PS of 4, and 67% (1/3) for a 5PS of 5 ( P < 0·001). Patients with positive eoc-PET-CT scans who were selected for salvage RT alone had experienced a very good partial response to ABVD. Risk factors for recurrence in this subgroup included a small reduction in tumour size and a 'bounce' in ≥1 PET-CT parameter (reduction then rise from interim to final scan). Thus, a positive eoc-PET-CT is associated with inferior FFP; however, appropriately selected patients can be cured with RT alone. [ABSTRACT FROM AUTHOR]

Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P = .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen. [ABSTRACT FROM AUTHOR]

Survival outcome of patients with peripheral T-cell lymphoma-not otherwise specified ( PTCL- NOS) and angioimmunoblastic T-cell lymphoma ( AITL) who experience disease progression/relapse remains very poor. A total of 321 patients, newly diagnosed with PTCL- NOS ( n = 180) or AITL ( n = 141) between 1999 and 2015, were analysed. Failure-free survival ( FFS) and overall survival ( OS) were calculated from the time of first disease progression ( FFS1, OS1), from second disease progression ( FFS2, OS2) and from third progression ( FFS3, OS3). With a median follow-up duration of 52 months, 240 patients (135 PTCL- NOS, 105 AITL) experienced progression/relapse. In patients with PTCL- NOS, the median durations of FFS1, FFS2 and FFS3 were 3·1, 2·5 and 2·1 months, respectively. In patients with AITL, they were 5·5, 2·9 and 2·3 months, respectively. There was no improvement in FFS1 and OS1 by the time of recurrence during this period (1999-2004, 2005-2009 and 2010-2015). The median FFS after pralatrexate and romidepsin was only 3·0 and 2·5 months, respectively. The 5-year OS rates after salvage autologous and allogeneic transplant were 32% and 52%, respectively; while the 5-year OS rates for patients who did not undergo transplant was 10%. Further research for novel therapeutic approaches with higher efficacy and better safety profile are needed. [ABSTRACT FROM AUTHOR]

Background: The number of elderly patients with diffuse large B-cell lymphoma (DLBCL) in our aging society continues to rise, although the optimal management of very elderly patients with DLBCL is unknown.Methods: This study evaluated 207 patients who were 80 years old or older at the diagnosis of DLBCL from 2002 to 2014 at The University of Texas MD Anderson Cancer Center. Analyzed features included clinical characteristics, treatment outcomes, and tolerability of therapy. Cox proportional hazards models examined relations between the treatment regimen and survival.Results: The median age was 83 years (range, 80-96 years). Fifty-four percent of the patients had intermediate- to high-risk or high-risk International Prognostic Index scores. Fifteen percent had scores of 4 or higher on the Charlson Comorbidity Index (CCI). The initial therapies included rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 70%); rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH; 6%); and non-anthracycline-based therapies, including rituximab, cyclophosphamide, etoposide, vincristine, and prednisone (R-CEOP) and rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP; 10%). With a median follow-up of 38.1 months, the 3-year failure-free survival (FFS) and overall survival (OS) rates were 55% and 54%, respectively. Eighty-eight patients experienced relapse during the follow-up, but only 3 patients (3.4%) experienced relapse beyond 3 years. Patients who received R-CHOP or R-EPOCH had significantly longer FFS than those who received R-CEOP or R-CVP, with 3-year FFS rates of 63% for R-CHOP, 74% for R-EPOCH, and 23% for R-CEOP and R-CVP. Male sex, a monocyte count ≥ 500 × 107 /L, and a CCI score ≥ 4 were significantly associated with inferior OS. Extranodal disease (≥2) and a higher CCI score were associated with a high risk of treatment-related mortality.Conclusions: With anthracycline-based regimens such as R-CHOP and R-EPOCH, very elderly patients with DLBCL had superior outcomes similar to those achieved for younger patients with DLBCL. Cancer 2016;122:3145-51. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

There are limited reports that baseline peripheral absolute neutrophil count ( ANC), absolute monocyte count ( AMC), absolute lymphocyte count ( ALC) and serum β2-microglobulin level independently predict survival in patients with diffuse large B-cell lymphoma ( DLBCL). To confirm these findings, we analysed these parameters together with components of the International Prognostic Index ( IPI) in patients with newly-diagnosed DLBCL. We evaluated baseline clinical features for their ability to predict survival in 817 newly diagnosed, previously untreated patients with DLBCL who received frontline treatments between October 2001 and December 2011. The median age at diagnosis was 58 years. Multivariate analysis identified elevated baseline ANC ( P = 0·036), AMC ( P = 0·028) and serum β2-microglobulin level ( P < 0·001), poor performance status ( P < 0·001) and high number of extranodal disease sites ( P = 0·0497) as independent unfavourable predictors of OS; serum β2-microglobulin level was the strongest predictor of survival outcomes among all the parameters. High baseline serum β2-microglobulin, ANC and AMC levels are independent prognostic factors for short overall survival in patients with newly diagnosed DLBCL. Our new model, based on the above five parameters, better stratifies patients into various risk categories than the IPI for newly diagnosed DLBCL. [ABSTRACT FROM AUTHOR]

Intensive chemotherapy regimens containing cytarabine have substantially improved remission durability and overall survival in younger adults with mantle cell lymphoma (MCL). However, there have been no long-term follow-up results for patients treated with these regimens. We present long-term survival outcomes from a pivotal phase II trial of rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with methotrexate and cytarabine (R-HCVAD/MA). At 15 years of follow-up (median: 13·4 years), the median failure-free survival (FFS) and overall survival (OS) for all patients was 4·8 years and 10·7 years, respectively. The FFS seems to have plateaued after 10 years, with an estimated 15-year FFS of 30% in younger patients (≤65 years). Patients who achieved complete response (CR) after 2 cycles had a favourable median FFS of 8·8 years. Six patients developed myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) whilst in first CR. The 10-year cumulative incidence of MDS/AML of patients in first remission was 6·2% (95% confidence interval: 2·5-12·2%). In patients with newly diagnosed MCL, R-HCVAD/MA showed sustained efficacy, with a median OS exceeding 10 years in all patients and freedom from disease recurrence of nearly 15 years in almost one-third of the younger patients (≤65 years). [ABSTRACT FROM AUTHOR]

A phase II study was performed to evaluate the efficacy of hyper-fractionated cyclophosphamide, vincristine, pegylated liposomal doxorubicin and dexamethasone alternating with methotrexate/cytarabine ( HCVIDD/ MA) in patients with newly diagnosed peripheral T-cell lymphoma ( PTCL), excluding ALK-positive anaplastic large cell lymphoma. Fifty-three patients were enrolled. Treatment was planned for up to 8 cycles but only 9% of patients received more than 6 cycles due primarily to disease progression ( n = 13) or prolonged thrombocytopenia ( n = 12). The overall response rate was 66% with a complete response rate of 57%. Median progression-free survival ( PFS) was 7·5 months. With a median follow-up of 7·6 years, 5-year PFS and overall survival ( OS) were 21% and 48%, respectively. The patients with extranodal Natural Killer-cell lymphoma had a shorter PFS (median, 2·4 months) than other subtypes. Grade 3/4 anaemia, neutropenia and thrombocytopenia were observed in 66%, 74% and 79% of patients, respectively. Of note, 23% of patients discontinued therapy due to prolonged thrombocytopenia. In conclusion, HCVIDD/ MA for the first-line treatment of PTCL patients is associated with significant myelosuppression leading to poor treatment adherence, and the response and survival outcomes with this regimen are similar to standard CHOP. This study was registered at as # NCT00290433. [ABSTRACT FROM AUTHOR]

Purpose Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P =.0069) and OS (91% vs 68%, P =.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P =.014) with a trend toward an OS benefit (HR=0.30, P =.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy ( P =.71 PFS and P =.31 OS). Conclusion Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS. [ABSTRACT FROM AUTHOR]

Summary Background Standard treatments for indolent non-Hodgkin lymphomas are often toxic, and most patients ultimately relapse. Lenalidomide, an immunomodulatory agent, is effective as monotherapy for relapsed indolent non-Hodgkin lymphoma. We assessed the efficacy and safety of lenalidomide plus rituximab in patients with untreated, advanced stage indolent non-Hodgkin lymphoma. Methods In this phase 2 trial, undertaken at one instution, patients with follicular lymphoma and marginal zone lymphoma were given lenalidomide, orally, at 20 mg/day on days 1–21 of each 28-day cycle. For patients with small lymphocytic lymphoma, dosing began at 10 mg/day to avoid tumour flare, with an escalation of 5 mg/month to 20 mg/day. Rituximab was given at 375 mg/m 2 as an intravenous infusion on day 1 of each cycle. Patients responding after six cycles could continue therapy for up to 12 cycles. The primary endpoint was overall response, defined as the proportion of patients who achieved a partial or complete response; patients were assessed for response if they had any post-baseline tumour assessment. This trial is registered with ClinicalTrials.gov , number NCT00695786 . Findings 110 patients with follicular lymphoma (n=50), marginal zone lymphoma (n=30), and small lymphocytic lymphoma (n=30) were enrolled from June 30, 2008, until Aug 12, 2011. 93 of 103 evaluable patients had an overall response (90%, 95% CI 83–95). Complete responses occurred in 65 (63%, 95% CI 53–72) and partial responses in 28 patients (27%, 19–37). Of 46 evaluable patients with follicular lymphoma, 40 (87%) patients had a complete response and five (11%) had a partial response. Of 27 evaluable patients with marginal zone lymphoma, 18 (67%) had a complete response and six (22%) had a partial response. Of 30 evaluable patients with small lymphocytic lymphoma, seven (23%) had a complete response and 17 (57%) had a partial response. The most common grade 3 or 4 adverse events were neutropenia (38 [35%] of 110 patients), muscle pain (ten [9%]), rash (eight [7%]), cough, dyspnoea, or other pulmonary symptoms (five [5%]), fatigue (five [5%]), thrombosis (five [5%]), and thrombocytopenia (four [4%]). Interpretation Lenalidomide plus rituximab is well tolerated and highly active as initial treatment for indolent non-Hodgkin lymphoma. An international phase 3 study ( NCT01476787 ) to compare this regimen with chemotherapy in patients with untreated follicular lymphoma is in progress. Funding Celgene Corporation and Richard Spencer Lewis Memorial Foundation and Cancer Center Support Grant. [ABSTRACT FROM AUTHOR]

The article discusses findings of a study on premature closure of a clinical trial of bendamustine, mitoxantrone and rituximab for patients with untreated high-risk follicular lymphoma caused by severe haematological and infectious toxicity. It states that bendamustine and rituximab resulted in progression-free survival and tolerability, and mentions exclusion criteria for the study like uncontrolled illness, pregnancy/breastfeeding. It notes that computerized tomography was performed.

Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings. [Copyright &y& Elsevier]

Summary: Background: Endogenous or iatrogenic antitumour immune responses can improve the course of follicular lymphoma, but might be diminished by immune checkpoints in the tumour microenvironment. These checkpoints might include effects of programmed cell death 1 (PD1), a co-inhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. We did this phase 2 trial to investigate the activity of pidilizumab, a humanised anti-PD1 monoclonal antibody, with rituximab in patients with relapsed follicular lymphoma. Methods: We did this open-label, non-randomised trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Adult (≥18 years) patients with rituximab-sensitive follicular lymphoma relapsing after one to four previous therapies were eligible. Pidilizumab was administered at 3 mg/kg intravenously every 4 weeks for four infusions, plus eight optional infusions every 4 weeks for patients with stable disease or better. Starting 17 days after the first infusion of pidilizumab, rituximab was given at 375 mg/m2 intravenously weekly for 4 weeks. The primary endpoint was the proportion of patients who achieved an objective response (complete response plus partial response according to Revised Response Criteria for Malignant Lymphoma). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00904722. Findings: We enrolled 32 patients between Jan 13, 2010, and Jan 20, 2012. Median follow-up was 15·4 months (IQR 10·1–21·0). The combination of pidilizumab and rituximab was well tolerated, with no autoimmune or treatment-related adverse events of grade 3 or 4. The most common adverse events of grade 1 were anaemia (14 patients) and fatigue (13 patients), and the most common adverse event of grade 2 was respiratory infection (five patients). Of the 29 patients evaluable for activity, 19 (66%) achieved an objective response: complete responses were noted in 15 (52%) patients and partial responses in four (14%). Interpretation: The combination of pidilizumab plus rituximab is well tolerated and active in patients with relapsed follicular lymphoma. Our results suggest that immune checkpoint blockade is worthy of further study in follicular lymphoma. Funding: National Institutes of Health, Leukemia and Lymphoma Society, Cure Tech, and University of Texas MD Anderson Cancer Center. [ABSTRACT FROM AUTHOR]

Response to primary treatment in diffuse large B-cell lymphoma (DLBCL) is highly predictive of long-term outcome. We evaluated the value of computed tomography (CT) findings relative to positron emission tomography (PET) findings, after the completion of chemotherapy. We retrospectively reviewed records from 491 patients with DLBCL at M. D. Anderson in 2001-2007; 22 patients were excluded for uncertain pathology and 169 for having received consolidative radiation, leaving 300 patients for the present analysis (median age, 61 years; 53% men, 47% women; 27% stage I-II, 73% stage III-IV; 73% completed 6-8 cycles of doxorubicin-based therapy). Factors associated with outcome on univariate analysis were response according to PET/CT and CT ( p < 0.0001 for overall survival [OS], disease-specific survival [DSS] and progression-free survival [PFS]); number of chemotherapy cycles received ( p < 0.0001 OS, p < 0.0001 DSS, p < 0.002 PFS); the combined presence of Ki-67 > 50%, PET SUV ≥ 13 and bulky (> 5 cm) disease ( p = 0.005 OS, p = 0.001 DSS, p = 0.001 PFS); and International Prognostic Index (IPI) score ( p = 0.004 OS, p = 0.005 DSS, p = 0.004 PFS). On multivariate analysis, PET/CT-negative, CT residual mass (> 2 cm) significantly influenced OS, DSS and PFS ( p < 0.0001). The presence of a residual mass >2 cm on CT, coupled with negative findings on PET/CT, has prognostic value in DLBCL. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding the clinical trial of vorinostat in patients with peripheral T-cell lymphoma (PTCL) in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (VHOP). It informs that common toxicity in patients related to virinostat is diarrhoea and a patient started suffering from neutropenic fever despite giving granulocyte colony-stimulating factor (G-CSF). Other topics included angioimmunoblastic T-cell lymphoma and Histone deacetylase inhibitors.

In the present study, we evaluated the efficacy and safety of rituximab In combi-nation with standard doxorubicin, bleomy-cin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lym-phoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m2 weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respec-tively. The 5-year EFS for patients with stage lll/IV cHLwas 82%. Furthermore, the 5-year EFS for patients with an Interna-tional Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutro-penia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in pa-tients with advanced-stage cHL. These data are currently being confirmed in a multi-center randomized trial. This trial has been completed and is registered with www.clini-caltrials.gov as NCT00504504. {Blood. 2012; 119(18):4123-4128) [ABSTRACT FROM AUTHOR]

BACKGROUND: Pixantrone dimaleate (pixantrone) has been shown to have antitumor activity in leukemia and lymphoma in vitro models and to lack delayed cardiotoxicity associated with mitoxantrone in animal models. FND-R, a combination regimen of fludarabine, mitoxantrone, dexamethasone, and rituximab, has been shown to be an effective regimen for low-grade lymphomas. METHODS: This dose-escalation study, with an expansion cohort, was conducted to evaluate the safety and preliminary efficacy of FPD-R, in which pixantrone was substituted for mitoxantrone in the FND-R regimen, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (NHL). Escalated doses of pixantrone were administered to newly enrolled patients on day 2 of each 28-day cycle of FPD-R. RESULTS: Twenty-eight of 29 enrolled patients received at least 1 cycle of FPD-R (median, 5 cycles). Pixantrone 120 mg/m2 was identified as the recommended dose in this regimen. Grade 3-4 adverse events were primarily hematologic; grade 3-4 lymphopenia occurred in 89% of patients and leukopenia in 79%. No patients developed congestive heart failure or grade 3-4 cardiac adverse events. Left ventricular ejection fraction decreases occurred in 8 (29%) patients, and most were grade 1 or 2, transient, and asymptomatic. The overall response rate was 89%. Estimated survival was 96% after 1 year and 92% after 3 years. CONCLUSIONS: The FPD-R regimen was well-tolerated and highly active in patients with relapsed or refractory indolent NHL. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) usually responds well to initial therapy but is prone to relapses with chemoresistant disease, indicating the need for novel therapeutic approaches. Inhibition of the p53 E3 ligase human homolog of the murine double minute protein-2 (HDM-2) with MI-63 has been validated as one such strategy in wild-type (wt) p53 models, and our genomic and proteomic analyses demonstrated that MI-63 suppressed the expression of the ribonucleotide reductase (RNR) subunit M2 (RRM2). This effect occurred in association with induction of p21 and cell-cycle arrest at G1/S and prompted us to examine combinations with the RNR inhibitor 2',2'-difluoro-2'-deoxycytidine (gemcitabine). The regimen of MI-63-gemcitabine induced enhanced, synergistic antiproliferative, and proapoptotic effects in wtp53 MCL cell lines. Addition of exogenous dNTPs reversed this effect, whereas shRNA-mediated inhibition of RRM2 was sufficient to induce synergy with gemcitabine. Combination therapy of MCL murine xenografts with gemcitabine and MI-219, the in vivo analog of MI-63, resulted in enhanced antitumor activity. Finally, synergy was seen with MI-63-gemcitabine in primary patient samples that were found to express high levels of RRM2 compared with MCL cell lines. These findings provide a framework for translation of the rational combination of an HDM-2 and RNR inhibitor to the clinic for patients with relapsed wtp53 MCL. [ABSTRACT FROM AUTHOR]

The article examines the prognostic factors in patients with marginal zone lymphoma (MZL). The patients in the study were divided into three groups according to the type of MZL such as extranodal, nodal and splenic. The results of the study revealed that splenic MZL patients had the best prognosis among the three groups despite the increased prevalence of negative prognostic indicators. The patients with extranodal and nodal MZL had similar prognosis. The study was able to provide a prognostic scoring system for patients with extranodal MZL.

A letter to the editor is presented in response to the article regarding the randomized phase II study of the comparison between rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) and R-CHOP + enzastaurin in B-cell lymphoma patients.

: PurposeTo analyze the long-term outcomes and pattern of failures for Stage III follicular lymphomas.: Methods and materialsA retrospective review of all patients with Stage III follicular lymphoma presented to our institution between 1978 and 1993 was performed. One hundred ten patients were eligible and form the basis of this analysis. Fifty-seven patients were male. The median age was 57 years (range: 21–82 years). The treatments were as follows: chemotherapy alone (CTX), 39 patients; combined modality with chemotherapy and radiation therapy (CMT), 69; radiation therapy alone, 2. Radiation therapy fields were as follows: regional, 13 patients; extended, 6; subtotal, 44; and central lymphatic, 8. The median number of chemotherapy cycles was 8, and 98 patients received doxorubicin-containing regimens. Enough information was available to calculate the International Prognostic Index for 107 patients. The following prognostic factors were examined for predictive value in overall survival (OS) and freedom from progression (FFP) by univariate and multivariate analyses: International Prognostic Index, gender, lactate dehydrogenase (LDH) (normal vs. elevated), B symptoms, performance status, β-2 microglobulin, presence or absence of a bulky disease, age (≤ vs. >60 years), number of sites of involvement, treatment (CTX vs. CMT), and pathology. To minimize patient selection biases given the nature of the retrospective analysis, the patterns of relapse were analyzed only for the patients who achieved a complete response.: ResultsThe median follow-up for the alive patients was 9.5 years (range: 1.1–19.5 years). Complete response was achieved in 80 patients: 24 of 39 patients in the CTX group (62%), 54 of 69 patients in the CMT group (78%), and 2 of 2 patients in the radiation therapy alone group. The actuarial 5- and 10-year OS rates were 65% and 42%, respectively. The 5- and 10-year FFP was 42% and 26%, respectively. Significant prognostic factors by multivariate analyses were age and LDH for OS and LDH for FFP. For complete responders, 5-year freedom from recurrence in the original sites of involvement (with or without recurrence in the new sites) was 43% for CTX and 60% for CMT patients (p = 0.03, Wilcoxon). Five-year freedom from isolated recurrence in the original sites of involvement was 60% for CTX and 69% for CMT patients (p = 0.17). The 5-year overall FFP was 43% for CTX patients and 56% for CMT patients (p = 0.06).: ConclusionCombined modality treatment seems to give an advantage in terms of disease control in the primary sites compared to chemotherapy alone, though the advantages in OS and FFP were not statistically significant in our patient population. By multivariate analyses, LDH was a significant prognostic indicator for OS and FFP, whereas age was for OS. [Copyright &y& Elsevier]

The article discusses Bcl-2 overexpression in classic Hodgkin lymphoma (cHL) which confers poor prognosis of the disease. It examines phase II clinical trials of obatoclax mesylate (GX15-070) inhibitors, antagonistic properties on Bcl-2 family of proteins in patients with relapsed or refractory cHL. It proposes that obatoclax mesylate showed limited clinical activity in heavily pretreated patients with cHL.

A letter to the editor about the rare involvement of the testicle in a mantle cell lymphoma is presented.