Incidence and Risk Factors of Osteonecrosis of Femoral Head in Multiple Myeloma Patients Undergoing Dexamethasone-Based Regimens

Objectives. To investigate the incidence and risk factors for osteonecrosis of femoral head (ONFH) in multiple myeloma (MM) patients undergoing dexamethasone-based regimens (DBRs). Methods. A retrospective study was conducted in MM patients administered DBRs between December 2012 and April 2015. Demographic, clinical, and laboratory data were extracted to compare between two groups. Incidence of ONFH were calculated and risk factors identified by both univariate and multivariate analysis. Results. The study group comprised 105 patients undergoing DBRs. Seven patients with ONFH after DBRs were classified as the ONFH group, and the other 98 patients without ONFH were included in the non-ONFH group. Incidence of ONFH was 6.7%. Median age of developing ONFH was 51 years (45–64), and the male to female ratio was 6 : 1. A total of 12 femoral heads were involved, including unilateral in 2 patients and bilateral in 5 patients. After the multivariate analysis, four risk factors were confirmed including male, younger age, cumulative dose of dexamethasone, and hyperlipidemia. Conclusion. The overall incidence of ONFH in MM patients treated with DBRs is 6.7%, and 4 risk factors are confirmed including male, younger age, cumulative dose of dexamethasone, and hyperlipidemia in our study.

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Geographical distribution of the associated factors of osteonecrosis of the femoral head, using the designated intractable disease database in Japan

Modern Rheumatology ◽

10.1093/mr/roab065 ◽

2021 ◽

Author(s):

Wataru Ando ◽

Masaki Takao ◽

Tetsuro Tani ◽

Keisuke Uemura ◽

Hidetoshi Hamada ◽

...

Keyword(s):

Risk Factors ◽

Femoral Head ◽

Age Distribution ◽

Female Ratio ◽

Registry System ◽

Registration Rate ◽

The Mean ◽

Associated Risk Factors ◽

Epidemiological Characteristics ◽

Male To Female

ABSTRACT Objectives Osteonecrosis of the femoral head (ONFH) is a designated intractable disease (DID) in Japan. The Ministry of Health, Labour, and Welfare launched an online registry system for DIDs. We aimed to investigate the epidemiological characteristics of patients with ONFH using the DID database. Methods Data of patients with ONFH registered in the DID database between January 2004 and December 2013 were extracted. The incidence of new cases and distributions of sex, age, and associated risk factors were investigated. The prevalence of the two categories, ‘steroid-associated’ and ‘alcohol-associated’ risk factors, was estimated for each prefecture. Results New 15,049 cases of ONFH were investigated. The mean registration rate-corrected annual ONFH incidence per 100,000 individuals was 1.77. The male-to-female ratio was 1.33. Age distribution peaked in the 40s and 50s for male and 60s for female. The prevalence of steroid-associated ONFH was lower in males (28.6%) than in females (49.8%), while that of alcohol-associated ONFH was higher in males (47.2%) than in females (9.3%). No clear region was identified for the steroids. The incidence of alcohol-associated ONFH was significantly higher in Tokyo and Okinawa, regardless of sex. Conclusions Alcohol-associated ONFH incidence varies geographically across Japan, suggesting that it has regional characteristics.

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Risk of Venous Thromboembolism in Multiple Myeloma: Identification of Risk Factor

Blood ◽

10.1182/blood.v128.22.4726.4726 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4726-4726 ◽

Cited By ~ 3

Author(s):

Kristen M. Sanfilippo ◽

Natasha Catherine Edwin ◽

Brian F. Gage ◽

Suhong Luo ◽

David Calverley ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Multivariate Analysis ◽

Venous Thromboembolism ◽

Research Funding ◽

Laboratory Data ◽

Cell Transplant ◽

Filter Placement ◽

Blood Institute ◽

Increased Risk

Abstract Background Compared to the general population, patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). VTE is a preventable disease that causes death and morbidity. Thromboprophylaxis is a safe and effective way to decrease VTE in other high-risk populations (i.e. atrial fibrillation). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors. However, putative risk factors vary across guidelines and lack validation. Recently, an attempt to validate the International Myeloma Working Group 2014 guidelines for thromboprophylaxis found current risk factors to be inadequate. Identification of risk factors for VTE in MM can allow for effective risk-stratification to clarify thromboprophylaxis in the MM population. We sought to identify risk factors for VTE in patients with MM. Methods We identified patients diagnosed with MM within the Veterans Administration Central Cancer Registry from September 1, 1999 and December 31, 2013 and followed them through October 2014. We excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. Using a previously validated algorithm, (Thromb Res, 2015), we identified patients diagnosed with VTE after MM diagnosis by a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement. We obtained information on baseline patient demographics, medical comorbidities, laboratory data, MM-directed therapy, and use of aspirin and/or warfarin. Univariate analyses identified the association between individual variables and VTE in the cohort. Clinically meaningful and significant associations were included in the multivariate model. Multivariate analysis was done using competing risks regression modeling. The study was approved by the Saint Louis VHA Medical Center and Washington University institutional review boards. Results A total of 3,384 patients comprised the final cohort of whom 414 developed a VTE. Patients who developed VTE were more likely to be younger (66.2 vs 68.5, p < .001), have a body mass index (BMI) ≥ 25 (p < .001), be diagnosed with MM prior to 2007 (p < .001), have a VTE before MM diagnosis (p < .001), have a lower comorbidities (p < .001), have received autologous stem cell transplant (ASCT) (p < .001), have received lenalidomide, thalidomide, or bortezomib (p < .001), and less likely to have received warfarin (p < .001). Among predefined risk factors, age (Hazard Ratio (HR) 0.99, 95% Confidence Interval (CI) 0.98-1.00, p = 0.02), VTE before MM diagnosis (HR 4.13, 95% CI 2.81-6.05, p < .001), heart failure (HR 0.70, 95% CI 0.51-0.96, p = 0.03), treatment with thalidomide (HR 2.02, 95% CI 1.63-2.50, p < 0.001), BMI ≥ 30 (HR 1.34, 95% CI 1.03-1.74, p = 0.03), and diabetes mellitus (HR 0.79, 95% CI 0.63-0.99, p = 0.04) were associated with VTE. After inclusion into multivariate analysis and adjusting for warfarin/aspirin use; age, BMI, year of MM diagnosis, VTE before MM, thalidomide, warfarin, and aspirin were all associated with VTE in MM (Table 1). Conclusion We identified several risk factors associated with VTE in MM. Incorporation of these risk factors into a MM-specific risk model has the potential to reduce risk of VTE in MM. Disclosures Sanfilippo: National Heart, Lung, and Blood Institute: Research Funding. Gage:National Heart, Lung, and Blood Institute: Research Funding. Carson:American Cancer Society: Research Funding.

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Striking age differences of multiple myeloma (MM) diagnosis in patients of Indian and Pakistani descent in the United States compared to native countries.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13070 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13070-e13070 ◽

Cited By ~ 2

Author(s):

Athira Unnikrishnan ◽

Abdullah Mohammad Khan ◽

Preeti Narayan ◽

Maxim Norkin

Keyword(s):

United States ◽

Multiple Myeloma ◽

Retrospective Studies ◽

The United States ◽

Published Data ◽

Female Ratio ◽

Younger Age ◽

The Us ◽

Age Of Diagnosis ◽

Male To Female

e13070 Background: Several studies from India and Pakistan have reported a median younger age of MM diagnosis as compared that of western population. The exact reason for the younger age of myeloma diagnosis in this population is not well understood. Methods: We used the SEER database to analyze age of MM diagnosis in subjects of Indian and Pakistani descent in the United States and compared it to the published data of MM diagnosis in India and Pakistan. Patients with ICD—O-3 morphologic codes (9732/3) and race code 15/16/17 identifying Asian Indians and Pakistanis were identified in the SEER registry data (1973-2013). Data on year of diagnosis, race, sex and age were collected. Four published retrospective studies involving local Indians or Pakistanis patients identified using PUBMED. Average Median age and male to female ratio (M: F) was calculated in both groups and compared for any difference Results: 146 myeloma patients of either Indian or Pakistani descent were identified from the SEER registry. The median age of diagnosis was 67 years with a mean age of 66.1 years. The male to female ratio was 1.41. The retrospective studies analyzed had a total of 495 myeloma patients with median age at diagnosis of 56 years and male to female ratio of 2.01, suggesting that multiple myeloma presented almost a decade earlier in native Indian and Pakistani patients compared to their US counter parts. Conclusions: Subjects in India and Pakistan were significantly younger at the time of MM diagnosis as compared to subjects of Indian and Pakistani descent diagnosed with MM in the US suggesting an environmental factor involved with myeloma genesis in subjects living in India and Pakistan. [Table: see text]

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COMPARISON OF CLINICO-SOCIAL PROFILE OF PULMONARY AND EXTRA PULMONARY TUBERCULOSIS IN TERTIARY CARE HOSPITAL IN A RURALAREA: A RETROSPECTIVE STUDY

10.36106/ijsr/4605295 ◽

2021 ◽

pp. 70-72

Author(s):

Gaurav Santosh Nemade ◽

Sumit Nitin Dhus ◽

Arushi Ramesh Shetty ◽

Neha Dhananjay Firake

Keyword(s):

Tertiary Care ◽

Care Hospital ◽

Female Ratio ◽

Extra Pulmonary Tuberculosis ◽

Younger Age ◽

Tobacco Addiction ◽

History Of ◽

Early Case ◽

Male To Female ◽

Clinical Characteristic

BACKGROUND AND OBJECTIVES: The burden of tuberculosis (TB) in India is the highest accounting for 26% of the global incidence. A total of 1.4 million people died from TB in 2019 (including 208 000 people with HIV). India accounts for a fourth of the global burden of TB and 29% of global mortality. Therefore, we carried out this study to compare demographic, lifestyle and clinical characteristic between pulmonary TB (PTB) and extrapulmonary TB (EPTB). MATERIALS AND METHODOLOGY:Aretrospective analysis was carried of 348 patients diagnosed in DOTS centre, Pravara Rural Hospital, Loni. Characteristics of demographic and clinical characteristics were obtained from medical case records. RESULTS:Among the 348 cases, 71.3% were PTB and 28.7% were EPTB including, pleural (36%), meningeal (27%) and lymphatic (20%) cases. The male to female ratio in PTB and EPTB are 1.99 and 1.22 respectively. EPTB was more common at younger age (<25 years). Tobacco addiction (10.9%), diabetes mellitus (4.03%), HIV positivity (12.1%) and history of contact with Tb patients (17.7%) were more likely to be associated with PTB. CONCLUSION:Increased awareness of the risk factors may facilitate early case nding and better management outcomes for these patients.

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Development and Analysis of a Weighed Prognostic Model in Newly Diagnosed Multiple Myeloma Patients

Blood ◽

10.1182/blood-2020-140464 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 47-48

Author(s):

Xue-Han Mao ◽

Yan Xu ◽

Yuting Yan ◽

Jiahui Liu ◽

Huishou Fan ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Multivariate Analysis ◽

Prognostic Factors ◽

High Risk ◽

Prognostic Factor ◽

Prognostic Model ◽

Cytogenetic Abnormalities ◽

Total Score Range ◽

Prognosis Model

Background and Objective: Multiple myeloma (MM) is characterized with significant cytogenetic changes and complex tumor microenvironment, thus patient survival is extremely heterogeneous. Various disease-related or patient-related factors affect the prognosis of patients. This study tried to analyze the prognostic indicators of patients with newly-treated MM, especially explored the prognosis of multiple cytogenetic abnormalities and the ratio of lymphocytes to monocytes (LMR). Additionally, we established a comprehensive prognostic model to help determine the patient prognosis. Methods: After screening, 603 patients of untreated MM from January 2008 to June 2017, with complete baseline indicators were enrolled into the study. By univariate and multivariate Cox analysis, risk factors related to the prognosis of patients were evaluated, and a weighted prognosis model was established to compare the survival differences of patients in each risk stratification. Result: Optimal thresholds of ALC, LWR, NLR and LMR were determined by ROC curve and Youdex index: ALC = 1.415, LWR = 0.325, NLR = 1.935, LMR = 2.95. Survival analysis showed that patients with LMR ≤ 2.95, ALC ≥ 1.415 and LWR ≥ 0.325 had significantly better survival compared with their respective control groups. Cox multivariate analysis showed that among the four indicators, only LMR≤2.95 was an independent adverse prognostic factor for overall survival (OS)(Figure 1A). 17p deletion, 1q21 amplification, t (4; 14) / t (14; 16) were define as high-risk cytogenetic abnormalities (HRA). Of the 603 patients, about 60% were associated with at least one high-risk cytogenetic event. Among them, the occurrence of cumulative 0, 1, 2, and 3 HRA were 39.6% (239/603), 42.5% (256/603), 16.6% (100/603), and 1.3% (8/603), respectively. There was no significant difference in survival among patients with same number of HRAs. The median OS of patients with 0, 1 and ≥ 2 HRA were not reached, 62.1 months (95% CI, 49.3-74.9) and 30.4 months (95% CI, 24.5-36.3), respectively (p <0.001)(Figure 1B).Final Cox regression model showed that age 65 ~ 74 (HR=1.77, 95%CI, 1.24-2.51, p=0.001), age ≥75 (HR=2.46, 95%CI, 1.69-3.58, p < 0.001), LDH≥247 U/L (HR =1.65, 95%CI, 1.07-2.51, p=0.023), ISS stage III (HR=1.76, 95%CI, 1.24-2.50, p=0.002), LMR≤2.95 (HR=1.53, 95%CI, 1.08-2.18, p=0.017), 1 HRA (HR=1.87, 95%CI, 1.27-2.75, p=0.002) and ≥2 HRA (HR=3.48, 95%CI, 2.22-5.45, p<0.001) are independent adverse prognostic factors for OS. Then weighted risk factors were summed to establish a comprehensive prognosis model, with a total score range of 0-6 points. Accordingly, the whole cohort was divided into low risk (0-1 points, 45.4%), intermediate risk (2 points, 27.9%), high risk (3 points, 19.2%) and ultra-high risk (4-6 points, 7.5 %) groups. The median OS of the four risk groups were 85.8 months (67.1-104.5), 49.0 months (44.7-53.3), 35.4 months (31.3-39.5), and 23.2 months (18.8-27.6), respectively (p<0.001). The C-statistics of this prognostic model is 0.68 (95% CI, 0.64-0.71), which is significantly better than the D-S stage (C-statistics = 0.52, 95% CI, 0.50-0.55, p <0.001), ISS (C-statistics = 0.60, 95% CI, 0.57-0.64, p <0.001) and R-ISS stage (C-statistics = 0.60, 95% CI, 0.57-0.63, p <0.001). Bootstrap resampling and calibration curve showed that the model has an accurate predictive effect on both short-term and long-term prognosis of patients(Figure 1C). Conclusion: In our analysis, ALC, LWR, LMR were associated with poor prognosis in NDMM patients, while NLR had no significant prognostic significance. Among the four indicators, LMR≤2.95 was the only independent prognostic factor. In NDMM patients, survival of patients with the same number of high-risk cytogenetic abnormalities were comparable with each other, regardless of whichever combination of HRA. Higher number of high-risk cytogenetic abnormalities were associated with worse prognosis. Cox multivariate analysis showed that, old age (65-74 years old, ≥75 years old), increased LDH (≥247 U/L), decreased LMR (≤2.95), ISS III, 1 HRA and ≥ 2 HRA were independent adverse prognostic factors that affect the OS of MM patients. 4. A comprehensive weighted prognostic model was established with the above factors, which was proved to effectively distinguish different prognosis of patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Asthma in the Critically Ill Patient

Mayo Clinic Critical and Neurocritical Care Board Review ◽

10.1093/med/9780190862923.003.0021 ◽

2019 ◽

pp. 150-156

Author(s):

Jonathan J. Danaraj ◽

Augustine S. Lee

Keyword(s):

United States ◽

Risk Factors ◽

Immunoglobulin E ◽

Age Distribution ◽

The United States ◽

Critically Ill Patient ◽

Common Condition ◽

Female Ratio ◽

Genetic And Environmental Factors ◽

Male To Female

Asthma is a common condition that affects an estimated 24 million children and adults in the United States (prevalence, 8%-10%). Globally, over 300 million people are affected and the number is expected to increase. The age distribution is bimodal, but in most patients, asthma is diagnosed before age 18 years (male to female ratio, 2:1 in children; 1:1 in adults). Susceptibility to asthma is multifactorial with both genetic and environmental factors. The strongest risk factor is atopy, a sensitivity to the development of immunoglobulin E (IgE) to specific allergens. A person with atopy is 3- to 4-fold more likely to have asthma than a person without atopy. Other risk factors include birth weight, prematurity, tobacco use (including secondary exposure), and obesity.

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Incidence and pattern of leukemia in Bhutanese population: a retrospective analysis of eight years (January 2008 to December 2015)

Bhutan Health Journal ◽

10.47811/bhj.27 ◽

2016 ◽

Vol 2 (2) ◽

pp. 6-9

Author(s):

Kuenzang Dorji ◽

Krishna Prasad Sharma ◽

Rinzin Jamtsho ◽

Puja Devi Samal ◽

Dorji Wangchuk ◽

...

Keyword(s):

Risk Factors ◽

Incidence Rate ◽

Blood Cells ◽

Statistical Significance ◽

Descriptive Statistics ◽

Haematological Malignancies ◽

Female Ratio ◽

Male To Female ◽

National Referral Hospital

Introduction: The burden of haematological malignancies in developing countries is on the rise. This burden may be further aggravated in Bhutan due to the aging population and rapid modernization of the nation. Despite this, there is a paucity of information about the incidence and pattern of leukemia in the Bhutanese population. In this retrospective study, we aim to investigate the incidence and pattern of leukemia in Bhutan using a database of leukemia diagnosed at Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan from January 2008 to December 2015. Methods: The diagnoses and classification of leukemias were based on the morphology of blood cells on peripheral blood and bone marrow smears. The data was analyzed with descriptive statistics. The age-standardized incidence rate per 100,000 populations and its 95% confidence interval was calculated to assess the statistical significance. Results: In total 118 patients were diagnosed with leukemia over the period of eight years. Leukemia was found to be more frequent in male (51.69%) compared to female (48.30%) with a male to female ratio of 1.1:1. Acute leukemia accounted for 66.95% of all leukemia case diagnosed, whereas chronic leukemia accounted for only 33.05% of the cases. The average, annual, age-standardized incidence rate of leukemia per 100,000 population was 2.30 (95% CI: 1.87-2.73). Conclusions: The incidence and pattern of leukemia in the Bhutanese population is similar to other published literature. Leukemia is not uncommon in the Bhutanese population, thus additional studies on risk factors for leukemia in the Bhutanese population is necessary.

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Risk Factors for Development of Symptoms Post Autologous Transplant for Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.1771.1771 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1771-1771

Author(s):

Erica Campagnaro ◽

Rima Saliba ◽

Karen Anderson ◽

Linda Roden ◽

Floralyn Mendoza ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Symptom Burden ◽

Disease Status ◽

Female Gender ◽

Patient Characteristics ◽

The United States ◽

Charlson Score ◽

Female Ratio ◽

Post Transplant

Abstract Background: Multiple myeloma (MM) is the most common indication for autografting in the United States. Although safe, autografting can be associated with substantial morbidity due to the toxic side effects of chemotherapy. Strategies aimed at minimizing symptoms post autografting may result in better tolerance. The risk factors for symptom development post autografting for MM have not been well characterized. Purpose: To define pretransplant conditions which may be predictive of post-transplant symptom burden. Methods: We performed prospective evaluation of symptom burden among 64 myeloma patients undergoing autograft at MDACC as well as retrospective review of pretransplant variables including patient demographics, performance status, albumin, disease status, and Charlson Comorbidity Index (CCI). Univariate analysis was performed to correlate pretransplant variables with posttransplant symptom burden as defined by M.D. Anderson Symptom Inventory (MDASI) scores at different timepoints post transplant. Results: 64 patients were studied from 6/2000 to 5/2003. Patient characteristics are summarized in Table 1. Symptom burden increased from baseline to day 0 to nadir, with most patients returning to their baseline by day 30 post transplant (Figure 1). Table 2 summarizes the potential impact of pre-transplant variables on median MDASI scores at nadir. Patients with the highest MDASI scores at baseline had the highest MDASI scores at nadir in quartile analysis(p=.001). Patients with Charlson score of ≥ 3, age > 60, β 2M > 3, albumin ≤ 4, and female gender had a trend towards higher nadir MDASI scores. Other pre-transplant variables, including Durie-Salmon stage, LDH, hemoglobin, disease status at time of autograft, and time from diagnosis to autograft had no apparent correllation with symptom burden throughout transplant (data not shown). Conclusions: Autografting for MM is associated with significant but reversible symptom burden during the first 30 days of the procedure. Baseline symptom burden is the most important predictor of post transplant symptom burden. Other potential predictors include Charlson score, age, β 2M, albumin, and female gender. The MDASI scoring system is a potentially useful means of following symptom burden post autografting that could be used to assess interventions aimed at reducing transplant related morbidity in MM patients. Patient Characteristics Median (range) Age at transplantation, years 55.2 (30–74) Time to SCT, months 7.5 (2.5–73.3) Albumin at transplantation 3.74 (2.9–4.5) β2M at transplantation 3.79 (1.4–19.3) Charlson score at transplantation 3.48 (2–6) Disease status at transplantation n (%) First remission 42 (65.6) Primary refractory 14 (21.9) Other 8 (13.6) Preparative regimen n (%) Melphalan 53 (82.8) Other 11 (17.2) Male to female ratio 1.5 : 1 Impact of Pre-transplant Variables on Nadir MDASI Scores n Median (range) Charlson score < 3 50 22 (1–97) ≥ 3 14 41 (3–72) .09 Age ≤ 60 years 43 23 (1–97) > 60 years 21 31 (3–72) .2 β 2M ≤3.0 34 20 (1–85) > 3.0 27 28 (4–97) .2 Albumin ≤ 4.0 50 27 (1–97) > 4.0 14 19 (1–16) .2 Gender Female 26 30 (5–85) Male 38 23 (1–97) .2 Figure Figure

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Prognostic Factors Influencing Survival in Solitary Plasmacytoma: A SEER Database Analysis.

Blood ◽

10.1182/blood.v112.11.1670.1670 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1670-1670

Author(s):

Paul Mehan ◽

Giridharan Ramsingh ◽

Jingqin Luo ◽

Daniel Morgansztern ◽

Ravi Vij

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Solitary Plasmacytoma ◽

Seer Database ◽

Disease Specific Survival ◽

Factors Influencing ◽

Younger Age ◽

Disease Specific

Abstract Solitary plasmacytoma (PCM) is a focal, neoplastic, plasma cell disorder without evidence of systemic disease. While PCM is a clinically distinct entity, survival can be limited by progression to multiple myeloma. Prior studies have attempted to identify factors influencing survival in PCM but have been limited by small patient cohorts. This study identified 1472 patients with PCM using the SEER database between 1988 and 2004. The median age of the patients was 64 years (range 12–97), 65.4% male, 34.6% female, 83% Caucasians, 10.7% African Americans and 6.3% other races. 63.8% had medullary PCM and 36.2% extramedullary PCM. 84% of medullary PCM occurred in axial skeleton and the rest in appendicular skeleton. Extramedullary PCM most frequently occurred in the head and neck region (51.4%) followed by skin/subcutaneous tissue (16.2%), GI tract 6% and other sites (26.4%). 55.2% were treated with radiation therapy alone, 29.5% with radiation therapy and surgery and 15.3% with surgery alone. 558 died during this period and the mean overall survival was 6.83 years (range, 0–16.9). The cause of death was multiple myeloma in 49.6%, other cancers 20.9% and cardiovascular diseases 12.9%. In all patients, survival probability at one year was 87.6% (95% CI, 85–89%), at five years was 58.9% (95% CI, 56–62%), and at 10 years was 40.0% (95% CI, 36–44%). The five year overall survival in the ≤40yo cohort was 83.5% as compared to 76.7% and 44.8% in the 40–60yo and >60yo groups, respectively (p<0.0001). The five year disease specific survival probability in the ≤40yo cohort was 94.5% as compared to 86.0% and 66.2% in the 40–60yo group and >60yo group, respectively (p<0.0001) (figure 1)). Overall survival in the extramedullary PCM was 65.9% at five years as compared to 54.6% in the medullary PCM (p<0.0001) and the disease specific survival in the extramedullary PCM was 86.2% compared to 70.1% in the medullary PCM (p<0.0001) (figure 1). Multivariate analysis of disease specific survival revealed that younger age, male gender, extramedullary type, and race other than African American or Caucasian were favorable prognostic factors (Table 1). Younger age, extramedullary site, treatment with XRT + surgery, and race other than African Americans were associated with improved overall survival by multivariate analysis (Table 1). To our knowledge, this is the largest published review of survival in PCM. This study identifies several prognostic risk factors influencing survival in PCM. These risk factors can be used to identify patients at high risk for progression to multiple myeloma. Those at highest risk could be considered for future trials comparing adjuvant systemic therapy compared to local therapy alone. Table 1. Multivariate Analysis of Prognostic Factors Disease Specific Survival Overall Survival Variable Category HR 95% CI P HR 95%CI P Abbreviations: HR, Hazard Ratio; Q, Confidence Inverval Sex Female --- -- --- -- --- --- Male 0.74 0.58~ 0.94 0.01 0.95 0.80~1.13 0.57 Age <40yo --- --- --- --- --- --- 40–60yo 2.68 115~ 6.2 0.02 1.74 1.04~2.91 0.03 >60yo 6.94 3.06~ 15.73 <0.01 5.55 3.40~9.06 <0.01 Race Black --- --- --- --- --- --- White 0.74 0.52~ 1.06 0.1 0.72 0.56~0.92 0.01 Others 0.31 0.13~ 0.75 <0.01 0.48 0.29~0.79 <0.01 Primary Site Extramedullary --- --- --- --- --- --- Medullary 2.35 1.74~.3.18 <0.01 1.37 1.13~1.65 <0.01 Treatment Surgery Only --- --- --- --- --- --- XRT Only 0.90 0.62~ 1.31 0.59 0.82 0.64~1.04 0.10 XRT + Surgery 0.84 0.55~1.26 0.39 0.68 0.52~0.89 <0.01 Period 1988–1993 --- --- --- --- --- --- 1994–1999 0.96 0.72~1.30 0.8 0.96 0.78~1.19 0.74 2000–2004 0.94 0.68~1.30 0.7 0.94 0.75~1.18 0.6 Figure 1: Figure 1:.

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Polyclonal Gamma Globulin Suppression and Risk Of MGUS Progression Into Multiple Myeloma

Blood ◽

10.1182/blood.v122.21.1875.1875 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1875-1875 ◽

Cited By ~ 1

Author(s):

Jawad Z. Sheqwara ◽

Mohammad Alhyari ◽

Shannon Keating ◽

Philip Kuriakose

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Plasma Cell ◽

Total Protein ◽

Gamma Globulin ◽

Conflicts Of Interest ◽

Significant Risk ◽

M Protein ◽

Plasma Cell Dyscrasia ◽

Female Ratio

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is the most common form of plasma cell dyscrasia, with a prevalence of 3% in the general population above age of fifty. MGUS has a malignant evolution rate of 1% per year. Large longitudinal studies have suggested that virtually all patients diagnosed with multiple myeloma (MM) had a preceding MGUS, with 75 % having detectible Monoclonal (M) protein ≥8 years prior to diagnosis. It is important to identify the features at diagnosis that can predict neoplastic transformation to MM. Purpose We identified 239 patients at our institute in whom MGUS was diagnosed between 2000 and 2010. The presenting clinico-hematologic features were correlated with the frequency of evolution into MM to identify early predictors of evolution. The primary end point was progression to MM. Results The patients' mean age was 70.7 years. The Male/Female ratio was 0.7. The mean concentration of the M component (MC) was 0.7 g/dL. IgG was the most frequent MC (77%), followed by IgA (13%). The median ratio of MC protein to total protein was 0.5. Single or multiple background polyclonal (PC) suppression was noted in 36% of patients. PC suppression of 50% or more was noted in 20.1% of patients, 49.8% had < 50% and 30.1% had no suppression. Mean bone marrow plasma cell percentage was 4.5 percent and mean hemoglobin was 12.4 g/dL. Eighteen of the 239 patients with MGUS progressed into MM over ten years of follow up. Univariate comparisons of all variables between those who progressed and those who did not, showed that the initial concentration of the serum M protein, ratio of M protein to the total protein, number of PC gamma globulins suppressed, degree of PC suppression and IgM gamma globulin suppression were statistically significant risk factors that correlated with progression into MM. Fourteen out of eighteen patients with progressive disease had either PC suppression or background IgM suppression. Conclusions Monoclonal protein concentration, ratio of M protein to the total protein and abnormal serum free light chain ratio are simple variables that have been shown in multiple previous studies to predict the progression of MGUS into MM. In our study, we additionally found that number of PC suppressed, degree of suppression and IgM suppression are also key risk factors that can predict progression. We believe that these variables can be potentially applied into an approach that uses a detailed risk stratification system to predict which cases of MGUS will progress into MM and to provide more intensive monitoring for patients more likely to progress. Disclosures: No relevant conflicts of interest to declare.

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