Cellular therapy in lymphoma.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has had a dramatic impact on the natural history and survival of patients with high-risk B-cell non-Hodgkin lymphoma. Accompanying this success has been the development of new fields of medicine and investigation into toxicity risks and mitigation therapies, mechanisms of resistance and the development of novel and next generation products and strategies in order to address relapse, and issues related to global access and health care economics. This article is a survey of each of these areas as it pertains to the rapidly evolving field of CAR T-cell therapy, written by an International community of lymphoma experts, who also happen to be women.

Extensive immunophenotypic sub-population analysis of StemRegenin1 expanded haematopoietic stem/progenitor cells.

BACKGROUND: Ex vivo haematopoietic stem/progenitor cell (HSPCs) expansion constitutes an important area of research, and has the potential to improve access to umbilical cord blood (UCB) as a source of stem cells for haematopoietic stem cell transplantation (HSCT). The ability to improve stem cell dose and thereby reduce delayed engraftment times, which has plagued the use of UCB as a stem cell source since inception, is a recognised advantage. The extent to which cluster of differentiation (CD)34 sub-populations are affected by expansion with StemRegenin1 (SR1), and whether a particular subtype may account for better engraftment than others, is currently unknown. The purpose of this study was to determine the impact of SR1-induced HSPC expansion on CD34+ immunophenotypic subsets and gene expression profiles. METHODS: UCB-derived CD34+ HSPCs were characterised before (D0) and after expansion (D7) with SR1 using an extensive immunophenotypic panel. In addition, gene expression was assessed and differentially expressed genes were categorised into biological processes. RESULTS: A dose-dependent increase in the number of CD34+ HSPCs was observed with SR1 treatment, and unbiased and extensive HSPC immunophenotyping proved to be a powerful tool in identifying unique sub-populations within the HSPC repertoire. In this regard, we found that SR1 promotes the emergence of HSPC subsets which may aid engraftment post expansion. In addition, we observed that SR1 has a minimal effect on the transcriptome of 7-day expanded CD34+ HSPCs when compared to cells expanded without SR1, with only two genes being downregulated in the former. CONCLUSION: This study revealed that SR1 selects for potentially novel immunophenotypic HSPC subsets post expansion and has a minimal effect on the transcriptome of 7-day expanded HSPCs when compared to vehicle controls. Whether these distinct immunophenotypic sub-populations possess greater engraftment capacity remains to be tested in animal models.

Childhood aplastic anaemia with paroxysmal nocturnal haemoglobinuria clones: A retrospective single-centre study in South Africa.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia. Objective: This study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation. Methods: Patients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14. Results: Twenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p = 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p = 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group. Conclusion: More than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.