Two-Year Surveillance Study of Nosocomial Infections in Patients with Hematological Malignancies: Risk Factors for Antimicrobial Resistance and Their Impact in Mortality

Abstract Background: Infections are a leading cause of morbidity and mortality in patients suffering from hematological malignancies, with resistant bacteria being a major contributor. Special precaution is needed in these patients due to immunosuppression and safety measures are warranted to reduce related complications. Surveillance studies can offer a better understanding of risk factors associated with resistant strains and mortality. Materials and Methods: All patients hospitalized in our department of hematology, hematopoietic stem cell transplantation (HSCT) and post-transplant unit during 2014 and 2015 who presented an infectious episode were included in our study. An infectious episode was defined as a clinically detected infection not necessarily associated with specific bacteria or a positive surveillance culture. A retrospective epidemiological study was conducted using clinical data and positive cultures along with information about resistance. Our goal was to explore risk factors for infections by resistant bacteria and examine the impact of resistance on mortality. Results: During the two-year period, we identified 439 infectious episodes, 55.4% deriving from the department of hematology and 44.6% from the HSCT and post-transplant unit. Hematological malignancy was diagnosed in 429 patients, with 62.2% suffering from acute leukemia. Prevalence of resistant bacteria in our study population was 37.1%, more frequently isolated in the HSCT and post-transplant unit (52.2% vs 34.7%, p=0.001). Most of them were gram-negative, with the main representative being KPC klebsiella pneumoniae (38.7%), followed by pseudomonas aeruginosa (17.2%). Gram-positive species accounted for 19% of resistant bacteria, including MRSA staphylococcus and VRE enterococcus species. During the first semester of 2014, we identified a burkholderia cepacia outbreak with a total of 13 cases, that was successfully handled and the microorganism was eradicated. Possible risk factors for the isolation of resistant bacteria were examined. Factors included in our analysis were diagnosis, department of hospitalization, transplantation, prior chemotherapy, the presence of central venous catheter (CVC) and the presence of neutropenia. In multivariate analysis, the only significant risk factor associated with isolation of resistant bacteria was the department of hospitalization (OR 2.57, CI 1.31-5.02, p= 0.006). Duration of neutropenia was not correlated with increased rates of antimicrobial resistance (p=0.91). Mortality rate was 5.2%, mostly related to infection. Of the 23 patients that died, only six deaths were attributed to refractory disease. However, from the remaining 17, we identified 7 who presented severe immunosuppression after transplantation due to graft versus host disease (GVHD). Mortality was increased in patients with isolation of a resistant strain (73.9% vs 26.1%, p=0.001) but was not related to resistant disease or in combination with GVHD (52.9% vs 50%, p= 0.9). Using multivariate analysis, significant factors predicting mortality were neutropenia, the presence of resistant bacteria and presence of CVC. Other factors included in our analysis were the department of hospitalization, transplantation, diagnosis and preceding chemotherapy. The most powerful factor was the isolation of resistant bacteria (OR 4.08, CI 1.48-11.25, p=0.006) followed by the presence of CVC (OR 3.78, CI 1.14-12.54, p=0.03). Finally, we compared the impact of resistant bacteria between 2014 and 2015 and we observed a significant reduction in 2015 (57.1% vs 33.9%, p<0.001). We assume that this reduction is the result of more robust safety measures, including isolation of contaminated patients, intensive surveillance cultures in all patients that were routinely hospitalized and personnel discipline according to the guidelines. Conclusion: From our study we can conclude that patient colonization and possibly personnel behavior play a significant role in spreading of resistant bacteria, as the department of hospitalization was the only significant factor of bacteria isolation. Our two departments are localized in different floors of the same building with different staff on each floor, which makes cross contamination difficult. Resistance has a major impact on mortality, but appropriate measures can change distribution and improve survival in patients with hematological malignancies. Disclosures No relevant conflicts of interest to declare.

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Risk Factors and Outcome of Chronic GVHD: Analysis of 5,660 Patients Undergoing Unrelated Bone Marrow Transplantation through the Japan Marrow Donor Program.

Blood ◽

10.1182/blood.v106.11.139.139 ◽

2005 ◽

Vol 106 (11) ◽

pp. 139-139

Author(s):

Chiaki Nakaseko ◽

Miki Nishimura ◽

Shinnichi Ozawa ◽

Ryuko Cho ◽

Chikako Ohwada ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Cumulative Incidence ◽

Hematological Malignancies ◽

Chronic Gvhd ◽

Post Transplant ◽

Risk Of Death ◽

Significant Difference ◽

Late Morbidity

Abstract Background: Chronic GVHD (cGVHD) remains the major cause of late morbidity and mortality after allogeneic stem cell transplantation. However, there are limited data available on cGVHD after unrelated BMT (UR-BMT). We retrospectively analyzed the data of 5,660 patients who underwent UR-BMT through the Japan Marrow Donor Program (JMDP) between January 1993 and June 2004. Methods: Data were collected by the JMDP using a standard report form. Follow-up reports were submitted at 100 days, 1 year, and then annually after transplantation. Overall survival (OS) was estimated by the Kaplan-Meier method and patients surviving beyond day 100 after transplant were analyzed for the development of cGVHD. The log-rank test was used for univariate analysis and time-dependent Cox proportional hazards modeling was used for multivariate analysis. The cumulative incidence of cGVHD and of relapse was calculated using the Gray method considering death without cGVHD and death without relapse as respective competing risks. Results: The median age of all patients was 28 years and the median follow-up was 433.5 days after transplant. Estimated 5-year OS of all patients and those with hematological malignancies was 47.4% and 45.5%, respectively. A total of 3,974 patients survived beyond day 100 after transplant and their cumulative incidence of cGVHD was 43.2% at day 500 and 44.9% at day 2,000 post-transplant. The cumulative incidence of extensive cGVHD was 28.8% at day 2,000 post-transplant. In multivariate analysis, variables predicting cGVHD were recipient age (p=0.000), donor age (p=0.002), diagnosis of hematological malignancy (HR=1.99, p=0.000), HLA class I mismatch by either serology or DNA typing (HR=1.24, p=0.020), acute GVHD (I: HR=1.50, p=0.000; II: HR=2.07, p=0.000; III and IV: HR=2.25, p=0.000) and no platelet recovery over 50,000/mm3 before day 100 (HR=1.36, P=0.002). There was a significant difference between patients <20 and ≥20 years old (HR=1.27, p=0.000). However, there were no significant differences between any adults grouped by age decade (p=0.894). OS at 5 years in patients surviving >100 days post-transplant was 62.4% without cGVHD, 68.0% with limited cGVHD, and 55.4% with extensive cGVHD (p=0.000). In the patients with hematological malignancies, OS at 5 years was 58.8%, 67.3% and 55.8%, respectively (p=0.000). Cumulative incidence of relapse of hematological malignancies at day 2,000 in patients surviving >100 days post-transplant was 17.6% with limited cGVHD, 18.4% with extensive cGVHD and 27.1% without cGVHD (P=0.000). Conclusions: This study provides strong evidence of risk factors for developing cGVHD after UR-BMT and suggests that limited cGVHD provides a survival benefit to patients with hematological malignancies by reducing the risk of relapse without increasing the risk of death from cGVHD. There was a significant difference in occurrence of cGVHD between patients <20 and ≥20 years old but no differences comparing any age ≥20 years.

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Calcium and phosphate levels after kidney transplantation and long-term patient and allograft survival

Clinical Kidney Journal ◽

10.1093/ckj/sfaa061 ◽

2020 ◽

Author(s):

Julio Chevarria ◽

Donal J Sexton ◽

Susan L Murray ◽

Chaudhry E Adeel ◽

Patrick O’Kelly ◽

...

Keyword(s):

Risk Factors ◽

Renal Transplant ◽

Graft Failure ◽

Graft Function ◽

Renal Transplant Recipients ◽

Post Transplant ◽

All Cause Mortality ◽

Transplant Function ◽

The Republic ◽

The Impact

Abstract Background Non-traditional cardiovascular risk factors, including calcium and phosphate derangement, may play a role in mortality in renal transplant. The data regarding this effect are conflicting. Our aim was to assess the impact of calcium and phosphate derangements in the first 90 days post-transplant on allograft and recipient outcomes. Methods We performed a retrospective cohort review of all-adult, first renal transplants in the Republic of Ireland between 1999 and 2015. We divided patients into tertiles based on serum phosphate and calcium levels post-transplant. We assessed their effect on death-censored graft survival and all-cause mortality. We used Stata for statistical analysis and did survival analysis and spline curves to assess the association. Results We included 1525 renal transplant recipients. Of the total, 86.3% had hypophosphataemia and 36.1% hypercalcaemia. Patients in the lowest phosphate tertile were younger, more likely female, had lower weight, more time on dialysis, received a kidney from a younger donor, had less delayed graft function and better transplant function compared with other tertiles. Patients in the highest calcium tertile were younger, more likely male, had higher body mass index, more time on dialysis and better transplant function. Adjusting for differences between groups, we were unable to show any difference in death-censored graft failure [phosphate = 1.14, 95% confidence interval (CI) 0.92–1.41; calcium = 0.98, 95% CI 0.80–1.20] or all-cause mortality (phosphate = 1.10, 95% CI 0.91–1.32; calcium = 0.96, 95% CI 0.81–1.13) based on tertiles of calcium or phosphate in the initial 90 days. Conclusions Hypophosphataemia and hypercalcaemia are common occurrences post-kidney transplant. We have identified different risk factors for these metabolic derangements. The calcium and phosphate levels exhibit no independent association with death-censored graft failure and mortality.

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The Presurgical Controlling Nutritional Status (CONUT) Score is Independently Associated with Severe Peristomal Skin Disorders: A Single-center Retrospective Cohort Study

10.21203/rs.3.rs-343567/v1 ◽

2021 ◽

Author(s):

Takuya Shiraishi ◽

Hiroomi Ogawa ◽

Chika Katayama ◽

Katsuya Osone ◽

Takuhisa Okada ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Nutritional Status ◽

Laparoscopic Approach ◽

Skin Disorders ◽

Nutritional Interventions ◽

Stoma Creation ◽

Peristomal Skin ◽

The Impact ◽

Conut Score

Abstract Purpose: While nutritional interventions may potentially lower the risk of peristomal skin disorders (PSDs) and their exacerbation, no prior studies have evaluated the relationship between PSDs and nutritional status using the Controlling Nutritional Status (CONUT) score. Therefore, the purpose of this study was to assess the impact of preoperative nutritional status on stoma development, and determine risk factors for postoperative PSDs and their increased severity. Methods: A retrospective analysis was performed in 116 consecutive patients with rectal cancer who underwent radical surgery with stoma creation, including ileostomy and colostomy. Results: PSDs were diagnosed in 32 patients (27.6%); 10 (8.7%) cases were defined as severe based on the ABCD-stoma score. A multivariate analysis indicated that the laparoscopic approach (odds ratio [OR], 3.221; 95% confidence interval [CI], 1.001–10.362; P = 0.050) and ileostomy (OR, 3.394; 95% CI, 1.349–8.535; P = 0.009) were both independent risk factors for PSD. In a separate multivariate analysis for severe PSD, the only independent risk factor was the CONUT score (OR, 11.298; 95% CI, 1.382–92.373; P = 0.024). Conclusion: Severe PSDs are associated with preoperative nutritional disorders, as determined via the CONUT score. Furthermore, PSDs may potentially increase in severity, regardless of stoma type.

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Onset, timing and risk for depression and anxiety in family caregivers to heart transplant recipients

Psychological Medicine ◽

10.1017/s0033291703001387 ◽

2004 ◽

Vol 34 (6) ◽

pp. 1065-1082 ◽

Cited By ~ 68

Author(s):

MARY AMANDA DEW ◽

LARISSA MYASKOVSKY ◽

ANDREA F. DIMARTINI ◽

GALEN E. SWITZER ◽

HERBERT C. SCHULBERG ◽

...

Keyword(s):

Risk Factors ◽

Psychiatric Disorder ◽

Family Caregivers ◽

Heart Transplant ◽

Transplant Recipients ◽

Post Traumatic Stress ◽

Entire Study ◽

Post Transplant ◽

Potential Risk Factors ◽

The Impact

Background. Family members adopt key caregiving roles in the maintenance of transplant recipients' health. While the bulk of the caregiving literature suggests that rates of psychiatric disorder should be high in these caregivers, the potential benefits of transplantation may instead lead to less distress than in other caregiving situations. We examined prevalence and risk factors for depressive and anxiety-related disorders in caregivers throughout 3 years after their family member's heart transplant.Method. A total of 190 caregivers (97% of eligible respondents) were enrolled. They received psychiatric and psychosocial evaluations at 2, 7, 12 and 36 months post-transplant. Survival analysis determined cumulative rates of psychiatric disorders and the impact of potential risk factors.Results. Rates of depressive and anxiety-related disorders met or exceeded other caregiver populations' rates. By 3 years post-transplant, cumulative onset rates were: Major Depressive Disorder (MDD), 31·6%, Adjustment disorders, 35·4% (29·4% with anxious mood); Post-Traumatic Stress Disorder related to the transplant (PTSD-T), 22·5%, Generalized Anxiety Disorder, 7·3%, and any assessed disorder, 56·3%. PTSD-T occurred primarily during the first year post-transplant. Other disorders' rates increased over the entire study period. Risk for disorder was elevated by positive lifetime history of psychiatric disorder, greater post-transplant caregiving responsibilities, and a poorer relationship with the patient. Risk for MDD was further increased by caregiver unemployment, and risk for anxiety disorders was further increased by younger age, low sense of personal mastery, and high use of avoidance coping strategies.Conclusions. Transplantation is associated with costs and benefits for not only patients but family caregivers. Caregivers' risk for psychiatric illness should be considered when developing interventions to promote families' long-term adjustment to the transplant process.

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Antimicrobial resistance three ways: healthcare crisis, major concepts and the relevance of biofilms

FEMS Microbiology Ecology ◽

10.1093/femsec/fiz115 ◽

2019 ◽

Vol 95 (8) ◽

Cited By ~ 8

Author(s):

Paula Jorge ◽

Andreia Patrícia Magalhães ◽

Tânia Grainha ◽

Diana Alves ◽

Ana Margarida Sousa ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Molecular Mechanisms ◽

Resistant Bacteria ◽

Adaptive Resistance ◽

Considerable Research ◽

Ecological Aspects ◽

The Social ◽

Healthcare Crisis ◽

The Impact ◽

First World

ABSTRACTWorldwide, infections are resuming their role as highly effective killing diseases, as current treatments are failing to respond to the growing problem of antimicrobial resistance (AMR). The social and economic burden of AMR seems ever rising, with health- and research-related organizations rushing to collaborate on a worldwide scale to find effective solutions. Resistant bacteria are spreading even in first-world nations, being found not only in healthcare-related settings, but also in food and in the environment. In this minireview, the impact of AMR in healthcare systems and the major bacteria behind it are highlighted. Ecological aspects of AMR evolution and the complexity of its molecular mechanisms are explained. Major concepts, such as intrinsic, acquired and adaptive resistance, as well as tolerance and heteroresistance, are also clarified. More importantly, the problematic of biofilms and their role in AMR, namely their main resistance and tolerance mechanisms, are elucidated. Finally, some of the most promising anti-biofilm strategies being investigated are reviewed. Much is still to be done regarding the study of AMR and the discovery of new anti-biofilm strategies. Gladly, considerable research on this topic is generated every day and increasingly concerted actions are being engaged globally to try and tackle this problem.

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Impact of Reappraisal of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints in Gram-Negative Bloodstream Isolates

Antibiotics ◽

10.3390/antibiotics9040189 ◽

2020 ◽

Vol 9 (4) ◽

pp. 189 ◽

Cited By ~ 2

Author(s):

Stephanie C. Shealy ◽

Matthew M. Brigmon ◽

Julie Ann Justo ◽

P. Brandon Bookstaver ◽

Joseph Kohn ◽

...

Keyword(s):

Risk Factors ◽

South Carolina ◽

Minimum Inhibitory Concentration ◽

Antimicrobial Resistance ◽

Inhibitory Concentration ◽

Clinical Laboratory ◽

Gram Negative ◽

Resistance Risk ◽

Serious Infections ◽

The Impact

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of Enterobacteriaceae to ciprofloxacin declined by 5.2% (95% CI: −6.6, −3.8; p < 0.001) after reappraisal. The largest impact was demonstrated among Pseudomonas aeruginosa bloodstream isolates (MD −7.8, 95% CI: −14.6, −1.1; p = 0.02) despite more conservative revision in ciprofloxacin MIC breakpoints. Among antimicrobial resistance risk factors, fluoroquinolone exposure within the previous 90 days was associated with the largest change in ciprofloxacin susceptibility (MD −9.3, 95% CI: −16.1, −2.6; p = 0.007). Reappraisal of fluoroquinolone MIC breakpoints has a variable impact on the susceptibility of bloodstream isolates by microbiology and patient population. Healthcare systems should be vigilant to systematically adopt this updated recommendation in order to optimize antimicrobial therapy in patients with bloodstream and other serious infections.

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Bacterial Vaginosis and Risk Factors in Pregnant Women in Senegal

10.21203/rs.3.rs-153819/v1 ◽

2021 ◽

Author(s):

Marion Bonneton ◽

Bich-Tram Huynh ◽

Abdoulaye Seck ◽

Raymond Bercion ◽

Fatoumata Diene Sarr ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Bacterial Vaginosis ◽

Pregnant Women ◽

Rural Areas ◽

Vaginal Flora ◽

Obstetric Outcomes ◽

Vaginal Smear ◽

Sub Saharan ◽

The Impact

Abstract Background Bacterial vaginosis (BV) is associated with a higher risk of preterm delivery and spontaneous abortion. Yet little data on BV prevalence exist for sub-Saharan countries. The aim of this study was to estimate the prevalence of bacterial vaginosis and associated risk factors among pregnant women in Senegal.MethodsFrom October 2013 to December 2018, pregnant women in their third trimester were recruited in two primary health centers (one suburban, one rural) in Senegal. Healthcare workers interviewed women and collected a lower vaginal swab and a blood sample. Vaginal flora were classified into four categories using vaginal smear microscopic examination and Gram’s coloration. In our study, BV was defined as vaginal flora with no Lactobacillus spp. Variables associated with BV were analyzed using STATA® through univariate and multivariate analysis.Results A total of 457 women provided a vaginal sample for analysis. Overall, BV prevalence was 18.6% (85/457) [95% CI: 15.4-22.6]) and was similar in suburban and rural areas (18.9 % versus 18.1%, p=0.843). Multivariate analysis showed that primigravidity was the only factor independently associated with a lower risk of BV (aOR=0.35 [95% CI 0.17-0.72]).Conclusions Our study showed significant BV prevalence among pregnant women in Senegal. Although the literature has underscored the potential consequences of BV for obstetric outcomes, data are scarce on BV prevalence in sub-Saharan African countries. Before authorities consider systematic BV screening for pregnant women, a larger study would be useful in documenting prevalence, risk factors and the impact of BV on pregnancy outcomes.

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Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome: a randomized, controlled trial

10.1101/2021.03.02.20215632 ◽

2021 ◽

Author(s):

Harry Pickering ◽

John D. Hart ◽

Sarah Burr ◽

Richard Stabler ◽

Ken Maleta ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Drug Administration ◽

Mass Drug Administration ◽

Gut Microbiome ◽

Controlled Trial ◽

Diarrhoeal Disease ◽

Childhood Mortality ◽

Resistant Bacteria ◽

Clinical Benefits ◽

The Impact

AbstractBackgroundMass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities.MethodsThis study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.FindingsThe proportion of bacteria carrying macrolide resistance increased after azithromycin treatment; the effect was enhanced in children treated within six months of sampling. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.InterpretationThe impacts of MDA with azithromycin, including increased carriage of macrolide-resistant bacteria, were enhanced in children treated more recently, suggesting effects may be transient. Increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage.FundingBill and Melinda Gates Foundation

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Post-treatment heterogeneity of cardio-metabolic risk in acromegalic patients: The Impacts of GH and IGF-1

10.21203/rs.3.rs-49264/v1 ◽

2020 ◽

Author(s):

Mahshid Heydari ◽

Nahid Hashemi Madani ◽

Zahra Emami ◽

Alireza Khajavi ◽

Mohammad Ghorbani ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Multivariate Analysis ◽

Regression Models ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Metabolic Abnormalities ◽

Logistic Regression Models ◽

The Impact ◽

Prevalence Of Diabetes Mellitus

Abstract Background: Metabolic abnormalities are frequently seen in patients with acromegaly. However, it is not clear to what extent GH /IGF-1 contribute to the development of these abnormalities. This study aimed to explore the impact of GH/IGF-1 on different aspects of metabolic abnormalities in patients with acromegaly. Methods: This retrospective, registry-based study conducted on 102 patients with acromegaly. Prevalence of diabetes mellitus (DM), hypertension (HTN), and dyslipidemia (DLP) at the time of diagnosis has been explored. Moreover, the impact of GH/IGF-1 on these cardio-metabolic risk factors at 3-12 months after surgery has been investigated using linear and logistic regression models.Results: At the time of diagnosis, the prevalence of cardio-metabolic risk factors was 79.17 % for DLP, 29.41% for DM, and 15% for HTN. Furthermore, each 1 ng/ml increase in the level of GH was significantly associated with 2 mg/dl increase in the level of FBS, 0.54 mmHg increase in the level of SBP, and 0.88 mmHg increase in the level of DBP. Upon multivariate analysis GH, but not IGF-1, significantly increased the odds of DM (OR; 1.17, 95% CI; 1.02-1.35, p= 0.025). Conclusions: Our findings showed at early postoperative stage, GH is significantly associated with the levels of FBS, SBP, and DBP. Moreover, GH, but not IGF-1, appears as a predictive factor for the presence of DM. However, neither GH nor IGF-1 could predict the presence of HTN, or DLP in this study.

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Autologous Stem Cell Transplantation for Primary Mediastinal B Cell Lymphoma in the Rituximab Era: A Retrospective Study By the EBMT Lymphoma Working Party

Blood ◽

10.1182/blood.v124.21.1195.1195 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1195-1195

Author(s):

Irit Avivi ◽

Ariane Boumendil ◽

Hervé Hervé Finel ◽

Arnon Nagler ◽

Aïda Sousa Bothello ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Retrospective Study ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Refractory Disease ◽

Post Transplant ◽

The Impact

Abstract Introduction: The addition of rituximab to induction therapy had improved the outcome of patients with primary mediastinal B cell lymphoma (PMBCL). For those patients who are primary refractory or relapse after having achieved a remission, high-dose therapy and autologous stem cell transplantation (ASCT) is considered as standard treatment. Only scanty information, however, is available regarding the role of ASCT in patients with relapsed / refractory PMBCL in the rituximab era. Moreover, the impact of pre- and post-transplant irradiation remains uncertain. The objective of the current study was to investigate the results of ASCT for PMBCL in the rituximab era, identify variables predictive for outcome, and assess the role of adjuvant radiotherapy. Patients and methods: For this retrospective study, all EBMT registered patients with PMBCL aged between 18 and 70 years who were treated with a first ASCT between 2000 and 2012 were eligible. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers with potentially eligible patients were contacted to provide additional treatment and follow-up information including a written histopathology report. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression models. Curves of cumulative incidence of relapse (IR) were compared by Gray's test. Multivariate analysis of IR used Fine and Gray models. Results: 86 patients with confirmed PMBCL were eligible and had the full data set required for this analysis. 51% were female, median age was 34 years (range 20-69). Median time from diagnosis to ASCT was 12 months (12-299). 63.5% of the patients presented with a bulky mediastinal mass, larger than 10cm at diagnosis, 30.5% had stage IV disease, and 44% had B symptoms. 92% had received at least 2 lines of therapies, 85% had rituximab and 30% had received radiotherapy prior to transplantation. At ASCT, 11% still had a mass greater than 10 cm, and 19% a mass of 5-10cm. Remission status at ASCT was CR/PR1 in 21% of the patients, CR/PR>1 in 51%, and refractory disease in 28%. 31 patients (41%) received irradiation post-transplant. Thirteen patients of 24 patients (54%) transplanted in PR attained CR at day +100 post ASCT. With a median follow-up of 39 months (24-73), 3-year non-relapse mortality, IR, event-free survival (EFS) and overall survival (OS) for the whole series were 9%, 33%, 58% and 71%, respectively. By univariate analysis, refractory disease at ASCT and residual mass > 5cm at ASCT were significant adverse predictors for IR, EFS, and OS. 3-year EFS was 35% in refractory subjects vs 66% in chemosensitive patients (p=0.001), and 100% in those autografted in CR/PR1 vs 60% in those transplanted in more advanced response p=0.018. Notably, patients transplanted with refractory disease with a history of irradiation prior to ASCT had a superior outcome compared with non-irradiated refractory patients.Multivariate analysis suggested post-transplant irradiation to be associated with a significantly reduced IR (HR=0.24; p=0.028) and improved EFS (HR=0.24; p=0.018) and OS (HR=0.21; p=0.032). Discussion: In conclusion, this analysis gives first specific evidence that ASCT can provide durable remissions in patients with relapsed / refractory PMBCL in the rituximab era. Pre or post-transplant irradiation appears to be important, though deserves further studies. Disclosures No relevant conflicts of interest to declare.

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