Poor outcome and high prevalence of invasive fungal infections in patients with adult T-cell leukemia/lymphoma exposed to zidovudine and interferon alfa.

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα.

Revised international surveillance case definition of transfusion-associated circulatory overload: a classification agreement validation study.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a major cause of transfusion-related morbidity and mortality in countries with well developed transfusion services. The International Society of Blood Transfusion, the International Haemovigilance Network, and AABB (formerly American Association of Blood Banks), have developed and validated a revised definition of TACO. METHODS: International Haemovigilance Network-member haemovigilance systems (Australia, Austria, Denmark, Finland, Greece, India, Ireland, Italy, Japan, Malta, Netherlands, New Zealand, Norway, Slovenia, United Kingdom and United States) provided cases of respiratory complications categorised by their systems, including clinical parameters listed in the 2017 draft definition (part 1). Individual transfusion professionals were then invited to assess 24 case descriptions according to the draft definition (part 2). Positive and negative agreement and inter-rater agreement (κ) were calculated. Based on validation results, cases were reanalysed and slight adjustments made to yield the final 2018 TACO definition. FINDINGS: In part 1, 16 (44%) of 36 haemovigilance systems provided 178 cases, including 126 TACO cases. By use of the 2018 definition, 96 (76%) of 126 cases of TACO were in positive agreement. 19 (37%) of 52 cases were recognised as non-TACO respiratory complications. In part 2 (47 experts from 20 countries), moderate all-case agreement (κ=0·43) and TACO-specific agreement (κ=0·54) were observed. Excluding cases missing some clinical information (eg, N terminal pro-brain natriuretic peptide, distinctive chest x-ray findings, and relationship with existing respiratory co-morbidities like pneumonia and chronic obstructive pulmonary disease) improved all-case agreement to κ=0·50 (moderate) and κ=0·65 (good) for TACO cases. INTERPRETATION: The two-part validation exercise showed that the revised 2018 TACO surveillance case definition captures 76% of cases endorsed as TACO by participating haemovigilance systems. This definition can become the basis for internationally consistent surveillance reporting and contribute towards increased awareness and mitigation of TACO. Further research will require reporting more complete clinical information to haemovigilance systems and should focus on improved distinction between TACO and other transfusion respiratory complications. FUNDING: International Society of Blood Transfusion, International Haemovigilance Network, and AABB.

Comparing transfusion reaction risks for various plasma products - an analysis of 7 years of ISTARE haemovigilance data.

Plasma transfusions may result in transfusion reactions. We used the International Surveillance of Transfusion-Associated Reactions and Events (ISTARE) database, containing yearly reported national annual aggregate data on transfusion reactions from participating countries, to investigate risks of plasma transfusion reactions and compare transfusion reaction risks for different plasma types. We calculated risks for plasma transfusion reactions and compared transfusion reaction risks between plasma types using random effects regression on repeated measures. The ISTARE database contains data from 23 countries, reporting units issued and/or transfused and transfusion reactions observed for some portion of 7 years (2006-2012). Interquartile ranges (IQRs) of plasma transfusion reaction risks were: allergic reactions (5·6-72·2 reactions/105 units transfused); febrile non-haemolytic transfusion reactions (0-9·1); transfusion-associated circulatory overload (0-1·9); transfusion related acute lung injury (TRALI) (0-1·2); and hypotensive reactions (0-0·6). Apheresis plasma was associated with more allergic reactions [odds ratio (OR) = 1·29 (95% confidence interval: 1·19-1·40)] and hypotensive reactions [OR = 2·17 (1·38-3·41)] than whole blood-derived plasma. Pathogen-inactivated plasma was associated with fewer transfusion reactions than untreated plasma.

Blood transfusion during World War I (1914 - 1918).

In august 1914, at the start of World War I, blood transfusion remains quite infrequent, with rough methods, inaccurate indications and poor results. The direct surgical techniques of arteriovenous anastomosis proved ill-adapted to the emergency conditions of war wounds. Indirect techniques with syringes and storage tubes were frequently limited, and complicated, by blood-clotting. Moreover, despite Landsteiner's discovery of ABC blood groups in 1901, compatibility testing was poorly known and often considered unnecessary. At the beginning of the war, none of the belligerent armies'medical services was specifically organized for blood transfusion. In the early years of the war (1914-1916), blood transfusions remain rare. The first transfusion in the French army was performed by Emile Jeanbrau on 16 October 1914. The main impulse, however, came from surgeons of the Canadian Army Medical Corps (CAMC), who had learned about transfusion from doctors in the United States (Bruce Robertson, Edward Archibald). Transfusions became increasingly frequent, particularly as part of pre-operative preparation in cases of wound shock and hemorrhage. The last years (1917-1918) were marked by the arrival of the American Army in France, with a growing medical influence of American doctors. Oswald Robertson introduced the use of citrated blood in glass bottles, being subsequently called "the first blood banker". Blood transfusion remained throughout the war infrequent and technically imperfect. Wartime, however, by the efforts of some young Canadian and American doctors, was a tremendous opportunity for diffusion and improvement.

Transfusion-related acute lung injury: reports to the French Hemovigilance Network 2007 through 2008.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related mortality and morbidity. Epidemiologic studies using data from national transfusion schemes can help achieve a better understanding of TRALI incidence. STUDY DESIGN AND METHODS: A multidisciplinary working group analyzed TRALI cases extracted from the French Hemovigilance Network Database (2007-2008). All notified cases were reviewed for diagnosis. Those meeting the Canadian Consensus Conference criteria for TRALI were classified according to imputability to transfusion and clinical severity. Patient data (clinical characteristics, number and types of products transfused, and serology results) were obtained. RESULTS: There were 62 TRALI cases and 23 possible TRALI cases during the 2-year period. An immune-mediated mechanism was identified in 30 of 50 TRALI cases with complete serology. TRALI was considered to be the cause of death in 7.1% of patients and might have contributed to death in an additional 9.4% of TRALI or possible TRALI patients. Occurrence ranked high in obstetrics (15%), after surgery (34%), and in hematologic malignancies (21%). Single-donor high-plasma-volume components were involved in half of the cases where the implicated blood product could be determined and carried the highest risk per component (1:31,000 for single-donor fresh-frozen plasma units and apheresis platelet [PLT] concentrates, and 1:173,000 for red blood cells). No incident could be definitively related to the transfusion of solvent/detergent-treated pooled plasma (>200,000 units transfused), nor to pooled PLT concentrates. CONCLUSION: The proportion of TRALI cases related to plasma-rich components was lower than previously described.

The challenge of AIDS-related malignancies in sub-Saharan Africa.

BACKGROUND: With the lengthening of life expectancy among HIV-positive subjects related to the use of highly active antiretroviral treatments, an increased risk of cancer has been described in industrialized countries. The question is to determine what occurs now and will happen in the future in the low income countries and particularly in sub-Saharan Africa where more than two-thirds of all HIV-positive people live in the world. The objective of our paper is to review the link between HIV and cancer in sub-Saharan Africa, putting it in perspective with what is already known in Western countries. METHODS AND FINDINGS: Studies for this review were identified from several bibliographical databases including Pubmed, Scopus, Cochrane, Pascal, Web of Science and using keywords "HIV, neoplasia, epidemiology and Africa" and related MesH terms. A clear association was found between HIV infection and AIDS-classifying cancers. In case-referent studies, odds ratios (OR) were ranging from 21.9 (95% Confidence Interval (CI) 12.5-38.6) to 47.1 (31.9-69.8) for Kaposi sarcoma and from 5.0 (2.7-9.5) to 12.6 (2.2-54.4) for non Hodgkin lymphoma. The association was less strong for invasive cervical cancer with ORs ranging from 1.1 (0.7-1.2) to 1.6 (1.1-2.3), whereas ORs for squamous intraepithelial lesions were higher, from 4.4 (2.3-8.4) to 17.0 (2.2-134.1). For non AIDS-classifying cancers, squamous cell conjunctival carcinoma of the eye was associated with HIV in many case-referent studies with ORs from 2.6 (1.4-4.9) to 13.0 (4.5-39.4). A record-linkage study conducted in Uganda showed an association between Hodgkin lymphoma and HIV infection with a standardized incidence ratio of 5.7 (1.2-17) although OR in case-referent studies ranged from 1.4 (0.7-2.8) to 1.6 (1.0-2.7). Other cancer sites found positively associated with HIV include lung, liver, anus, penis, vulva, kidney, thyroid and uterus and a decreased risk of female breast cancer. These results so far based on a relatively small number of studies warrant further epidemiological investigations, taking into account other known risk factors for these tumors. CONCLUSION: Studies conducted in sub-Saharan Africa show that HIV infection is not only strongly associated with AIDS-classifying cancers but also provided some evidence of association for other neoplasia. African countries need now to implement well designed population-based studies in order to better describe the spectrum of AIDS-associated malignancies and the most effective strategies for their prevention, screening and treatment.

Epidemiology of Transfusion Related Acute Lung Injury in France: Preliminary Results.

SUMMARY: The French Hemovigilance Network has been established in 1994 and records all adverse events associated with the transfusion of a labile blood products (LBP) regardless of their severity. From 1994 to 2006 35,423,172 LBP were issued, 85,812 adverse transfusion reactions notified, and 139 cases of transfusion related acute lung injury (TRALI) observed. The LBP most at risk is fresh frozen plasma (FFP), followed by platelets concentrates (PC) and packed red cells (PRC). However, because the use of FFP is not frequent in France, it only accounts for about 10% of TRALI, whereas PRC and PC are involved in the remaining cases. In no case, pooled FFP treated with solvent-detergent were involved. Patients' profiles are peculiar with a high disease burden. Therefore, targeting a prevention policy only on FFP would result in a marginal reduction of TRALI in France.

Generalized pustular psoriasis (Zumbusch): a French epidemiological survey.

A retrospective epidemiological survey of generalized pustular psoriasis (GPP) was carried out in France in 2005. 121 dermatological wards received a questionnaire concerning the patients treated in 2004. It related to demographic data, morbidity, mortality, failures and the therapeutic practices of each ward. CNAMTS, the main French health insurance, was also questioned about its registry concerning GPP.112 wards (92.5%) answered the questionnaire, totalling 99 cases (sex ratio male/female: 0.77, mean age 52.5 years +/- 18), which were handled by 46 wards. Incidence and prevalence were estimated in 2004 at a minimum of 0.64 and 1.76/million respectively. Incidence deduced from the CNAMTS data in 1998 and 2001 was similar. The treatment habits were the same in the 46 wards, which used acitretin as first line treatment (89%), followed by methotrexate (8%). High potency dermatocorticosteroids (DC) were most often used (87%). Complications and death were noted in 17% and 2% of the cases respectively, recalcitrant GPP in 42%. Immunobiologics were required in 13% of patients. Univariate analysis showed that treatment failure was related to: i) management in a university ward (OR: 2.9, p = 0.03) probably reflecting the management of the more severe cases ii) prescription of high or very high potency DC as first line local therapy (OR: 7.6, p = 0.05) iii) therapies other than retinoids as first line systemic therapy (OR: 5.5, p = 0.04). The systemic treatment is well codified but future studies will have to confirm the usefulness of DC in the management of GPP.

Hepatitis C virus infection and B-cell non-Hodgkin's lymphoma: a cross-sectional study in Lyon, France.

OBJECTIVES: The role of hepatitis C virus (HCV) infection in the pathogenesis of non-Hodgkin's lymphoma (NHL) is controversial. A high prevalence of HCV infection in patients with NHL has been reported in Italy and Japan. By contrast, several studies in Northern Europe and Canada have not found any increased prevalence of HCV in B-cell NHL, suggesting a possible geographic variation. We sought to determine whether such an association could be found in patients treated in the Rhone-Alpes region in south-east France. Our main interest was to identify histological subtypes preferentially linked to HCV. METHODS: We determined the prevalence of anti-HCV antibodies in 212 consecutive patients with B-cell NHL diagnosed in our institution between January 1997 and December 1998. The comparison group comprised 974 patients tested for HCV before transfusion at the same hospital during the same period. RESULTS: Anti-HCV antibodies were found in six (2.8%) NHL patients. The distribution by histopathological category was as follows: three gastric mucosa-associated lymphoid tissue (MALT) lymphomas, one marginal lymphoma and two diffuse large-cell lymphomas. Anti-HCV antibodies were found in 20 (2%) of 974 comparison patients. Overall, there was a positive but non-significant trend towards an association between NHL and HCV infection (odds ratio 1.31; 95% confidence interval 0.51-3.36). However, the prevalence of HCV antibodies was significantly higher in MALT lymphoma patients than in the comparison group (odds ratio 9.87; 95% confidence interval 2.59-37.69). CONCLUSIONS: To our knowledge, this is the first French study to show an association between HCV and MALT lymphoma. These results, although derived from a small number of patients, suggest a possible role of HCV in gastric MALT lymphomagenesis.

Failure and success of HIV tests for the prevention of HIV-1 transmission by blood and tissue donations.

French blood banks recently implemented nucleic acid testing (NAT) of all blood donations to reduce the risk of HIV transmission during the pre-seroconversion period. For tissue donation, HIV infection screening relies on HIV p24 antigen and anti-HIV-1 and 2 antibody detection. In this report, two related cases of infectious donations are described from a cornea donor during the preseroconversion window who was infected by an HIV antibody and NAT negative blood donor. After investigation, the blood donor was found to be herself in the preseroconversion window. Two months after donation, she was found to be HIV positive. The residual risk of HIV infectious blood donations since NAT has been introduced is estimated to be lower than one out of 2.5 millions. Individual NAT instead of minipool testing would not increase significantly the blood transfusion safety. In contrast, introduction of NAT should be considered to increase tissue donation safety as soon as such screening will be possible technically.

Smoking and non-Hodgkin's lymphoma: a case-control study in the Rhône-Alpes region of France.

OBJECTIVE: To study the relation between smoking and non-Hodgkin's lymphoma (NHL), in the Rhône-Alpes region of France. METHODS: We conducted a hospital-based case-control study that included 180 cases of NHL and 360 age-, gender-matched hospital controls. Matched univariable and multivariable logistic regression models were used for analysis. RESULTS: For the whole study population as well as for men, smoking does not elevate the risk of NHL. However, the risk of NHL is higher for women who currently smoke compared to women who have never smoked (odds ratio [OR] = 2.40, 95% confidence interval [95% CI] = 1.19-4.84). Among ever smokers, the OR of NHL is 5.04 (95% CI = 1.40-18.12) for women who have smoked for more than 30 years compared with those who have never smoked. Similarly, women who started to smoke before the age of 20 years compared with women who have never smoked are at greater risk of developing NHL (OR = 2.40, 95% CI = 0.99-5.85). In the total population (women and men), smoking may be associated with one histologic subtype, follicular NHL with an adjusted OR for the current smokers compared to subjects having never smoked of 3.20, 95% CI = 0.79-12.97. CONCLUSIONS: In spite of the small number of subjects in the subgroups, a relation is observed between smoking and NHL among women, but not men, and in the total population a relation is suggested between smoking and follicular NHL.