No abstract

Haematopoietic stem cell transplantation was proposed as a treatment strategy just over 60 years ago. Owing to great advances in the field, haematopoietic stem cell transplantation has become an established method for the treatment of many haemato-oncological, immunological and hereditary conditions with the potential of cure. The number of haematopoietic stem cell transplants performed worldwide reached one million by 2012. This review provides an overview of autologous and allogeneic haematopoietic stem cell transplantation including disease indications, the individual steps of the procedure and outcome, and highlights achievements in the treatment of autoimmune diseases. Although autoimmune conditions account for only 1% of indications for autologous haematopoietic stem cell transplant, this is increasingly used to treat high-risk autoimmune diseases. Haematopoietic stem cell transplantation can induce long-term remission by resetting the immune system via eradication of autoreactive immune cells and the generation of a de novo self-tolerant immune system. Data seem most encouraging in multiple sclerosis and systemic sclerosis and it is likely that the number of procedures performed to treat these conditions will rise in the future.

Background: The germline telomerase reverse transcriptase (TERT) rs2736100_C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN).Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100_C and Janus kinase 2 (JAK2) rs12343867_C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals.Results: TERT rs2736100_C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.7%AE2.8% vs. 48.8%AE3.5%, P < 0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero-or homozygosity conferred even higher risk for classic MPN. Common complications (throm-

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT) with high mortality rate. We retrospectively studied the frequency, clinical and genetic associations and prognostic effect of TA-TMA, in a total of 425 consecutive adult patients, who underwent allo-HSCT for a malignant haematological condition between 2007 and 2013 at our single centre. TA-TMA developed in 19% of the patients. Unrelated donor type (P o 0.001), acute GvHD grades II-IV (P o0.001), myeloablative conditioning regimens (P = 0.003), tacrolimus-based GvHD prophylaxis (P = 0.003), CMV infection (P = 0.003) and carriership for HLA-DRB1*11 (P = 0.034) were associated with the development of TA-TMA. Survival was adversely affected by the presence of TA-TMA (P o 0.001). Among patients with TA-TMA, the outcome of HLA-DRB1*11 carriers was significantly better compared with non-carriers (P = 0.003). As a new finding, our observations suggest that the presence of HLA-DRB1*11 antigen contributes to the development of TA-TMA and affects the outcome.