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In the absence of an HLA-matched donor, the best treatment for acquired aplastic anemia patients refractory to immunosuppression is unclear. We collected and analyzed data from all acquired aplastic anemia patients who underwent a haploidentical transplantation with posttransplant cyclophosphamide in Europe from 2011 to 2017 (n = 33). The cumulative incidence of neutrophil engraftment was 67% (CI95%: 51–83%) at D +28 and was unaffected by age group, stem cell source, ATG use, or Baltimore conditioning regimen. The cumulative incidence of grades II–III acute GvHD was 23% at D +100, and limited chronic GvHD was 10% (0–20) at 2 years, without cases of grade IV acute or extensive chronic GvHD. Two-year overall survival was 78% (64–93), and 2-year graft-versus-host disease-free survival was 63% (46–81). In univariate analysis, the 2-year OS was higher among patients who received the Baltimore conditioning regimen (93% (81–100) versus 64% (41–87), p = 0.03), whereas age group, stem cell source, and ATG use had no effect. Our results using unmanipulated haploidentical transplantation and posttransplant cyclophosphamide for treating refractory AA patients are encouraging, but warrant confirmation in a prospective study with a larger number of patients and longer follow-up.

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group ( P  = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group ( P  = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679.

From a liquid biopsy, cell-free DNA (cfDNA) can provide information regarding basal tumoral genetic patterns and changes upon treatment. In a prospective cohort of 30 diffuse large B-cell lymphomas (DLBCL), we determined the clinical relevance of cfDNA using targeted next-generation sequencing and its correlation with PET scan imaging at the time of diagnosis and during treatment. Using a dedicated DLBCL panel, mutations were identified at baseline for 19 cfDNAs and profiles were consistent with expected DLBCL patterns. Tumor burden-related clinical and PET scan features (LDH, IPI, and metabolic tumor volume) were significantly correlated with the quantity of tumoral cfDNA. Among the four patients presenting additional mutations in their cfDNAs, three had high metabolic tumor volumes, suggesting that cfDNA more accurately reflects tumor heterogeneity than tissues biopsy itself. Mid-treatment, four patients still had basal mutations in their cfDNAs, including three in partial response according to their Deauville scores. Our study highlights the major interests in liquid biopsy, in particular in the context of bulky tumors where cfDNA allows capturing the entire tumoral mutation profile. Therefore, cfDNA analysis in DLBCL represents a complementary approach to PET scan imaging.

This prospective study aimed to investigate the prognostic effect of sarcopenia, geriatric, and nutritional status in older patients with diffuse large B-cell lymphoma (DLBCL). Ninety-five patients with DLBCL older than 70 years who were treated with immunochemotherapy were included. The lumbar L3 skeletal muscle index (L3-SMI) was measured by computed tomography at baseline, and sarcopenia was defined as low L3-SMI. Geriatric assessment included G8 score, CIRS-G scale, Timed Up and Go test, and instrumental activity of daily living. Nutritional status was assessed using the Mini Nutritional Assessment and the body mass index, and several scores used in the literature incorporating nutritional and inflammatory biomarkers, namely the Nutritional and inflammatory status (NIS), Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Glasgow Prognostic Score.Fifty-three patients were considered sarcopenic. Sarcopenic patients displayed higher levels of inflammation markers and lower levels of prealbumin than non-sarcopenic patients. Sarcopenia was associated with NIS, but was not associated with severe adverse events and treatment disruptions. They were, however, more frequent among patients with elevated NIS. Sarcopenia did not appear in this study as a prognostic factor for progression-free survival (PFS) or overall survival (OS). However, NIS emerged as predictive of the outcome with a 2-year PFS rate of 88% in the NIS ≤ 1 group and 49% in the NIS > 1 group and a significant effect in a multivariate analysis for both PFS (p = 0.049) and OS (HR = 9.61, CI 95% = [1.03–89.66], p = 0.04). Sarcopenia was not associated with adverse outcomes, but was related to NIS, which appeared to be an independent prognostic factor.

Background Alveolar soft part sarcoma is a rare tumour of soft tissues, mostly localized in muscles or deep soft tissues of the extremities. In rare occasions, this tumour develops in deep tissues of the abdomen or pelvis. Case presentation In this case report, we described the case of a 46 year old man who developed a primary splenic alveolar soft part sarcoma. The tumour displayed typical morphological alveolar aspect, as well as immunohistochemical profile notably TFE3 nuclear staining. Detection of ASPSCR1 Exon 7::TFE3 Exon 6 fusion transcript in molecular biology and TFE3 rearrangement in FISH confirmed the diagnosis. Conclusion We described the first case of primary splenic alveolar soft part sarcoma, which questions once again the cell of origin of this rare tumour.

The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO ( N   =  61) or MRD ( N   =  90) between January 2011 and January 2016. GRFS was defined as the probability of being alive without evidence of relapse, grade 3–4 acute GVHD or chronic GVHD. In multivariable analysis, MRD donors were independently associated with lower GRFS compared to HAPLO donors (HR  =  2.95, P    < 0.001). Disease status at transplant other than CR was also associated with lower GRFS in multivariable analysis (HR  =  1.74, P   =  0.01). In addition, the administration of ATG was independently linked to higher GRFS (HR  =  0.52, P   =  0.009). In summary, we observed significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT-Cy platform compared to MRD.

Chronic graft versus host disease is a major cause of morbidity after allogeneic haematopoietic cell transplantation. Belumosudil has recently been approved for the treatment of cGVHD refractory after two lines of treatment. However, few data are available to evaluate its efficacy and safety in real life. 68 patients with cGVHD received belumosudil through a compassionate access program in France. The median follow-up was 337 days from belumosudil initiation. Eighty-two percent of patients had severe cGVHD with a median of three organs involved. Patients had received a median of three prior treatment lines. Median treatment duration was 251 days. The best overall response rate (ORR) was 57.3%, including 14.7% complete remission (CR) and 42.6% partial response (PR). The ORR at three and six months was 47% and 45.6%, respectively. Liver and mouth involvement showed the highest response rates (72.7% and 70.4%), while lung involvement had the lowest (17.2%). Median failure-free survival (FFS) was not reached, with 6- and 12-month FFS rates of 89.1% and 80.4%, respectively. Nine patients died, mainly from GVHD ( n  = 5). Ten adverse events were reported, leading to treatment discontinuation in three cases. These results support the efficacy and safety of belumosudil in refractory cGVHD.

Background: Acquired aplastic anemia (AA) is a rare immunological disease resulting in bone marrow failure. Patients can be treated either by immunosuppressive therapy (IST) or by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT is the recommended treatment in patients younger than 40 years old with an available matched-related donor. IST is the recommended option for other patients: from the randomized trial published by Scheinberg in 2011, ATGAM® (horse anti-human T lymphocyte immunoglobulin) in addition to cyclosporine was the reference first-line IST for moderate to severe AA.Aims: This retrospective, multicentric study was conducted to report safety and efficacy data from ATGAM use in patients with AA utilizing surveillance data.Methods: This Temporary Use Authorization (ATU) program was initiated to collect surveillance data from the ATGAM Named Patients Program for French authorities before ATGAM was registered. This is the final report from this program. Safety and efficacy data was collected from the program and reported every 6 months. ATGAM was dosed at 40 mg/kg for 4 days in all patients that received treatment. Severity of AA was classified according to Camitta and EBMT scores. Response criteria followed the British Committee for Standards in Haematology Guidelines. For severe AA, no response: still severe; partial response: transfusion independence and the patient no longer met criteria for severe disease; complete response: hemoglobin was normal, neutrophil count >1.5x109/L, and platelet count >150x109/L. For moderate AA: no response: worse or did not meet criteria for response that included transfusion independence (if previously dependent) or doubling or normalization of at least 1 cell line or an increase of baseline hemoglobin, or an increase of baseline neutrophils or increase of baseline; complete response: the same criteria as for severe AA.Results: 634 patients (including 148 children) with moderate to very severe AA received ATGAM (n=537 first line; n=68 refractory/relapse; n=29 not classified) in addition to cyclosporine from January 2012 to August 2022. Overall hematologic response (Complete + Partial) at 6 months was 62.3% in the combined population. By severity, response rates were 84.4%, 50.8%, and 36.4% among patients with moderate, severe, and very severe AA, respectively, receiving first-line therapy (n=537; Table). By age, response rates were respectively 54.3%, 65.2%, and 64.4% in children (≤17 years), adults (≥18-<65 years), and elderly (≥65 years) patients. The overall survival rate (95% confidence interval) at 3 years was 96.9% (91.9-98.8%) in children, 83.4% (77.1-88.1%) in adults, and 79.7% (65.9-88.3%) in elderly patients. Treatment was well tolerated for the majority of patients. In total, 1087 adverse events (485 serious adverse events) were reported, with 48 fatal events.Summary/Conclusion: Reported response rate and overall survival in this real-life surveillance study are in line with a 2011 randomized controlled study comparing horse versus rabbit ATG (Scheinberg, et al [2011]) and control group of the most recent study RACE (Peffault de Latour, et al [2022]). The relatively large number of patients in this study compared with other similar studies in patients with AA adds to the robustness of this real-world data study. No new safety risks were identified, and this study showed that use of ATGAM remains favorable in this patient population.

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.

We describe what we believe to be the first two cases of patients who received an allograft in intensive care unit (ICU) despite severe septic shock with multi-organ failure (MOF). One patient had aggressive large B-cell lymphoma. After allograft, the patient initially improved after withdrawing norepinephrine and renal replacement therapy but he subsequently died thirty-two days later because of a new relapse of the disease. The second patient had acute myeloid leukemia type 1 with a need for an allograft after a first complete remission. She was discharged from ICU at D23 after allograft and still alive 7 months later with complete remission. For the two patients, allograft conditioning was performed before admission to our ICU. These two cases highlight one major problem in such situations which is to find the best time to perform the allograft, particularly in ventilated patients with septic shock and MOF. We performed the allograft when we thought that the risk-benefit ratio was in favor of restoring immunity. Allograft should be considered as a rescue therapy in ICU for patients with aplasia, during septic shock with multi-organ failure, however close multidisciplinary discussion is required between intensivists and onco-hematologists.