HSR19-088: Severe Obesity Does Not Worsen Transplantation Outcome in Multiple Myeloma

Background: Obesity, and in particular severe obesity, is increasingly prevalent in the United States. Epidemiological studies have shown an association in multiple myeloma (MM) between obesity and mortality (Teras et al, Br J Haematol 2014). Autologous peripheral blood stem cell transplantation (autoPBSCT) remains a crucial aspect of treating MM, and the NCCN Guidelines recommend all eligible patients be evaluated for transplant. There is limited data analyzing the relationship between severe obesity and transplant outcomes in MM patients in the era of modern therapy, routine post-transplant maintenance, and genetic-based risk stratification. Methods: We retrospectively reviewed consecutive patients undergoing autoPBSCT for MM at our institution from 2010–2017. Patients were categorized by body mass index (BMI) and Revised International Staging System (R-ISS) score. Patients were followed from time of first transplant until death. Surviving patients and those lost to follow-up were censored at last point of contact. Cox proportional hazard regression models and associated log-rank tests were used to assess whether age, BMI, lag time between diagnosis and transplant, and R-ISS score were associated with risk of death. Post-transplant hospital length of stay (LOS) was evaluated using generalized linear models with response following a gamma distribution. Results: 314 patients (59.2% male) were included. BMI was categorized as nonobese ([16, 30) kg/m2; n=178, 56.7%), obese ([30, 35) kg/m2; n=72, 22.9%) or severely obese ([35, 55) kg/m2; n=64, 20.4%) and was not found to be associated with risk of death following transplant, either independently (P=.17) or when adjusting for age, sex, lag, and R-ISS (P=.26). As expected, R-ISS score was associated (P=.006) with risk of death after transplant. No association was found between mean LOS and BMI (P=.875). Kaplan-Meier mortality estimates are shown in Figure 1. Conclusions: Obesity and severe obesity were not associated with an increased risk of mortality for MM patients receiving autoPBSCT. Although severe obesity is a health hazard, this should not be used to exclude patients from transplant.

Download Full-text

Older Adults in the United States and COVID-19: A Qualitative Study of Perceptions, Finances, Coping, and Emotions

Frontiers in Public Health ◽

10.3389/fpubh.2021.660536 ◽

2021 ◽

Vol 9 ◽

Author(s):

R. Turner Goins ◽

Elizabeth Anderson ◽

Hannah Minick ◽

Heather Daniels

Keyword(s):

Mental Health ◽

United States ◽

Older Adults ◽

News Media ◽

Emotional Health ◽

The United States ◽

Stress Appraisal ◽

Risk Of Death ◽

Increased Risk ◽

Precautionary Measures

Introduction: Older adults have the poorest coronavirus (COVID-19) prognosis with the highest risk of death due to complications, making their COVID-19 experiences particularly important. Guided by the stress-appraisal-coping theoretical model, we sought to understand COVID-related perceptions and behaviors of older adults residing in the United States.Materials and Methods: We used convenience sampling to recruit persons with the following inclusion criteria: Aged ≥ 65 years, English fluency, and U.S. residency. Semi structured in-depth interviews were conducted remotely and audio recorded between April 25, 2020 and May 7, 2020. Interviews were professionally transcribed with a final study sample of 43. A low-inference qualitative descriptive design was used to provide a situated understanding of participants' life experiences using their naturalistic expressions.Results: The mean age of participants was 72.4 ± 6.7. Slightly over half were female (55.8%), 90.6% were White, and 18.6% lived alone. The largest percentages of participants resided in a rural area (27.9%) or small city (25.6%). We identified four themes, including (1) risk perception, (2) financial impact, (3) coping, and (4) emotions. Most participants were aware of their greater risk for poor COVID-19 outcomes but many did not believe in their increased risk. Financial circumstances because of the pandemic varied with largely no financial impacts, while others reported negative impacts and a few reported positive impacts. Coping was problem- and emotion-focused. Problem-focused coping included precautionary efforts and emotion-focused coping included creating daily structure, pursuing new and/or creative activities, connecting with others in new ways, and minimizing news media exposure. Overall, emotional health was negatively affected by the pandemic although some participants reported positive emotional experiences.Conclusions: Perceiving themselves as high risk for COVID-19 complications, older adults used precautionary measures to protect themselves from contracting the virus. The precautionary measures included social isolation, which can negatively affect mental health. Older adults will need to be resourceful and draw on existing resources to cope, such as engaging in creative activities and new strategies to connect with others. Our findings underscore the importance of the preservation of mental health during extended periods of isolation by taking advantage of low-to-no-cost existing resources.

Download Full-text

Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients

American Journal of Nephrology ◽

10.1159/000507725 ◽

2020 ◽

Vol 51 (6) ◽

pp. 424-432 ◽

Cited By ~ 1

Author(s):

Salina P. Waddy ◽

Adan Z. Becerra ◽

Julia B. Ward ◽

Kevin E. Chan ◽

Chyng-Wen Fwu ◽

...

Keyword(s):

The United States ◽

Future Research ◽

Dialysis Patients ◽

Mortality And Morbidity ◽

Medication Prescription ◽

Risk Of Death ◽

Increased Risk ◽

Stage Renal Disease ◽

End Stage ◽

Dialysis Discontinuation

Background: The opioid epidemic is a public health emergency and appropriate medication prescription for pain remains challenging. Physicians have increasingly prescribed gabapentinoids for pain despite limited evidence supporting their use. We determined the prevalence of concomitant gabapentinoid and opioid prescriptions and evaluated their associations with outcomes among dialysis patients. Methods: We used the United States Renal Data System to identify patients treated with dialysis with Part A, B, and D coverage for all of 2010. Patients were grouped into 4 categories of drugs exposure status in 2010: (1) no prescriptions of either an opioid or gabapentinoid, (2) ≥1 prescription of an opioid and no prescriptions of gabapentinoids, (3) no prescriptions of an opioid and ≥1 prescription of gabapenbtinoids, (4) ≥1 prescription of both an opioid and gabapentinoid. Outcomes included 2-year all-cause death, dialysis discontinuation, and hospitalizations assessed in 2011 and 2012. Results: The study population included 153,758 dialysis patients. Concomitant prescription of an opioid and gabapentin (15%) was more common than concomitant prescription of an opioid and pregabalin (4%). In adjusted analyses, concomitant prescription of an opioid and gabapentin compared to no prescription of either was associated with increased risk of death (hazard ratio [HR] 1.16, 95% CI 1.12–1.19), dialysis discontinuation (HR 1.14, 95% CI 1.03–1.27), and hospitalization (HR 1.33, 95% CI 1.31–1.36). Concomitant prescription of an opioid and pregabalin compared to no prescription of either was associated with increased mortality (HR 1.22, 95% CI 1.16–1.28) and hospitalization (HR 1.37, 95% CI 1.33–1.41), but not dialysis discontinuation (HR 1.13, 95% CI 0.95–1.35). Prescription of opioids and gabepentinoids compared to only being prescribed opioids was associated with higher risk of hospitalizations, but not mortality, or dialysis discontinuation. Conclusions: Concomitant prescription of opioids and gabapentinoids among US dialysis patients is common, and both drugs have independent effects on outcomes. Future research should prospectively investigate the potential harms of such drugs and identify safer alternatives for treatment of pain in end-stage renal disease patients.

Download Full-text

370. Comparing Trends and Outcomes among HIV-Infected vs. HIV Uninfected Patients with Tuberculosis: A 5-Year Experience Within the Florida Department of Health in Hillsborough County

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.443 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S194-S194

Author(s):

Shylah M Moore-Pardo ◽

Anteneh Addisu ◽

Tea Reljic ◽

Sadaf Aslam ◽

Beata Casanas

Keyword(s):

United States ◽

The United States ◽

Homeless Persons ◽

Sputum Smear ◽

Foreign Born ◽

Female Ratio ◽

Risk Of Death ◽

Increased Risk ◽

The Difference ◽

Hiv Negative

Abstract Background Although the rate of tuberculosis (TB) has significantly declined in the United States, elimination has plateaued. Florida is one of the states with the greatest number of cases. The majority of cases occur in foreign-born individuals. Human immunodeficiency virus (HIV) is also a major contributor. HIV-TB coinfection leads to reciprocal interactions with significant clinical impact. We aim to compare the risk factors, clinical findings, and outcomes among HIV-infected vs. HIV uninfected patients. Methods A retrospective cohort study of TB cases over a 5 year period (2012–2017) was conducted. All patients with HIV co-infection with age- and gender-matched HIV negative controls were included. The diagnosis of TB was made via clinical, microbiological, radiological, and/or PCR based methods. SPSS was used for statistical data analysis. Results A total of 411 TB cases were identified and 66 patients (33 HIV-infected plus 33 HIV un-infected) were eligible for inclusion. The median age was 49 years (range 22–70). The male to female ratio was 21:12 and 50% of patients had TB symptoms; the rest had abnormal imaging or lab finding. Cases were confirmed via positive sputum smear, culture, or PCR (Figures 1–3). Only 11 patients were lost to follow-up, thus 83.3% completed therapy. A total of 5 persons died (Table 1). Conclusion The rate of HIV-TB coinfection in the United States was 5.3% in 2018; higher among injection drugs users, homeless persons, inmates, and alcoholics. In our study, the rate of HIV-TB coinfection was slightly higher (8%). The difference was not statistically significant in regards to foreign born, homelessness, and incarceration. Only 3 patients admitted to injection drug use and 9 used alcohol (all HIV negative). Traditionally, HIV-TB coinfected patients have extra-pulmonary TB with higher rates of negative sputum and are at increased risk of death. In our cohort, the difference was statistically significant (P = 0.009) only for cavitary TB (predominated in HIV un-infected) but no difference in outcomes was observed between the two groups. These findings suggest changing trends in HIV-TB coinfection which may be partly related to our setting and demographics but may be attributed to better access to care and antiretroviral therapy at large. Disclosures All authors: No reported disclosures.

Download Full-text

Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis

Viruses ◽

10.3390/v10110658 ◽

2018 ◽

Vol 10 (11) ◽

pp. 658 ◽

Cited By ~ 2

Author(s):

Paul Blair ◽

Maryam Keshtkar-Jahromi ◽

Kevin Psoter ◽

Ronald Reisler ◽

Travis Warren ◽

...

Keyword(s):

Proportional Hazards ◽

Clinical Laboratory ◽

Cynomolgus Macaque ◽

The United States ◽

Cox Proportional Hazards ◽

Marburg Virus ◽

Time To Death ◽

Risk Of Death ◽

Published Evidence ◽

Increased Risk

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.

Download Full-text

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

Download Full-text

The Risk of Day 100 Mortality Following Umbilical Cord Blood Transplantation Is Significantly Higher in Patients Who Do Not Achieve An ANC of 100 by Day +16 Post Transplant

Blood ◽

10.1182/blood.v118.21.3033.3033 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3033-3033 ◽

Cited By ~ 1

Author(s):

Ann Dahlberg ◽

Filippo Milano ◽

Ted A. Gooley ◽

Colleen Delaney

Keyword(s):

Cord Blood ◽

Severe Neutropenia ◽

Research Protocol ◽

Post Transplant ◽

Risk Of Death ◽

Cord Blood Transplant ◽

Number Of Patients ◽

Increased Risk ◽

Conditioning Regimens ◽

The Relationship

Abstract Abstract 3033 Background: Cord blood transplant (CBT) recipients have higher infection-related morbidity and mortality than recipients of other stem cells sources following allogeneic transplant due to delayed hematopoietic recovery and immune reconstitution. Even in recipients of myeloablative (MA) double cord blood transplant (dCBT), time to engraftment (defined as the first of two consecutive days with an absolute neutrophil count (ANC) ≥ 500/μl) is delayed more than three weeks resulting in higher rates of infection in the first 100 days post-transplant. However, a better understanding of the relationship between duration of neutropenia and risk of early transplant related mortality is needed to assess the clinical impact of methodologies aimed at reducing neutropenia post transplant. Previously, the relationship between severe neutropenia (ANC ≤ 100/μl) and risk of death was evaluated for allogeneic bone marrow transplant recipients using proportional hazards models and demonstrated a significantly increased risk for those with severe neutropenia at day 15 or beyond following transplantation (Offner et al, Blood, 1996; 88(10): 4058–62). Here we use a similar model to determine how duration of severe neutropenia relates to risk of death following CBT. Methods: All patients (n=137) who received a CBT on a research protocol at a single institution from 2006–2010 were eligible. On each day from day 0 to day +100, surviving patients were divided into those with ANC ≤ 100/μl and those with ANC >100/μl and the number of patients who died by day +100 determined for each group. Hazard ratios (HR) with 95% confidence intervals for day +100 mortality were then calculated for day post-CBT with the HR representing the risk of day +100 death among those with ANC ≤ 100/μl relative to those with ANC >100/μl for each day. Results: Of the 137 patients who received a CBT on a research protocol, 99 patients (72%) received MA conditioning regimens and 38 patients (28%) received reduced-intensity conditioning regimens (RIC). Twenty-two patients (16%) received a single cord blood unit while the remainder received dCBT. As the overall results and trends observed for patients receiving MA or RIC regimens were similar, only the combined results are presented. Thirty-one patients (23%) died before day +100. Causes of death were primary graft failure (17), infection (7), disease relapse (5), multi-organ failure (1), and leukoencephalopathy (1). The median time to engraftment was the same (20 days) for those with death before day+100 (9–39 days) as those alive at day+100 (6–69 days). The hazard ratio for day 100 mortality by day post-CBT was significantly higher for patients with ANC ≤ 100/μl beginning on day +16 and remained so through day +50, at which point the number of patients with ANC ≤ 100/μl was small and thus the calculations were no longer significant. The HRs for each day post-CBT from day 0 to day +50 are plotted in Figure 1 along with their 95% upper and lower confidence intervals. From the graphical plot of these HRs, one can identify date ranges (days 0–12, days 13–23, days 24–40, days 41–100) where the HRs are roughly equivalent with a clear increase in HR in the next date range. Modeling ANC ≤ 100/μl as a time-dependent covariate, we calculated HRs for each of these date ranges and found a significantly increased risk of day 100 mortality for days 12–23 (HR=2.96, p=0.01), days 24–40 (HR=5.53, p=0.0004), and days 41–100 (HR=14.59, p<0.0001) for patients with ANC ≤ 100/μl. The HR was 1.16 (0.49–2.76, p=0.73) for days 0–12; however, some of these patients had initial autologous recovery following RIC regimens and poor outcomes. Conclusions: Our study demonstrates that severe neutropenia, defined as ANC ≤ 100, poses a significant increased risk of day 100 mortality for recipients of CBT as early as 12–23 days post-CBT. Importantly, this patient cohort was transplanted in the modern era of aggressive supportive care, including use of newer antimicrobials. However, despite this, severe neutropenia remains a significant risk factor for day 100 mortality in recipients of CBT. Interestingly, median time to engraftment (ANC ≥ 500/μl) was the same for those with death before day+100 as those alive at day+100 suggesting that time to ANC of 100 may be a better predictor of early death following CBT. Thus, strategies that result in more rapid myeloid recovery (to an ANC of 100) remain essential for recipients of CBT. 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

Age Related Outcomes for Multiple Myeloma Patients Following Autologous Transplantation

Blood ◽

10.1182/blood.v124.21.3968.3968 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3968-3968 ◽

Cited By ~ 1

Author(s):

Justin LaPorte ◽

Stacey Brown ◽

Xu Zhang ◽

Asad Bashey ◽

Lawrence E. Morris ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Age Groups ◽

Disease Status ◽

The United States ◽

Disease Stage ◽

Age Group ◽

Post Transplant

Abstract Multiple myeloma is the second most common hematological malignancy in the United States. The risk of developing multiple myeloma increases with age; with approximately 85% of patients are over age 55 and 62% over age 65. Through improved supportive care, increased access to hematopoietic stem cell transplantation, and introduction of new biologic agents, survival has increased over the past 20 years. Currently, autologous stem cell transplantation (ASCT) is the standard of care after primary therapy for eligible patients. Research has suggested a greater survival benefit after ASCT for patients < 60 years, but the role of ASCT in older individuals remains less clear. In order to better understand the impact of age on the outcome of myeloma patients receiving ASCT, we analyzed the presenting features and outcomes of 256 consecutive patients at our institution that received a first ASCT between January 2004 and December 2013. Patient characteristics were: median age 61 (range 32-76), Sex: M=55% F=45%, Immunochemical subtype: IgG=59%, IgA =21%, Light chain=16%, Other=4%, Durie-Salmon System (DSS) stage at diagnosis: Stage I=9%, Stage II=20%, Stage III=68%, Unknown=4%, Disease status at transplant: CR/sCRsp=18%, VgPR=27%, PR=49%, Stable=6%, Melphalan preparative dose: 200mg/m2=93%, 140mg/m2=7%. Second ASCT was eventually performed in 60 (23%) of patients, with 39 (15%) of these being planned tandem ASCT. Patient survival and disease status were collected prospectively as part of our comprehensive database. For purposes of analysis, patients were divided by age into three groups: age<55 (n=80), age 55-64 (n=90), age ≥ 65 (n=86). Groups were similar in regards to disease subtype, stage, status at the time of transplant, comorbidity index, and year of transplant; differences included more second transplants and tandem transplants in the youngest age group and more reduced dose melphalan in the oldest age group. At day +100 post-transplant, disease response was CR, VGPR, PR, and <PR in 35%, 24%, 39%, and 2%, respectively and did not differ statistically by age group. Non-relapse mortality at one-year post-transplant was 1%, and did not differ among the <55, 55-64, and ≥ 65 age-groups (0%, 3%, and 0%, respectively). With a median follow-up of 39 months, the estimated 4-year OS, DFS, and relapse incidence (RI) was 73%, 43%, and 48%, respectively. Survival and RI were significantly better in the younger age group (4-yr OS 84%, 70%, 64%; DFS 58%, 35%, 39%; RI 34%, 53%, 53%, respectively in the <55, 55-64, and ≥ 65 age-groups; see figure). Outcomes were extremely favorable in patients <55 years of age transplanted in CR or VGPR with a 4-yr OS, DFS, and RI of 96%, 75%, and 21%, respectively. Even in the older age groups, median overall survival had not been reached by 5 years, suggesting that all age groups benefit from ASCT. There were no statistically significant differences in measured outcomes between patients age 55-64 years and those age ≥ 65 years, confirming that age ≥ 65 years should not be used to determine transplant eligibility. In multivariate analysis, variables predictive of OS included age, disease stage, and year of transplant; whereas for DFS, predictive variables also included disease status at transplant and planned tandem ASCT (see table). This analysis builds on a growing body of evidence suggesting improved outcomes in patients with multiple myeloma. Patients regardless of age appear to benefit from ASCT, with median survival now exceeding 5 years in all age groups. Patients less than 55 years of age and particularly those achieving at least a VGPR prior to ASCT seem to represent a patient population with an extremely favorable prognosis post-transplant. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Download Full-text

DNA methylation status of Smurf2 promoter in patients with multiple myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e19537 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e19537-e19537

Author(s):

E. Hatzimichael ◽

A. Dasoula ◽

J. Stebbing ◽

G. Dranitsaris ◽

T. Crook ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Serum Albumin ◽

Cpg Island ◽

Methylation Status ◽

Risk Of Death ◽

Extramedullary Disease ◽

Increased Risk ◽

Beta 2 ◽

Beta 2 Microglobulin

e19537 Background: Multiple myeloma (MM) is an incurable interleukin (IL)-6 dependent plasma-cell malignancy. Transforming growth factor-β (TGF-β) is the major inducer of IL-6 secretion by bone marrow stromal cells. The signaling responses to TGF-b are mediated by the Smad proteins. The Smurf2 gene (Smad ubiqitiniation regulatory factor 2) encodes a Smad-specific E3 ubiquitin ligase and targets Smad2 and Smad3 for proteasome-dependent degradation. Methods: Bone marrow samples from individuals with MM were obtained at diagnosis and in 5 cases at disease progression as well. Genomic DNA was isolated and bisulphite modification was performed using commercially available kits. The methylation-specific polymerase chain reaction was employed to study the methylation status of the CpG island. Logistic regression analysis was used to measure the association between gene methylation and the development of advanced disease (DS≥ II), extramedullary disease, bone disease, anemia (Hb 10 mg/dl), serum albumin and beta 2 microglobulin levels. Results: We analysed the methylation of Smurf2 in 45 cases of MM (24 male, 21 female, mean age 66.4 years). No sample from the control population was found methylated. The Smurf2 gene promoter was found to be methylated in 11/45 MM patients (24%). Interesting trends were noted where patients with methylated Smurf2 promoter had an increased risk of death (HR = 1.3; p = 0.68), anemia (OR=2.1, p=0.2) and advanced stage (OR=1.3, p=0.6) and a reduced risk of extramedullary disease (OR= 0.2, p=0.2). No association was found between Smurf2 methylation status and bone lytic lesions, serum albumin levels or beta-2 microglobulin levels. Conclusions: Interesting associations between Smurf2 methylation and some relevant clinical parameters in patients with MM were suggested by the data. These findings warrant further evaluation in a larger sample of patients in order to enhance our statistical power and better define the prognostic and clinical value of Smurf2 methylation in MM. No significant financial relationships to disclose.

Download Full-text