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In their paper, the authors present their experience with the use of chimeric antigen receptor T cells targeting CD7 as a bridge to allogeneic haematopoietic cell transplantation in patients with relapsed/refractory T‐cell acute lymphoblastic leukaemia/lymphoblastic lymphoma. Commentary on: Cao et al. A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T‐cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T‐cell therapy. Br J Haematol 2024;204:2351‐2364. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is incurable with conventional therapies. Limited retrospective data have shown durable remissions after haematopoietic cell transplantation (HCT) [allogeneic (allo) or autologous (auto)]. We conducted a multicentre retrospective study in BPDCN patients treated with allo-HCT and auto-HCT at 8 centres in the United States and Canada. Primary endpoint was overall survival (OS). The population consisted of 45 consecutive patients who received an allo-HCT (n = 37) or an auto-HCT (n = 8) regardless of age, pre-transplant therapies, or remission status at transplantation. Allo-HCT recipients were younger (50 (14–74) vs. 67 (45–72) years, P = 0·01) and had 1-year and 3-year OS of 68% [95% confidence interval (CI) = 49–81%] and 58% (95% CI = 38–75%), respectively. Allo-HCT in first complete remission (CR1) yielded superior 3-year OS (versus not in CR1) [74% (95% CI = 48–89%) vs. 0, P < 0·0001]. Allo-HCT outcomes were not impacted by regimen intensity [3-year OS for myeloablative conditioning = 61% (95% CI = 28–83%) vs. reduced-intensity conditioning = 55% (95% CI = 28–76%)]. One-year OS for auto-HCT recipients was 11% (95% CI = 8–50%). These results demonstrate efficacy of allo-HCT in BPDCN, especially in patients in CR1. Pertaining to auto-HCT, our results suggest lack of efficacy against BPDCN, but this observation is limited by the small sample size. Larger prospective studies are needed to better define the role of HCT in BPDCN. [ABSTRACT FROM AUTHOR]

Infections contribute greatly to the morbidity and mortality of allogeneic haematopoietic cell transplantation (HCT), an important part of this is due to viral infections, some of which are respiratory viruses (Dignan I et al. i , [2]; Hill I et al i , [4]). A common clinical problem is, for example, the patient with chronic GvHD acquiring a respiratory viral infection, this triggering GvHD of the lung, e.g. obstructive bronchiolitis syndrome, which may ultimately lead to death of the patient. We do not know however, how patients were selected for immediate HCT as compared to deferred HCT, hence, other decision-guiding patient-related characteristics might have significantly contributed to the difference observed. [Extracted from the article]

We aimed to use a novel standardized whole‐blood stimulation system to evaluate differences in the functional immune reconstitution in patients early after allogeneic haematopoietic cell transplantation (HCT). Between April and September 2018, 30 patients undergoing HCT had whole blood samples collected around day −21 (day 0 being the day of haematopoietic cell infusion) and day +28. Whole blood was transferred to TruCulture assays comprising prefilled incubation tubes with cell culture medium and a standardized stimulus. We used a panel of four stimuli (lipopolysaccharide, resiquimod, heat‐killed Candida albicans and polyinosinic:polycytidylic acid) and a blank, designed to evaluate the function of critical extra‐ and intracellular immunological signalling pathways. For each stimulus, the cytokine response was assessed by the concentration of interferon‐γ, interleukin (IL)‐12p40, IL‐10, IL‐1β, IL‐6, IL‐8, IL‐10, IL‐12p40, IL‐17A and tumour necrosis factor‐α using a multiplex Luminex assay. Pre‐HCT cytokine responses were globally decreased across several different stimuli. Despite patients receiving immunosuppressive prophylaxis at the time, post‐HCT cytokine responses were higher and less intercorrelated than pre‐HCT responses, also after adjusting for differences in the leukocyte differential counts. For the resiquimod and heat‐killed Candida albicans stimuli, we identified a cluster of patients in whom post‐HCT responses were lower than average across several cytokines, indicating a possible functional immune deficiency. Our findings suggest that the standardized whole blood stimulation system can be used to reveal heterogeneity in the in vitro cytokine responses to various stimuli after HCT. Larger studies are needed to address if the functional immune reconstitution after HCT can predict the risk of infections. [ABSTRACT FROM AUTHOR]

Summary: In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3–CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16–75) years. AML was de novo in 58%, therapy‐related (t‐AML) in 37% and secondary after myelodysplastic syndrome (s‐AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3–CREBBP, whole‐genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9‐1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow‐up was 5·48 years; five‐year survival rate was 17%. Patients with s‐/t‐AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo‐HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo‐HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo‐HCT in CR1 was effective in de novo AML but not in patients with s‐AML/t‐AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo‐HCT performed in CR1. [ABSTRACT FROM AUTHOR]

Summary: T memory stem cells (TSCMs) are a subset of primitive T cells capable of both self‐renewal and differentiation into all subsets of memory and effector T cells. Therefore, TSCMs may play a role in immune reconstitution and graft‐versus‐host disease (GVHD) in patients receiving allogeneic haematopoietic cell transplantation (HCT). We conducted a cross‐sectional study to evaluate the proportions, absolute counts, phenotypes and functions of TSCMs in 152 adult patients without disease recurrence at least 12 months after undergoing HCT. CD4+TSCMs were negatively correlated with number of months after transplantation in HCT patients that received cord blood transplantation, but not in patients that received bone marrow transplantation or peripheral blood stem cell transplantation. The proportions and absolute counts of CD4+TSCMs and expression levels of inducible co‐stimulator (ICOS) in CD8+TSCMs were significantly higher in patients with mild and moderate/severe cGVHD compared to patients without cGVHD. These data suggested that, more than 12 months after allogeneic HCT, the kinetics of CD4+TSCMs were dependent on the type of donor source, and further that CD4+TSCMs and ICOS levels in CD8+TSCMs were associated with cGVHD. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic cell transplantation continues to be an important curative therapy for acute lymphoblastic leukaemia (ALL). Traditionally accepted indications for allografting adult ALL patients need reevaluation in light of outcomes with paediatric-like intensive regimens. Minimal residual disease status and oncogenetics can be used for restratification of standard risk patients. A greater body of data on haematopoietic cell transplantation (HCT) outcomes from haploidentical and cord blood donor sources has been generated in recent years. In this review, we describe the indications for allografting adult ALL patients in first complete remission (CR1). Role of minimal residual disease (MRD) in optimising HCT for ALL is delineated. We also discuss how alternative donors, haploidentical and cord blood and reduced intensity conditioning make allografts more accessible to patients with high-risk ALL. Recent data on use of monoclonal antibodies and chimeric antigen receptor (CAR)-modified T cells in adult ALL patients are also reviewed. [ABSTRACT FROM AUTHOR]

Umbilical cord blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia ( AML), other haematological malignancies and metabolic diseases who can be cured by allogeneic haematopoietic cell transplantation, but who do not have a human leucocyte antigen compatible related or unrelated donor. Although the first cord blood transplants were done in children, there are currently more cord blood transplants performed in adults. In this review, we explore the history of umbilical cord blood transplantation, paediatric and adult outcome results, and novel trends to improve engraftment and reduce infection. Umbilical cord blood transplantation cures approximately 30-40% of adults and 60-70% of children with AML. Controversial issues, including the use of double versus single cord blood units for transplantation, optimal cord blood unit selection, infection prophylaxis, conditioning regimens and graft versus host disease prophylaxis, will be reviewed. Finally, comparison to other graft sources, cost, access to care, and the ideal graft source are discussed. [ABSTRACT FROM AUTHOR]