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Optimal red cell transfusion support in myelodysplastic syndromes (MDS) has not been tested and established. The aim of this study was to demonstrate feasibility of recruitment and follow-up in an outpatient setting with an exploratory assessment of quality of life (QoL) outcomes (EORTC QLQ-C30 and EQ-5D-5L). We randomised MDS patients to standardised transfusion algorithms comparing current restrictive transfusion thresholds (80 g/l, to maintain haemoglobin 85-100 g/l) with liberal thresholds (105 g/l, maintaining 110-125 g/l). The primary outcomes were measures of compliance to transfusion thresholds. Altogether 38 patients were randomised (n = 20 restrictive; n = 18 liberal) from 12 participating sites in UK, Australia and New Zealand. The compliance proportion for the intention-to-treat population was 86% (95% confidence interval 75-94%) and 99% (95-100%) for restrictive and liberal arms respectively. Mean pre-transfusion haemoglobin concentrations for restrictive and liberal arms were 80 g/l (SD6) and 97 g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm. Our findings support the feasibility and need for a definitive trial to evaluate the effect of different red cell transfusion thresholds on patient-centred outcomes., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines that are secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA). We investigated the intracytoplasmic expression of type-1 [interferon gamma (IFN-gamma), interleukin (IL)-2] and type-2 (IL-4, IL-10) cytokines in CD4+ and CD8+ T cells before and after in vitro activation in 16 patients with AAA and 17 normal controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ T cells that produced IFN-gamma and IL-2 whereas the IL-4 and IL-10 producing T cells did not differ from that of controls, resulting in a shift of IFN-gamma/IL-4 ratio towards a type-1 response. Patients in remission had also increased proportion of IFN-gamma-producing unstimulated CD4+ and CD8+ cells, with a parallel rise of IL-4- and IL-10-producing cells and normal IFN-gamma/IL-4 ratio. These data indicate that, in newly diagnosed and refractory patients with AAA, CD4+ cells are polarized towards a type-1 response that in turn leads to activation of cytotoxic CD8+ cells and finally to haemopoietic stem cell destruction. The type-1 response persists in patients in remission although this effect is compensated by the increase of IL-4 and IL-10 production.

A case of Evans' syndrome with IgM deficiency and lymphopenia was studied before and after splenectomy. The lymphopenia was as a result of profound reduction of CD4 and CD8 cells. Study of cytokine secretion before splenectomy revealed a spontaneous Th1- and Th2-type cytokine production, and complete suppression of transforming growth factor (TGF)-beta. After splenectomy, the patient achieved clinical remission, the natural killer (NK) cell number increased and the pattern of cytokine production showed normalization of interleukin (IL)-2, IL-4, IL-10, TGF-beta and abolition of interferon (IFN)-gamma production. We conclude that splenectomy had a beneficial effect owing to an increase in NK cells and an associated increase in TGF-beta production.

Aplastic anaemia (AA) is a disease of bone marrow failure. Evidence has been produced for both a stem cell and a stromal cell defect in this disease. The contribution of deficient or defective cell adhesion molecules (CAMs) has not been determined. CAMs have been shown to be important in stem cell-stromal cell interactions and maintenance of haemopoiesis. In this study the expression of CAMs (LFA-1, LFA-3, ICAM-1. VLA-4, CD44, sLex and L-selectin) on CD34+ progenitor cells from 10 normal donors and eight patients with AA was investigated using double immunofluorescence. There was no significant difference in the percentage of CD34+ cells that were CAM+ between normal and AA bone marrow, suggesting that abnormal CAM expression on AA progenitor cells is not responsible for nor contributes to the pathogenesis of the disease. However, these findings do not exclude abnormal CAM function on progenitor cells, or abnormal expression or function of CAM ligands or counter-receptors on AA stromal cells.

We investigated sialylated Lewis x (sLe(x)) antigen expression on CD34 positive (CD34+) haemopoietic progenitors in the bone marrow of eight healthy volunteers using monoclonal antibodies. We found that in all the samples examined, CD34+ bone marrow progenitors strongly expressed the sLe(x) antigen. This contradicts previous publications which reported sLe(x) expression on malignant blast cells but not on normal CD34+ progenitor cells.