Characteristics and Outcome Among 116 Patients with HIV Associated Lymphoma Included in the French ANRS CO16 Lymphovir Cohort Study.

Abstract Abstract 2147 Background: Human Immunodeficiency Virus (HIV) infection is associated with an increased risk of Hodgkin lymphoma (HL) and B-cell non-Hodgkin lymphoma (NHL). Increased risk of NHL is strongly correlated to the severity of the underlying immunodeficiency. Introduction of combined antiretroviral therapy (cART) has reduced the incidence of NHL -but not of HL's- among HIV-infected individuals. Outcomes are reported to be poorer among HIV-infected patients with HL or NHL than among non-HIV-infected patients. We carry out a cohort with the aim to study the characteristics and outcome of HIV-related lymphomas. Methods: The multicentric prospective Cohort of HIV related lymphomas (ANRS-CO16 Lymphovir cohort) enrolled 116 adult patients in 32 centers between October 2007 and April 2012. Investigations were performed after approval of the ethic committee. Patients were included at diagnosis of lymphoma (n=108) or at first relapse (1 HL, 7 NHL). Data collection concerned HIV infection history, clinical, biological and histological presentation, treatment and evolution of lymphoma. Pathological materials were centralized and 91 cases were reviewed. Diagnoses were based on World Health Organization criteria. Each patient was followed every 6 months during 5 years. Results: Among the 116 patients, 39.7% (46) were diagnosed with HL and 60.3% (70) with NHL. Median age was 43.5 years (ranging from 20 to 61) among patients with HL and 47 years (23 to 67) among those with NHL. Gender (male/female) ratio was 8.2 (41/5) among patients with HL, 1.7 (44/26) among those with NHL. The histological distribution of NHL were diffuse large B-cell lymphoma (DLBCL) 54.3% (38), Burkitt lymphomas (BL) 18.6% (13), plasmablastic lymphoma 10% (7), marginal zone/lymphoplasmocytic lymphoma 7.1% (5), others 10%: PTLD- like lymphoma (2), primary effusion lymphoma (1), follicular lymphoma (1), anaplastic lymphoma (1), unclassified (2). There was a predominance of clinical stages III/IV versus I/II among HL (76.7%, 33/43) and NHL patients (73.5%, 50/68). Among patients with DLBCL, LDH level was elevated in 68.4% (26/38) and performance status altered (2–4 versus 0–1) in 38.5% (15/39). HIV infection had been diagnosed for a median of 151 months (0 to 312) among HL patients and 117 (0 to 327) among those with NHL. The interval between diagnoses of HIV infection and lymphoma was shorter than 3 months for 2 patients with HL and 13 with NHL. All other patients except 6 NHL patients had been treated with ART at diagnosis of lymphoma. Median durations of ARV were 128 months (2 to 238) among HL patients and 119 months (1 to 236) among those with NHL. Patients with HL had a median CD4 T-cell count at diagnosis of lymphoma of 353/mm3 (range 37–1120), those with NHL, 261/mm3 (range 7–1322)]. The median interval between lymphoma occurrence and last follow-up was 21 months (range 0–41). During follow-up, all patients were treated with ARV. Among first-line HL patients, 39 out of 40 were treated with ABVD. Out of 40 patients with DLBCL or BL, 30 received chemotherapies combined with rituximab. At 24 months, overall survival is 95% among patients with HL and 78% among those with NHL (Figure 1). Two HL patients died during follow-up: one HL patient included in relapse from progression, another from a second cancer. Sixteen NHL patients died during follow-up: there were 10 early deaths (<6 months) from complications of treatment (9) or disease progression (1) and 6 later deaths from disease progression (4), second cancer (1), unknown (1). None of the patients who died during the first 6 months following diagnosis had received rituximab. Conclusions: The present study points out the high proportion of HL among HIV infection with lymphoma in the cART era and their favourable outcome compared to previous reports. This study also strengthens the heterogeneity of HIV-related lymphomas and the frequency of early deaths among patients with NHL. Disclosures: No relevant conflicts of interest to declare.

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How I treat double-hit lymphoma

Blood ◽

10.1182/blood-2017-04-737320 ◽

2017 ◽

Vol 130 (5) ◽

pp. 590-596 ◽

Cited By ~ 50

Author(s):

Jonathan W. Friedberg

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Central Nervous System Involvement ◽

B Cell Lymphoma ◽

World Health ◽

Large B Cell Lymphoma ◽

Double Hit Lymphoma ◽

Increased Risk ◽

Double Hit ◽

Large B Cell

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.

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Immunohistochemical Expression of CD10, BCL6, and MUM1 in Primary Nodal Diffuse Large B-Cell Lymphoma: MUM1 Expression Alone (but Not Germinal Center B-Cell Immunophenotype) Is an Independent Prognostic Factor.

Blood ◽

10.1182/blood.v106.11.4706.4706 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4706-4706

Author(s):

Nicholas Wongchaowart ◽

Ena Segota ◽

Tao Jin ◽

Brad Pohlman ◽

Eric D. Hsi

Keyword(s):

B Cell ◽

Disease Progression ◽

Lower Risk ◽

B Cell Lymphoma ◽

Primary Therapy ◽

Large B Cell Lymphoma ◽

Germinal Center B Cell ◽

Risk Of Progression ◽

Bcl6 Expression

Abstract Introduction: Diffuse large B-cell lymphoma (DLBL) is a biologically and clinically heterogeneous lymphoma. Gene expression profiling studies using cDNA microarray have led to the development of a new paradigm for the subclassification of DLBL into germinal center B-cell (GCB) and activated B-cell types with a favorable and an unfavorable prognosis, respectively. The expression pattern of CD10, BCL6 and MUM1 by immunohistochemistry (IHC) has been proposed as a surrogate to distinguish GCB from non-GCB types. This immunohistochemical model must be validated in other data sets. Methods: We identified 57 cases of primary nodal DLBL for which the initial diagnostic biopsy, International Prognostic Index (IPI), and clinical follow-up were available. These patients (pts) received CHOP (n=51) or CHOP-like (n=6) chemotherapy, rituximab (n=12), radiation therapy (n=20), and high dose therapy with stem cell transplantation (SCT)(n=6) as planned primary therapy with curative intent. A tissue microarray (TMA) was constructed and cases were assessed for expression of CD10, BCL6, and MUM1. GCB and non-GCB immunophenotypes (IP) were defined as previously described (Hans et al. Blood 2004, 103:272–85). Clinical endpoints were disease progression and death. Analyses were performed using Cox proportional hazards testing. Results: The pts consisted of 32 men and 25 women with median age of 60 (range 29–82) years. 26 pts progressed and 25 pts died. Median follow-up of surviving pts was 69.9 (range 8.3–148.1) months. 64%, 82%, and 58% of cases expressed CD10, BCL6, and MUM 1, respectively, and 69% had a GCB IP using the Hans criteria. Univariate analysis showed that high IPI and MUM1 expression predicted a higher risk of progression (P<.001 and P=.027) while IPI, MUM1, and GCB IP predicted a higher risk of death (P<.001, P=.031, and P=.023). BCL6 expression was associated with a trend toward a lower risk of progression (P=.10) but not death (P=.38). By multivariate analysis, high IPI and MUM1 expression remained independent predictors of both progression (HR 7.07, 95% CI 2.68–18.63, P<.001 and HR=3.88, 95% CI 1.51–9.95, P=.005, respectively) and death (HR 6.48, 95% CI 2.57–16.34, P<.001 and HR 3.21, 95% CI 1.25–825, P.015, respectively) while BCL6 expression predicted a lower risk of progression only (HR 0.29, 95% CI 0.11–0.74, P=0.01). Two re-analyses excluding pts that received rituximab or SCT as a planned part of primary therapy gave similar results. Conclusions: We were unable to confirm the significance of GCB vs non-GCB types using CD10, BCL6, and MUM1 immuhistochemical expression patterns as independent predictors of either progression or death in this cohort of nodal DLBL. However, MUM1 expression (in addition to high IPI) was an independent predictor of a higher risk of both disease progression and death. BCL6 was an independent predictor of a lower risk of disease progression. BCL6 and MUM1 assessment using IHC in nodal DLBL provides useful prognostic information and simplifies pathological risk stratification of nodal DLBL from 3 to 2 markers. These data require confirmation in a larger, independent cohort of nodal DLBL pts treated with a rituximab-containing chemotherapy regimen.

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Heritable Predisposition To Richter Syndrome In Patients With Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v122.21.2867.2867 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2867-2867 ◽

Cited By ~ 3

Author(s):

Sameer A. Parikh ◽

Susan L Slager ◽

Kari G. Rabe ◽

Neil E. Kay ◽

James R Cerhan ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Research Funding ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Chromosome 18 ◽

Richter Syndrome ◽

Increased Risk ◽

Translocation Breakpoints

Abstract Background Approximately 2-8% patients with chronic lymphocytic leukemia (CLL) will transform to diffuse large B-cell lymphoma (DLBCL, Richter syndrome [RS]). Clinical characteristics and molecular markers at the time of CLL diagnosis are associated with the risk of RS; however, there are no data regarding germline genetic variations and the risk of RS. Genomewide association studies (GWAS) have shown several single-nucleotide polymorphisms (SNPs) that are associated with a higher risk of familial CLL. It is not known whether any of these polymorphisms also predispose to RS. Methods Since 2002, all consecutive patients with newly diagnosed (<9 months diagnosis) CLL at Mayo Clinic were offered enrollment into a prospective genetic epidemiology study. Patients completed extensive epidemiologic questionnaires and baseline clinical, laboratory, and biologic data were abstracted using a standard protocol. Genotyping of germline tissue at diagnosis was performed using an Illumina iSelect panel and Affymetrix 6.0 SNP chip. All patients were prospectively and longitudinally followed at defined time-points with systematic collection of data on treatments, second cancers, and RS. All patients with biopsy-proven DLBCL during follow-up were considered to have undergone transformation into RS. Time to RS was calculated from CLL diagnosis date until RS or until last follow-up date for those with no RS. SNPs were modeled in two ways: ordinal and dominant. Cox regression was used to estimate hazard ratio (HR) for individual SNPs with time to transformation. Results Thirteen of the GWAS-discovered SNPs associated with risk of developing CLL were available and genotyped on 620 CLL patients. Median age at diagnosis of CLL was 62 years (range 27-88), and 428 (69%) were male. Three hundred and ten (51%) patients were low (0) Rai stage, 271 (45%) were intermediate (I-II) Rai stage, and 22 (4%) were advanced (III-IV) Rai stage. The immunoglobulin heavy chain gene was unmutated in 189 (40%) patients; 157 (32%) patients expressed ZAP-70, 163 (29%) expressed CD38 and 104 (31%) expressed CD49d. Fluorescence in-situ hybridization (FISH) revealed that 210 (41%) patients had del13q, 90 (18%) patients had trisomy 12, 37 (7%) had del11q, 23 (5%) had del17p and 141 (28%) had no detectable FISH abnormalities. As of last follow-up, 239 (39%) patients received therapy for CLL. After a median follow-up of 5.9 years (range 0-11), 15 (2.4%) patients developed biopsy-proven RS. The median time to RS in these 15 patients was 4.5 years (range 1.0-8.7 years). The ordinal HR for the 13 SNPs tested, their corresponding genes, and p-values are shown in Table 1. Germline polymorphisms in a single SNP, rs4987852, encoding for BCL2 (chromosome 18), was significantly associated with an increased risk of RS (ordinal HR=3.9; 95% CI=1.6-9.8; p-value=0.004). This allele was present in 48/605 (8%) non-transformed CLL patients compared to 4/15 (27%) of patients with RS. Time to RS according to the Kaplan-Meier analysis for rs4987852 is shown in Figure 1. This SNP is located in a region in which t(14;18) translocation breakpoints commonly occur in follicular lymphoma and overexpression of BCL2 leads to an increased incidence of B-cell lymphomas in mice. Conclusion Our results suggest that inherited genetic polymorphisms predispose CLL patients to develop RS. Specifically, SNP (rs4987852) present on the BCL2 gene on chromosome 18 in CLL is associated with an increased risk of transformation to RS. These observations require replication in other CLL cohorts. Disclosures: Shanafelt: Genentech: Research Funding; Glaxo-Smith-Kline: Research Funding; Cephalon: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Polyphenon E International: Research Funding.

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Autologous Stem Cell Transplantation (autoSCT) for HIV-Associated Lymphoma in the Era of Combination Antiretroviral Therapy (cART): A Retrospective Analysis of the EBMT Lymphoma Working Party

Blood ◽

10.1182/blood.v128.22.2257.2257 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2257-2257 ◽

Cited By ~ 1

Author(s):

Kai Huebel ◽

Alessandro Re ◽

Ariane Boumendil ◽

Herve Finel ◽

Marcus Hentrich ◽

...

Keyword(s):

Multivariate Analysis ◽

B Cell ◽

Hodgkin Lymphoma ◽

Dose Regimen ◽

Research Funding ◽

B Cell Lymphoma ◽

High Dose ◽

Hiv Patients ◽

High Dose Regimen

Abstract Introduction: Patients infected with HIV have an increased risk of developing aggressive B-cell non-Hodgkin lymphoma and Hodgkin lymphoma (HL). The continuous development of cART during the last decade has improved the prognosis of HIV-associated lymphoma considerably. However, a significant proportion of these patients will experience lymphoma relapse and may be candidates for autoSCT. The purpose of the present study was to investigate if recent advances in anti-lymphoma therapy and anti-infectious strategies have influenced the outcome of autoSCT for HIV-related lymphoma. Patients and methods: For this retrospective study, all EBMT-registered patients aged 18 years or older with HIV-positive serostatus who were treated with a first autoSCT between 2007 and 2013 were eligible. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were requested to provide additional HIV and lymphoma treatment and follow-up information. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression models. Curves of cumulative incidence of relapse (IR) and non-relapse mortality (NRM) were compared by Gray's test. Results: 138 patients from 25 European centers met the eligibility criteria and had the full data set required for this analysis available. 86% were male, median age was 44 years (range 24-69). Underlying diagnoses were diffuse large B cell lymphoma (DLBCL) in 46%, HL in 21%, Burkitt lymphoma in 14%, plasmablastic lymphoma (PBL) in 10%, and other lymphoma in 9% of the patients. Disease status at autoSCT was complete remission (CR) in 51%, partial remission (PR) in 33%, and less than PR in 16% of the patients, achieved after 1 (28%), 2 (58%), or more than 2 lines of chemotherapy (14%). With HIV load below the threshold of detection in 74% of the patients, the median CD4+ cell count was 187/µl (range 0-800) at transplant. 95% of the patients continued with cART during salvage and high-dose chemotherapy. BEAM was used as high-dose regimen in 77% of the patients. With a median follow-up of 4 years, 2-year NRM, IR, progression-free survival (PFS) and overall survival for the whole series were 9%, 23%, 68% and 70%, respectively. By multivariate analysis, diagnosis DLBCL or PBL (vs HL), increasing number of chemotherapy pretreatment lines, and less than PR at autoSCT were significant predictors of an unfavorable PFS; whilst age, high-dose regimen, performance status, and viral load had no significant impact. 2-year PFS in patients with 1st-line CR, later CR, PR, or less than PR at autoSCT was 91%, 80%, 64%, and 23%, respectively. Conclusions: This series, which is the largest ever on lymphoma transplants in HIV+ patients, suggests that in the cART / chemoimmunotherapy era, the outcome of autoSCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of HIV infection. AutoSCT under ongoing cART therapy remains the treatment of choice for HIV+ patients with PBL or recurrent DLBCL or HL. Disclosures Kröger: Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Montoto:Roche: Honoraria; Gilead: Research Funding. Dreger:Novartis: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Gilead: Consultancy; Janssen: Consultancy; Roche: Consultancy.

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Impact of absolute lymphocyte count on prognosis of aggressive non-Hodgkin lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e19034 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e19034-e19034

Author(s):

Anahat Kaur ◽

Punita Grover ◽

Sheetal Bulchandani ◽

Thomas A Odeny ◽

Sheshadri Madhusudhana ◽

...

Keyword(s):

Multivariate Analysis ◽

B Cell ◽

Hodgkin Lymphoma ◽

Lymphocyte Count ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Absolute Lymphocyte Count ◽

Intermediate Risk ◽

Non Hodgkin Lymphoma

e19034 Background: Multiple studies have attempted to identify parameters to predict prognosis and overall survival (OS) in Non-Hodgkin Lymphoma (NHL). Revised International Prognostic Index (R-IPI) is commonly used but does not capture all predictive risk factors in the Rituximab era. Low absolute lymphocyte count (ALC) on follow up after first line therapy has been reported to predict relapse. The prognostic value and exact cut off for low ALC at diagnosis is not known. We aimed to investigate whether ALC at time of diagnosis is an independent predictor for OS in aggressive NHL. Methods: We retrospectively evaluated patients with aggressive NHL treated at our center from 1/2000 to 12/2016 with at least 2 year longitudinal follow up after diagnosis. We retrieved data for baseline characteristics including age, sex, Ann Arbor stage, R-IPI score, HIV status, histopathological diagnosis (Diffuse Large B Cell Lymphoma (DLBCL), Burkitt′s lymphoma, Follicular Lymphoma Grade IIIB, high-grade B cell lymphoma), type of chemotherapy and clinical response. Patients were divided into four subgroups based on ALC at diagnosis: < 500, 501-1000, 1001-1500 and > 1500X109/L. Statistical analysis was done using REDCAP and Stata v13. Results: A total of 92 patients were identified. The average age at diagnosis was 53.4 years, 63% were male and 73.5% were diagnosed with DLBCL. Per R-IPI score, 16.3% were high risk, 31.3% were high intermediate risk, 22.5% low intermediate risk and 30% were low risk. The median OS for patients with ALC < 500 x109/L (5.4%) was 1.5 years, ALC 501-1000 (38%) was 2.3 years, ALC 1001-1500 (23.9%) was 4.25 years and ALC > 1500 (32.6%) was 5.2 years. On multivariate analysis this difference was not statistically significant due to small sample size. Conclusions: We found that low ALC at diagnosis trended towards worse OS in aggressive NHL but did not reach statistical significance on multivariate analysis. Our study is limited by retrospective nature and sample size. Multicenter studies need to be done to validate these results. Studies are also needed to know the exact cut off for low ALC. [Table: see text]

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Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

Blood ◽

10.1182/blood-2010-07-295097 ◽

2011 ◽

Vol 117 (2) ◽

pp. 585-590 ◽

Cited By ~ 26

Author(s):

Yingtai Chen ◽

Tongzhang Zheng ◽

Qing Lan ◽

Francine Foss ◽

Christopher Kim ◽

...

Keyword(s):

Body Mass Index ◽

B Cell ◽

Hodgkin Lymphoma ◽

Body Mass ◽

Significant Interaction ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Non Hodgkin Lymphoma ◽

Increased Risk

Abstract We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and IL7R (rs1494555 Pforinteraction = .016) for NHL overall; IL7R (rs1494555 Pforinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 Pforinteraction = .006), IL13 (rs20541 Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 Pforinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.

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Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma: a Finnish Nationwide population-based study

Blood Cancer Journal ◽

10.1038/s41408-021-00586-1 ◽

2021 ◽

Vol 11 (12) ◽

Author(s):

Ilja Kalashnikov ◽

Tomas Tanskanen ◽

Janne Pitkäniemi ◽

Nea Malila ◽

Sirkku Jyrkkiö ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Relative Survival ◽

B Cell Lymphoma ◽

Population Based ◽

Population Based Study ◽

Entire Study ◽

Risk Of Death ◽

Increased Risk ◽

Histological Transformation

AbstractNodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49−16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.

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Epidemiologic and Clinical Patterns of Lymphoma in Qatar 2013-2017: A Population-Based Cohort Study

Blood ◽

10.1182/blood-2021-144637 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4584-4584

Author(s):

Ahmed A Adel ◽

Aimilia Exarchakou ◽

Anas Hamad ◽

Ruba Yasin ◽

Hafedh Ghazouani ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

B Cell Lymphoma ◽

Descriptive Statistics ◽

World Health ◽

Treatment Modalities ◽

Epidemiological Characteristics

Abstract Background: Lymphoma: either most common non-Hodgkin (NHL) or less common Hodgkin (HL), are well-known hematological malignancies. With advancement in treatment modalities, the survival in both lymphomas especially the "poor prognosis" non-Hodgkin lymphoma has evolved in the last decades. Hence, patient's outcome may be diverse and quite complicated; with some need extended time for observation, and others having multiple chemotherapy treatments. In this review, we will focus on the clinic-epidemiological patterns of various malignant lymphoma subtypes in Qatar in recent years (2013-2017) Objective: The primary aim is to investigate and compare the overall survival (OS) for both types of lymphoma; HL and NHL at 1, 3 and 5-years of follow up in adult lymphoma patients in Qatar between January 2013 - December 2017. Other objectives include comparing between the most frequent histological varieties, clinical and epidemiological characteristics of HL and NHL lymphoma in Qatar. The secondary objectives included clinical characteristics, treatments used, treatment response, disease-free survival and overall survival. Methods: A retrospective, descriptive study of consecutive cases was carried out at NCCCR, Qatar between 2013-2017. Inclusion criteria included: ≥ 18 years of age, male or female, any clinical stage at diagnosis, who had received any chemotherapy regimen, with a known outcome. Descriptive statistics was performed for all variables, and survival was assessed using Kaplan-Meier curves. Data was abstracted by Qatar National Cancer Registry and the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors is used as reference for disease staging and pathological classification. We used STATA version 13.0 (StataCorp., College Station, TX) for exploratory data analysis and descriptive statistics. Results: During the period 2013-2017, 414 men and women were diagnosed with lymphoma in the state of Qatar. The median age at diagnosis being 49 years (interquartile range IQR 36-95 years; p<0.001)) for all lymphoma patients combined. Males were more likely to develop both lymphoma types; HL and NHL than females; accounting for 2/3 of cases in each, yet statistically insignificant (74% and 70%, p=0.45). Based on subtypes, mature B-cell neoplasms (61 cases, 60%) were the most common among 13 identifiable NHL-B subtypes. Majority of HL cases belonged to Lymphocyte rich subtype (54 cases, 49%). With a median follow up of 17.3 months, the 1-year, 3-year and 5-year OS for the entire population of lymphoma patients were 99%, 82% and 64% (Figure 12). When stratified by major subtypes; HL and NHL, some trends became evident at 3-years follow-up (94% versus 82%). The 5-year OS were 67% and 60%, respectively. Throughout the study period, the OS in HL group were higher than NHL (p<0.001), yet median OS was not reached. Conclusions: Diffuse large B-cell lymphoma constitutes the most frequent subtype for all lymphomas in Qatar. Overall, the survival was generally better for HL than NHL 67% and 60% respectively. Survival can be slightly deflated than other countries or regions especially HL, this is in part due to higher immigration rate in the country, so changes in survival over time (especially for longer periods) need to be examined alongside trends in incidence rates to interpret improvement in cancer control policies implemented. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Second cancer risk 40 years after cure for Hodgkin lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8039 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8039-8039

Author(s):

Michael Schaapveld ◽

Berthe M Aleman ◽

Anja M Eggermond ◽

Cecile P Janus ◽

Augustinus Krol ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Risk ◽

Hodgkin Lymphoma ◽

Hazard Ratio ◽

Treatment Modalities ◽

Second Cancer ◽

Radiation Fields ◽

Increased Risk ◽

The Impact

8039 Background: During the last decades Hodgkin Lymphoma (HL) treatment changed towards less toxic chemotherapy schemes and smaller radiation fields. The impact of these changes on second cancer (SC) risk is still unknown. Methods: We calculated standardized incidence ratios (SIR), comparing SC risk after HL treatment with expected risk, based on cancer incidence in the general population, and compared SC risk between treatment modalities, accounting for competing events, in a large Dutch cohort comprising 3,390 5-years HL survivors, aged 15-51 years at HL treatment and diagnosed between 1965-2000. Results: The median follow-up was 18.2 years; 23% of the patients was followed ≥25 years. During follow-up 734 SCs and 92 third cancers (TC) occurred. The SIR for any SC was 4.5 (95% confidence interval (95%CI) 4.1-4.9). SC risk was still elevated after 35 years of follow-up (SIR 3.9; 95%CI 2.5-5.8) and cumulative incidence (CI) reached 47.1% (95%CI 43.6-50.5) at 40 years follow-up. For TCs the SIR was 5.5 (95%CI 4.4-6.9); the 20-year CI was 22.3% (95%CI 17.8-27.2). Risks of NHL and leukemia strongly decreased in more recent treatment periods (P-trend <0.001). The CI of solid tumors (ST) between 5-19 years after HL treatment did not differ for patients treated between 1965-1979, 1980-1989 or 1990-2000 (P=0.21; 19-year CI 9.1%, 11.6% and 11.4%, respectively). Radiotherapy (RT) above the diaphragm increased risk of STs above the diaphragm (hazard ratio (HR) 2.4, P<0.001), while subdiaphragmatic RT was associated with a 1.7-fold increased HR of a subdiaphragmatic ST (P=0.001). An incomplete mantle field was associated with significantly lower breast cancer (BC) risk (hazard ratio (HR) 0.4, 95%CI 0.2-0.8). A cumulative procarbazine dose >4.2 g/m2 yielded a 1.3-fold increased HR (95%CI 1.0-1.7) for non-breast STs and a 2-fold (95%CI 1.2-3.1) increased HR for gastrointestinal STs, but was associated with a strongly decreased BC risk (HR 0.3, 95%CI 0.2-0.6). Conclusions: SC risk after HL has decreased with treatment changes over the last decades, due to strongly decreasing risk of leukemia and NHL. Smaller radiation fields and procarbazine doses >4.2 g/m2 are associated with lower breast cancer risk, while high procarbazine doses increase risk of gastrointestinal STs.

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Treatment-specific risk of second malignancies in five-year survivors of diffuse large B-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.12072 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 12072-12072

Author(s):

Yvonne M. Geurts ◽

Suzanne I.M. Neppelenbroek ◽

Cynthia So-Osman ◽

Joost S.P. Vermaat ◽

Dick Johan van Spronsen ◽

...

Keyword(s):

General Population ◽

B Cell ◽

Cumulative Incidence ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Malignant Neoplasms ◽

Large B Cell Lymphoma ◽

Increased Risk ◽

Large B Cell

12072 Background: Due to the historically less favorable prognosis of diffuse large B cell lymphoma (DLBCL), the burden of second malignant neoplasms (SMNs) has been rarely studied in DLBCL survivors. However, radiotherapy and chemotherapy may increase SMN risk among DLBCL patients. Anthracyclines may increase the risk of hematological malignancies, but it is not clear whether they also increase solid cancer risk. Methods: We established a multicenter cohort of 2,384 5-year DLBCL survivors treated at ages 15-60 years with radiotherapy and/or immuno-chemotherapy between 1989 and 2012. Observed numbers of SMNs were compared with expected cancer incidence in the general population to compute standardized incidence ratios (SIRs), absolute excess risks (AERs, per 10.000 person-years) and cumulative incidence. Treatment specific incidence was compared with general population rates and assessed within the cohort using Cox regression. Results: Most DLBCL patients received alkylating agents (95%), anthracycline-containing chemotherapy (95%) or radiotherapy (61%); 46% received rituximab. Median follow-up was 13.3 years; 17% of patients was followed ≥20 years. In total, 308 5-year survivors developed an invasive SMN (SIR 1.6; 95% confidence interval (CI), 1.4 to 1.8), translating into 56.2 excess cancers per 10.000 person-years (see Table for specific sites). In 20-year survivors of DLBCL, the SIR was 1.8 (95% CI 1.3-2.6). The 20-year cumulative incidence of any SMN was 18.7% (95% CI 16.5-21.0%). The SIR for any SMN was higher in patients <40 years at first treatment (SIR ≤40 years: 2.8, SIR >40 years: 1.4; p<0.001). Treatment specific results will be presented at ASCO21. Conclusions: DLBCL survivors experience higher risk of SMNs than the general population. Identification of patients at increased risk could improve follow-up care.[Table: see text]

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