TPH

Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT...

Epstein-Barr virus-related disease (EBVD) is a serious clinical complication in patients who have undergone haploidentical hematopoietic stem cell transplantation (haploHSCT). Some recipients develop EBVD relatively late after haploHSCT, and most of these patients suffer a poor outcome. This retrospective cohort study characterized the early adaptive immune recovery of patients with acute leukemia presenting with EBVD more than 100 d after haploHSCT. Patients with acute leukemia who received haploHSCT and developed EBVD 100 d later (n = 8) were compared with a matched control group without EBVD (n = 24) with regard to peripheral WBC, lymphocytes, and neutrophils (at 30, 60, and 90 d) and recoveries of B and T lymphocytes (at 30 and 90 d, via immunophenotyping/flow cytometry)...

A record number of 39,209 HSCT in 34,809 patients (14,950 allogeneic (43%) and 19,859 autologous (57%)) were reported by 658 centers in 48 countries to the 2013 survey. Trends include: more growth in allogeneic than in autologous HSCT, increasing use of sibling and unrelated donors and a pronounced increase in haploidentical family donors when compared with cord blood donors for those patients without a matched related or unrelated donor. Main indications were leukemias, 11,190 (32%; 96% allogeneic); lymphoid neoplasias, 19,958 (57%; 11% allogeneic); solid tumors, 1543 (4%; 4% allogeneic); and nonmalignant disorders, 1975 (6%; 91% allogeneic)...

Hematopoietic stem cells (HSCs) possess the ability to generate all hematopoietic cell types and to self-renew over long periods, but the mechanisms that regulate their unique properties are incompletely understood. Herein, we show that homozygous deletion of the miR-29a/b-1 bicistron results in decreased numbers of hematopoietic stem and progenitor cells (HSPCs), decreased HSC self-renewal, and increased HSC cell cycling and apoptosis. The HSPC phenotype is specifically due to loss of miR-29a, because miR-29b expression is unaltered in miR-29a/b-1-null HSCs, and only ectopic expression of miR-29a restores HSPC function both in vitro and in vivo...