Therapeutic approaches for relapsed/refractory adult acute lymphoblastic leukemia (ALL), a review on monoclonal antibodies and targeted therapies.

Acute lymphoblastic leukemia (ALL) is the malignant transformation of lymphoid progenitors that affects both children and adults. Although the outcome of pediatric patients has been improved dramatically, there are still many challenges in the treatment of adults. Patients with primary resistant or relapsed disease have the worst outcome and despite the administration of intensified multi-agents chemotherapies, the outcome of this group remains very poor. Accordingly, the development of novel therapeutic options is considered necessary. Having a comprehensive insight into the pathophysiology of ALL and aberrant signaling pathways is crucial for introducing effective targeted therapies. Combination therapies with new drugs and innovative targeted therapies with the aim of affecting the main aberrant signaling pathways in the disease are considered as new approaches. Here we tried to have a comprehensive review on the potential molecular targets in the treatment of refractory/relapsed ALL and the current therapeutic agents.

Analysis of bioinspired non-interlocking geometrically patterned interfaces under predominant mode I loading.

Geometrically patterned interfaces seem to be a common motif in Nature. In particular, geometry plays an important role in increasing the strength, toughness and damage tolerance among different species. Here, we investigate the role of the shape of the opening crack behind the crack tip as the crack propagates along the interface. In particular, we studied the shape of the interface behind the crack tip for different amplitude-to-wavelength aspect ratios with two analytical models and compared with finite element simulations through the J-integral. Additionally, we explore the role of material length scale by investigating the relationship between the geometrical characteristic lengths and the emerging material length scale using a finite element-based cohesive zone model. The results suggest that geometrical toughening is influenced by a size effect, but it is bounded between two extreme conditions.

Relationship Between Single-Nucleotide Polymorphisms of Tumor Necrosis Factor Alpha, Interleukin-10, Factor II and Factor V with Risk of Inhibitor Development in Patients with Severe Hemophilia A.

BACKGROUND: About one-fourth of patients with hemophilia A (HA) develop alloantibodies against factor (F) VIII, as the main treatment challenge. Here, we assessed the relationship between interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), FII and FV polymorphisms and risk of inhibitor formation in patients with severe HA. METHODS: We divided 39 patients with severe HA in two groups of case (n: 19) and control (n: 20). Genotyping was performed by multiplex amplification tetra arms refractory mutation systempolymerase chain reaction (ARMS-PCR) and PCR-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: TNFα rs1800629 G>A polymorphism decreased the risk of inhibitor development in codominant and dominant inheritance pattern. Moreover, TNFα rs1800629 A allele, decrease the risk of inhibitor formation, while IL10 rs1800896 A>G, FV rs6025 G>A, and FII rs1799963 G>A polymorphisms were not associated with risk of inhibitor development. CONCLUSION: It seems that TNFα rs1800629 G>A polymorphism decreased the risk of inhibitor formation in Iranian patients with HA.

Long-term prophylaxis in patients with severe congenital factor XIII deficiency is not complicated by inhibitor formation.

: Congenital factor XIII (FXIII) deficiency is a rare bleeding disorder accompanied by a variety of bleeding events. Severely deficient patients require regular replacement therapy. With development of FXIII concentrate, the risk of viral infections transmitted by fresh frozen plasma and cryoprecipitate is diminished, but the possibility of inhibitor development remains a challenging issue in the management of these patients. The aim of this study was to assess FXIII inhibitor development in Iranian patients with FXIII deficiency (FXIIID). This study enrolled 50 (30 women and 20 men) patients with severe congenital FXIIID from southeast Iran who underwent long-term (more than 4 years or more than 50 injections) prophylaxis with FXIII concentrate (Fibrogammin P, Dade Behring, Marburg, Germany). We evaluated plasma FXIII activity and FXIII inhibitor on day 28 after the last prophylaxis administration. The method for investigation of FXIII inhibitor was based on Bethesda assay. The mean age of the study population was 13.8 ±â€Š8.3 years. The minimum and maximum FXIII activity levels were less than 1-4.5% (mean ±â€ŠSD, 2.6 ±â€Š0.7%). Our investigations showed that all patients with severe form of FXIIID were treated without inciting inhibitor development. Despite long-term prophylaxis in the studied patients, none was found to have developed FXIII inhibitors.