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The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age <70 years should be considered as candidates for allo-SCT. Patients with intermediate-1-risk disease and age <65 years should be considered as candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood (PB) >2%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2- or high-risk disease lacking an human leukocyte antigen (HLA)-matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted. [ABSTRACT FROM AUTHOR]

The article discusses the study on the prognostic effect of calreticulin (CALR) mutations in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation. It notes a separate trial suggesting lower white blood cell counts and higher platelet counts in patients with CALR mutated primary myelofibrosis as compared with JAK2 tyrosine kinase. It also mentions the somatic frameshift mutations of CALR identified in a large proportion of JAK2 and essential thrombocythemia.

To investigate the impact of anti-lymphocyte globulin (ATG-Fresenius) as part of the HLA-sibling transplantation, we evaluated 238 patients (median age 48 years) with different diagnoses (AML, ALL, CML and lymphoproliferative disorders). A total of 79 patients received ATG and 159 patients did not. In the ATG group, there were more HLA-mismatched donors (6% vs 1%, p=0.02), bad risk patients (70% vs 55%, P=0.04), reduced intensity conditioning (RIC) regimens (65% vs 34%, P=<0.001) and older patients (median age 51 vs 48 years, P=0.002). The median time to leukocyte engraftment was significantly faster in the non-ATG group (13 vs 15 days, P < 0.001). EBV reactivation was more often seen in the ATG group (9% vs 2%, P=0.05). Cumulative incidence of acute and chronic GVHD was less observed in the ATG group (27% vs 40%, P=0.004, and 33% vs 54%, P=0.002). The cumulative incidence rates of non-relapse mortality and of relapse at 5 years were 20 and 34%, respectively, for ATG and 34 and 29%, respectively, for non-ATG (P=0.06 and P=0.3). ATG can prevent GVHD without an obvious risk of relapse but should be confirmed in a randomized study. [ABSTRACT FROM AUTHOR]

In a retrospective study of 168 patients with AML in CR who underwent allo-SCT, we compare the impact of young unrelated donors (UD) vs older matched related donors (MRD) on 5-year OS (5-yr OS). Median follow-up was 59 months and median donor age was 39 years, which was used as cutoff for young vs older donors. Kaplan-Meier-estimated 5-yr OS was better with UD 39 years vs MRD >39 years (66% vs 34%, P=0.001). In multivariate analysis, only donor age and cytogenetic risk impacted 5-yr OS. Compared with UD 39 years, both MRD >39 years (relative risk (RR): 4.31, P=0.001) and UD >39 years (RR: 2.14, P=0.03) were associated with poorer 5-yr OS. Standard-risk cytogenetics was associated with better 5-yr OS compared with bad-risk cytogenetics, (RR: 0.53, P=0.02). Subgroup analyses of patients 50 years (n=76) revealed similar results, with 5-yr OS of 62% for UD 39 yrs and 26% for MRD >39 yrs (P=0.022). In patients undergoing allo-HSCT for AML, young UD may improve outcome as compared with older MRD. [ABSTRACT FROM AUTHOR]

We investigated whether a young human leukocyte antigen (HLA)-matched unrelated donor (MUD) should be preferred as donor to an HLA-identical sibling (MRD) for older patients with myelodysplastic syndrome (MDS) (50 years) who underwent allogeneic stem cell transplantation (AHSCT). Outcomes of 719 MDS patients with a median age of 58 years (range, 50-73 years) who received AHSCT from related (n=555) or unrelated (n=164) donors between 1999 and 2008 and reported to the European Group for Blood and Marrow Transplantation were analyzed. The median donor age of the MRD was 56 years (range: 35-78), in contrast to 34 years (range: 19-64) for the MUDs. Influence of donor's age on survival was not observed for MRD (hazard ratio (HR): 1.01 (95% confidence interval (CI): 0.99-1.02), P=0.2), but there was a significant impact of MUD's age on outcome (HR: 1.03 (95% CI: 1.01-1.06); P=0.02). Transplantation from younger MUDs (<30 years) had a significant improved 5-year overall survival in comparison with MRD and older MUDs (>30 years): 40% vs 33% vs 24% (P=0.04). In a multivariate analysis, AHSCT from young MUD (<30 years) remained a significant factor for improved survival in comparison with MRD (HR: 0.65 (95% CI: 0.45-0.95), P=0.03), which should be considered in donor selection for older patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the improvement in the overall survival and progression of donor inhibitory killer cell immunoglobulin-like receptors (KIRs) haplotype B patients after undergoing an allogeneic hematopoietic stem cell transplantation used for multiple myeloma.

Monitoring of minimal residual disease (MRD) after allogeneic (allo)-SCT for myelofibrosis (MF) allows recognizing the depth of remission and thus guides application of appropriate therapeutic interventions. MPL W515L/K mutations, which are detected in 5–10% of JAK2V617F-negative patients, may be useful for this purpose. Using a highly sensitive quantitative PCR method, we tested 90 patients with MF who underwent allo-SCT for the presence of MPL W515L/K mutations. Two patients with primary MF were found to harbor MPLW515L while no patient was positive for MPLW515K mutation. Both patients were JAK2V617F negative and cleared the mutation rapidly after allo-SCT and remained negative for a median follow-up of 19 months. The results of molecular monitoring correlated well with other remission parameters such as normalization of peripheral blood counts and morphology and complete donor chimerism. We conclude that MPLW515L can be cleared after allo-SCT and hence may be used as an MRD marker in a proportion of JAK2V617F-negative MF patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which association of SRSF2 and U2AF1 mutations in primary myelofibrosis with JAK2 and MPL without calreticulin mutation that may independently reoccur after allogeneic stem cell transplantation is being discussed.

A letter to the editor is presented concerning ruxolitinib and Janus kinase (JAK) inhibition as pretreatment for allogeneic stem cell transplantation (ASCT).

A letter to the editor is presented on a study which investigated CD34+PB as a potential biomarker for follow-up and prognosis of myelofibrosis patients undergoing allo-stem cell transplant (SCT).

A letter to the editor is presented regarding a retrospective study on the frequency of calreticulin (CALR) mutations in patients with myelodysplastic syndromes (MDSs).