Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC.

peer reviewedLate relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity

Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS.

peer reviewedAllogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2-4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32-1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28-1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Prophylaxie antivirale pour le CMV, l’HSV/VZV et le VHB après allogreffe de cellules souches hématopoïétiques chez l’adulte : recommandations de la Société francophone de greffe de mœlle et de thérapie cellulaire (SFGM-TC)

International audienceThe Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organizes annual workshops in the attempt to harmonize clinical practices among different francophone transplantation centers. Here, we report our recommendations regarding the prophylaxis of cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV) and hepatitis B virus infection after allogeneic hematopoietic cell transplantation in adult patients

Patients Participating in Nasogastric Tube Insertion through Hypnoanalgesia during High-dose Chemotherapy-induced Aplasia

International audienceThe insertion of a nasogastric (NG) tube is often a difficult experience for both patients and caregivers. This often results in a high failure rate of NG insertion. This pilot study aimed to evaluate the effectiveness, tolerance, and acceptability of hypnoanalgesia to assist self-insertion of an NG tube. Patients undergoing high-dose chemotherapy for autologous or allogeneic hematopoietic stem cell transplantation (HSCT) or acute leukemia and with high risk of aplasia were included in the study. A total of 38 patients were included during 6 consecutive months. They all achieved successful NG tube self-insertion. The NG tube remained in place during hospitalization in 32 cases for an average duration of 15 days. Six patients rejected the NG tube during vomiting but they all voluntarily attempted it again later on and succeeded. The discomfort related to NG-tube insertion was mild. This pilot study suggests that NG tube self-insertion assisted by hypnoanalgesia may be effective, well-accepted, and well-tolerated in patients. These promising findings will need further confirmation

Dépistage des bactéries multirésistantes (BMR) et hautement résistantes émergentes (BHRe) aux antibiotiques en allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

International audienceThe Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organizes annual workshops in the attempt to harmonize clinical practices among different francophone transplantation centers. Here we report our recommendations regarding detection of the multidrug-resistant bacteria in hematology

Contribution of voriconazole N-oxide plasma concentration measurements to voriconazole therapeutic drug monitoring in patients with invasive fungal infection

International audienceBACKGROUND: Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient’s drug metabolism capacity. OBJECTIVES: Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm. PATIENTS AND METHODS: Sixty-one patients treated with VRC were prospectively included in the study, and VRC and NOX levels were assayed by LC-MS/MS. A mixed logistic model on repeated measures was implemented to analyze risk factors for the patient’s concentration to be outside the therapeutic range. RESULTS: Based on 225 measurements, the median and interquartile range were 2.4 μg/mL (1.2; 4.2), 2.1 μg/mL (1.5; 3.0), and 1.0 (0.6; 1.9) for VRC, NOX, and the MR, respectively. VRC C(min) &lt; 2 μg/mL were associated with a higher MR during the previous visit. MR values &gt; 1.15 and &lt; 0.48 were determined to be the best predictors for having a VRC C(min) lower than 2 μg/mL and above 5.5 μg/mL, respectively, at the next visit. CONCLUSIONS: Measurement of NOX resulted useful for TDM of patients treated with VRC. The MR using NOX informed interpretation and clinical decision-making and is very interesting for complex patients. VRC phenotyping based on the MR is now performed routinely in our institution. A dosing algorithm has been suggested from these results

Suivi au moyen-terme des patients faisant l’objet d’un traitement par CAR-T cells : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Chimeric antigen receptor (CAR) T cells are a new class of anti-cancer therapy that involves manipulating autologous or allogeneic T cells to express a CAR directed against a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) has marketing authorization for the treatment of relapsed / refractory acute lymphoblastic leukemia (ALL) in children and young adults, in addition to the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL); the marketing authorization for axicabtagene ciloleucel (Yescarta™) is for the treatment of relapsed / refractory high-grade B-cell lymphoma and for the treatment of primary mediastinal B-cell lymphoma. Both cell products are genetically modified autologous T cells directed against CD19. These recommendations, drawn up by a working group of the Francophone Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC) relate to the management of patients and the supply chain: medium-term complications, in particular cytopenias and B-cell aplasia, nursing and psychological supportive care. In another work, we will address long-term monitoring, post-marketing authorization pharmacovigilance and issues relating to JACIE and regulatory authorities. These recommendations are not prescriptive; their aim is to provide guidelines for the use of this new therapeutic approach. The purpose of this workshop is to outline the organizational aspects of this new therapeutic approach.</p