Graft failure, poor graft function erythroblastopenia: Actualization of definitions, diagnosis and treatment: Recommendations of the Francophone Society of Bone Marrow Transplantation and cell therapy (SFGM-TC) 2021.

peer reviewedIn this article, we discuss again the definition, the risk factor and guideline to treat the graft failure, the poor graft function and erythrobalstopenia. Graft failure is a severe but rare complication after hematopoietic cell transplantation (HCT). Despite disparity in the literature, we defined this complication and discussed the factor risks and recommendation for treatment based on new studies. Poor graft function is also a more frequent complication after HCT. New studies will soon be available to prove or not the current recommendation suggested in this article based on therapeutics medicine or cellular therapy. Erythroblastopenia, is a rarer complication post HCT. Despite anticipation for a better choice of compatibility donor/recipient, some patients still suffer from this complication

Vaccination of allogeneic haematopoietic stem cell transplant recipients: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

peer reviewedDuring immune reconstitution following allogeneic haematopoietic stem cell transplantation (allo-HSCT), (re)vaccination of allo-HSCT recipients is recommended. Herein, we propose an update of practical recommendations regarding vaccination of allo-HSCT recipients. These recommendations, based on data from the literature, national and international guidelines and the consensus of the participants when no formally proven data are available, were elaborated during the workshop of practice harmonization organized by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) in Lille in September 2022

QPCR detection of Mucorales DNA in bronchoalveolar lavage fluid to diagnose pulmonary mucormycosis

International audienceEarly diagnosis and treatment are essential to improving the outcome of mucormycosis. The aim of this retrospective study was to assess the contribution of quantitative PCR detection of Mucorales DNA in bronchoalveolar lavage fluids for early diagnosis of pulmonary mucormycosis.Bronchoalveolar lavage fluids (n=450) from 374 patients with pneumonia and immunosuppressive conditions were analyzed using a combination of 3 quantitative PCR assays targeting the main genera involved in mucormycosis in France (Rhizomucor, Mucor/Rhizopus, Lichtheimia).Among these 374 patients, 24 had at least one bronchoalveolar lavage with a positive PCR; 23/24 patients had radiological criteria for invasive fungal infections according to consensual criteria : 10 patients with probable or proven mucormycosis, and 13 additional patients with other invasive fungal infections (4 probable aspergillosis, 1 proven fusariosis, and 8 possible invasive fungal infections). Only 2/24 patients with a positive PCR on bronchoalveolar lavage had a positive Mucorales culture.PCR was also positive on serum in 17/24 patients. In most cases, PCR was first detected positive on sera (15/17). However, a positive PCR on bronchoalveolar lavage was the earliest and/or the only biological test revealing mucormycosis in 4 patients with a final diagnosis of probable or proven mucormycosis, 3 patients with probable aspergillosis and one patient with a possible invasive fungal infection.Mucorales PCR performed on bronchoalveolar lavage could provide additional arguments for earlier administration of Mucorales-directed antifungal therapy, thus improving the outcome of lung mucormycosis

Indications de l’autogreffe de cellules souches hématopoïétiques dans la polyradiculonévrite inflammatoire démyélinisante chronique : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

International audienceChronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure

CT-198 Pooled Fecal Allogeneic Microbiotherapy for Refractory Gastrointestinal Acute Graft-Versus-Host Disease: Results from the Early Access Program in Europe

International audienceIntroductionWe report clinical outcomes from 140 steroid-refractory (SR) or steroid-dependent (SD) GI-aGvHD patients treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in Europe.Patients and MethodsThe 140 patients with SR/SD GI-aGvHD, who had been treated unsuccessfully with 1 to 6 systemic lines, received MaaT013 therapy. For each patient, a total of 3 MaaT013 administrations were planned every 7 ± 2 days.ResultsThe GI objective response rate (GI-ORR) on day 28 (D28) was 52%: 39 complete responses (CR, 28%), 26 very good partial responses (19%), 8 partial responses (PR, 6%). OS was 54% at month 6 (M6), 47% at M12, and 42% at M18. OS was significantly higher in patients achieving at least GIPR at D28 (Responder, R; n=73) than in patients with treatment failure (Non-responder, NR; n=67): 74% versus 33% at M6, 68% versus 24% at M12, 58% versus 24% at M18 (P<.0001). GI-ORR was higher in 49 patients previously treated with ruxolitinib (2nd line) and MaaT013 (3rd line): 63% at D28, with 49% CR. OS was 52% at M6, 49% at M12, and 42% at M18. OS was significantly higher in R patients than in NR patients (M6, 76% versus 11%; M12, 76% versus 6%, M18, 64% versus 6% for R and NR respectively, P<.0001). MaaT013 displayed a good overall safety profile: 22 pharmacovigilance cases were considered possibly related to MaaT013 by either the physician or the company: sepsis in 6, bacteremia in 10, rectal bleeding in 3, Clostridioides difficile colitis in 1, Escherichia coli osteoarthritis in 1, Geotrichum silvicola in stools in 1. No pathogen transmission was reported. In 2 patients, non-pathogenic commensal bacteria isolated following infectious events were detected in the administered MaaT013. Causality could not be formally excluded in these cases. No death was related to MaaT013 administration.ConclusionEAP clinical data showed that MaaT013 was safe and effective for the treatment of SR/SD-GI-aGvHD, especially after ruxolitinib failure. GI response correlated with increased OS, suggesting a favorable benefit-risk profile for MaaT013. A Phase 3 trial is currently ongoing to confirm these results in ruxolitinib-refractory patients (NCT04769895)

Management of patients developing acute gastro-intestinal graft-versus-host-disease: guidelines from the francophone society of bone marrow transplantation and cellular therapy (sfgm-tc)

International audienceGraft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic cell transplantation (allo-HCT) with a frequency range of 30% to 50%. GVH is the leading cause of non-relapse-related deaths and a cause early mortality. Gastro-intestinal (GI) GVH results in digestive manifestations that involve the small intestine and the colon. The patient may then have diarrhea, intestinal bleeding, abdominal pain but also clinical signs such as nausea and vomiting may lead to anorexia. GI-GVHD promotes undernutrition as well as significant losses of vitamins and trace elements. In the case of post-transplant diarrhea, differential diagnosis can include GI-GVHD, infection and drug toxicity. Although, corticosteroids w/wo calcineurin inhibitors represent the standard of care in first line treatment, there is no consensus regarding salvage therapy in case of corticoresistant GI-GVH. In addition, assessment of early nutritional status would help combating undernutrition, which is an independent risk factor for mortality in patients with GI-GVHD. In this workshop of the Fancophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) we focused on the management of patients developing GI-GVHD following allo-HCT.La maladie du greffon contre l’hôte (GVH) est la complication la plus fréquente après allogreffe de cellules souches hématopoïétiques dont la fréquence varie entre 30 % et 50 %. La GVH est la principale cause de décès non liés à la rechute et une cause de mortalité précoce. La GVH digestive se traduit par des manifestations digestives qui impliquent l’intestin grêle et le colon. Le patient peut alors présenter des diarrhées, des hémorragies intestinales, des douleurs intestinales mais aussi des signes cliniques comme des nausées et des vomissements pouvant conduire à une anorexie. La GVH digestive favorise la dénutrition ainsi que des pertes importantes en vitamines et oligo-éléments. En cas de diarrhée isolée, le diagnostic différentiel n’est pas aisé entre une GVH digestive, infection ou intolérance médicamenteuse. Les corticostéroïdes avec ou sans inhibiteurs de la calcineurine représentent le traitement de choix en première ligne. Toutefois, il n’existe pas de consensus sur le traitement de rattrapage de deuxième ligne en cas de GVH digestive corticorésistante. L’évaluation de l’état nutritionnel précoce permettrait également de lutter contre la dénutrition, qui est un facteur de risque indépendant de mortalité. Dans cet atelier, nous nous sommes focalisés sur la prise en charge des patients allogreffés présentant une GVH digestive, en particulier, corticorésistante

In-depth time-dependent analysis of the benefit of allo-HSCT for elderly patients with CR1 AML: a FILO study

The benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute myeloid leukemia (AML) aged > 60 years remains a matter of debate, notably when performed in first complete remission (CR1). To clarify this issue, the French Innovative Leukemia Organization (FILO) performed a 10-year real-world time-dependent analysis. The study enrolled patients between 60 and 70 years of age with AML in CR1 after intensive chemotherapy with intermediate (IR) or unfavorable (UR) risk according to the European LeukemiaNet (ELN) 2010 classification. The impact of allo-HSCT was analyzed through three models: (1) time-dependent Cox; (2) multistate for dynamic prediction; and (3) super landmark. The study enrolled 369 (73%) IR and 138 (27%) UR patients with AML, 203 of whom received an allo-HSCT. Classical multivariate analysis showed that allo-HSCT significantly improved relapse-free survival (RFS; hazard ratio [HR] [95% confidence interval (CI)], 0.47 [0.35-0.62]; P < .001) and overall survival (OS; HR [95% CI], 0.56 [0.42-0.76]; P < .001), independently of the ELN risk group. With the multistate model, the predicted 5-year probability for IR and UR patients to remain in CR1 without allo-HSCT was 8% and 1%, respectively. Dynamic predictions confirmed that patients without allo-HSCT continue to relapse over time. Finally, the super landmark model showed that allo-HSCT significantly improved RFS (HR [95% CI], 0.47 [0.36-0.62]; P < .001) and OS (HR [95% CI], 0.54 [0.40-0.72]; P < .001). allo-HSCT in CR1 is reported here as significantly improving the outcome of fit older patients with AML. Long-term RFS without allo-HSCT is very low (< 10%), supporting allo-HSCT as being the best curative option for these patients