Abstract. Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT

Lung cancer is the leading cause of cancer-related death in males, and the second leading cause of death in females worldwide (1). Non-small cell lung cancer (NscLc) accounts for 85% to 90% of all lung cancer. There are different subtypes of NscLc that are grouped together because, until recently, the approach to treatment as well as prognosis was often similar. These subtypes are squamous cell carcinoma (sqNscLc), adenocarcinoma, large cell carcinoma and more poorly differentiated variants (2). squamous cell carcinoma constitutes about 25-30% of all lung cancer. it originates from the bronchial lining, and is often linked to a history of smoking. Adenocarcinoma represents around 40% of lung cancer. it emerges from mucus-secreting cells. While this type of cancer occurs mainly in current and former smokers, it is the most common type of lung cancer occurring in non-smokers. Large-cell carcinoma accounts for about 10% to 15% of lung cancer and tends to grow and spread quickly (1).Treatment options for NscLc have evolved tremendously over the past 15 years, especially with the advent of genetic and molecular techniques to characterize the driver mutations at the cellular level. overall survival (os) rates from lung cancer have been increasing slowly over the past decade for both men and women. This is mainly due to reduction in smoking over the past 50 years, although the decline in the rates of lung cancer in men started significantly before that in women (3). several treatment modalities are being used including surgery, radiation therapy, chemotherapy, targeted therapy, laser therapy, photodynamic therapy, radiofrequency ablation, cryosurgery, electrocautery, and watchful waiting. New modalities are being tested in clinical trials and they include immunotherapy, combination therapies and chemoprevention (4). To date, there are no studies that evaluate the best sequence of available therapies, and as such, the choice of therapy is highly personalized and likely depends on the setting in which available drugs were investigated, stage of disease, cytogenetic or molecular profile, performance status, toxicities, and medical comorbidities.For a long time, lung cancer has been considered to be non-immunogenic. However, after the success of immunotherapies in melanoma (5), there has been great interest and investigation in the immune checkpoint inhibitors in NscLc. These immune inhibitors have shown promising results in front-line therapy and after failure of multiple lines, as well as in monotherapy and combination 377Τhis article is freely accessible online.Correspondence to: imad Tabbara, MD,

For decades, researchers have looked into the pathophysiology of acute myeloid leukemia (AML). With the advances in molecular techniques, the two-hit hypothesis was replaced by a multi-hit model, which also emphasizes the importance of aberrant epigenetic regulation in the pathogenesis of AML. IDH1 and IDH2 are two isoforms of isocitrate dehydrogenase that perform crucial roles in cellular metabolism. Somatic mutations in either of these two genes impart a neomorphic enzymatic activity upon the encoded enzymes resulting in the ability to convert α-ketoglutarate (αKG) into the oncometabolite R2-hydroxyglutarate (R2-HG), which can competitively inhibit multiple αKG-dependent dioxygenases. Inhibition of various classes of αKG-dependent dioxygenases results in dramatic epigenetic changes in hematopoietic cells, which has been found to directly impair differentiation. In addition to a global dysregulation of gene expression, other mechanisms have been described through which R2-HG promotes leukemic transformation including the induction of B cell lymphoma 2 dependency and stimulation of the EglN family of prolyl 4-hydroxylases (EglN). Due to the fact that mutations in IDH1 and IDH2 are acquired early during AML clonal evolution as well as because these mutations tend to remain stable during AML progression, the pharmaceutical industry has prompted the development of specific mutant IDH enzyme inhibitors. More recently, the FDA approved the first mutant IDH2 inhibitor, enasidenib (AG-221), for patients with relapsed or refractory IDH2-mutated AML (RR-AML). This has brought a lot of excitement to researchers, clinicians, and patients, especially because the treatment of AML remains challenging and is still associated with a high mortality.

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.

Rituximab generally is a well-tolerated medication used in a variety of haematological and autoimmune conditions. The safety profile of the medication has been reviewed in the literature. Infusion reactions due to cytokine release are the most common side effects. With the increased use of rituximab, there is an increase incidence of cytopenias, most commonly thrombocytopenia and leucopenia. Coagulopathy is quite rare, reported previously in four cases in the literature. We highlighted the clinical course of a 39-year-old patient with precursor B-cell acute lymphoblastic leukaemia who was started on rituximab infusion. The patient developed a cytokine-release syndrome with haemodynamic instability, followed by rapid-onset cytopenias and disseminated intravascular coagulation abnormalities characterised by coagulopathy with fibrinolysis and mucocutaneous bleeding. The report is followed by a review of the literature. It is important to recognise rituximab-induced coagulopathy early as part of the differential diagnosis of thrombocytopenia and disseminated intravascular coagulation following rituximab administration.