Present and Future Role of Immune Targets in Acute Myeloid Leukemia

It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on AML cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets and effectors of this immune-based therapy could be monoclonal antibodies directed against LSC antigens such as CD33, CD123, and CLL-1 (either as direct targets or via several bispecific T-cell engagers), immune checkpoint inhibitors acting on different co-inhibitory axes (alone or in combination with conventional AML drugs), and novel cellular therapies such as chimeric antigen receptor (CAR) T-cells designed against AML-specific antigens. Though dozens of clinical trials, mostly in phases I and II, are ongoing worldwide, results have still been negatively affected by difficulties in the identification of the optimal targets on LSCs

The role of allogeneic stem-cell transplant in myelofibrosis in the era of JAK inhibitors: a case-based review

Allogeneic hematopoietic stem-cell transplantation (HSCT) is, at present, the only potentially curative therapy for myelofibrosis (MF). Despite many improvements, outcomes of HSCT are still burdened by substantial morbidity and high transplant-related mortality. Allogeneic transplant is generally considered in intermediate-2 and high-risk patients aged <70 years, but the optimal selection of patients and timing of the procedure remains under debate, as does as the role of JAK inhibitors in candidates for HSCT. Starting from a real-life clinical case scenario, herein we examine some of the crucial issues of HSCT for MF in light of recent refinements on MF risk stratification, data on the use of ruxolitinib before and after transplant and findings on the impact of different conditioning regimens and donor selection

How could patient reported outcomes improve patient management in chronic myeloid leukemia?

Introduction: Patients reported outcome (PRO) are still under-used in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), though data on the correlation between quality of life (QoL) and therapeutic efficacy are increasingly known. Chronic low-grade toxicities can reduce patient's QoL and negatively impact on adherence.Areas covered: This review will focus on the role of QoL questionnaires in patients with CML, receiving imatinib or newer TKIs (dasatinib, nilotinib, bosutinib, ponatinib). Physicians tend to underestimate the impact of TKI-related symptoms, in particular fatigue, that negatively affect QoL and can be a reason of poor adherence to therapy, with detrimental effect on long-term response. Few studies pointed out the role of PRO in CML, and there is paucity of questionnaires specifically designed for CML patients.Expert commentary: We recommend a wider use of PRO to join the pursuit of a rapid and deep responses with an optimization of QoL

Annals Impact Factor 1.67. Welcome to the IF club: achievement and challenges

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Relationship between fatty liver and glucose metabolism: A cross-sectional study in 571 obese children

BACKGROUND AND AIMS: Early onset type 2 diabetes mellitus (T2DM) is associated with obesity, insulin resistance and impaired beta-cell function. Non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for T2DM. We investigated the relationship between NAFLD and glucose metabolism in a large sample of obese children. METHODS AND RESULTS: A total of 571 obese children (57% males and 43% females) aged 8-18 years were consecutively studied at a tertiary care centre specialised in paediatric obesity. Liver ultrasonography was used to diagnose NAFLD after exclusion of hepatitis B and C and alcohol consumption. Oral-glucose tolerance testing (OGTT) was performed; insulin sensitivity was evaluated by using the insulin sensitivity index (ISI) and beta-cell function by using the ratio between the incremental areas under the curve (AUC) of insulin and glucose (incAUCins/incAUCglu). A total of 41% of the obese children had NAFLD. Impaired glucose tolerance or T2DM was present in 25% of the children with NAFLD versus 8% of those without it (p<0.001). Children with NAFLD had higher body mass index (BMI), fasting glucose, 120-min OGTT glucose, incAUCins/incAUCglu and lower ISI as compared with children without NAFLD (p</=0.002). At bootstrapped multivariable median regression analysis controlling for gender, age, pubertal status and BMI, NAFLD was an independent predictor of 120-min OGTT glucose and ISI, but not of incAUCins/incAUCglu. Similar findings were obtained using continuous liver steatosis as the predictor, instead of dichotomous NAFLD. CONCLUSION: NAFLD was present in 41% of our obese children and was associated with higher insulin resistance, but not with impaired beta-cell function

The Role of Meningioma-1 (Mn1) Gene as Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: A Concise Review

Molecular markers are necessary for prognostic stratification and monitoring of Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML) [1,2]. Cytogenetic aberrations have long been recognized as the most important prognostic variable in AML, and are still the major determinant for post-remission therapy [3]. Unfortunately, only 50-60% of AML patients present an abnormal karyotype at diagnosis, while the remaining cases display a Normal Karyotype (NK). NK AML patients are generally included in an “intermediate risk” prognostic group, that is however characterized by a heterogeneous clinical course. To stratify prognosis of NK AML patients, numerous studies have led, in the last decade, to the introduction of different molecular markers such as FLT3, NPM1, BAALC and CEBPA [4-7]. Still, their use to monitor disease, either defining remission status and detecting relapse as early as possible, is still somehow controversial, due to fluctuations during disease course, low incidence rates in AML and sensitivity of the technologies detecting the single marker [8-10]. These limitations have, to date, precluded a timely and precise quantification of disease in NK AML patients, thus preventing from a complete individualization of post-remission therapy and early treatment in case of impending relapse. In other words, in NK AML it has not been reached the precision achieved in BCR/ABL-positive chronic myeloid leukemia and PML/RAR alpha mutated acute promyelocytic leukemia