Medical History, Lifestyle, Family History, and Occupational Risk Factors for Diffuse Large B-Cell Lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

Abstract Non-Hodgkin lymphoma (NHL) consists of a heterogeneous group of tumors. Population-based data on the familial risk for specific histopathologic subtypes have not been established. Such data are useful for clinical counseling and for searching tumor subtypes sharing common genetic pathways. We used the Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for histopathology-specific subtypes of NHL in 4455 offspring with NHL whose parents or siblings were affected with different types of lymphoproliferative malignancies. A familial history of NHL significantly increased the risk for NHL (SIRparent = 1.8; SIRsibling = 1.9) and for diffuse large B-cell lymphoma (SIRparent = 2.3), follicular lymphoma (SIRsibling = 2.3), and B-cell lymphoma not otherwise specified (NOS) (SIRsibling = 3.4). For a parental history of histopathology-specific concordant cancer, the risks were significantly increased for diffuse large B-cell lymphoma (SIR = 11.8), follicular NHL (SIR = 6.1), plasma cell myeloma (SIR = 2.5), and chronic lymphocytic leukemia (SIR = 5.9). Familial clusters for NHL seemed stronger in females and in siblings. Our study provides the first quantification of the familial risks for NHL by histopathology. The present findings give evidence for a strong familial association of NHL, with little differences in the magnitude of risks for various histopathologic subtypes. The patterns of risks in parents and siblings support the hypothesis of an autosomal-dominant component for diffuse large B-cell NHL and a recessive one for follicular NHL. (Blood. 2005;106:668-672)

Download Full-text

Numbers and Percentages Of Peripheral Monocytes Is a Prognostic Marker For CNS Involvement In Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v122.21.1775.1775 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1775-1775

Author(s):

Hideaki Nitta ◽

Yasuhito Terui ◽

Masahiro Yokoyama ◽

Noriko Nishimura ◽

Kyoko Ueda ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Peripheral Blood ◽

Clinical Course ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cns Involvement ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background In the rituximab era, there are several studies that have reported the risk factors for central nervous system (CNS) involvement in non-Hodgkin lymphoma, but the same factors emerge, such as high international prognostic index (IPI) score, >1 extranodal site, elevated lactate dehydrogenase (LDH) level, poor performance status (PS), advanced stage, bone marrow involvement. Macrophages are an important component of the tumor microenvironment and the immune response to malignancy. Recently, elevated peripheral blood monocyte counts have been shown to be an independent marker associated with poor prognosis in patients with both non-Hodgkin and Hodgkin lymphoma. Patients and methods We reviewed data from a total of 1238 lymphoma patients(1185 non-Hodgkin lymphoma, 53 Hodgkin lymphoma) at our institution between February 2005 and May 2013. Of these, 42 patients (3.4%) developed CNS complications during the clinical course. Thirty patients out of these 42 (71.4%) were diagnosed with diffuse large B-cell lymphoma (DLBCL). Therefore, we focused on DLBCL. In this study, we retrospectively analyzed data from a total of 557 DLBCL patients, 30 patients (5.4%) who developed CNS involvement and 527 patients with DLBCL but without CNS involvement. This study was approved by the Institutional Review Board of the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The clinical features of all 557 DLBCL patients, including 30 patients with CNS involvement, are summarized in Table 1. CNS involvement was defined by the presence of at least one histologically confirmed CNS involvement; neuroimaging findings compatible with CNS involvement with lymphoma, in conjunction with consistent clinical presentation; and the absence of other clinically feasible diagnosis or positive cerebrospinal fluid (CSF) (lymphoma cells detected by cytology). The absolute monocyte counts (AMC) and monocyte ratio were derived from pre-treatment complete blood counts. Pathological studies Immunohistochemical analysis was carried out using mAbs against CD68 at our institution. Results The incidence of CNS involvement was 5.4%, 1.3% having CNS involvement at diagnosis with DLBCL. Intriguingly, absolute monocyte counts (AMC) ≥0.6 (×109/L) at diagnosis were significantly frequent in 30 DLBCL patients (p=0.0420) with CNS involvement, compared with in 527 DLBCL patients without CNS involvement. Furthermore, the monocyte ratio ≥8% in peripheral blood at diagnosis was significantly frequent in 30 DLBCL patients (p=0.0325) with CNS involvement, compared with in 527 DLBCL patients without CNS involvement. DLBCL patients with CNS involvement showed age ≤60 years, stage III-IV, IPI score ≥3, and PS ≥2, elevated soluble IL-2 receptor levels was significantly frequent, compared with in DLBCL patients without CNS involvement. Neither gender, elevated LDH level, white blood cell counts (WBC) differed significantly in the two groups. With regard to pathological immunohistochemistry, the numbers of CD68 positive cells in or around lymphoma samples did not differ in the 14 DLBCL patients with CNS involvement that we were able to analyze, compared with DLBCL patients without CNS involvement. CNS involvement free survival rate in DLBCL patients was significantly lower in AMC ≥0.6 (×109/L) and/or the monocyte ratio ≥8% (Log-rank test, P=0.0102) in peripheral blood at diagnosis, compared with in AMC less than 0.6 (×109/L) and the monocyte ratio less than 8%. Conclusions These results suggest that in DLBCL patients, AMC and monocyte ratios in peripheral blood at diagnosis are closely correlated with the risk of eventual CNS involvement. AMC and monocyte ratios in peripheral blood at diagnosis in DLBCL patients could be a useful prognostic marker for the risk of CNS involvement during the clinical course. Disclosures: Yokoyama: Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy.

Download Full-text

CNS Involvement in Childhood and Adolescence Non-Hodgkin Lymphoma: Prevalence and Patient’s Outcome Differ According to the Subtype.

Blood ◽

10.1182/blood.v106.11.233.233 ◽

2005 ◽

Vol 106 (11) ◽

pp. 233-233 ◽

Cited By ~ 2

Author(s):

Janina Salzburg ◽

Birgit Burkhardt ◽

Olga Wachowski ◽

Martin Zimmermann ◽

Reza Parwaresch ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Stage Iii ◽

Childhood And Adolescence ◽

Cns Involvement ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract We evaluated the prevalence and clinical significance of CNS involvement in childhood and adolescence Non-Hodgkin Lymphoma (NHL). Between 10/86 and 12/02, 2,086 eligible patients (pts) were registered in the subsequent multicenter trials NHL-BFM86, −90, −95. Median follow up was 6.5 years (0.3–17.7 years). Initial staging included examination of cerebrospinal fluid (CSF) and cranial CT or MRI. CNS involvement was diagnosed in case of CSF blasts, and/or intracerebral mass (ICM), and/or cranial nerve palsy (CNP), not caused by an extradural mass. Epidural NHL without any of the above criteria was not considered as CNS disease. CNS positive (pos) pts with lymphoblastic lymphoma (LBL) received an 8-drug induction, consolidation, re-intensification, and maintenance up to 2 years. CNS therapy included dexamethason, methotrexate (MTX) 5 g/m2 i.v., 13 dosis of intrathecal (i.th.) MTX, and cranial radiotherapy (CRT). CNS pos pts with non-LBL received six 5-day courses based upon vincristine, vindesine, dexamethason, oxazophorins, cytarabine, etoposide, doxorubicin, MTX 5 g/m2 i.v., and intraventricularely or i.th. applied chemotherapy. CRT was omitted since study BFM90, except for pts with anaplastic large cell lymphoma (ALCL). 111 of the 2,086 analyzed NHL pts were initially diagnosed as CNS pos. 1,933 pts were CNS negative (neg) and in 42 pts the CNS status was questionable or not evaluable due to incomplete diagnostics. Prevalence and outcome of CNS pos pts according to NHL subtypes were as follows. In the total group, the probability of event free survival at 5 years (pEFS) was 63 ± 5% for CNS pos pts compared to 81 ± 1% for CNS neg pts with stage III/IV NHL (n=1,323) (p< 0.0001). In LBL pts pEFS was 81 ± 10% for CNS pos pts and 84 ± 2% for CNS neg pts with stage III/IV (n=359) (p=0.54), while in Burkitt/B-ALL pEFS was 60 ± 5 % for CNS pos pts versus 85 ± 1% for CNS neg pts with stage III/IV (n=599) (p<0.0001). For CNS pos Burkitt/B-ALL pts pEFS was 57 ± 7% for 57 pts with and was 67 ± 10% for 24 pts without bone marrow involvement (p=0.31). Total LBL (T-, pB-) Burkitt/B-ALL PMLBL* DLBL° ALCL Others *primary mediastinal large B-cell lymphoma, °diffuse large B-cell lymphoma Number of pts 2086 433 1003 40 222 215 173 CNS pos pts 111 16 81 0 4 5 5 Percentage 5,3% 3,7% 8,1% 0 1,8% 2,3% 2,9% Chracteristics and outcome of CNS pos pts CSF blasts +/ − others 81 13 60 0 1 4 3 ICM (without CSF blasts) 18 2 11 0 2 1 2 CNP 12 1 10 0 1 0 0 Death unrelated to tumor 6 0 6 0 0 0 0 Relapse/Nonresponse 30 2 24 0 0 2 2 CNS involved 18 1 15 0 0 2 0 In summary, CNS-disease was most frequent in pts with Burkitt/B-ALL, while it was rare in DLBL pts. In Burkitt/B-ALL, CNS pos pts had a worse outcome compared to CNS neg pts with advanced stage disease, while in LBL pts outcome was comparable for CNS pos and CNS neg pts.

Download Full-text

Composite Nodular Sclerosis Hodgkin and Diffuse Large B Cell Non-Hodgkin Lymphoma Arising from the Thymus.

Blood ◽

10.1182/blood.v110.11.4432.4432 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4432-4432

Author(s):

Luis D. Sumoza ◽

Jeffrey L. Jorgensen ◽

Ilia R. Sumoza

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Mitotic Rate ◽

Nodular Sclerosis ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

First Case ◽

Large B Cell

Abstract We report the first case of composite Nodular Sclerosis Hodgkin and Diffuse Large B-Cell Non-hodgkin’s lymphoma of the mediastinum. We present a case of an inmunocompetent patient operated on for a mediastinal tumor similar to a Thymoma, which the histological examination morphological, and immunophenotyping were performed and confirmed the existence of 2 independent, unrelated tumors. The pathology blocks submitted show a composite lymphoma, with components of both classical Hodgkin lymphoma (Hodgkin’s disease), nodular sclerosis type, grade 2 of 2 in all three blocks. One block also shows non-Hodgkin lymphoma, namely diffuse large B-cell lymphoma, with a distinct immunophenotype. The Hodgkin-Reed-Sternberg cells were positive for CD15, CD20, CD30, PAX-5 (weak/partial), and EBV (EBERs), and negative for CD45. In contrast, the large B-cells are positive for CD20, PAX-5 (strong), CD45, and CD30 (very focal), and negative for CD15 and EBERs. The large B-cell area had an increased mitotic rate. Taken together, these data indicate that these Hodgkin and the Non-Hodgkin’ lymphomas arose as a consequence of independent malignant transformation events.

Download Full-text

DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes

Molecular Cancer ◽

10.1186/s12943-021-01437-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Atish Kizhakeyil ◽

Nurmahirah Binte Mohammed Zaini ◽

Zhi Sheng Poh ◽

Brandon Han Siang Wong ◽

Xinpeng Loh ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Prognostic Marker ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Download Full-text

Clinical And Prognostic Features Of Non Hodgkin Lymphoma And Preliminary Effective Evaluation Of R-Chop Regimen In Patients With Diffuse Large B-Cell Lymphoma

Journal of Clinical Medicine- Hue Central Hospital ◽

10.38103/jcmhch.2020.64.7 ◽

2020 ◽

Author(s):

Thuy Nguyen Thi

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Intermediate Risk ◽

Chop Regimen ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Who 2008

Background: WHO 2008 classification of Non Hodgkin Lymphoma (NHL) has been introduced and got consensus internationally. However, studies on NHL according to WHO 2008 classification are limited in Vietnam. In terms of treatment, the R-CHOP regimen is still the most commonly used regimen for the treatment of moderate or high grade malignant lymphoma tumors. However, its effectiveness on each type has not been specifically studied. Purpose of this research is to evaluate of clinical and subclinical characteristics of NHL patients according to the 2008 WHO classification on lymphoid neoplasms and to evaluate preliminary effective of diffuse large B cell lymphoma (DLBCL) patients with R-CHOP regimen. Materials and methods: A prospective descriptive study was conducted on 48 patients diagnosed with NHL undergoing treatment at the Hue University Hospital from July 2019 and Hue Central Hospital from April 2020 to present. Results: The mean age was 52.4 years, male/female ratio = 1.3/1, the most common primary tumor site was lymph nodes with 54.3%. Stage IV was found in 37.5% of all cases. DLBCL was the most common type, accounted for 58.3%, whereas marginal zone lymphoma had the lowest incidence (2.1%). According to the International Prognostic Index (IPI), low risk, low-intermediate risk, high-intermediate risk, high risk group were 43.6%; 25.0%; 18.8%; 12.6% respectively. 34.8% patients responsed completely after 3 cycles and after 6 – 8 cycles, 58.8% patients achieved complete response. Grade III, IV neutropenia, grade I, II peripheral neuropathy and grade I, II thrompocytopenia were the most common side effect observed. Conclusions: DLBCL is the most common Non Hodgkin Lymphoma. R-CHOP regimen has a good response after 6-8 cycles in DLBCL diseases and is well tolerated that the adverse events are mostly able to control effectively.

Download Full-text

Primary mantle cell lymphoma complicated with cutaneous diffuse large B-cell lymphoma, leg type: a rare case report of composite non-Hodgkin lymphoma in different organs

10.21203/rs.3.rs-70686/v1 ◽

2020 ◽

Author(s):

Yanfeng Jiang ◽

Zhiming Zeng ◽

Lihua Yang ◽

Jie Zeng ◽

Fengyan Qin ◽

...

Keyword(s):

B Cell ◽

Mantle Cell Lymphoma ◽

Hodgkin Lymphoma ◽

Rare Case ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Mantle Cell ◽

Large B Cell

Abstract Background Composite lymphomas (CLs) are a kind of rare disease that two distinct categories of lymphomas occur in the same patient. Histologically, composite lymphomas can be composed of a Hodgkin’s lymphoma and a non-Hodgkin lymphoma or two distinct non-Hodgkin lymphomas. So far, most of the cases have been reported to occur in a single anatomical site or mass. Case presentation: A 61-year-old man without any B-type symptoms complained of an enlarging mass in the abdomen for one month. A 10 × 10 cm abdominal mass could be touched in the hypogastric region. Through pathological biopsy, mantle cell lymphoma can be diagnosed. After one cycle chemotherapy regimen of FCD, red rashes and blisters came out on the patient's right lower extremity. Cutaneous diffuse large B-cell lymphoma (DLBCL) was diagnosed by skin biopsy. In this report, we describe a case of composite lymphoma occurring in different organs, which consisted of primary mantle cell lymphoma (MCL) and cutaneous DLBCL, leg type. The patient then received a series of chemotherapy regimens without rituximab then achieved partial response (PR). Conclusions To our knowledge, this is a rare case of CLs occurring in different anatomic sites that were treated by chemotherapy and achieved PR. As we learn more about the mechanisms and treatment of CLs, we look forward to more treatment options in the future for patients to give them a better prognosis.

Download Full-text

A Phase 2 Clinical Trial of SGN-40 Monotherapy in Relapsed Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v112.11.1000.1000 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1000-1000 ◽

Cited By ~ 1

Author(s):

Ranjana Advani ◽

Sven De Vos ◽

Stephen M. Ansell ◽

Brad Kahl ◽

Bruce D. Cheson ◽

...

Keyword(s):

B Cell ◽

Disease Progression ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

Phase 1 ◽

B Cell Lymphoma ◽

Phase 2 ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract BACKGROUND: SGN-40 is a humanized monoclonal antibody that targets CD40. Upon binding to CD40, SGN-40 triggers pro-apoptotic signal transduction pathways and mediates effector cell functions (ADCC and ADCP). SGN-40 demonstrated preliminary anti-tumor activity in a phase 1 study of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL) patients (ASH 2006, Abstract 695). METHODS: We conducted a multicenter, phase 2, open-label study to determine the overall response rate and toxicity profile of SGN-40 in patients with relapsed DLBCL. Tumor samples were assessed by a central lab for pathology confirmation and CD40 expression. Eligible patients had de novo or transformed DLBCL at diagnosis and were excluded if previously treated for indolent lymphoma. Required prior therapy consisted of combination chemotherapy with rituximab and, if eligible, autologous stem cell transplantation. Patients received 6 intravenous infusions of SGN-40 over 5 weeks (Cycle 1) with intra-patient dose loading (1 mg/kg on Day 1; 2 mg/kg on Day 4; 4 mg/kg on Day 8) and 8 mg/kg/wk thereafter. Responding patients and those with stable disease were eligible to continue therapy until disease progression or a maximum of 12 cycles. RESULTS: Forty-six patients (28 M, 18 F), with a median age of 72 years (range 17–85), were enrolled at 10 centers in the US. Patients were heavily pre-treated, with a median of 4 prior systemic chemotherapy regimens (range 1–10). Immunohistochemistry analysis of patient tumor samples demonstrated high expression of CD40 in all patients with the exception of 1 patient who was negative. Thirty-eight of the 46 patients met predefined criteria for evaluation (completed dose loading and had no major protocol violations). Best responses seen were CR (n=2, 5%) and PR (n=2, 5%), yielding an ORR of 10%. Furthermore, 9 (24%) patients had SD as best response. Reductions in tumor size were seen in approximately one-third of patients. Twenty (53%) patients had PD and 5 (13%) patients have yet to be assessed. Treatment with SGN-40 was generally well tolerated. Grade 3/4 events that occurred in more than 1 patient in the intent-to-treat population (N=46), regardless of drug attribution were thrombocytopenia (n=5); neutropenia (n=4); and anemia, fatigue, pneumonia, hyponatremia, DVT, and disease progression (n=2 pts each). Of these events, only fatigue (n=2) and neutropenia (n=2) were considered drug related by the investigator. CONCLUSION: Monotherapy with SGN-40 in DLBCL patients is well tolerated and resulted in objective responses consistent with the previous phase 1 experience. These data support further evaluation of SGN-40 in combination with chemotherapy in non-Hodgkin lymphoma; 3 combination clinical trials are ongoing. Retrospective correlation of clinical outcome and a gene signature that includes baseline CD40 activation status are planned.

Download Full-text

Non-Hodgkin lymphoma: The Indian scene.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e20063 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e20063-e20063

Author(s):

Ajay Gogia ◽

Sukesh Nair ◽

Atul Sharma ◽

Lalit Kumar ◽

Saumyaranjan Mallick ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Bulky Disease ◽

Female Ratio ◽

Non Hodgkin Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

e20063 Background: There is a lack of data available regarding the distribution of Non-Hodgkin lymphoma (NHL) subtype, according to a recent WHO- 2016 classification and outcome of diffuse large B cell lymphoma (DLBCL) on the basis of cell of origin (COO) from developing country in Rituximab era. Methods: This is an ambispective study of newly diagnosed patients with NHL, treated in the Department of Medical Oncology, AIIMS, New Delhi. A total of 775 cases of adult ( > 18 years) lymphoma were registered over a period of 5 years (January 2014 to December 2018). Outcome of DLBCL patients who have received uniform RCHOP protocol separately analysed. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification Results: NHL constituted 622 (80.26%) and Hodgkin's lymphoma 153 (19.74%) of the cases. B- cell constituted 553 (88.9%) among all NHL and rest 69 (11.1%) cases were T cell in origin.. Diffuse large B cell lymphoma (DLBCL) was the most common NHL 417(67%) followed by follicular lymphoma 60 (9.64%), mantle cell lymphoma 35 (5.62%), PTCL-NOS 25 (4.01%), ALCL 16 (2.57%),marginal zone lymphoma 14 (2.25%), T-LBL 13(2.1%) and the rest of the cases were rare NHL( < 1% cases each) for e.g. SLL, NK-T, BL, SLVL, AITL etc. Among the 417 cases of DLBCL, 262 (62.8%) cases received rituximab along with CHOP regimen. The median age of RCHOP treated patients was 47.6 years with male female ratio of 2.3:1. B symptoms were seen in 39% patients and bulky disease in 33%. ECOG performance status of 0-2 was present in 67% and 51% presented with advanced disease. GCB was seen in 42% and 44% were ABC. Low risk IPI was seen in 48 % and 40% were intermediate risk IPI. The overall response rate (ORR) was 82 % with a complete response rate (CR) of 75.6 %. Presence of bulky disease and non-radiotherapy treatment protocols were associated with inferior CR rate. After a median follow up of 30 months, the 3-year event free (EFS) survival and overall survival (OS) were 78 % and 88 % respectively. Low albumin ( < 4 gm/dl) and age > 60 years were associated with inferior EFS whereas high IPI risk score was associated with inferior OS. Pre-phase was used in 20% of cases. Grade III/ IV anaemia, neutropenia and thrombocytopenia were seen in 5%, 13% and 2% of patients respectively. Febrile neutropenia was seen in 7 % of patients and there were 3 treatment related death. Rituximab infusion related toxicity was seen in 7 patients. Conclusions: DLBCL is the most common NHL ( GC-42%, ABC-44%). The distribution according to COO dose not impact on CR rate and EFS and OS . RCHOP is well tolerated in our patients and results are comparable with the western data.

Download Full-text