We studied COVID-19 associated mucormycosis based on 17 cases reported nationwide and assessed the differences with India. They differed by frequencies of diabetes mellitus (47% in France versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites (12% versus >80% rhino-orbito-cerebral) and prognosis (88% mortality versus <50%).

Since the emergence of the Omicron variant of SARS-CoV-2, though considered less virulent, hospitalization and death rates among immunocompromised patients remain high, especially for poor responders to vaccination. We conducted a retrospective multicentric study to evaluate pre-exposure prophylaxis with AZD7442 (tixagevimab/cilgavimab) for preventing COVID-19 in adult allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Among the 161 patients of our cohort, 22 (14%) contracted COVID-19 after a median follow-up of 105 days, but no severe form was observed. Only one major adverse event was reported: an acute coronary syndrome, resolved without sequelae. Pending randomized controlled trial results, our data support the use of AZD7442 as pre-exposure prophylaxis for COVID-19 during Omicron wave in allo-HSCT patients who failed to develop humoral immunity to vaccination, to prevent severe and potentially lethal forms of SARS-CoV-2 infection.

Liver blood test anomalies are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their cause often remains difficult to identify. Our objective was to evaluate the safety and utility of liver biopsies in patients who underwent allo-HSCT. In a retrospective single-center cohort study, we reviewed all cases of patients who underwent liver biopsy between June 2005 and July 2017. During this period, 54 biopsies were performed in 45 patients, in which 38 patients underwent allo-HSCT for malignant and 7 for nonmalignant hematological disorders. Median time between allo-HSCT and liver biopsy was 213 days. Seven biopsies were percutaneous, and 47 were transjugular. No adverse event related to the biopsy procedure occurred; 94.5% biopsies (51 of 54) led to a histological diagnosis. Cholestatic graft-versus-host disease was histologically demonstrated in 16 biopsies (30%); hepatitis-like graft-versus-host disease in 9 biopsies (17%); nonalcoholic steatohepatitis in 6 biopsies (9%); regenerative nodular hyperplasia in 4 biopsies (5%); and drug-induced liver injury, sinusoidal obstruction syndrome, and viral hepatitis each in 3 biopsies (5%). Association between clinical, laboratory, imaging and pathological features was poor. Only 34% of physicians' prebiopsy hypotheses were confirmed by pathological findings. Patient management was influenced by liver biopsy results in 65% of cases, allowing us to identify a new diagnosis (n = 13), rule out a differential diagnosis (n = 14), or confirm the main hypothesis (n = 6). In conclusion, liver biopsy is a safe and useful technique to investigate liver blood test anomalies following allo-HSCT.

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Introduction: Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) with high-risk genetics and/or measurable residual disease (MRD) are at high-risk of disease recurrence. In the previous GRAALL-2005 study, we identified KMT2A rearrangements (KMT2A-r), IKZF1 intragenic deletion (IKZF1del) and post-induction (TP1, week 6) MRD ≥ 0.01% as independent factors to predict relapse in Ph-negative B-cell precursor (BCP) ALL (Beldjord K, Blood 2014). In the GRAALL-2014 trial, high-risk (HR) patients were thus defined by the presence of at least one of these three factors. Among them, only those with higher MRD levels defined as TP1-MRD ≥ 0.1% and/or week 12 (TP2) MRD ≥ 0.01% were considered at very high risk (VHR) and proposed allogeneic hematopoietic stem cell transplant (alloSCT) in first remission (Dhedin et al., Blood 2015). Since October 2018, all these patients were eligible to be included in the GRAALL-2014-QUEST phase 2 study to receive blinatumomab as part of consolidation and maintenance phases or as a bridge to transplant. Methods: From October 2018 to December 2020, 95 patients with high-risk Ph-negative BCP-ALL without central nervous system involvement at diagnosis and in continuous complete remission after induction and consolidation 1, were prospectively included to start blinatumomab at week 12. One patient was excluded because of T-ALL phenotype (with CD19 aberrant expression). Patients with alloSCT indication and a stem cell source received blinatumomab 28 microg/d administered by continuous intravenous infusion (cIV) until transplant. A minimum of 4 weeks blinatumomab was recommended before proceeding to transplantation. All other patients received 5 cycles of blinatumomab 28 microg/day cIV (for 28 days), during consolidation 2 and 3 and at months 1/3/5 of the maintenance phase respectively. The primary objective was disease-free survival (DFS). Secondary objectives included post-blinatumomab MRD response at TP3 (after consolidation 2 or before alloSCT), overall survival (OS), and safety. Early results are reported here. Results: Median age was 35 years old (range, 18-60). Median white blood cell count (WBC) at diagnosis was 12 G/L (range, 1-449). Oncogenetic analyses allowed classifying ALL as Ph-like (18%), KMT2A-r (17%), DUX4/ERGdel (13%), ZNF384-r (11%), low hypodiploidy/near triploidy (7%), B-other (26%) or unknown (9%). An IKZF1del was found in 37/93 (40%). A TP1-MRD ≥ 0.01% was found in 46/94 patients (49%). Final risk group was HR for 45 patients and VHR for 49 patients. Last pre-blinatumomab MRD was <0.01% in 49/88 (56%) of evaluable patients. A total of 40 patients (42%) received an alloSCT. The median number of blinatumomab cycles received in patients not proceeding to alloSCT was 4 cycles (range, 1-5). Thirty-nine severe adverse events (SAEs) were reported: 1 CRS (grade 2), 8 neurotoxicities (1 grade 2, 3 grade 3, 3 grade 4, 1 grade 5), 19 infections, and 11 others. The only grade 5 SAE occurred after alloSCT (seizures). After blinatumomab, a complete MRD response (with at least 0.01% sensitivity) was achieved in 61/82 (74%) evaluable patients and in evaluable patients with pre-blinatumomab detectable MRD. MRD response to blinatumomab was lower in patients with high pre-blinatumomab MRD level, while not impacted by age, WBC, or oncogenic subgroup. With a median follow-up of 20 months, 18-month DFS and OS was 78.8% (95% CI [66.9-86.8]) and 92.1% (95% CI [83.2-96.4]) respectively (Figure 1). Patients with VHR diseases had a worse DFS (68.8%, 95% CI [51.1-81.2]) as compared to other patients (90.6%, 95% CI [72.1-97.1]); p=0.018). This difference of DFS was abrogated by censoring patients at transplant (VHR 88.1%, 95% CI [65.5-96.3] versus others 90.6%, 95% CI [72.1-97.1%], p=0.10). Other factors significantly associated with better DFS were DUX4/ERGdel subgroup, low pre-blinatumomab MRD, and complete MRD response after blinatumomab. Conclusion. In patients wih high-risk BCP-ALL, blinatumomab added to consolidation is safe and gives promising results. A comparison to similar patients treated in the same GRAALL-2014 study before October 2018 is planned with a longer follow-up. Figure 1 Figure 1. Disclosures Boissel: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; SANOFI: Honoraria; Servier: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; CELGENE: Honoraria; JAZZ Pharma: Honoraria, Research Funding; PFIZER: Consultancy, Honoraria. Huguet: Novartis: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Celgene: Other: Advisor; BMS: Other: Advisor; Amgen: Other: Advisor; Pfizer: Other: Advisor. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. Chalandon: Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Amgen: Other: Advisory Board; Incyte: Speakers Bureau; Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Gilead, Amgen, Jazz, Astra Zenec: Other: Travel EXpenses, Accomodation. Delabesse: Astellas: Consultancy; Novartis: Consultancy. Dombret: Abbvie: Honoraria; Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; NOVARTIS: Research Funding; pfizer: Honoraria, Research Funding; servier: Research Funding; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. OffLabel Disclosure: Blinatumomab in frontline high-risk acute lymphoblastic leukemia

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