The HDAC6‐selective inhibitor is effective against non‐Hodgkin lymphoma and synergizes with ibrutinib in follicular lymphoma

2019 ◽  
Vol 58 (6) ◽  
pp. 944-956 ◽  
Author(s):  
Dong Hoon Lee ◽  
Go Woon Kim ◽  
So Hee Kwon
2009 ◽  
Vol 48 (7) ◽  
pp. 1073-1074
Author(s):  
Pasquale Niscola ◽  
Massimiliano Palombi ◽  
Stefano Fratoni ◽  
Malgorzata Monika Trawinska ◽  
Laura Scaramucci ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4648-4648
Author(s):  
Wendy Cozen ◽  
Engels A. Eric ◽  
James R. Cerhan ◽  
Martha Linet ◽  
Leslie Bernstein ◽  
...  

Abstract Subtle differences in immune response may play a role in non-Hodgkin lymphoma (NHL) etiology. Because adult immune response may be influenced by early childhood exposures, we examined the role of childhood crowding, history of atopic disease, and other childhood immune-related exposures on the risk of non-Hodgkin lymphoma in a multi-center case-control study. Interviews were completed with 1,321 cases ascertained from population-based cancer registries in Seattle, Detroit, Los Angeles and Iowa, and with 1,057 frequency-matched controls, selected by random-digit dialing and from the Health Care Financing Administration (HCFA) database. The association between NHL risk in relation to atopy and other exposures was assessed using multivariable logistic regression methods. Most types of allergy were associated with protection from NHL, with hay fever especially protective against all NHL combined (Odds Ratio [OR] = 0.71, 95% confidence interval [CI]= 0.54–0.94), diffuse large B-cell lymphoma [DLBCL] (OR=0.61, 95% CI=0.41–0.91), and follicular lymphoma (OR=0.70, 95% CI=0.45–1.09). A history of eczema increased risk of follicular lymphoma (OR=1.92, 95% CI= 1.08–3.41) but not DLBCL (OR=1.06, 95% CI= 0.55.2.04). Asthma in childhood was not associated with risk of NHL. Risk of DLBCL (OR =1.72, 95% CI=1.17–2.52), but not follicular lymphoma (OR=1.15, 95% CI=0.75–1.76) was elevated for the youngest compared to the oldest of siblings. Neither number of siblings nor years between births of siblings were significantly associated with risk. These results suggest that some immune-related exposures may affect NHL risk.


2015 ◽  
Vol 33 (30) ◽  
pp. 3467-3474 ◽  
Author(s):  
Laurie H. Sehn ◽  
Andre Goy ◽  
Fritz C. Offner ◽  
Giovanni Martinelli ◽  
M. Dolores Caballero ◽  
...  

Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20+ indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m2). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm. Conclusion Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1789-1789
Author(s):  
Brenda M. Birmann ◽  
Yu-Han Chiu ◽  
Kimberly A. Bertrand ◽  
Shumin Zhang ◽  
Francine Laden ◽  
...  

Abstract Introduction: Circulating fatty acids, which can serve as biomarkers of diet or activity of specific metabolic pathways, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. We performed prospective studies to evaluate red blood cell (RBC) membrane fatty acids as biomarkers of future NHL risk, hypothesizing a positive association for RBC saturated and trans fatty acids and an inverse association for polyunsaturated fatty acids (PUFAs) with risk of NHL and major NHL subtypes. Methods: We conducted a nested case-control study among Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) participants who provided blood samples in 1989-90 (NHS) or 1993-4 (HPFS). We confirmed 583 incident NHL cases through 2010 and matched one control per case on age, gender, race, and blood draw date. By gas chromatography we identified and determined membrane concentrations of 33 individual fatty acids in RBCs. We estimated the odds ratio (OR) and 95% confidence interval (CI) of NHL per 1 standard deviation (SD) increase in RBC level of specific fatty acids using unconditional logistic regression adjusted for matching factors. We also analyzed three common B-NHL subtypes individually (chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma) and examined all B-NHLs in aggregate with and without CLL/SLL. Results: We observed no associations between specific fatty acids and NHL risk overall (data not shown). In subtype-specific analyses, RBC very long chain saturated fatty acid (VLCSFA) levels (including the 20:0, 22:0, 23:0 fatty acids) were inversely associated with the group of all B-NHLs except CLL/SLL, with ORs suggesting 18% to 19% decreases in risk per SD increase in concentration (Table 1). We observed suggestive inverse associations of similar magnitude for follicular lymphoma and DLBCL but no clear association with CLL/SLL for these 3 VLCSFAs (Table 1). These three VLCSFAs had moderate to strong pairwise correlations; Spearman correlations were 0.61 for 20:0 with 22:0, 0.42 for 20:0 with 23:0 and 0.64 for 22:0 with 23:0. PUFAs were also inversely associated with all B-NHL except CLL/SLL, a finding primarily driven by RBC arachidonic acid levels [OR (95%CI) per SD: 0.83 (0.71, 0.90)] and suggestive also for follicular lymphoma [OR, 95% CI per SD: 0.79 (0.61, 1.02)] and DLBCL [OR, 95% CI per SD: 0.82 (0.64, 1.06)]. The remaining RBC fatty acids, including trans fatty acids, had no clear association with any NHL endpoint (data not shown). We did not observe heterogeneity by follow-up interval or age, although we had limited statistical power to detect significant heterogeneity for specific NHL subtypes. Conclusion: RBC levels of VLCSFAs and PUFAs may be associated with lower risk of several types of B-NHL other than CLL/SLL. The specific fatty acids found to be related with NHL risk are not good biomarkers of diet, suggesting that the observed relations may instead be due to endogenous metabolic processes. Investigation is warranted into biologic mechanisms by which circulating fatty acids and their determinants may influence NHL risk, as is further examination of these associations in larger (ideally pooled) study populations. Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Author(s):  
Kieron Dunleavy ◽  
Wyndham H Wilson

Lymphoma is the fifth most common type of cancer in the United States, with 74,490 new cases estimated in 2009. Approximately 15% of patients with lymphoma have Hodgkin lymphoma; the remainder have one of the non-Hodgkin lymphomas. The incidence of non-Hodgkin lymphoma has increased steadily over recent decades. This chapter reviews the epidemiology, classification, clinical features, pathology, diagnostic evaluation, staging and prognosis, and treatment of Hodgkin and non-Hodgkin lymphoma. Other topics discussed include the acute and chronic effects of therapy for Hodgkin disease, as well as the subtypes of non-Hodgkin lymphomas, including indolent B cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone lymphoma, diffuse large B cell lymphoma (DLBCL), primary central nervous system lymphoma (PCNSL), Burkitt lymphoma, and HIV-related non-Hodgkin lymphoma. Figures illustrate the cellular appearance of Hodgkin lymphoma subtypes and DLBCL, diagnosis of DLBCL subtypes by gene expression, computed tomography and plain chest film in primary mediastinal cell lymphoma, MRI of the brain in PCNSL, and gene expression and gene expression predictors of survival among patients with DLBCL treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], and prednisone (R-CHOP). Tables describe the Ann Arbor classification and the Cotswold modification for staging of lymphoma; the International Prognostic Score for advanced Hodgkin lymphoma; the World Health Organization classification of hematopoietic neoplasms; chromosomal translocations in non-Hodgkin lymphoma; the Eastern Cooperative Oncology Group performance scale; the International Prognostic Index for aggressive non-Hodgkin lymphoma; and the Follicular Lymphoma International Prognostic Index. This chapter has 185 references. This review contains 9 tables, 7 figures and 185 references


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1999-1999
Author(s):  
Veronika Bachanova ◽  
Celalettin Ustun ◽  
Qing Cao ◽  
Froelich Jerry ◽  
Linda J Burns

Abstract Abstract 1999 Allogeneic donor hematopoetic stem cell transplantation (HCT) is increasingly used for patients with non-Hodgkin lymphoma (NHL). Positron emission tomography (PET) has become a standard for lymphoma evaluation and a valuable prognostic tool to risk-stratify treatment and time of the autologous HCT. Role of PET imaging in allogeneic HCT setting is controversial. We sought to investigate the value of PET status pre-transplantation and at day 100 post donor HCT as an indicator predictive of relapse and survival post allograft. Seventy-three patients (median age 50 years [range 2–69 years]) with NHL received allogeneic HCT at University of Minnesota from 2004–2010 and had PET imaging within 4 weeks pre-transplant. All PET and CT images were reviewed centrally by nuclear medicine radiologist. Follicular lymphoma (n=26) was more common than large cell, mantle cell lymphoma and others. PET scan pre-transplant was positive in 44 patients (PET+ group 57% vs PET- group 43%). Two thirds of PET+ group were in partial remission (PR), 7% CR and 16% were chemo-refractory prior to transplant compared to 25% in PR, 68% in CR and 7% refractory in PET+ cohort (p<0.01). Forty percent had PET-avid extra-nodal involvement. In both PET positive and negative groups the two thirds received reduced intensity conditioning and related donor (52% and 51%) or umbilical cord blood grafts (55% and 41%, respectively). 5-years disease-free survival (DFS) and overall survival (OS) of the cohort was 51% (95%CI 35– 64%) and 60% (95%CI 44–73%). DFS and OS of PET+ group was similar to PET- group (DFS: 50% vs 52%, p=0.31; OS: 63% vs 56%, p=0.63). In univariate analysis, the lymphoma subtype, disease status at transplant, extranodal disease, elevated LDH, high B2 macroglobulin or marrow involvement at the time of transplant had no impact on survival or relapse rate. At median follow-up of 3.33 years (range 1.00–6.74) the cumulative 2 year relapse rate was 17%; similar in PET+ and PET- groups (19% [95% CI 7– 31%] vs 15% [95% CI 1– 28%]; p=0.48). Transplant mortality at 1-year was low for entire cohort (11% [95% CI 3–18%]) and particularly low in follicular lymphoma (4% [95%CI 0–10%]) compared to DL/MCL (10% [95%CI 0–21%]) and other NHL (25% [95%CI 4–46%]; p=0.51). PET status (pos vs neg) had no impact on grade III-IV acute GVHD and chronic GVHD. Fifty-four patients with available surveillance PET evaluation at day 100 post-transplant. The 1-year relapse rate and 5 yr DFS was significantly improved for those patient who were PET-negative (day 100 PET- vs PET+ group: relapse 9% vs 42%; p<0.01; DFS 57% vs 25%, p<0.01 and OS 68% vs 59%, p=0.63). In conclusion, pre-allo HCT PET scan for NHL does not predict transplant outcomes, however negative PET scan 100 days post-allo SCT is a valuable tool predictive of superior transplant DFS. Future studies evaluating role of PET in patients with specific lymphoma subsets and development of novel peri-transplant or post-transplant interventions for patients at high relapse risk are warranted. Disclosures: Off Label Use: decitabine for relapsed ALL vorinostat for relapsed ALL.


Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4820-4823 ◽  
Author(s):  
Sophia S. Wang ◽  
Amr M. Abdou ◽  
Lindsay M. Morton ◽  
Rasmi Thomas ◽  
James R. Cerhan ◽  
...  

Abstract Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.


2021 ◽  
Vol 2 (1) ◽  

Ovarian lymphoma is an infrequent disease, accounting for less than 1% of all non-Hodgkin lymphoma diagnosis. Symptoms include abnormal vaginal bleeding or discharge, abdominal pain, and urinary obstruction due to the large mass. In our case, a 60-year-old woman, underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy, as she presented with low-grade follicular lymphoma (FL) in both the ovaries and the left ovary was observed to be enlarged. The tumor is categorized as lymphoma based upon immunohistochemical markers. Computed tomography (CT) scan of the chest, abdomen, and pelvis and bone marrow biopsy are important for the staging of primary lymphoma of the ovary. The first-line chemotherapy regimen includes rituximab ,cyclophosphamid ,doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP) for rapidly proliferative non-Hodgkin lymphoma (NHL). Lymphomas with slower growth patterns can be treated with Bendamustine-Rituximab and don’t need aggressive R-CHOP treatment.


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