Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial.

Background: Failure of gastrointestinal acute graft-versus-host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD. Methods: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980). Findings: Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (ORR) was 38% in the prospective population, including 5 complete responses (CR), 2 very good partial responses (VGPR) and 2 partial responses (PR). In the EAP, the GI-ORR was 58% (17 CR, 9 VGPR and 4 PR). The 12-month overall survival (OS) was 25% in the prospective study and 38% in the EAP. Regarding safety, five infectious complications, including 3 sepsis, could not be excluded from being related to the study procedure in HERACLES. Shotgun sequencing analyses of the identified strains suggest that none were found in MaaT013. In the EAP, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 bacteraemia/sepsis. In HERACLES, we observed in stools from responding patients at D28 a higher microbiota richness and increased levels of beneficial bacteria, in particular butyrate producers, along with increased levels of short-chain fatty acid and bile acids. In contrast, stools from non-responding (NR) patients displayed increased levels of pathogenic pro-inflammatory bacteria along with increased systemic inflammatory parameters. Interpretation: Overall, MaaT013 was safe in this population of highly immunocompromised patients and was associated with responses in some patients with GI-aGvHD and deserves further investigation. Funding: MaaT Pharma.

Allogeneic hematopoietic stem cell transplantation for adults with therapy-related acute myeloid leukaemia: a retrospective multicentre study on behalf of the SFGM-TC.

We report the results from a multicentre retrospective study of 220 adult patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) for therapy-related acute myeloid leukaemia (t-AML). Median age at t-AML diagnosis was 56 years, with a prior history of haematological (45%) or breast (34%). Median time from cytotoxic exposure to t-AML diagnosis was 54.7 months. At transplant, around 20% of patients had measurable residual disease and 3% of patients were not in complete remission. The median follow-up was 21.4 months (Q1-Q3, 5.9-52.8). At 12 months, overall survival (OS), event-free survival (EFS), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS) were 60.7% (95% CI 54.6-67.5), 52.8% (95% CI 46.5-68.4), and 44.1% (95% CI 37.6-51.8), respectively. At 5 years, OS, EFS, and GRFS were 44.1% (95% CI 37.4-52.1), 40.4% (95% CI 33.9-48.1), and 35.3% (95% CI 28.8-43.3), respectively. At last follow-up, 44% of patients were in complete remission (n = 96) and transplant-related mortality accounted for 21% of all deaths (n = 119). Multivariable analysis revealed that uncontrolled t-AML at transplant was associated with lower EFS (HR 1.94, 95% CI 1.0-3.7, p = 0.041). In conclusion, alloHSCT for t-AML shows encouraging results and offers additional opportunity with the emergence of novel pre-graft therapies.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome in the intensive care unit: a case report.

BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome is a newly discovered inflammatory disease affecting male subjects, for which few data exist in the literature. Here, we describe the case of a patient with known Sweet's syndrome admitted to the intensive care unit and for whom a vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome was diagnosed, allowing for appropriate treatment and the patient's discharge and recovery. CASE PRESENTATION: A 70-year-old male White patient was hospitalized in the intensive care unit following an intrahospital cardiac arrest. History started a year before with repeated deep vein thrombosis and episodes of skin eruption compatible with Sweet's syndrome. After a course of oral steroids, fever and inflammatory syndrome relapsed with onset of polychondritis, episcleritis along with neurological symptoms and pulmonary infiltrates. Intrahospital hypoxic cardiac arrest happened during patient's new investigations, and he was admitted in a critical state. During the intensive care unit stay, he presented with livedoid skin lesions on both feet. Vasculitis was not proven; however, cryoglobulinemia screening came back positive. Onset of pancytopenia was explored with a myelogram aspirate. It showed signs of dysmyelopoiesis and vacuoles in erythroid and myeloid precursors. Of note, new deep vein thrombosis developed, despite being treated with heparin leading to the diagnosis of heparin-induced thrombocytopenia. The course of symptoms were overlapping multiple entities, and so a multidisciplinary team discussion was implemented. Screening for UBA1-mutation in the blood came back positive, confirming the vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome. Corticosteroids and anti-IL1 infusion were started with satisfactory results supporting patient's discharge from intensive care unit to the internal medicine ward. CONCLUSIONS: Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome should be suspected in male patients presenting with inflammatory symptoms, such as fever, skin eruption, chondritis, venous thromboembolism, and vacuoles in bone marrow precursors. Patients with undiagnosed vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome may present with organ failure requiring hospitalization in intensive care unit, where screening for UBA1 mutation should be performed when medical history is evocative. Multidisciplinary team involvement is highly recommended for patient management, notably to start appropriate immunosuppressive treatments.

An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.

Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups.

Outcome of patients with newly diagnosed AML admitted to the ICU, including preemptive admission - a multi-center study.

Acute myeloid leukemia (AML) can lead to life-threatening complications that may require intensive care unit (ICU) management. It has been advocated that early preemptive (ePE) ICU admission, before the onset of organ failure, could benefit some high-risk patients such as those with hyperleukocytosis. The aim of this study was to retrospectively analyze the outcome of newly diagnosed AML patients who required ICU admission in five academic centers with a special focus on patients with an ePE admission strategy, i.e., those transferred to the ICU without any organ failure (modified SOFA score ≤ 2 [omitting thrombocytopenia] and no life-sustaining intervention in the first 24 h following ICU admission) before the start of induction therapy. Between January 2017 and December 2019, 428 patients were included among which 101 were admitted to the ICU. Among patients requiring life-sustaining interventions (n = 83), 18 (22%) died while in the ICU but ICU survivors had the same survival as those not admitted to the ICU. Patients with an ePE admission (n = 18) had more comorbidities and high-risk disease features such as hyperleukocytosis but required no life-sustaining interventions while in the ICU. In a subgroup analysis of patients with hyperleukocytosis ≥ 50 G/l at diagnosis (n = 85), patients not admitted to the ICU and those admitted with an ePE strategy had similar outcomes. This study provides encouraging results about ICU outcome in AML patients during induction therapy but the potential benefit of an ePE strategy must be confirmed prospectively.

Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study.

BACKGROUND: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs. METHODS: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting. FINDINGS: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group. INTERPRETATION: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission. FUNDING: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.

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

Allogeneic 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.

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

Late 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.

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

The 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.

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

BACKGROUND: 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 analyse 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 Cmin <2 µg/ml were associated with a higher MR during the previous visit. MR values >1.15 and <0.48 were determined to be the best predictors for having a VRC Cmin 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.

Combining blinatumomab and donor lymphocyte infusion in B-ALL patients relapsing after allogeneic hematopoietic cell transplantation: a study of the SFGM-TC.

Relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic stem cell transplantation (allo-HCT) still represents a major concern with poor outcomes. The aim of this study is to compare the efficacy and safety of blinatumomab and donor lymphocyte infusion (DLI) versus blinatumomab alone in this setting. This is a multicenter retrospective study from centers of SFGM-TC. All transplanted patients who received blinatumomab salvage therapy were included. Patients who received DLI from 1 month before to 100 days after the starting of blinatumomab were included in the blina-DLI group. Seventy-two patients were included. Medium follow-up was 38 months. Fifty received blinatumomab alone and 22 the association blinatumomab-DLI. Two-year overall survival (OS) was 31% in the blinatumomab group and 43% in the blinatumomab-DLI group (p = 0.31). Studying DLI as a time dependent variable, PFS did not significantly differ between the 2 groups (HR:0.7, 95% CI: 0.4-1.5). In multivariate analysis, DLI was not a prognostic factor for OS, progression-free survival and progression/relapse incidence. Adverse events and graft-versus-disease rates were comparable in the 2 groups. In conclusion, adding DLI between 1 month before and 100 days after start of blinatumomab is safe and does not seem to improve outcomes in B-ALL patients who relapsed after allo-HCT.

Comparison of scoring systems evaluating suitability for intensive chemotherapy in adults with acute myeloid leukemia-a Grand Ouest Against Leukemia (GOAL) study.

Several scoring systems have been developed to assess suitability of individual patients for intensive acute myeloid leukemia (AML) therapy. We sought to compare the performance of these scores in a cohort of 428 consecutive adults with AML who received conventional induction chemotherapy in five academic centers in France. All scoring systems identified a subset of patients with increased 28 and 56-day mortality although the prediction accuracy was overall limited with C-statistics of ranging from 0.61 to 0.71 Overall survival (OS) prediction was more limited and restricted to scoring systems that include AML-related parameters. The outcome of 104 patients (24%) considered unsuitable for intensive chemotherapy based on criteria used in recent randomized trials was similar to that of the other 324 patients (28-day mortality, odds ratio [OR] = 1.88, P = 0.2; 56-day mortality, OR = 1.71, P = 0.21; event-free survival, hazard ratio [HR] = 1.08, P = 0.6; OS, HR = 1.25, P = 0.14) with low discrimination (C-statistic: 0.57, 0.56, 0.50, and 0.52 for 28-day, 56-day mortality, EFS, and OS, respectively). Together, our findings indicate that the accuracy of currently available approaches to identify patients at increased risk of early mortality and shortened survival after intensive AML therapy is relatively limited. Caution regarding the use of available scoring systems should be warranted in clinical decision-making.

Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia.

BACKGROUND: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).

Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT.

The optimal CD34 + cell dose in the setting of RIC allo-HCT for myelofibrosis (MF) remains unknown. We retrospectively analyzed 657 patients with primary or secondary MF transplanted with use of peripheral blood (PB) stem cells after fludarabine/melphalan or fludarabine/busulfan RIC regimen. Median patient age was 58 (range, 22-76) years. Donors were HLA-identical sibling (MSD) or unrelated (UD). Median follow-up was 46 (2-194) months. Patients transplanted with higher doses of CD34 + cells (>7.0 × 106/kg), had an increased chance of achievement of both neutrophil (hazard ratio (HR), 1.46; P < 0.001) and platelet engraftment (HR, 1.43; P < 0.001). In a model with interaction, for patients transplanted from a MSD, higher CD34 + dose was associated with improved overall survival (HR, 0.63; P = 0.04) and relapse-free survival (HR, 0.61; P = 0.02), lower risk of non-relapse mortality (HR, 0.57; P = 0.04) and higher rate of platelet engraftment. The combined effect of higher cell dose and UD was apparent only for higher neutrophil and platelet recovery rate. We did not document any detrimental effect of high CD34 + dose on transplant outcomes. More bulky splenomegaly was an adverse factor for survival, engraftment and NRM. Our analysis suggests a potential benefit for MF patients undergoing RIC PB-allo-HCT receiving more than 7.0 × 106/kg CD34 + cells.

[Medium-term follow-up of patients treated with chimeric antigen receptor T cells (CAR T cells): Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / 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.

Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT).

The role of spleen size and splenectomy for the prediction of post-allogeneic hematopoietic stem cell transplant (allo-HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000-2017 after either fludarabine-busulfan or fludarabine-melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000-2009 vs 14.1% in 2010-2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44-0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01-2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67-1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28-0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14-0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87-2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.

[Indications and management of hematologic microtransplantation: Recommendations of the French Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC)]. / Atelier d'harmonisations 2019 : indications et organisation d'une microtransplantation de cellules souches hématopoïétiques.

Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete remission rates and longer disease free survival and overall survival have been reported. Safety seems acceptable. The most frequent adverse event is non-severe cytokine release syndrome. Risk of GVHD remains very low. Here, we summarize the published data and detail the practical aspects of the procedure. Current data are not strong enough to provide recommendations on indications. Nevertheless, it seems reasonable to propose MT to patients with AML or HR-MDS, regardless of age, presenting an indication for allogeneic stem cell transplantation but ineligible for it. MT is still under investigation and rather be proposed within clinical trials.

[Multidrug-resistant bacteria detection in patients undergoing allogeneic hematopoietic cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / 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).

The 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.