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Abstract Myelofibrosis (MF) is a clonal malignancy frequently characterized by anemia and in 10%–20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with reduced survival and ‐in primary MF‐ also with an increased probability of BP. Conventional treatments for anemia have limited effectiveness in MF. Within a dataset of 1752 MF subjects largely unexposed to ruxolitinib (RUX), BP incidence was 2.5% patients per year (p‐y). This rate reached respectively 4.3% and 4.5% p‐y in case of patients with common terminology criteria for adverse events (CTCAE) grade 3/4 and grade 2 anemia, respectively, that represented together 32% of the cohort. Among 273 MF cases treated with RUX, BP incidence was 2.89% p‐y and it reached 4.86% p‐y in subjects who started RUX with CTCAE grade 2 anemia (one third of total). Within patients with red blood cell transfusion‐dependency at 6 months of RUX (21% of the exposed), BP rate was 4.2% p‐y. Our study highlights a relevant incidence of BP in anemic MF patients, with a similar rate whether treated with or without RUX. These findings will help treating physicians to make decisions on the safety profile of innovative anemia treatments.

Abstract Emergence of clones carrying point mutations in the BCR‐ABL1 kinase domain (KD) is a common mechanism of resistance to tyrosine kinase inhibitor (TKI)‐based therapies in Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL). Sanger sequencing (SS) is the most frequently used method for diagnostic BCR‐ABL1 KD mutation screening, but it has some limitations—it is poorly sensitive and cannot robustly identify compound mutations. Next‐generation sequencing (NGS) may overcome these problems. NSG is increasingly available and has the potential to become the method of choice for diagnostic BCR‐ABL1 KD mutation screening. A group discussion within an ad hoc constituted Panel of Experts has produced a series of consensus‐based statements on the potential value of NGS testing before and during first‐line TKI‐based treatment, in relapsed/refractory cases, before and after allo‐stem cell transplantation, and on how NGS results may impact on therapeutic decisions. A set of minimal technical and methodological requirements for the analysis and the reporting of results has also been defined. The proposals herein reported may be used to guide the practical use of NGS for BCR‐ABL1 KD mutation testing in Ph+ ALL.

Abstract Patients with myeloproliferative neoplasms (MPN) are known to have higher incidence of nonhematological second primary malignancies (SPM) compared to general population. In the MYSEC study on 781 secondary myelofibrosis (SMF) patients, the incidence of SPM after SMF diagnosis resulted 0.98/100 patient‐years. When including non‐melanoma skin cancers (NMSC), the incidence arose to 1.56/100 patient‐years. In SMF, JAK inhibitor treatment was associated only with NMSC occurrence. Then, we merged the MYSEC cohort with a large dataset of PV and ET not evolving into SMF. In this subanalysis, we did not find any correlation between SPM and SMF occurrence. These findings highlight the need of studies aimed at identifying MPN patients at higher risk of SPM.

Acute myeloid leukemia (AML) is widely considered a distinct clinical entity with a well-defined molecular and genetics-based prognosis. Particularly in a younger patient, the therapeutic approach depends largely on diagnostic risk stratification, which has an impact on the outcome after therapy. We added Treg evaluation to the usual molecular and cytogenetics profile in the AML younger patients’ diagnostic bone marrow aspirate (dBMA) in order to search for any correlation between Tregs and overall response (OR) as well as survival (OS) rates. We studied 23 AML young patients, all treated with standard induction chemotherapy: OR (complete remission (CR) + CR incomplete (CRi)) was documented in 10 of 23 patients (44%); there were two partial responder patients. The optimal dBMA Treg cut-off value for predicting response to treatment (≥21/μL) was obtained by ROC curve analysis. However, in multivariate analysis, apart from the expected impact of the molecular/cytogenetic risk (p=0.049) and NPM mutation (p=0.001), dBMA Tregs ≥ 21/μL was not correlated with OR. Actually, higher dBMA Tregs were associated with the good intermediate molecular/cytogenetic risk group (p=0.02), whose median OS was confirmed to be better as compared with that of the poor risk group (18 versus 5 months, p=0.05) and equal to the dBMA Tregs ≥ 21/μL group (5 versus 5 months, p=0.902), respectively. The possible prognostic value of such an immunological player as BMA Tregs in the diagnostic and successive phases of AML needs to be confirmed in larger patient numbers.