Clostridioides difficile(C. difficile) genotyping is essential for surveillance of emerging strains, transmissions, and outbreak investigations, but culture is lengthy and may not be routinely ...performed, which necessitates culture-independent genotyping methods. We aimed to develop a direct from stool C. difficile PCR ribotyping algorithm using capillary electrophoresis. Ribotypes were generated directly from 66.8% of stools with 33.2% requiring broth enrichment. 16S and tcdB cycle thresholds (Ct) were significantly lower (P< 0.001) in directly ribotyped stools compared to enriched stools, and Ct correlated with direct ribotyping (area under the curve: 0.97 and 0.96, respectively). Direct and isolate ribotypes were 94.7% concordant. Mixed C. difficile ribotypes were presumptively identified in 14 (7.5%) samples with 12 (6.4%) mixtures confirmed. We have developed a rapid PCR ribotyping algorithm allowing for direct C. difficile genotyping from stool using capillary electrophoresis with occasional detection of mixed C. difficile populations in stool, which is a limitation of conventional isolate genotyping.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sorafenib significantly improves survival of FLT3-ITD mutated AML patients when used as a post-allogeneic HSCT maintenance. Importantly, clinical trials reported a low rate of toxicities requiring ...sorafenib discontinuation. The aim of our analysis was to evaluate the real-world experience in patients treated with post-allogeneic HSCT sorafenib maintenance therapy for FLT3-ITD AML with a particular focus on tolerability and toxicity-related treatment interruption. We conducted a single-center retrospective study on 30 FLT3-ITD AML patients undergoing allogeneic HSCT in complete remission between 2017 and 2020 and who received sorafenib maintenance. 26 patients (87%) experienced toxicities leading to dose reduction (n=9) or direct interruption (n=17). Average time on sorafenib was 125 days (range 1-765). Most common toxicities were skin, gastrointestinal, and hematologic. Among patients who had a dose reduction, 4 eventually interrupted the drug and 5 were able to continue. Among patients who interrupted sorafenib because of toxicities, 7 were re-challenged with good tolerance in 3 cases. Overall, 18 patients (60% of the entire cohort) definitively discontinued sorafenib because of toxicities. 14 patients were thereafter switched to midostaurin. Importantly, with a median follow-up of 12 months, the median overall survival was not reached suggesting a positive impact of sorafenib maintenance despite the high rates of treatment interruption. In conclusion, our real-world analysis reveals high rates of toxicity-related interruption of sorafenib maintenance after allogeneic HSCT. Interestingly, our results suggest the feasibility of re-challenging with sorafenib and/or of switching to other maintenance approaches in case of intolerance.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with highly chemorefractory Hodgkin lymphoma (HL). The CD30-targeting ...antibody-drug conjugate Brentuximab-Vedotin (BV) and programmed cell death protein-1 (PD-1) blocking agents have demonstrated clinical activity with durable responses in relapsed/refractory (r/r) HL. However, patients with a history of allo-HSCT were frequently excluded from clinical trials due to concerns about the risk of graft-versus-host disease (GVHD). We report the clinical history of a patient with refractory classical HL who underwent two allo-HSCTs (first from matched unrelated and second from haploidentical donor) after relapsing on BV and nivolumab and for whom durable remission was finally obtained using BV-pembrolizumab combination for relapse after haploidentical HSCT. Such treatment was associated with the onset of GVHD after only two cycles which led to treatment discontinuation. However, the side effects were rapidly controlled, and after 2 years of follow-up, the patient is still in remission. Our data support the feasibility and efficacy of combining PD-1 blockade with BV to enhance the graft-versus-lymphoma effect after allo-HSCT.
Anaphylactic reactions at the time of chimeric antigen receptor T (CAR‐T) cell infusion are adverse events that have not been reported in pivotal clinical trials or in real‐world series. We report ...the case of patient with severe anaphylaxis with cardiac arrest after tisagenlecleucel injection for Diffuse Large B cell Lymphoma, who recovered after resuscitation and intensive care treatment; we also conducted a Food and Drug Administration Adverse Event Reporting System database analysis and found several cases of severe anaphlyaxis after CAR‐T cell injection. Although not reported in pivotal CAR‐T cell studies, anaphylaxis can occur after CAR‐T cell injection, highlighting the need to include anaphylaxis as a possible side effect in future studies.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative treatment for a wide variety of hematological diseases. In 30% of the cases, a geno-identical donor is available. Any other ...situation displays some level of human leukocyte antigen (HLA) incompatibility between donor and recipient. Deleterious effects of anti-HLA immunization have long been recognized in solid organ transplant recipients. More recently, anti-HLA immunization was shown to increase the risk of primary graft failure (PGF), a severe complication of AHSCT that occurs in 3-4% of matched unrelated donor transplantation and up to 15% in cord blood transplantation and T-cell depleted haplo-identical stem cell transplantation. Rates of PGF in patients with DSA were reported to be between 24 and 83% with the highest rates in haplo-identical and cord blood transplantation recipients. This led to the recommendation of anti-HLA antibody screening to detect donor-specific antibodies (DSA) in recipients prior to AHSCT. In this review, we highlight the role of anti-HLA antibodies in AHSCT and the mechanisms that may lead to PGF in patients with DSA, and discuss current issues in the field.
Purpose
The purpose of this study is to describe the management and outcome of critically ill cancer patients with Superior Vena Cava Syndrome (SVCS).
Methods
All cancer patients admitted to the ...medical intensive care unit (ICU) of the Saint-Louis University Hospital for a SVCS between January 2004 and December 2016 were included.
Results
Of the 50 patients included in the study, obstruction of the superior vena cava was partial in two-thirds of the cases and complete in one-third. Pleural effusion was reported in two-thirds of the patients, pulmonary atelectasis in 16 (32%), and pulmonary embolism in five (10%). Computed tomography of the chest showed upper airway compression in 18 (36%) cases, while echocardiography revealed 22 (44%) pericardial effusions. The causes of SVCS were diagnosed one (0–3) day after ICU admission, using interventional radiology procedures in 70% of the cases. Thirty (60%) patients had hematological malignancies, and 20 (40%) had solid tumors. Fifteen (30%) patients required invasive mechanical ventilation, seven (14%) received vasopressors, and renal replacement therapy was implemented in three (6%). ICU, in-hospital, and 6-month mortality rates were 20, 26, and 48%, respectively. The cause of SVCS was the only factor independently associated with day 180 mortality by multivariate analysis. Patients with hematological malignancies had a lower mortality than those with solid tumors (27 versus 80%) (odds ratio 0.12, 95% confidence interval (0.02–0.60),
p
< 0.01).
Conclusion
Airway obstruction and pleural and pericardial effusions contributed to the unstable condition of cancer patients with SVCS. The vital prognosis of SVCS was mainly related to the underlying diagnosis.
Introduction: FLT3-Internal Tandem Duplication (FLT3-ITD) mutations of the gene encoding the FLT3 tyrosine kinase receptor are found in 25-30% of AML patients and are associated with a poor prognosis ...despite intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). FLT3 tyrosine kinase inhibitors (TKI) significantly improve survival of FLT3 mutated AML patients in large prospective trials (Stone, NEJM 2017; doi:10.1056/NEJMoa1614359). Post-HSCT maintenance with sorafenib - a broad-spectrum TKI with strong activity against FLT3 - was recently shown to reduce the risk of relapse and improve survival in the phase II SORMAIN trial (Burchert, JCO 2020; doi: 10.1200/JCO.19.03345). Importantly, clinical trials reported a low rate of toxicities requiring sorafenib discontinuation (Chen et al, BBMT 2014; doi: 10.1016/j.bbmt.2014.09.007; Burchert et al., J Clin Oncol. 2020; doi: 10.1200/JCO.19.03345). The aim of our single-center retrospective analysis was to evaluate the real-life experience in patients treated with post-allogeneic HSCT sorafenib maintenance therapy for FLT3-ITD AML with a particular focus on tolerability and toxicity-related treatment interruption.
Methods: We conducted a single-center retrospective study on 33 FLT3-ITD AML patients undergoing allogeneic HSCT in complete remission between 2013 and 2020, including 20 patients who received sorafenib maintenance and 13 who did not. Sorafenib was started at hematologic reconstitution at 200 mg BID and increased at 400 mg BID after a week in case of good tolerance. Treatment was maintained until two years if tolerated. In case of toxicity, the drug was either reduced to 200mg BID, or stopped. Among the 13 patients in the untreated group, 8 were transplanted between 2013 and 2016 before we started to routinely use sorafenib maintenance, and 5 were transplanted in 2017 or later. Among the latter, sorafenib maintenance was not started because of aGVHD and insufficient hematologic reconstitution (n=3), low-allelic ratio of FLT3-ITD (n=1), early death due to PTLD (n=1).
Results: In the sorafenib group (n=20), median time from transplant to sorafenib initiation was 68 days (range 40-213). Overall, 16 patients (80%) experienced toxicities leading to dose reduction (4 patients, 20%) or interruption (12 patients, 60%). In these patients, the average time on sorafenib before toxicity occurrence was 98 days (range 1-717; only one patient stopped treatment after 1 day because of severe diarrhea). Most common toxicities were skin (7, grade II), gastrointestinal (5, grade II), and hematologic (5, grade II and III). One patient experienced uveitis (grade III) and pneumonia (grade IV), both resolutive after sorafenib interruption. One patient experienced severe hypertension (grade III), 1 had hepatitis (grade III) and another one a PRESS syndrome (grade IV) possibly related to sorafenib.
Other causes of sorafenib interruption included FLT3-ITD negative relapse in 1 patient, relapse in 1 patient, and end of scheduled maintenance in 1 patient. Among the 12 patients who interrupted sorafenib because of toxicities, 3 patients were re-challenged with good tolerance in 2 cases, while 7 were switched to midostaurine. Among these 7, 4 completed the 2-y treatment and 3 interrupted midostaurine because of toxicities (2 patients experienced digestive intolerance and 1 pneumonia).
The average time of sorafenib exposure in the whole sorafenib group was 180 days (range 1-765). Importantly, the analysis of patients' outcome confirmed the previously reported positive impact of sorafenib maintenance on overall survival (Figure 1B) despite high rates of treatment interruption.
Conclusion: Our real-life analysis reveals higher rates of toxicity-related interruption of sorafenib maintenance after allogeneic HSCT than previously reported in clinical trials. Interestingly, our results confirm the favorable impact of sorafenib maintenance on clinical outcome despite a high rate of toxicity-related treatment interruption, suggesting the feasibility of switching to other maintenance approaches in case of low tolerability.
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sorafenib as a maintenance treatment to prevent FLT3-ITD mutated AML reccurence after allogeneic transplantation
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Macrophage activation syndrome (MAS) is a rare life-threatening condition characterized by cytokine-mediated tissue injury and multiorgan dysfunction.
We describe the unique case of young man who ...developed MAS as the sole manifestation of an otherwise paucisymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Clinical and biological criteria led to the diagnosis of MAS; cytokine profile was highly suggestive reverse transcription polymerase chain reaction for SARS-CoV-2 in nasopharyngeal swabs was negative, but serum anti-SARS-CoV-2 immunoglobulin A and immunoglobulin G resulted positive leading to the diagnosis of SARS-CoV-2 infection.
The patient was treated with empiric antibiotic and hydroxychloroquine.
Clinical improvement ensued. At follow-up, the patient is well.
SARS-CoV-2 infection may trigger develop life-threatening complications, like MAS. This can be independent from coronavirus disease 2019 gravity.
Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive ...immunity.
This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia. The CMV status of those patients was reclassified from R+ to R- (CMVR- reclassification group). We compared those patients to allo-HCTRs with negative (CMV IgG titer <0.6 U/mL) pretransplant CMV IgG (CMVR- group). We describe the number and type of patients whose pretransplant CMV status was reclassified from indeterminate/positive to negative. We reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups to assess the safety of this approach.
Among 246 (84.5%) of 291 transplanted patients identified as CMVR+ pretransplant, 60 (24.4%) were reclassified from CMV serology indeterminate (N:10)/low-positive (N:50) to R-. Only 1 of 60 patients (1.67%) in the CMVR- reclassification group versus 3 of 44 (6.8%; P = .30) in the CMVR- group developed CMV DNAemia during the follow-up period. There were no significant differences in the number of CMV DNAemia tests performed, CMV DNAemia range, and time posttransplant between the 2 groups.
One of 4 allo-HCT CMVR+ may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV serology testing at hematologic malignancy diagnosis in allo-HCT candidates and careful review of pretransplant CMV IgG titers may help correctly classify CMV serology status.
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