Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Despite its indolent clinical course, therapy refractoriness and disease progression still represent an unmet clinical need. Before the advent of pathway inhibitors, chemoimmunotherapy (CIT) was the commonest option for CLL treatment and is still widely used in areas with limited access to pathway inhibitors. Several biomarkers of refractoriness to CIT have been highlighted, including the unmutated status of immunoglobulin heavy chain variable genes and genetic lesions of TP53, BIRC3 and NOTCH1. In order to overcome resistance to CIT, targeted pathway inhibitors have become the standard of care for the treatment of CLL, with practice-changing results obtained through the inhibitors of Bruton tyrosine kinase (BTK) and BCL2. However, several acquired genetic lesions causing resistance to covalent and noncovalent BTK inhibitors have been reported, including point mutations of both BTK (e.g., C481S and L528W) and PLCG2 (e.g., R665W). Multiple mechanisms are involved in resistance to the BCL2 inhibitor venetoclax, including point mutations that impair drug binding, the upregulation of BCL2-related anti-apoptotic family members, and microenvironmental alterations. Recently, immune checkpoint inhibitors and CAR-T cells have been tested for CLL treatment, obtaining conflicting results. Potential refractoriness biomarkers to immunotherapy were identified, including abnormal levels of circulating IL-10 and IL-6 and the reduced presence of CD27+CD45RO− CD8+ T cells.
Imatinib (Glivec(®)/Gleevec(®)) has shown long-term efficacy and safety in randomized trials. No large-scale studies have prospectively assessed the benefit-risk profile of an imatinib copy drug. We prospectively evaluated the response of patients with chronic myeloid leukemia in chronic phase in one institution. Patients with a complete hematologic response (n = 126) switched from branded imatinib to an imatinib copy drug. Subsequently, all patients switched back to the branded imatinib. Many patients in this study had a loss of hematologic response and tolerability issues with the imatinib copy drug. Hematologic response and tolerability improved upon retreatment with branded Glivec.
Objective: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML). During therapy, a few patients may develop hematological and non-hematological adverse effects. Materials and Methods: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day.Results: Two hundred CML patients in chronic phase were included in this study; the male:female ratio was 0.7:1 with mean age 39.06±13.21 years (ranged from 15-81 years). The study showed that the commonest hematological side effects were grade 2 anemia (12.5%) followed by leukopenia (8%) and thrombocytopenia (4%), while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%), followed by musculoskeletal pain (35.5%), then gastro-intestinal symptoms (vomiting, diarrhea) (19%). Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity.Conclusion: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectivelyConflict of interest:None declared.
Refractory/relapsed acute leukemia has always been a challenging problem for hematologist. Over the past decade emphasis has been made in the development of regimens containing fludarabine, combined with cytosine arabinoside for the treatment of refractory/relapsed acute leukemias. The aim of this study is to evaluate the efficacy and toxicity of the combination of fludarabine, high dose cytarabine, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a prospective study is being conducted at the National Center of Hematology and hematology unit/Baghdad teaching hospital from July 2008 to July 2010. Twenty Patients with refractory/relapsed acute leukemia were treated with fludarabine 30 mg/m(2) and cytosine arabinoside (Ara-C) 2 g/m(2) for 5 days, and granulocyte colony stimulating factor G-CSF 300 µg/day from day 0 till neutrophil recovery (ANC > 1.0 × 10(9)/L). Response was evaluated by bone marrow examination on day 30 post chemotherapy. Patients included were refractory acute lymphoblastic leukemia (ALL) (five patients), relapsed ALL (four patients), refractory acute myeloid leukemia (AML) (eight patients), relapsed AML (three patients). Complete remission (CR) was achieved in nine (45 %) patients, while three (15 %) patients got partial remission. Three (15 %) patients died because of post chemotherapy complications and five (25 %) patient failed to achieve remission. Major complications encountered were: anemia, fever, bleeding, mucositis and bacterial infections. FLAG protocol is well tolerated and effective regimen in relapsed/refractory acute leukemias. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures.
Objective: The assessment of neopterin and interferon-gamma (IFN-γ) levels as a part of immune system response about serum iron status in β-thalassemia (TM) major patients.Methods: Spectrophotometry applied for the estimation of iron status including serum iron level, total iron-binding capacity, and unsaturated iron-binding capacity. Enzyme-linked immunosorbent assay (ELISA) applied for the estimation of the serum cytokines included neopterin and IFN-γ also serum ferritin estimation by ELISA from 130 β-TM major patients where they divided according to serum ferritin level (< and ≥2500 ng/mL).Results: The neopterin and IFN-γ concentration showed significantly increased with direct correlation among TM patient group when compared to the normal healthy control group. However, there was no significant difference between different levels of serum ferritin.Conclusion: The increased serum level of neopterin and IFN-γ found in patients with β-TM may be due to the direct effect of iron on cellular immune cells beside of immune system response to the effect of iron toxicity on different body organs. There was a direct moderate relationship between neopterin and IFN-γ.
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