Azacitidine-venetoclax versus azacitidine salvage treatment for primary induction failure or first relapsed acute myeloid leukaemia patients.

OBJECTIVES: To compare the efficacy of venetoclax-azacitidine (VEN-AZA) with AZA in the real-life for patients with first relapsed or refractory acute myeloid leukaemia (R/R AML). METHODS: We retrospectively analysed R/R AML patients treated with VEN-AZA at the Institut Paoli Calmettes between September 2020 and February 2022. We compared them to a historical cohort of patients treated with AZA between 2010 and 2021. RESULTS: Thirty-five patients treated with VEN-AZA were compared with 140 patients treated with AZA. There were more favourable cytogenetics (25.7% vs. 8.6%; p = 0.01) and less FLT3-ITD mutated AML (8.8% vs. 25.5%; p = .049) in the VEN-AZA group. The overall 30-day mortality rate was 7.4% and the overall 90-day mortality was 20%, with no difference between the groups. The complete remission rate was 48.6% in the VEN-AZA group versus 15% (p < .0001). The composite complete response rate was 65.7% in the VEN-AZA group versus 23.6% (p < .0001). OS was 12.8 months in the VEN-AZA group versus 7.3 months (p = 0.059). Patients with primary refractory AML, poor-risk cytogenetics, prior hematopoietic stem-cell transplantation (HSCT) and FLT3-ITD mutated AML had lower response and survival rates. CONCLUSION: VEN-AZA was associated with a better response rate and a longer survival than AZA monotherapy in AML patients who relapsed after or were refractory to intensive chemotherapy.

Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients.

PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. RESULTS: During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2-28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8-2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1-66.6%) for VAP, 8.9% (95% CI, 6.2-11.5%) for primary, 15.1% (95% CI 11.6-18.5%) for secondary and 5.0% (95% CI 3.2-6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. CONCLUSIONS: This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy.

Tracking the spread routes of opportunistic premise plumbing pathogens in a haematology unit with water points-of-use protected by antimicrobial filters.

BACKGROUND: Water networks in hospitals are frequently contaminated by opportunistic premise plumbing pathogens (OPPPs) leading to installation of antimicrobial filters on water points-of-use (POU) in order to limit patients' exposure. AIM: To assess the spread of OPPPs through secondary water routes (outside the plumbing system) in an adult haematology unit in which 52 out of 73 water POU were high risk for patients and protected by antimicrobial filters. METHODS: An observational audit identified six secondary water routes for which bacteria tracking and typing were performed in 315 surface samplings. Bacterial isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and compared to the infra-species level by multiplex repetitive element sequence-based polymerase chain reaction and/or by restriction fragment length polymorphism in pulse-field gel electrophoresis. FINDINGS: Pseudomonas aeruginosa and Stenotrophomonas maltophilia, as well as non-pathogenic OPPP indicators, were detected in water collected upstream of antimicrobial filters. P. aeruginosa was the sole OPPP retrieved from tested surfaces (5.1%). The same clone of P. aeruginosa spread from water source to dry surfaces in the same room and cross-contaminated two sinks in different rooms. Three clones of non-pathogenic OPPP indicators spread more widely in different rooms. CONCLUSION: A strategy based on filtration of most (but not all) water POU in a haematology unit could be sufficient to limit the spread of OPPPs to the environment, provided a functional mapping of 'high-risk' POU has been undertaken. The residual spread of OPPPs and OPPP indicators linked to non-filtered water POU argues for careful monitoring of non-filtered water use.

[Kinetic and organization of granulocytes transfusion: a case report]. / Transfusion thérapeutique de granulocytes : cinétique et aspects organisationnels autour d'un cas clinique.

BACKGROUND: Therapeutic granulocyte transfusion remains an indication for neutropenic sepsis associated with prolonged neutropenia. However, harvest complexity and lack of proved efficacy mark the limits of its development. CASE REPORT: A 58-year old man received allogeneic stem cell transplantation for osteomyelofibrosis. Six months later, after a transplant rejection, he presented with perineal cellulitis from hemorrhoid origin, without any microbiological documentation. The evolution was unfavorable despite antibiotic and antifungal therapy. A set of seven granulocytes transfusions was initiated. Re-circulation of granulocytes analysis showed an initial increase (H2) followed by a decrease (H8) reaching the basal rate at H16. No toxicity has been reported during or following the transfusions. Clinical improvement has been reported five days after the first transfusion, scaring over at D15, without any neutrophil recovery. CONCLUSION: In 2014, granulocyte transfusion therapy is indicated for severe infection associated with long-term neutropenia. Minimal circulation of transfused cells in our observation and fast clinical improvement suggest the concentration of granulocytes on the infected area.

Quality controls on cord blood unit contiguous segments: recommendation of the SFGM-TC.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. Literature and intra-laboratories studies suggest that attached segment is representative of cord blood unit (CBU). Nevertheless, some discrepancies have been observed when analyzing large data registries. To address these issues, we have listed recommendations to increase the standardization of segment processing and quality control (QC), information on units of measurement and specifications and action to be taken in case of out of specifications QC results on segment.

[Diagnosis and treatment of CMV and EBV Reactivation as well as Post-transplant Lymphoproliferative Disorders following Allogeneic Stem Cell Transplantation: An SFGM-TC report]. / Prise en charge d'une réactivation/infection à CMV chez l'allogreffé et prise en charge de la réactivation EBV/syndrome lymphoproflifératif à EBV chez l'allogreffé de cellules souches hématopoïétiques.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here the SFGM-TC addressed the issue of post-transplant CMV and EBV reactivation, and EBV-related Lymphoproliferative Disorders.

[Hematopoietic Stem Cell Transplantation using unrelated cord blood: which unit to choose? A report of the SFGM-TC]. / Allogreffe de cellules souches hématopoïétiques à partir d'un sang cordon non apparenté: quelle unité choisir?

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the choice of optimal unrelated cord blood unit in terms of cell dose, HLA-matching and other characteristics.

Environmental prevention of infection in stem cell transplant recipients: a survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: The developments of peripheral blood stem cells in autologous hematopoietic stem cell transplantation (auto-HCT), and of reduced-intensity conditioning (RIC) regimens in allogeneic HCT (allo-HCT), have considerably changed the transplant approach. Prolonged neutropenia combined with severe mucosal damage and organ dysfunction is no longer the rule in the early post-HCT pancytopenic phase. Although strict isolation during pancytopenia was followed by most HCT units in the past, this may not be the current practice. METHODS: In 2008, a questionnaire was sent out to the 463 European Group for Blood and Marrow Transplantation centers, enquiring about their current environmental protection procedures; 89 (20%) returned the questionnaire. RESULTS: Most centers housed auto-HCT recipients in high-efficiency particulate air (HEPA)-filtered rooms without (52%) or with laminar air flow (LAF) (29%) after total body irradiation (TBI), whereas HEPA-filtered rooms were used in 53% of auto-HCT conditioned without TBI. During the initial pancytopenic phase after allo-HCT, patients were housed in HEPA/LAF rooms in 50% and 42% of the centers, if a high-dose myeloablative conditioning regimen or a RIC regimen was used, respectively. Surprisingly, 8-24% of the centers reported that no isolation procedures were used in patients colonized or infected with highly transmissible pathogens (i.e., Clostridium difficile, respiratory viruses, and varicella zoster virus). CONCLUSION: In conclusion, universal recommendations for infected or colonized patients may be poorly known or applied in many HCT units.

Antifungal prophylaxis in haematology patients: the role of voriconazole.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in haematopoietic stem cell transplant (HCT) recipients and patients with haematological malignancies. Early treatment initiation is vital for improving survival, but is hampered by difficulties in timely diagnosis. Prophylaxis with a broad-spectrum antifungal, such as voriconazole, has the potential to decrease the incidence of IFI in haematology patients. Based on a growing body of data, voriconazole appears to be effective for the primary and secondary prevention of IFIs in HCT recipients, with generally good tolerability.

Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire.

This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.

The epidemiology of invasive Streptococcus pneumoniae infections in onco-haematology and haematopoietic stem cell transplant patients in France. Are the serotypes covered by the available anti-pneumococcal vaccines?

The pneumococcal antigens contained in the polysaccharide (PPV23) and conjugate (7-valent, PCV7; 13-valent, PCV13) vaccines have been chosen since they represent the serotypes that more frequently cause invasive pneumococcal disease. Whether these vaccines cover the serotypes most frequently isolated in haematology patients is unclear. The serotype distribution among Streptococcus pneumoniae in 25 consecutive pneumococcal infections that occurred over the last 3 years in two French haematology departments was investigated. The pneumococcal vaccines PCV7, PCV13 and PPV23 were found to cover 76, 84 and 92%, respectively, of the serotypes found.

Correlation between galactomannan antigen levels in serum and neutrophil counts in haematological patients with invasive aspergillosis.

The detection of circulating galactomannan (GM) in serum samples is an important step in the diagnosis of invasive aspergillosis (IA). The assay has been mainly explored in neutropenic patients, and is now used to monitor patients at high risk for IA. However, the performance of the assay varies greatly among studies. The objective of this study was to explore the impact of the neutrophil count on the GM serum index at the time of IA diagnosis. Ninety-nine episodes of proven or probable, microbiologically documented IA in 91 patients with haematological malignancies were studied retrospectively. Three groups were identified: groups 1-3, with <100 polymorphonuclear neutrophils (PMN)/mm(3) (n = 18), between 100 and 500 PMN/mm(3) (n = 21), or >500 PMN/mm(3) (n = 60), respectively. The mean GM index was significantly higher in group 1 than in the other groups (p <0.05). This finding did not change after stratifying the analysis with regard to the use of antibiotics likely to give false-positive GM results or with regard to treatment effective against fungi before the diagnosis of IA. This finding could be considered in the routine use of the GM antigenaemia test in non-neutropenic patients; a negative result or a low GM index should not eliminate the diagnosis of IA. This limitation calls for other microbiological tests, including analysis of bronchoalveolar lavage fluid, to establish a definitive diagnosis of IA.

[ABO incompatibility and non myeloablative allogeneic stem cell transplantation]. / Incompatibilité ABO et greffe allogénique de cellules souches hématopoïétiques à l'ère des conditionnements non myéloablatifs.

ABO incompatibility is not a barrier for allogeneic hematopoietic stem cell transplantation but is associated with specific complications. Major ABO incompatibility is associated with delayed erythroid engraftment, increased transfusion requirement and cases of pure red cell aplasia. Minor ABO incompatibility may be responsible for acute haemolytic reactions in the first months following transplantation. The widely used non myeloablative conditioning regimens might modify the management of ABO incompatibility. They could favour pure red cell aplasia development in the setting of major ABO mismatch since they are associated with a prolonged persistence of host anti-donor isohemagglutinins after allogeneic hematopoietic stem cell transplantation. In the setting of minor ABO incompatibility, the use of peripheral blood stem cells and the nature of graft-versus-host disease prophylaxis regimen may have an impact on the incidence of haemolytic reactions. In that review, the clinical and therapeutic aspects of ABO incompatibility are studied, especially regarding the impact of the conditioning regimen intensity.