Trends in the Risk of Second Primary Malignancies (SPMs) Among Survivors of Chronic Lymphocytic Leukemia(CLL)

Abstract Background: CLL is the most common leukemia diagnosis in adults and its treatment has undergone significant change from chemotherapy, to immunotherapy and now targeted kinase inhibitors, leading to improved overall survival (OS). With improving survivorship, SPMs can occur but an in-depth analysis of risks and trends of SPMs in CLL survivors is lacking. We performed a population-based analysis to evaluate this. Methods: Patients in the Surveillance, Epidemiology and End Results (SEER) database diagnosed with CLL between 1973-2015 were included. Due to variation in management techniques over time, the cohort was divided in four time periods: 1973-1982, 1983-1992, 1993-2002 and 2003-2015. We evaluated differences in risk for SPMs among CLL survivors compared to risk of individual malignancies expected in the general population during these time periods and studied the effect of demographics and time since CLL diagnosis. Results: Over a nearly 270,000 person-year follow up, 6,467 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI 1.17-1.23), which resulted in a 39 excess cancers per 10,000 population. The CLL survivors had a 20% overall increased risk of developing SPMs (excluding non-squamous skin cancer) compared to the general population. The risks for both solid (SIR 1.15 CI 95% 1.12-1.18) and hematological malignancies (SIR 1.61 95% CI 1.5-1.73) was higher than the expected in the general population. However, the risk for individual cancers was heterogeneous. The tumors associated with the highest risk were Hodgkin lymphoma (almost 8 times higher), Kaposi Sarcoma (4 times), non-epithelial skin cancers (4 times), salivary gland cancer (3 times) and acute lymphocytic leukemia (3 times). In contrast, tumors in the hepatobiliary system, female breast and female genital system were associated with a lower risk than the general population. The highest SIR across the study periods was observed in the younger population (ages 15-49). Although the risk increased in all ethnicities, it was statistically significant only in Caucasians. There was no gender-wise difference in SIR during any of the four time periods. A statistically significant increase in SIR was observed for both men and women from 1973-1982 to 2003-2015. This was mostly due to an increase in risk of hematological malignancies from 1.08 early in the study to 2.56 in the most recent study period. The SIR in solid tumors did not change significantly over time; in absolute terms, however, lung carcinoma contributed the most to the excess risk, followed by non-epithelial skin cancers and non-Hodgkin's lymphoma. The risk of developing a SPM was higher for the CLL survivors during most of the latency periods, but it was statistically significant during the 2-5 months and 12-59 months after diagnosis. A multivariate analysis was conducted to evaluate the impact of period of diagnosis on the development of SPMs among these patients. After adjusting for gender, ethnicity, radiation therapy, chemotherapy, and age at diagnosis of CLL, patients diagnosed with CLL in the most recent time period were at 45% higher risk of developing SPMs as compared to the patient diagnosed during 1973-1982 (Hazard ratio(HR) =1.45 95%CI:1.34-1.6, p<0.001). Moreover increased HRs were also observed for 1983-1992 and 1993-2002 time periods (Fig. 1) Conclusions: With improving therapeutics for cancer treatment, survivorship is improving as well and the risk of SPMs needs to be better understood and addressed. This is truer for CLL, where majority of patients have a favorable survival. The risk of SPMs was 20% higher in CLL survivors than in the general population and was most prominent in the survivors aged 15-49 years at the time of CLL diagnosis. The risk of individual malignancies may be heterogenous but there has been an increase in risk of SPMs over time, mainly due to an increase of secondary hematological malignancies in recent years. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL. Disclosures Ailawadhi: Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.

Download Full-text

Significant Improvement of the Survival of Patients with Multiple Myeloma Presenting with Severe Renal Impairment After the Introduction of Novel Agents

Blood ◽

10.1182/blood.v120.21.948.948 ◽

2012 ◽

Vol 120 (21) ◽

pp. 948-948

Author(s):

Meletios A Dimopoulos ◽

Sosana Delimpasi ◽

Eirini Katodritou ◽

Eleftheria Hatzimichael ◽

Marie-Christine Kyrtsonis ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Impairment ◽

Conflicts Of Interest ◽

Early Death ◽

Novel Agents ◽

The Past ◽

Increased Risk ◽

Time Periods ◽

The Impact ◽

Over Time

Abstract Abstract 948 Renal impairment (RI) is a common presenting complication of multiple myeloma (MM) and is associated with increased risk of treatment related toxicity and early death. The management of RI in patients with MM requires vigorous supportive measures and the immediate institution of antimyeloma therapy. After the introduction of novel agents a significant improvement of the survival of patients with MM has been observed; however, the impact of these therapies on the survival of MM patients who present with RI has not been extensively studied. In order to analyze the impact of RI in newly diagnosed patients with MM over the past 20 years, we analyzed 1773 patients with symptomatic myeloma who were treated within the Greek Myeloma Study Group (GMSG). Patients were divided in groups according to the date of initial treatment (1/1/1990-31/12/1994, 1/1/1995-31/12/1999, 1/1/2000-31/12/2004, after 1/1/2005). Thalidomide became available in Greece after 1/1/2000 and bortezomib after 1/1/2005. eGFR was calculated by the modified MDRD formula and the degree of RI was rated as severe when eGFR was <30 ml/min, moderate when eGFR was 30–59 ml/min and mild (or no RI) when eGFR >60 ml/min. The frequency of RI over time was similar as well as the proportion of patients who presented with severe RI (17% vs. 21% vs. 17% vs. 19%) for the respective time periods (p=0.496). More patients >65 years started therapy after 2000 (44% vs. 50% vs. 59% vs. 59%, respectively, p<0.001), especially patients >75 years (13% vs. 18% vs. 24% vs. 32%, respectively, p<0.001). Anemia (Hb <10 g/dl; p=0.007) and ISS-3 disease (p=0.001) were more common after 1/1/1995; there were no other significant differences in the characteristics of the patients during the respective time periods. No patients received upfront novel agents before 31/12/1999, while 20% received upfront novel agent in the period 2000–2004 (almost exclusively thalidomide) and 73% after 1/1/2005 (mostly thalidomide and bortezomib). Myeloma response (≥PR) to frontline therapy was achieved in 56.5% & 54% of patients in the period 1990–1994 & 1995–1999 vs. 67% and 72% of patients in the periods 2000–2004 and after 2005 (p<0.001). The median survival of patients has improved significantly during the past 20 years: 39 months (1990-1994), 31 months (1995-1999), 40.5 months (2000-2004), 54 months after 2005 (p<0.001). The median OS for patients with severe RI has improved significantly from 18 months & 19.5 months in the 1990–1994 & 1995–1999 to 29 months and 32 months for the periods 2000–2004 and after 2005 (p=0.005). For patients with moderate RI the OS improved from 33 & 26 months between 1990–1994 & 1995–1999 to 40 & 44 months in the periods 2000–2004 and after 2005 (p=0.003). For patients with an eGFR ≥60 ml/min the OS improvement was less pronounced (48.5 months vs. 45 months vs. 51 months for the periods 1990–1994 & 1995–1999 & 2000–2004 respectively (p=0.076) and only after 2005 a significant improvement in OS is observed (median OS has not been reached; 3-year OS rate is 73%, p<0.001). For patients with severe RI early death rates (<2 months from initiation of therapy) were 12% vs. 7% for patients with moderate RI vs. 3% for patients with mild or no RI (p<0.001) and remained unchanged over time. We then adjusted for differences between groups in a multivariate model: treatment after 1/1/2000 was independently associated with improved survival compared to patients treated before 31/12/1999 (p<0.001). After adjusting for the degree of RI in the model, the hazards ratios (HR) for death for patients with severe RI for the 2000–2004 and after 2005 periods were 0.485 & 0.387 respectively compared to patients treated before 2000 (p<0.001 for both comparisons). For patients with moderate RI the respective HRs were 0.65 (p=0.003) & 0.57 (p=0.001), while for patients with mild or no RI the HRs were 0.85 (p=0.1) & 0.66 (p=0.003) for the 2000–2004 and after 2005 periods, respectively. In conclusion, the incidence of RI at diagnosis of MM has remained unchanged during the past 20 years, despite the increasing numbers of older patients who are diagnosed and treated for MM. The risk of early death is almost 2 to 4-fold higher in patients with severe RI vs. patients with moderate or no RI and has not improved over time. However, after the introduction of novel therapies there has been a significant improvement of the survival of patients with RI, which is more pronounced in patients with severe RI. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

O39 VTE risk in the general population: applying context to the impact of JAK inhibition

Rheumatology ◽

10.1093/rheumatology/keaa110.038 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Serena Baroncini ◽

Mark Yates ◽

Katie Bechman ◽

Sanjeev Patel ◽

Andrew Rutherford ◽

...

Keyword(s):

General Population ◽

Statistical Significance ◽

Primary Diagnosis ◽

Linear Pattern ◽

Background Population ◽

Increased Risk ◽

Trends Over Time ◽

Event Rates ◽

The Impact ◽

Over Time

Abstract Background Trial data indicate an increased risk of VTE with JAK inhibition. The EMA and FDA have given regulatory advice for their use as a result. To understand the context of any association, we need to understand VTE risk in the background population. Our objective was to describe the changing epidemiology of VTE risk including a breakdown of DVT and PE in the general population in England, over a 20-year period. Methods We utilised hospital episodes statistics data to study all patients presenting for hospital care in England between 1 January 1998 and 31 December 2017. We identified VTE events using ICD10 codes I26.0, I26.9, I80.1, I80.2 and I80.3. To estimate annualised event rates, we used the number of finished consultant episodes for admitted care where the primary diagnosis was VTE for the numerator; the denominator was the whole population estimate, from the office for National Statistics, for the relevant year for England. Rates were calculated per 100,000 population, and the Cochrane Armitage test was used to evaluate statistical significance of trends over time. Linear regression allowed modelling of estimates over time, with model assumptions tested using residual versus fitted plots. To explore non-linearity, we used a cubic spline model. Results The average VTE rate across the 20 years was 127/100,000. VTE rates have increased over time, climbing from 108/100,000 in 1998, to 151/100,000 in 2017. The relative frequency of DVTs and PEs has changed over this time: in 1998 DVT was more frequent than PE (rates 68/100,000 and 40/100,000 respectively). By 2018 this ratio had reversed (DVT 52/100,000: PE 98/100,000). This change was statistically significant (p < 0.0001). DVT rates declined in a linear manner over time. PE rates increased with a non-linear pattern, with a sharp rise apparent between 2008 and 2010. Conclusion The inversion in the frequency of DVTs and PEs is consistent with previous findings using European data. One possible explanation is changing diagnostics (CTPA replacing V/Q), capturing previously subclinical PE events. Limitations include our ecologic design as well as lack of linkage to mortality records. The presumed VTE risk associated with JAK inhibition is small. It is plausible that future shifts in population wide patterns of VTE could obscure or amplify any effect attributable to JAK inhibitors. As longer-term observational data become available, it is crucial they are interpreted in the context of background population trends. Disclosures S. Baroncini: None. M. Yates: None. K. Bechman: None. S. Patel: None. A. Rutherford: None. A. Kleymann: None. J. Galloway: None.

Download Full-text

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

Current Pharmaceutical Design ◽

10.2174/1381612825666190830175424 ◽

2019 ◽

Vol 25 (29) ◽

pp. 3098-3111 ◽

Cited By ~ 6

Author(s):

Luca Liberale ◽

Giovanni G. Camici

Keyword(s):

Atherosclerotic Plaque ◽

Molecular Mechanisms ◽

Driving Forces ◽

Plaque Burden ◽

Vascular Aging ◽

Age Related ◽

Plaque Development ◽

Increased Risk ◽

The Impact ◽

Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

Download Full-text

1628 Vaccination for Safe Surgery During The SARS-Cov-2 Pandemic: Modelling Study

British Journal of Surgery ◽

10.1093/bjs/znab258.064 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

Keyword(s):

General Population ◽

Elective Surgery ◽

Risk Difference ◽

Cancer Surgery ◽

Number Needed To Treat ◽

Worst Case ◽

Registration Data ◽

Increased Risk ◽

One Year ◽

The Impact

Abstract Introduction Compared to the general population, in the postoperative period, surgical patients are both at increased risk of SARS-CoV-2 infection and increased mortality in the event of SARS-CoV-2 infection. This study modelled the impact of preoperative vaccination of patients aged ≥70 years having elective inpatient surgery. Method The primary outcome was the number needed to treat (NNT) to prevent one death over one year following SARS-CoV-2 vaccination. Postoperative SARS-CoV-2 incidence and adjusted mortality risk difference for SARS-CoV-2 infection were estimated from the prospective GlobalSurg-CovidSurg Week study (90,146 elective surgery patients across 1,595 hospitals in 115 countries), were used to estimate lives saved by vaccination in the first 30 postoperative days. SARS-CoV-2 case and death registration data from the Office for National Statistics was used to estimate NNTs for the general population. Best and worst-case scenarios were used to describe uncertainty around estimates. Results Among patients aged ≥70 years undergoing any type of surgery, NNT was estimated to be 332 (best case: 213; worst case: 690). NNT was lower in the cancer surgery subgroup (245 [150-545]). This was more favourable than the NNT for vaccination of the general population aged ≥70 (588 [403-1032]). Globally, vaccinating elective surgery patients aged ≥70 years preoperatively was projected to save 27,356 lives in one year compared to vaccinating the same patients after surgery. Conclusions Preoperative pathways should be set up for the vaccination of patients aged ≥70. In settings with limited vaccine availability, elective cancer surgery patients should be prioritised for vaccination.

Download Full-text

Ethnic differences in participation in diabetes education programmes

European Journal of Public Health ◽

10.1093/eurpub/ckz186.063 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

A Juul ◽

C Glümer ◽

S S Jervelund ◽

N F Hempler

Keyword(s):

Type 2 Diabetes ◽

General Population ◽

Social Relations ◽

Diabetes Education ◽

Household Composition ◽

Participation Rates ◽

Increased Risk ◽

Depth Analysis ◽

Study Population

Abstract Background Immigrants from non-Western countries have a higher prevalence of type 2 diabetes. In addition, immigrants have an increased risk of developing diabetes complications, compared with the general population. Diabetes education programmes facilitate essential knowledge and skills that enable people to manage their condition in daily life. However, fewer immigrants attend and complete diabetes education compared with the general population. The aim of this study is to explore what characterises those who decline and accept participation in diabetes education in relation to ethnicity, household composition and diabetes burden in the family. Methods The study population consisted of adults with type 2 diabetes referred to a municipal diabetes centre (n = 1819). Individual medical record data was linked to national registry data. Descriptive statistics and logistic regression models were applied. Results Preliminary results showed that 23% of individuals from the study population participated in diabetes education. We found no overall differences in participation rates between the general population and non-Western immigrants (24% vs. 18%, P = 0.12). However, when examining the immigrant groups by language (Arabic, Urdu and Turkish), the results indicated a non-significant tendency: Urdu speaking groups’ participation was similar to the general population (24%), whereas Arabic and Turkish speaking groups had lower participation rates (17% and 11%, P = 0.25/0.40). Conclusions The results suggest that there are differences in participation between some immigrant groups and the general population. Increased knowledge about which mechanisms affecting participation in diabetes education programme is required to ensure equal access. Further studies and analyses will explore how immigrants’ social relations enable and/or hamper participation in diabetes education and investigate which factors can be changed to improve participation rates. Key messages There are differences in participation in diabetes education programmes across different ethnic groups, which suggests a need for in-depth analysis into which mechanisms that affect participation. The results will be used to give input for future practices that can increase immigrant’s participation and retention in diabetes education programmes.

Download Full-text

Risk of eating disorders in international adoptees: a cohort study using Swedish national population registers

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796020000451 ◽

2020 ◽

Vol 29 ◽

Author(s):

M. Strand ◽

R. Zhang ◽

L. M. Thornton ◽

A. Birgegård ◽

B. M. D'Onofrio ◽

...

Keyword(s):

Mental Health ◽

Eating Disorders ◽

Cohort Study ◽

General Population ◽

Anxiety Disorders ◽

Elevated Risk ◽

Compulsive Disorder ◽

International Adoptees ◽

Increased Risk ◽

The Impact

Abstract Aims Compared to the general population, adoptees are more often referred to specialist psychiatric treatment, exhibit increased risk of suicide and display more symptoms of attention-deficit/hyperactivity-disorder. However, little is known about the impact of being an adoptee on the risk of developing an eating disorder. The aim of the present study was to assess whether international adoptees have a higher risk for eating disorders than native Swedes. Methods In the present retrospective cohort study, data from the Swedish total population registers on individuals born between 1979 and 2005 were used to assess whether international adoptees residing in Sweden (n = 25 287) have a higher risk for anorexia nervosa (AN) and other eating disorders (OED) than non-adoptees with Swedish-born parents from the general population (n = 2 046 835). The patterns of these results were compared to those for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders to determine whether any observed effects were unique to eating disorders or reflected a more general impact on mental health outcomes. Results A survival analysis adjusting for relevant demographic covariates revealed an elevated risk of all examined psychiatric disorders in international adoptees: hazard ratios (95% confidence intervals) are 1.21 (1.04–1.41) for AN, 1.60 (1.44–1.79) for OED, 1.90 (1.81–2.00) for MDD, 1.25 (1.09–1.44) for OCD, and 1.69 (1.60–1.78) for anxiety disorders. Conclusions Elevated risk of eating disorders as well as of MDD, OCD, and anxiety disorders was found in international adoptees. A parallel pattern between AN and OCD was observed, which both display less elevated rates than the other diagnoses. A considerable number of biological, environmental, and societal factors have been suggested to explain the observed differences in mental health between adoptees and non-adoptees, but they remain primarily theoretical.

Download Full-text

Endocrine and Metabolic Diseases Among Colorectal Cancer Survivors in a Population-Based Cohort

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djz040 ◽

2019 ◽

Vol 112 (1) ◽

pp. 78-86

Author(s):

Makenzie L Hawkins ◽

Brenna E Blackburn ◽

Kerry Rowe ◽

John Snyder ◽

Vikrant G Deshmukh ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factor ◽

General Population ◽

Metabolic Diseases ◽

The United States ◽

Population Cohort ◽

Increased Risk ◽

General Population Cohort ◽

Time Periods

Abstract Background There are an estimated 1.4 million colorectal cancer (CRC) survivors in the United States. Research on endocrine and metabolic diseases over the long term in CRC survivors is limited. Obesity is a risk factor for CRC; thus it is of interest to investigate diseases that may share this risk factor, such as diabetes, for long-term health outcomes among CRC survivors. Methods A total of 7114 CRC patients were identified from the Utah Population Database and matched to a general population cohort of 25 979 individuals on birth year, sex, and birth state. Disease diagnoses (assessed over three time periods of 1–5 years, 5–10 years, and >10 years) were identified using electronic medical records and statewide ambulatory and inpatient discharge data. Cox proportional hazard models were used to estimate the risk of endocrine and metabolic disease. Results Across all three time periods, risks for endocrine and metabolic diseases were statistically significantly greater for CRC survivors compared with the general population cohort. At 1–5 years postdiagnosis, CRC survivors’ risk for diabetes mellitus with complications was statistically significantly elevated (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.09 to 1.70). CRC survivors also experienced a 40% increased risk of obesity at 1–5 years postcancer diagnosis (HR= 1.40, 99% CI= 1.66 to 2.18) and a 50% increased risk at 5–10 years postdiagnosis (HR = 1.50, 99% CI= 1.16 to 1.95). Conclusions Endocrine and metabolic diseases were statistically significantly higher in CRC survivors throughout the follow-up periods of 1–5 years, 5–10 years, and more than 10 years postdiagnosis. As the number of CRC survivors increases, understanding the long-term trajectory is critical for improved survivorship care.

Download Full-text

Prior Treatment with Chemotherapy Is Associated with Poor Outcomes of High Risk Skin Cancers in Patients with Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v120.21.3920.3920 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3920-3920

Author(s):

Matthew S. Davids ◽

Nicole F. Velez ◽

Pritesh Karia ◽

Ye Guo ◽

Alexander R. Vartanov ◽

...

Keyword(s):

High Risk ◽

Skin Cancer ◽

Local Recurrence ◽

General Population ◽

Head And Neck ◽

Lymphocytic Leukemia ◽

Nodal Metastases ◽

Cancer Outcomes ◽

Risk Of Death ◽

Skin Cancers

Abstract Abstract 3920 The increased incidence of skin cancer in patients with chronic lymphocytic leukemia (CLL) has been well-documented; however, the outcomes for CLL patients with high risk skin cancers are not as well-characterized. Moreover, little is known about the association between outcomes of high risk skin cancers and CLL prognostic factors or exposure to prior chemotherapy. We identified 225 patients at our institutions over the last 20 years with concurrent CLL and skin cancer, and we retrospectively examined outcomes for the 139/225 (61.8%) who had high risk skin cancer as defined by a diagnosis of squamous cell carcinoma (SCC), melanoma, or Merkel cell carcinoma (MCC). Poor skin cancer outcome (defined by local recurrence, nodal metastasis, and disease specific death) was determined by review of patient medical records and verified by pathology reports. Associations between various risk factors and poor skin cancer outcomes were evaluated via chi-square statistics (STATA 12.0 College Station, TX). The study group included a representative CLL population, with 98/139 (70%) males and a median age at diagnosis of 65 years (range 35–84), with a median follow-up of 120 months (range 2–410). Over the course of the study, 76 CLL patients remained alive (55%), 16 patients died due to CLL (12%), and 42 patients died from other causes (30%), including 18 (13%) from skin cancer. Median age at time of skin cancer diagnosis was 72 years (range 44–98), and median follow-up time after skin cancer diagnosis was 41 months (range 2–182). Skin cancer diagnoses included SCC in 122 patients (81%), melanoma in 22 patients (13%), and MCC in 8 patients (6%). Sixty-three (45%) patients had more than one skin cancer diagnosed. In the 122 patients with SCC, there were a total of 353 tumors, 297 of which occurred in males (84%). Half of the SCCs were in the head and neck (n=175, 49.6%). Fifty-four SCCs (15%) were greater than 2 cm in diameter. Rates of nodal metastases and death due to SCC were 12% and 6%, respectively. In the 22 patients with melanoma, 14 occurred in men (63.6%), with the largest number of tumors again located on the head and neck (n=8, 36.4%). Breslow thickness was greater than 1 mm in 12 patients (54.5%). Local recurrence and nodal metastases each occurred in 5 patients (22.7%). The five patients (22.7%) who died due to melanoma were the same patients with nodal metastases. In the 8 patients with MCC, 5 patients (62.5%) were male, and there was no location predominance. Five tumors (62.5%) were greater than 2 cm at time of diagnosis, local recurrence occurred in 1 patient (12.5%), and 5 patients (62.5%) had nodal metastases, with 4 of these 5 dying from MCC. Interestingly, prior treatment with any CLL chemotherapy was significantly associated with poorer skin cancer outcome, with increased rates of local recurrence, metastatic disease, or death due to skin cancer (p=0.001). We also explored whether high risk CLL prognostic factors were associated with poorer skin cancer outcomes. Eleven out of 18 patients tested (61%) had unmutated IGHV, 9/69 patients tested (13%) had del(17p) or del(11q) cytogenetics, and 71 patients did not have prognostic marker data available. In this limited prognostic marker data set, neither unmutated IGHV, poor risk cytogenetics, nor advanced Rai stage was associated with skin-cancer specific outcomes. Overall, the majority of the skin cancers in our cohort occurred in males, and the most common site of disease was the head and neck, highlighting an area in need of especially close surveillance. Relative to the historical experience of high-risk skin cancer patients in the general population, we found skin cancers in our CLL population to be more aggressive. For example, 2 of the skin-cancer related deaths were in CLL patients with stage I melanoma, which is unusual in the general population. Additionally, rates of nodal metastases and death in our SCC group were 12% and 6%, respectively, compared to rates of 4% and 2% in most studies of SCC in the general population. Strikingly, the risk of death from skin cancer was equivalent to the risk of death from CLL. The poor skin cancer outcomes in patients in our study were driven by the group who had received prior chemotherapy. Outcomes were not influenced by high risk CLL prognostic markers, although this latter analysis was limited by incomplete data. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Comorbidities Impact Survival in Multiple Myeloma: Analysis of the Veterans Health Administration National Database

Blood ◽

10.1182/blood.v120.21.760.760 ◽

2012 ◽

Vol 120 (21) ◽

pp. 760-760

Author(s):

Tanya Wildes ◽

Suhong Luo ◽

Graham A Colditz ◽

Kenneth R. Carson

Keyword(s):

Cardiovascular Disease ◽

Multiple Myeloma ◽

Renal Impairment ◽

Proportional Hazards ◽

First Year ◽

Risk Of Death ◽

Increased Risk ◽

Comorbidity Index ◽

The Impact ◽

Over Time

Abstract Abstract 760 Introduction: The incidence of multiple myeloma (MM) increases with age, and the prognosis worsens. Comorbidities increase in prevalence with age, yet little is known about the impact of comorbid medical conditions on outcomes in MM. Methods: In a retrospectively-assembled cohort study, all patients with MM diagnosed between 1998 and 2009 at a Veterans' Administration (VA) hospital were identified in the VA central cancer registry. Patients who received no treatment within 6 months of diagnosis were excluded, eliminating those with smoldering myeloma or who received supportive care only. Comorbidities were ascertained from ICD-9 codes present prior to the diagnosis of MM, and categorized using the Romano adaptation of the Charlson Comorbidity Index (CCI). The independent effects of age, race and comorbidities were examined using Cox proportional hazards modeling. The impact of individual comorbidities on survival was also examined, controlling for age and race. Results: A total of 2,968 patients were identified. The median age was 69 (range 27–92). The vast majority of patients (98%) were male; 28.6% of the patients were black. The median Charlson Comorbidity Index score was 2 (range 0–13). The frequencies of selected comorbidities were: diabetes (31%), renal impairment (23.8%), cardiovascular comorbidities (38.8%) and pulmonary (26.6%). The median overall survival (OS) for the entire cohort was 28.6 months at a median follow up of 26.8 months (range 0–137 months). On multivariate analysis, age was significantly associated with mortality [Hazard Ratio (HR) 1.03 per year (95% confidence intervals (CI) 1.03–1.04), p<0.0001]. Race was not significantly associated with survival [HR 0.99 (95% CI 0.90–1.09), p=0.81]. The median OS, adjusted for age and race, was 36.5 months for patients with no comorbidities, 33.9 months for patients with a CCI score of 1–2, 25.6 months for patients with a CCI score of 3–4 and 20.2 months for patients with a CCI score ≥5. The impact of comorbidities on survival violated the proportional hazards assumption, with a cut-point at 1 year, indicating that the influence of comorbidities varied over time. Relative to those with no comorbidities, the HR for death among those with a CCI score 1–2 was 1.20 (0.97–1.48) in the first year, and 1.03 (95% CI 0.89–1.18) subsequent to the first year; among those with a CCI score 3–4, the HR for death was 1.67 (95% CI 1.34–2.08) in the first year and 1.23 (95% CI 1.05–1.45) subsequently; among those with a CCI score ≥5, the risk of death in the first year doubled [HR 2.15 (95% CI 1.73–2.67)] and was increased 40% subsequently [HR 1.42 (95% CI 1.19–1.69)]. Individual prevalent comorbidities were then examined. Cardiovascular disease, renal impairment, and pulmonary disease were all significantly associated with mortality. In the first year after diagnosis, cardiovascular disease was associated with a 55% increase in mortality [HR 1.55 (95% CI 1.35–1.78)] while, subsequent to the first year, the risk was only increased about 20% [HR 1.19 (95% CI 1.07–1.39)]. The impact of renal impairment and pulmonary impairment did not vary over time; both were associated with a 25% increased risk of death [renal impairment HR 1.26 (95% CI 1.14–1.38); pulmonary disease HR 1.24 (95% CI 1.13–1.37)]. Diabetes was not associated with survival (HR 1.02, p=0.64) after controlling for age, race and cardiovascular, pulmonary or renal impairment. Conclusion: Age and comorbidities are independently associated with increased risk of mortality in MM. The influence of comorbidities varies over time, with the greatest impact noted in the first year after diagnosis of MM among those with a CCI score ≥3 and with cardiovascular disease. Further study is needed to determine whether this increased early mortality is related to increased risk of toxicity of therapy, inadequate MM therapy or both. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Chronic Lymphocytic Leukemia-Associated Chromosomal Abnormalities and Risk of Secondary Malignancies

Blood ◽

10.1182/blood.v124.21.5636.5636 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5636-5636

Author(s):

Shahzad Raza ◽

Paul J Hampel ◽

Belal Firwana ◽

Zhen Wang ◽

Yasar Shad ◽

...

Keyword(s):

Overall Survival ◽

Chromosomal Abnormalities ◽

Lymphocytic Leukemia ◽

Secondary Malignancy ◽

Secondary Malignancies ◽

Skin Cancers ◽

Increased Risk ◽

Trisomy 12 ◽

13Q Deletion ◽

Melanoma Skin

Abstract Introduction: Incidence of secondary malignant neoplasm in patients with chronic lymphocytic leukemia (CLL) is already established. Genetic predisposition has been considered to be a possible contributory factor for the preponderance of second cancers in this population. In the present study, we examined the frequency, characteristics, and clinical outcomes of secondary malignancies in patients with CLL based on their Interphase fluorescence in situ hybridization (FISH) panel. Methods: We reviewed the medical records of consecutive patients with CLL observed or treated at Ellis Fischel Cancer Center during the period from 2007-2014. We collected demographic data, CLL Rai stage, treatment history, Interphase fluorescence in situ hybridization (FISH) panel results and the presence of a secondary malignancy (skin cancers, solid tumors and hematologic malignancy excluding CLL transformation).Our aim was to investigate the association between secondary malignancy and chromosomal abnormalities and other risk factors using Chi2test for categorical variables and Wilcoxon rank-sum test for continuous variables. Cox proportional hazard models and logistic regression models were used to evaluate risk factors of developing secondary malignancy and overall survival. Results: We identified 142 CLL patients who were either observed (n=62) or had a history of treatment (n=80) for CLL. 67% were male and 33% were female. 85% of patients were Caucasians, 10% African Americans, and 5% other. Familial CLL was present in 6% of cases. 51% of patients were non-smokers. 5% of patients had cancers preceding the diagnosis of CLL (non-melanoma skin cancers=3, melanoma=1, Hodgkin's lymphoma=1, Prostate=2). 28% of patients developed secondary malignancies after the diagnosis of CLL; among them non-melanoma skin cancers were the most common (78%), followed by cutaneous melanoma (9.5%) and papillary thyroid cancer (4.7%). Other malignancies included lung (2.3%), kidney (2.3%), prostate (2.3%) and ocular melanoma (2.3%). 12% patients had aggressive non-melanoma recurrent skin cancers that require multiple treatments along-with systemic therapy for progressive CLL. CLL-FISH panel at diagnosis was available in 98 patients. Among these patients,13q deletion was present in 45%. Within the 13q deletion group, secondary malignancy was noted in 50% during a median follow up of 7 years. All cases of papillary thyroid cancers were also present in 13q deletion. In contrast, 11q deletion was detected in 15% and trisomy 12 in 18% of patients with incidence of secondary malignancy 40% and 10%, respectively. No solid malignancy other than skin was identified in the 11q deletion and trisomy 12 groups. 17p deletion was present in 5% of cases and 60% of 17p deletion cases had secondary cancers (skin 80%). Normal FISH panel was present in 17% cases and 20% of normal FISH had secondary malignancy (solid 10%, skin 10%). The median overall survival time is 6 years for the entire cohort (IRQ: 3-9 years). Secondary malignancy was associated with worse overall survival (OS) (HR=0.57, 95% CI:0.33-0.98, p=0.04) compare to patients who did not have secondary malignancy. The risk of secondary malignancy is increased in patients with advanced age (OR=1.05, 95% CI:1.00-1.10, p=0.04) and in those who were treated with alkylating agent for CLL OR=6.62, 95% CI:2.08-21.03, p=0.001. However, there were no significant difference on risk of developing secondary malignancy based on specific chromosomal FISH result, Rai stage, smoking, family history and gender. Conclusion: Secondary malignancies are frequent in patients with detectable chromosome abnormality on FISH panel. However, the increased risk of secondary malignancy does not correlate with specific cytogenetic abnormality. Non melanoma skin cancers are exceedingly common in CLL patients and carries aggressive couse in progressive CLL patients. Larger studies are required to identify subtype of CLL based on integrated mutational and cytogenetic subgroup that are at increased risk of specific secondary malignancies. Disclosures No relevant conflicts of interest to declare.

Download Full-text