Cardiac Outcomes in a Prospective Cohort of Adult Non-Hodgkin Lymphoma Survivors

Abstract Abstract 2656 Background Treatment of non-Hodgkin lymphoma (NHL) can lead to development of cardiovascular disease (CVD). We sought to describe the cumulative incidence of CVD in adult NHL survivors diagnosed in the recent treatment era (since 2002) and identify clinical and treatment predictors for its development. Methods All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). The MER offers enrollment to all consecutive patients with newly diagnosed NHL who are US residents and age >18 years. Clinical data from the time of diagnosis and treatment data are abstracted from medical records using a standard protocol. Patients are prospectively contacted via telephone or in person per protocol every 6 months for the first 3 years from diagnosis and yearly afterwards to assess disease status and development of comorbid conditions. CVD events, including heart failure (HF), myocardial infarction (MI), arrhythmia, pericarditis, and valvular heart disease, occurring after diagnosis were identified during follow-up and validated against medical records. HF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. MI was validated using case definition standards of coronary heart disease, while arrhythmia, pericarditis, and valvular heart disease were validated using clinical definitions. The prevalence of CVD and associations between CVD and clinical characteristics (sex, age) and treatment (radiation, anthracyclines) were performed using Cox models with a competing risk approach. Results 1164 patients with NHL were enrolled into the MER at Mayo Clinic between 9/1/2002–2/28/2008. 646 were male (56%) and median age at diagnosis was 62 years (range 20–93). Median follow-up of all cases was 59 months (range 1–105). 131 patients reported CVD prior to the diagnosis of NHL and were excluded from analyses. An additional 76 patients did not have follow-up and were excluded. Of the 957 remaining patients, 75 (7.8%) self-reported a new diagnosis of CVD. Of these, 71 cases had available medical records. 57 of the 71 reviewed cases (80%) were validated (18 HF, 9 MI, 21 arrhythmia, 2 pericarditis, and 10 valvular heart disease). Cumulative incidence of CVD at 1, 3, 5, and 7 years was 1.3%, 3.7%, 5.2%, and 7.4%, respectively. Median time from NHL diagnosis to CVD was 26.5 months (range 1–84). Older age was associated with increased risk of overall CVD (p-value<0.001). Gender (p=0.59), radiation therapy (p=0.61), and anthracycline treatment (p=0.25) were not associated with the incidence of overall CVD. Among types of CVD, anthracycline use was associated with development of HF (HR=5.30; p-value=0.008) and arrhythmia (HR=2.68; p-value=0.04). Radiation was associated with development of arrhythmia (HR=2.73; p-value=0.03), while older age was associated with development of HF (HR=1.36 per 5 year increment; p-value=0.003) and arrhythmia (HR=1.25 per 5 year increment; p-value=0.02). Conclusions The risk of CVD in patients with NHL is approximately 1% per year after the initial diagnosis of lymphoma. The most commonly occurring CVDs in this cohort of NHL survivors were arrhythmia and HF. Treatment with anthracyclines and radiation are associated with increased risk of developing some types of CVD. 80% of self-reported CVD events in NHL survivors were validated using epidemiologic criteria. Future studies will include building models incorporating comorbid health conditions and lifestyle factors to determine risk of CVD as well as the impact of CVD on quality of life. Disclosures: No relevant conflicts of interest to declare.

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Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

Hematology ◽

10.1182/asheducation-2016.1.323 ◽

2016 ◽

Vol 2016 (1) ◽

pp. 323-330 ◽

Cited By ~ 37

Author(s):

Flora E. van Leeuwen ◽

Andrea K. Ng

Keyword(s):

Risk Factors ◽

Heart Disease ◽

Hodgkin Lymphoma ◽

Valvular Heart Disease ◽

Premature Menopause ◽

Malignant Neoplasms ◽

Cardiovascular Toxicity ◽

Solid Malignancies ◽

Increased Risk

Abstract Long-term survivors of Hodgkin lymphoma (HL) experience several late adverse effects of treatment, with second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) being the leading causes of death in these patients. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies (thyroid dysfunction, infertility), neck muscle atrophy, and persistent fatigue. HL survivors have two- to fourfold increased risks to develop SMNs and CVD compared with the general population. With respect to SMNs, radiotherapy is associated with 1.5- to 15-fold increased risk of solid malignancies. The relative risk (RR) of solid tumors increases steadily with increasing follow-up time from 5 to 15 years since radiotherapy, and remains elevated for at least 40 years. The RR of solid SMNs increases strongly with younger age at first treatment. Risks of lung, breast, and gastrointestinal (GI) cancers increase with higher radiation dose. Alkylating agent chemotherapy, especially procarbazine, does not only increase risk of leukemia but also of solid malignancies, in particular, cancers of the lung and GI tract. In contrast, gonadotoxic chemotherapy decreases the risk of radiation-associated breast cancer, through induction of premature menopause. Smoking appears to multiply the radiation- and chemotherapy-associated risks of lung cancer. Both radiotherapy and chemotherapy for HL may cause cardiovascular toxicity. Radiotherapy increases the risk of coronary heart disease, valvular heart disease, congestive heart failure (HF), and pericarditis, whereas anthracycline-containing chemotherapy increases the risks of HF and valvular heart disease. Cardiovascular toxicity following radiotherapy is usually observed from 5 to at least 35 years after therapy, whereas anthracycline-related toxicity is already observed during treatment, up to at least 25 years. The joint effects of anthracyclines, radiotherapy, and conventional cardiovascular risk factors (eg, hypertension, smoking, and physical inactivity) appear to be additive rather than multiplicative. HL survivors need lifelong risk-based screening for selected SMNs and CVDs. Furthermore, preventive strategies should include lifestyle and drug-based interventions to minimize exposure to conventional risk factors for cancer and CVD.

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Atrial Fibrillation in Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood.v126.23.2950.2950 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2950-2950 ◽

Cited By ~ 4

Author(s):

Tait D. Shanafelt ◽

Kari G. Chaffee ◽

Timothy G. Call ◽

Sameer A. Parikh ◽

Susan M. Schwager ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Valvular Heart Disease ◽

Research Funding ◽

Newly Diagnosed ◽

Advisory Committees ◽

Increased Risk ◽

History Of ◽

Male Sex

Abstract BACKGROUND: Consistent with the advanced age at diagnosis (median age ~70 years), most patients with CLL have co-existent health problems. These co-morbidities influence the ability of many CLL patients to tolerate aggressive chemotherapy-based treatment and can also contribute to treatment-related side effects. The recent development of novel signaling inhibitors, particularly the Bruton's tyrosine kinase inhibitor ibrutinib, has been a major treatment advance for patients with CLL. While these agents generally have favorable toxicity profiles relative to standard chemotherapy-based treatments, they are chronic therapies which patients typically stay on for an extended period. Preliminary data suggests ibrutinib may be associated with an increased risk of atrial fibrillation (Afib). In one randomized trial comparing ibrutinib to ofatumumab in patient with relapsed CLL, incident grade 3+ Afib occurred in 3% of ibrutinib treated patients compared to 0% of ofatumumab treated patients (NEJM 371:213). Despite these observations, the baseline frequency of Afib in patients with CLL is not well described - particularly incident atrial fibrillation acquired during the course of the disease. METHODS: We used the Mayo Clinic CLL database to evaluate the prevalence of Afib at the time of CLL diagnosis as well as the incidence of Afib during follow-up. All patients with a new diagnosis of CLL after January 1995 who were seen at Mayo within 12 months of diagnosis were included in the analysis. Afib was identified by chart review and by billing search using ICD9 codes. Data on co-morbid conditions associated with risk of Afib was also abstracted (e.g. hypertension, coronary artery disease [CAD], valvular heart disease, cardiomyopathy, diabetes mellitus, pulmonary disease). RESULTS: A total of 2444 patients with newly diagnosed and previously untreated CLL were seen at Mayo Clinic within 12 months of diagnosis between 1/1995 and 4/2015.Median age at diagnosis was 65 years and 1626 (66.5%) patients were men. A history of Afib was present at the time of CLL diagnosis in 148 (6.1%) patients. Four additional patients had Afib documented in the record but the precise date of onset (e.g. prior to or after CLL diagnosis date) could not be determined. Age, male sex and history of CAD, valvular heart disease, cardiomyopathy, hypertension, and diabetes were associated with a greater likelihood of having a history of Afib at the time of CLL diagnosis (all p<0.01). Among the 2292 patients without a history of Afib at CLL diagnosis, 139 (6.1%) had incident Afib during the course of follow-up for their CLL. The incidence of Afib among patients without a history of Afib at diagnosis was approximately 1%/year (Figure 1A). Considering both Afib present at the time of CLL diagnosis or acquired during the course of the disease, 291 (11.9%) of the 2444 patients in this cohort experienced Afib (median follow-up: 59 months). Among patients without Afib at the time of CLL diagnosis, the following characteristics at the time of CLL diagnosis were associated with an increased risk of incident Afib on multivariate analysis: older age (age 65-74 HR=2.4, p<0.001; age ≥75 HR=3.6, p<0.001), male sex (HR=1.8, p=0.004); valvular heart disease (HR=2.4, p=0.007), and hypertension (HR=1.5; p=0.02). A predictive model for acquired Afib was subsequently constructed based on the independent factors in the Cox regression model. An individual weighted risk score was assigned to each independent factor based on the regression coefficients of the HRs. The Afib risk score (range 0-7) was defined as the sum of the scores of these independent factors. The risk of incident Afib among patients with risk scores of 0-1, 2-3, 4, and 5+ is shown in Figure 1B. Rates for these 4 groups were significantly different (p<0.001), with the 10-year Afib rates (95% C.I.) for those with a score of 0-1, 2-3, 4, and 5+: 4% (2-6%), 9% (6-13%), 17% (11-23%), and 33% (20-43%), respectively. CONCLUSIONS: A history of Afib is present in approximately 1 out of every 16 patients with newly diagnosed CLL. Among patients without Afib at diagnosis, the incidence rate of Afib is ~1%/year. The risk of incident Afib in newly diagnosed CLL patients can be predicted based on age, sex, and co-morbid health conditions present at diagnosis. These data provide context to help interpret data on the frequency of Afib in CLL patients treated with ibrutinib and other novel agents. Disclosures Shanafelt: Janssen: Research Funding; Polyphenon E Int'l: Research Funding; Glaxo-Smith_Kline: Research Funding; Cephalon: Research Funding; Genentech: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Pharmactckucs: Research Funding. Ding:Merek: Research Funding. Kay:Tolero Pharm: Research Funding; Hospira: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Increased Risk of Valvular Heart Disease in Systemic Sclerosis: An Underrecognized Cardiac Complication

The Journal of Rheumatology ◽

10.3899/jrheum.201005 ◽

2021 ◽

pp. jrheum.201005

Author(s):

Reto D. Kurmann ◽

Edward A. El-Am ◽

Yasser A. Radwan ◽

Avneek S. Sandhu ◽

Cynthia S. Crowson ◽

...

Keyword(s):

Heart Disease ◽

Systemic Sclerosis ◽

Valvular Heart Disease ◽

Cardiac Involvement ◽

Significant Risk ◽

Fold Increase ◽

Significant Risk Factor ◽

Increased Risk ◽

Incident Cases

Objective Cardiac involvement is a poor prognostic marker in systemic sclerosis (SSc). While diastolic dysfunction, myocardial fibrosis, and arrhythmias are traditionally considered features of primary cardiac involvement in SSc, the incidence of valvular heart disease (VHD) is not well reported. Our objective was to examine the prevalence of VHD at time of SSc diagnosis and incidence of VHD during follow up compared to non-SSc subjects. Methods Medical records of patients with suspicion of SSc were reviewed to identify incident cases. SSc subjects were matched 1:2 by age- and sex to non-SSc subjects. Results The study included 78 incident SSc cases and 156 non-SSc comparators [56 years (± 15.7), 91% female]. A nearly 4-fold increase in the prevalence of moderate/severe VHD prior to SSc diagnosis compared to non-SSc subjects (6% vs. 0%; P=0.004) was identified. During follow up, 18 SSc and 12 non-SSc patients developed moderate/severe VHD. The cumulative incidence of VHD at 10 years after SSc incidence/index was 17.9% (95% CI: 10.7-29.9%) in patients with SSc compared with 2.3% (95% CI: 0.7-6.3%) in non-SSc subjects (HR: 4.23; 95% CI: 2.03-8.83). Coronary heart disease was the only significant risk factor for VHD. Conclusion SSc patients have a 4-fold increase in the prevalence of moderate/severe VHD at diagnosis compared to non-SSc patients. They also have a 4-fold increased risk of developing moderate/severe VHD after diagnosis of SSc. Aortic stenosis and mitral regurgitation have a much higher prevalence in SSc patients, besides secondary tricuspid regurgitation. Underlying mechanisms for this association require further elucidation.

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Subsequent malignant neoplasms among children with Hodgkin lymphoma: A report from the Children's Oncology Group

Blood ◽

10.1182/blood.2020007225 ◽

2020 ◽

Author(s):

Lisa Giulino-Roth ◽

Qinglin Pei ◽

Allen Buxton ◽

Rizvan Bush ◽

Yue Wu ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Solid Tumors ◽

Cumulative Incidence ◽

Absolute Risk ◽

Combined Modality Therapy ◽

Early Response ◽

Malignant Neoplasms ◽

Oncology Group ◽

Increased Risk

Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children's Oncology Group Study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1,711 patients enrolled on AHOD0031. Patients were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to two additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% CI: 0.6%-2.0%). SMNs included 3 patients with AML, 11 with solid tumors, and 3 with non-Hodgkin lymphoma. Sixteen of 17 patients with an SMN had received combined modality therapy. The standardized incidence ratio for SMN was 9.5 (95% CI 4.5-15.2) with an excess absolute risk of 1.2 per 1,000 person-years. The cumulative incidence of SMNs was higher among patients who received RT (p=0.037). In multivariate analysis, RT, B-symptoms, and race were associated with SMN risk. Given the latency from exposure, we have likely captured all cases of secondary leukemia. Longer follow-up is needed to determine the risk of solid tumors. Avoidance of RT without sacrificing disease control should remain a goal for future therapeutic approaches. ClinicalTrials.gov Identifier: NCT00025259.

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Impact of Co-Morbidities on Outcome in a Predominantly Hispanic Population of Hodgkin and Non-Hodgkin Lymphoma Patients

Blood ◽

10.1182/blood-2019-129442 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2204-2204

Author(s):

Michelle Janania Martinez ◽

Juan F Garza ◽

Tyler W Snedden ◽

Prathibha Surapaneni ◽

Snegha Ananth ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Conflicts Of Interest ◽

Statistical Testing ◽

P Value ◽

Hispanic Population ◽

Poor Outcome ◽

Non Hodgkin Lymphoma ◽

Increased Risk ◽

Co Morbidity ◽

The Mean

BACKGROUND Evidence suggests that co-morbidities at diagnosis can influence treatment decisions and outcomes in lymphoma patients. Considering the bimodal presentation of Hodgkin Lymphoma (HL) and that the majority of Non-Hodgkin lymphoma (NHL) patients are over 65 years of age, it can be especially challenging to manage them as older patients have a higher number of co-morbidities. Studies have shown that comorbidity is associated with an inferior outcome and a lower likelihood of receiving treatment with curative intent. It must also be noted that older adults with significant co-morbidities are often excluded from clinical trials due to co-morbidities and that Hispanics (HI) have been historically underrepresented. There is a need to take a closer look at this precise patient population. The main objective of our study was to determine the common co-morbidities and their impact on outcome in a prevalently Hispanic population with both HL and NHL at the only NCI designated Cancer Center of South Texas. To our knowledge this is the largest cohort of HL patients from a single academic institution that serves primarily Hispanics. METHODS We located and retrospectively analyzed a total of 616 patients with diagnosis of Lymphoma (HL and NHL) by International Classification of Diseases (ICD) codes and identified 477 patients who met criteria for inclusion; the patients all received care at UT Health San Antonio, between 2008-2018. Key variables for each patient included age, gender, race/ ethnicity, comorbidities, and vitality status in 2018. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. The significance of variation in the mean with disease category was assessed with one way ANOVA and the significance of associations between categorical outcomes was assessed with Pearson's Chi Square or Fisher's Exact test as appropriate. Multivariate logistic regression was used to model binary outcomes in terms of covariates and indicators of disease. All statistical testing was two-sided with a significance level of 5%. R1 was used throughout. The study was approved by the local Institutional Review Board. The findings will be available to patients, funders and medical community through traditional publishing and social media. RESULTS We identified 477 patients with HL and NHL, 262 were Hispanic (HI) [55%], 205 non-Hispanic (NH) [43%], 10 not specified [2%]; there were 232 females (49%) and 245 males (51%). Co-morbidities that were identified and analyzed were: Diabetes Mellitus (DM), Hypertension (HTN), Chronic Kidney Disease (CKD), Coronary Artery Disease (CAD) and Congestive Heart Failure (CHF). The most common co-morbidity across all lymphoma subtypes was HTN. More than or equal to 50% of patients with Burkitt's, CTCL, Hodgkin's, Plasmablastic lymphoma, T cell lymphoma had no co-morbidities. In order to determine outcome, we took into consideration vitality status at the end of 2018. When comparing HI vs NH and adjusting for individual co-morbidities (HTN, DM, CAD, CHF, CKD) there is a trend towards a higher risk of poor outcome in NH patients when compared to HI (OR 1.17, CI 0.51-2.69, p-value= 0.7176). When we looked at patients who had both CAD and CHF and adjusted for other co-morbidities the trend remained with a higher risk for poor outcome in NH (OR 1.29, CI 0.57-2.91, p-value=0.53456). Looking at patients with a combination of CAD, CHF, CKD and DM (adjusting for other individual co-morbidities) there was also a trend towards poor outcome in NH (OR 1.26, CI 0.57-2.78, p-value= 0.569316). Overall, patients with CKD had an increased risk of poor outcome (OR 15.13, CI 1.5-153.13, p-value=0.0214) as well as patients with four co-morbidities including CAD, CHF, CKD and DM2 (OR 4.89, CI 1.68-14.23, p-value=0.003597). The absence of co-morbidities shows a trend towards a better outcome (OR 0.77, CI 0.19-3.17, p-value=0.721). CONCLUSION Within the limitations of sample size, our study demonstrates that in the prevalently Hispanic population of our institution, the presence of both CKD on its own as well as CKD with multiple co-morbidities (CKD, CAD, CHF, DM2) increases the risk of poor outcome. There is a trend towards a higher risk of poor outcome in the NH population with co-morbidities when compared to HI but further studies are needed. Disclosures No relevant conflicts of interest to declare.

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Does Insurance Status Interfere with Outcomes in Patients with Hodgkin and Non-Hodgkin Lymphoma?: The UT Health San Antonio Experience

Blood ◽

10.1182/blood-2019-129085 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2141-2141

Author(s):

Juan F Garza ◽

Michelle Janania Martinez ◽

Prathibha Surapaneni ◽

Tyler W Snedden ◽

Snegha Ananth ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

San Antonio ◽

P Value ◽

Insurance Status ◽

Non Hodgkin Lymphoma ◽

Age Of Diagnosis ◽

The Mean ◽

Indolent Lymphomas

Introduction: Historically, a lack of health insurance has been reported to correlate with decreased access to medical care, a delay in cancer treatment and poorer outcomes overall. Furthermore, access to preventive services for cancer screening also decrease with lack of medical insurance (1, 2). Also, studies report that an increase in Medicaid expansion help reduce racial disparities previously seen between African American and Caucasian patients (3). The aim of this study was to present and analyze vitality data based on insurance coverage among Hispanic (HI) and non-Hispanic (NH) population at the only NCI designated cancer center of South Texas primarily serving Hispanics. Methods: This is a retrospective observational study of a cohort of patients seen with diagnosis of lymphoma by International Classification of Diseases (ICD) codes from 2008 to 2018 at UT Health San Antonio. Diffuse Large B Cell Lymphoma (DLBCL) cases were not included. Variables included age of diagnosis, lymphoma subtype, stage at diagnosis, comorbidities, treatment received, lines of therapy, B symptoms present, death, and cause of death and current vitality status. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. The significance of variation in the mean with disease category was assessed with one-way ANOVA and the significance of associations between categorical outcomes was assessed with Pearson's Chi Square or Fisher's Exact test as appropriate. Multivariate logistic regression was used to model binary outcomes in terms of covariates and indicators of disease. All statistical testing was two-sided with a significance level of 5%. R1 was used throughout. Primary end point was to characterize insurance status. Secondary end points - overall 3 and 5-year survival based on insurance and demographics. Results: A total of 477 patients with lymphoma were identified. Hodgkin lymphoma (HL)( n = 116, 24%), non-Hodgkin lymphoma (NHL) (n = 308, 65%), T cell lymphoma (TCL) ( n = 53, 11%). Subtypes for all indolent lymphomas ( n = 217), of which included; Follicular lymphoma (FL) ( n = 123), Marginal Zone lymphoma (MZL) ( n = 53), Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) (n = 8), Small lymphocytic lymphoma (SLL) ( n = 28). Overall mean age of diagnosis for all lymphoma subtypes was 51, male patients (n = 244, 51%), female patients (n = 232, 49%), HI (n = 263, 56%) vs NH (n = 204, 44%), Mean BMI at diagnosis was 29 across all lymphoma groups. Most patients identified had Medicare (MC) (n = 115, 24%), or commercial insurance (CI) ( n = 222, 47%), others were approved for indigent care coverage (ICC) (n = 85, 18%), for Medicaid (MI) (n = 17, 4%), or unfunded (UF)( n = 35, 7%). Of those diagnosed with HL (n = 116); 60% (70) had MC or CI, 40% (46) had ICC, MI or were UF. Of those with Indolent Lymphomas (n = 217), 77% (166) had MC or CI and 23% (49) had ICC, MI or UF; and among patients with T cell lymphomas (n = 53), 63% (22) had MC or CI and 37% (13) ICC, MI or UF respectively. Overall number of HI patients alive at 3 years with MC or CI was 98 and 5 recorded deaths. Those with ICC or MI/UF were 52 and 11 respectively. Comparison of vitality data at 3 years follow up among both groups did not show a difference with a fisher p value of 0.056. Overall number of NH alive at 3 years with MC or CI was 90 and 11 recorded deaths. Those with ICC or MI/UF were 21 and 3 respectively. Comparison of vitality data at 3 years follow up among both groups did not show a difference with a fisher p value of 0.173. Overall number of HI alive at 5 years with MC or CI was 78 and 7 recorded deaths. Those with ICC or MI/UF were 36 and 11 respectively. Comparison of vitality data at 5 years follow up among both groups did not show a difference with a fisher p value of 0.064. Overall number of NH alive at 5 years with MC or CI was 70 and 14 recorded deaths and those with ICC or MI/UF were 16 and 4 respectively. Comparison of vitality data at 5 years follow up among both groups did not show a difference with a fisher p value of 0.169. Conclusion: Across all HI and NH, at the 3 and 5 year follow up mark, there was no significant vitality difference shown in our patient population between those with CI and or MC vs those with MI, ICC or UF. This study demonstrated that across all lymphoma subtypes, patients with access to healthcare had similar outcomes in vitality irrespective of demographics or insurance. Disclosures No relevant conflicts of interest to declare.

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Involved Field Radiation Therapy Following Autologous Stem Cell Rescue for Hodgkin and Non-Hodgkin Lymphoma - Is It Efficacious?.

Blood ◽

10.1182/blood.v108.11.3676.3676 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3676-3676

Author(s):

Tithi Biswas ◽

Sughosh Dhakal ◽

Sheema Chawla ◽

Nikhil Uppal ◽

Sarada Uppuliri ◽

...

Keyword(s):

Radiation Therapy ◽

Stem Cell ◽

Hodgkin Lymphoma ◽

P Value ◽

Stem Cell Rescue ◽

Non Hodgkin Lymphoma ◽

Field Radiation ◽

Involved Field ◽

Disease Free

Abstract Introduction: Patients with recurrent or refractory Hodgkin (HL) and non-Hodgkin lymphoma (NHL) treated with high dose chemotherapy and autologous stem-cell rescue (ASCR) commonly relapse (post-ASCR) (70–90%) in sites of previous disease. Although adjuvant involved field radiation therapy (IFRT) to sites of previous recurrence might be expected to enhance local control, translation of this into improved disease-free (DFS) or overall survival (OS) is controversial. We sought to evaluate IFRT following ASCR in terms of patterns of recurrence, OS and DFS. Methods and Materials: All 281 patients with recurrent or refractory HL and NHL who underwent ASCR between 5/92 and 7/03 were analyzed. Disease stratification at the time of transplant included HL, 24%, aggressive NHL (ANHL) 62%, and indolent NHL (INHL) 14%. Most, 46% underwent ASCR after 1st relapse, 18% after 2nd relapse, 4% after 3rd relapse and 26% had refractory disease at ASCR. IFRT was administered to 129 patients (46%). Physician and patient choice determined which patients received IFRT. Dose ranged from 20–36 Gy depending on response to salvage therapy before ASCR and the presence of visible imaging abnormalities following ASCR. For end point analysis 39 patients (14%) including 11 HL, 23 ANHL, and 5 INHL had insufficient data and were excluded. Results: Mean follow-up was 3 years (.3 – 12). The median age at ASCR was 45 years (8 – 73). Male to female ratio was 1.3:1. Thirty five percent of patients had prior RT. On univariate analysis, OS and DFS following IFRT for ANHL was superior (or approached this statistically) at 5 years. For HL, improved OS approached significance, whereas DFS did not despite an apparent benefit by disease-free percentages. IFRT appears to be disadvantageous in INHL, but patient numbers were very small. OS and DFS at 5 years are in the table. Survival Table 5-year OS (%) 5-year DFS (%) HL With IFRT 62 79 Without IFRT 37 68 p-value .07 .41 Aggressive NHL With IFRT 57 65 Without IFRT 37 49 p-value .02 .07 Indolent HNL With IFRT 50 67 Without IFRT 85 88 p-value .06 .30 On multivariate analysis, for ANHL, IFRT was protective (p = .002, Hazard Ratio = 0.39) and bulky disease was adverse (p = .04, HR = 2.04). For HL, an advantage of IFRT did not reach statistical significance (p = .63, HR = .8). For INHL, IFRT was associated with an inferior outcome (p = .23, HR = 4.9). Conclusion: Recognizing that bias exists in patient selection for IFRT post-ASCR (in both directions), a survival benefit appears to exist for patients with ANHL, and potentially for those with HL. The absence of a difference in DFS may relate to relapses in other sites or competing events with censored data. Longer follow-up or larger patient numbers are necessary to confirm a long- term improvement. INHL did not benefit from IFRT as might be expected since this group is more likely to have occult disseminated, chemotherapy insensitive disease. Determination of specific patterns of disease recurrence is in progress.

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Host Genetics and Risk of Cardiovascular Disease in a Prospective Cohort of Adult Non-Hodgkin Lymphoma Survivors

Blood ◽

10.1182/blood.v120.21.1573.1573 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1573-1573

Author(s):

Carrie A. Thompson ◽

Thomas M Habermann ◽

Matthew J Maurer ◽

Cristine Allmer ◽

Susan L Slager ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Heart Disease ◽

Medical Records ◽

Minor Allele ◽

Newly Diagnosed ◽

Cvd Risk ◽

Non Hodgkin Lymphoma ◽

A Minor

Abstract Abstract 1573 Background. Treatment of non-Hodgkin lymphoma (NHL) can lead to the development of cardiovascular disease (CVD). In a previous report, we found that the risk of CVD in patients with NHL diagnosed in the recent treatment era (since 2002) was approximately 1% per year after the initial diagnosis of lymphoma. We evaluated the association of 30 candidate single nucleotide polymorphisms (SNPs) in genes associated with anthracycline-induced cardiotoxicity in children (SLC10A2, SLC28A3, ABCC1, ABCB3, CBR3, FMO2, SPG7) and genes associated with venous thromboembolism (VTE) in adults (ABO, F2/CKPA5, F5, F11, KLKB1, SCUBE1, SLC19A, SELP) with the risk of new onset cardiovascular disease in a cohort of NHL patients. Methods. All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE, and were enrolled from 2002–2008. The MER offers enrollment to all consecutive patients with newly diagnosed NHL who are US residents and age >18 years. Clinical data from the time of diagnosis and treatment data are abstracted from medical records using a standard protocol. Patients are prospectively contacted via telephone or in person per protocol every 6 months for the first 3 years from diagnosis and yearly afterwards to assess disease status and development of comorbid conditions. CVD events, including heart failure (HF), myocardial infarction (MI), arrhythmia, pericarditis, and valvular heart disease, occurring after diagnosis were identified during follow-up and validated against medical records. HF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. MI was validated using case definition standards of coronary heart disease, while arrhythmia, pericarditis, and valvular heart disease were validated using clinical definitions. Genotyping was conducted using a custom Illumina iSelect platform. Cox regression was used to estimate Hazard Ratios (HRs) and 95% confidence intervals (CI) for individual SNPs with time to CVD, with death modeled as a competing risk. Each SNP was modeled with the most prevalent homozygous genotype used as the reference group, and each SNP was modeled as having a log-additive (per minor allele) effect in the regression model. An ordinal test was used to assess the trend, and p<0.05 was considered statistically significant. Results. There were 805 newly diagnosed NHL patients with no history of CVD at time of lymphoma diagnosis and had genotype data available for analysis. The median age at diagnosis was 61 years (range, 21–93) and 53% were male. The most common subtypes were follicular lymphoma (33%), diffuse large B-cell lymphoma (29%), and marginal zone lymphoma (14%). Anthracycline-based chemotherapy as initial therapy or at re-treatment was used in 51% of the patients and radiation therapy was used in 18%. Median follow-up of all cases was 59 months (range, 1–105). There were 36 incident CVD events (4.5%) and 139 deaths (17%). The most common CVD events were arrhythmia (N=17) and heart failure (N=14). There was no association with any of the anthracycline-induced cardiotoxicity genes and risk of CVD overall or in the subgroup of patients (N=406) who received an anthracycline. Of the venous thromboembolism (VTE) SNPs, rs4253399 in F11 (coagulation factor 11) with a minor allele frequency of 0.39 was associated with risk of CVD (HR=2.14; 95%CI 1.35–3.40; p=0.001). When restricted to anthracycline-treated patients, the HR for rs4253399 became stronger (HR=2.56; 95%CI 1.39–4.72; p=0.003), and an ABOSNP (rs660340) with a minor allele frequency of 0.43 became significant (HR=2.14; 95%CI 1.13–4.04; p=0.02). Conclusions. This is the first report that genes involved in VTE also predict CVD risk in NHL patients, particularly those treated with anthracycline chemotherapy. However, SNPs from genes previously associated with anthracycline-induced cardiotoxicity were not associated with CVD risk in this cohort, although those SNPs were identified in children and may not apply to adults. Future research will need to validate these findings and identify additional genetic markers that can be incorporated into risk assessment for CVD in this patient population. Disclosures: No relevant conflicts of interest to declare.

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Risk of Venous Thromboembolism in Hematological Malignancies: The Scandinavian Thrombosis and Cancer Cohort

Blood ◽

10.1182/blood.v126.23.628.628 ◽

2015 ◽

Vol 126 (23) ◽

pp. 628-628

Author(s):

Inger Lise Gade ◽

Sigrid K Brækkan ◽

Inger Anne Næss ◽

John-Bjarne Hansen ◽

Frits Rosendaal ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Hematological Malignancies ◽

Event Rate ◽

Population Based ◽

Indolent Lymphoma ◽

Non Hodgkin Lymphoma ◽

Increased Risk ◽

Hematological Cancers ◽

One Year

Abstract Background: Several studies have shown a high incidence of venous thromboembolism (VTE) in hematological cancers, comparable with solid cancers, although bleeding is also a prominent complication of the hematological patients. Cancer patients, who develop VTE, have a reduced survival and impaired quality of life if compared to those who do not develop VTE. Hematological cancers are rather rare diseases and most studies have described only some of the entities. Here we want to compare the incidence of VTE in seven subtypes in a large cohort. Aim: To investigate the risk of VTE in hematological malignancies compared to matched controls in a prospective population based cohort study, the Scandinavian Thrombosis and Cancer (STAC) Cohort. Methods: TheSTAC Cohort includes 144.952 participants from three population based prospective cohort studies, i.e. The Tromsø Study and the HUNT2 study from Norway, and the Danish Diet, Cancer and Health Study. The participants were enrolled during 1993-1997, and mean follow-up time was 11.7 years. The cohort profile and outcome of first time objectively confirmed VTE events have been described in prior studies. For this study we collected data from the national cancer registries using morphology codes to identify cohort subjects with hematological cancers, divided into 7 groups: multiple myeloma (MM), chronic lymphocytic leukemia (CLL), acute leukemia (myeloid and lymphoblastic) (AL), chronic myeloproliferative neoplasms and myelodysplastic syndrome (CMN/MDS), aggressive non-Hodgkin lymphoma (aggr. NHL), Hodgkin lymphoma (HL), and indolent lymphoma (Ind. L). Subjects with a VTE event more than one year before cancer diagnosis were excluded. For each of the cases 5 controls matched on country, sex and age were identified. We used Cox regression models to estimate the relative risk of VTE across the seven different subtypes of hematological malignancies with a time axis starting one year before the diagnosis of cancer (and similar for matched controls) and ending at a VTE event or end of follow-up. Data were adjusted for age by spline regression. Results: During follow-up 891 participants were diagnosed with a hematological malignancy, and in this group 41 VTE events were observed corresponding to an incidence of 12.0 events per 1000 person-years (10-3 p-y). In the control group of 4455 participants 55 VTE events were observed which gave an incidence of events on 2.3* 10-3 p-y. Having a hematological cancer including all seven investigated types was associated with a six-fold increased risk of developing VTE compared to the matched controls. During follow-up 203 participants were diagnosed with MM, and 10 VTE events were observed giving an event rate of 14.6*10-3 p-y; hazard ratio (HR) for VTE was 7.2, 95% confidence interval (CI): 3.6-14.3. CLL was diagnosed in 176 cases, and 11 VTE events were observed in this group (event rate 11.5*10-3 p-y; HR 5.3; 95% CI: 2.7-10.1). Among the 63 participants who were diagnosed with AL during follow-up 2 VTE events were observed corresponding to an event-rate on 12.8*10-3 p-y; (HR 6.9; 95% CI: 1.7-29.0). In the group of CMN/MDS 4 VTE events were observed among 104 patients (event-rate 12.0*10-3 p-y; HR 6.4, 95% CI: 2.3-18.0). In aggressive NHL 10 VTE events were observed among 158 patients resulting in an event-rate of 18.9*10-3 p-y (HR 10.4; 95% CI: 5.2-20.8). Forty-four participants were diagnosed with HL, and 2 VTE events were observed which corresponds to an event-rate of 10.6*10-3 p-y among these patients (HR 5.1; 95% CI: 1.2-21.4). Indolent lymphoma was diagnosed in 143 subjects, and 2 VTE events were observed (event-rate 3.5*10-3 p-y; HR 1.9; 95% CI: 0.47-8.0). The results are summarized in the table: Table. MM CLL AL CMN/MDS Aggr. NHL HL Ind. L N 203 176 63 104 158 44 143 VTE (n) 10 11 2 4 10 2 2 Incidence (*10-3 p-y) 14.6 11.5 12.8 12.0 18.9 10.6 3.5 HR 7.2 5.3 6.9 6.4 10.4 5.1 1.9 95 % CI 3.6-14.3 2.7-10.1 1.7-29.0 2.3-18.0 5.2-20.8 1.2-21.4 0.47-8.0 Conclusion: Indolent lymphoma was the only investigated hematological malignancy that was not associated with a significant increased risk of VTE. The other types of hematological malignancies had an increased risk of VTE ranging from approximately 5-10 times, highest in aggressive non-Hodgkin lymphoma and lowest in Hodgkin lymphoma. However a limitation of the study is the small numbers in some of the groups in spite of the large cohort. Disclosures No relevant conflicts of interest to declare.

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Risk of Diabetes Mellitus in Long-Term Survivors of Hodgkin Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2013.54.4379 ◽

2014 ◽

Vol 32 (29) ◽

pp. 3257-3263 ◽

Cited By ~ 40

Author(s):

Frederika A. van Nimwegen ◽

Michael Schaapveld ◽

Cecile P.M. Janus ◽

Augustinus D.G. Krol ◽

John M.M. Raemaekers ◽

...

Keyword(s):

Diabetes Mellitus ◽

Lymph Nodes ◽

Hodgkin Lymphoma ◽

Cumulative Incidence ◽

Cox Regression ◽

Study Cohort ◽

Increased Risk ◽

Increase Risk ◽

Long Term Survivors

Purpose Recently, an increased risk of diabetes mellitus (DM) was observed after abdominal irradiation for childhood cancer. Because many Hodgkin lymphoma (HL) survivors have also been treated with infradiaphragmatic radiotherapy, we evaluated the association between HL treatment and DM risk. Patients and Methods Our study cohort comprised 2,264 5-year HL survivors, diagnosed before age 51 years and treated between 1965 and 1995. Treatment and follow-up information was collected from medical records and general practitioners. Radiation dosimetry was performed to estimate radiation dose to the pancreas. Cumulative incidence of DM was estimated, and risk factors for DM were evaluated by using Cox regression. Results After a median follow-up of 21.5 years, 157 patients developed DM. Overall cumulative incidence of DM after 30 years was 8.3% (95% CI, 6.9% to 9.8%). After para-aortic radiation with ≥ 36 Gy, the 30-year cumulative incidence of DM was 14.2% (95% CI, 10.7% to 18.3%). Irradiation with ≥ 36 Gy to the para-aortic lymph nodes and spleen was associated with a 2.30-fold increased risk of DM (95% CI, 1.54- to 3.44-fold) whereas para-aortic radiation alone with ≥ 36 Gy was associated with a 1.82-fold increased risk (95% CI, 1.02- to 3.25-fold). Lower doses (10 to 35 Gy) did not significantly increase risk of DM. The risk of DM significantly increased with higher mean radiation doses to the pancreatic tail (P < .001). Conclusion Radiation to the para-aortic lymph nodes increases the risk of developing DM in 5-year HL survivors. Screening for DM should be considered in follow-up guidelines for HL survivors, and treating physicians should be alert to this increased risk.

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