Key Points When possible, ATG should be avoided in adults undergoing UCBT following Cy/Flu/TBI200 regimen.

This study aimed to assess the impact of antithymocyte globulin (ATG) on patient outcome in a retrospective series of 91 patients (median age: 12 years) who underwent unrelated single-unit cord blood transplantation (allo-CBT) following a myeloablative conditioning regimen. Cord blood units were HLA-matched (6/6, n = 18; 21%), one-Ag mismatched (n = 30, 35%) or two-Ag mismatched (n = 38; 44%). In this series, the OS, nonrelapse mortality (NRM) and cumulative incidence of relapse were 47 ± 6%, 23 ± 4% and 48 ± 5%, respectively. Among 46 patients who received ATG as part of the conditioning regimen, the incidence of acute and chronic GVHD was lower than that in the group of 45 patients who did not receive ATG (20% vs 43%; P = 0.03). However, multivariate statistical analysis revealed that the ATG use was associated with decreased OS and EFS rates and a high incidence of NRM (hazard ratio (HR) = 1.99, 95% confidence interval (CI): 1.11-3.59, P = 0.02), (HR = 1.83, 95% CI: 1.08-3.10, P = 0.02) and (HR = 2.54, 95% CI: 1.03-6.26, P = 0.04), respectively. Therefore, our results do not support the use of ATG as part of a myeloablativeconditioning regimen before single-unit allo-CBT in younger patients with hematological malignancies.

Physicians had a tendency to order excessive laboratory tests, an action which can be related to lack of knowledge and to divergence among guidelines. A more intensive educational effort regarding cancer prevention, directed towards teaching physicians in training, seems to be warranted.

Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P < 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 17% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT.

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SummaryThe status of umbilical cord blood transplantation (UCBT) in adults with Philadelphia-positive acute lymphoblastic leukaemia (Ph+ALL) and the impact of minimal residual disease (MRD) before transplant are not well established. We analysed 98 patients receiving UCBT for Ph+ALL in first (CR1) or second (CR2) complete remission (CR1, n = 79; CR2, n = 19) with MRD available before UCBT (92% analysed by reverse transcription polymerase chain reaction). Median age was 38 years and median followup was 36 months; 63% of patients received myeloablative conditioning and 42% received double-unit UCBT. Eighty-three patients were treated with at least one tyrosine kinase inhibitor before UCBT. MRD was negative (À) in 39 and positive (+) in 59 patients. Three-year cumulative incidence of relapse was 34%; 45% in MRD+ and 16% in MRDÀ patients (P = 0Á013). Three-year cumulative incidence of non-relapse mortality was 31%; it was increased in patients older than 35 years (P = 0Á02). Leukaemia-free survival (LFS) at 3 years was 36%; 27% in MRD+ and 49% in MRDÀ patients (P = 0Á05), and 41% for CR1 and 14% for CR2 (P = 0Á008). Multivariate analysis identified only CR1 as being associated with improved LFS. In conclusion, MRD+ before UCBT is associated with increased relapse. Strategies to decrease relapse in UCBT recipients with Ph+ALL and MRD+ are needed.

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