Ganesh Kasinathan

High-dose methotrexate (HDMTX) is an essential agent in hematological malignancies, the use of which is complicated by toxicities related to delayed elimination. Existing thresholds to define delayed elimination vary widely, creating inconsistencies in clinical practice. This multicenter retrospective study evaluated adult non-Hodgkin Lymphoma patients from Malaysia to establish a locally relevant delayed elimination threshold and identify factors influencing it. Patients who received HDMTX ≥ 500 mg/m² were included. Data extracted from medical records were HDMTX regimen, supportive therapy, renal and liver function, full blood count, MTX concentrations, and MTX-related toxicities. MTX thresholds at 48 h were assessed based on their association with post-treatment clinical outcomes. The selected threshold was subsequently used to categorize patients into delayed and nondelayed elimination groups, and factors associated with delayed elimination were evaluated using logistic regression. A toxicity-based receiver operating characteristic (ROC) approach identified ≥ 0.2 µmol/L at 48 h as the concentration at which lymphocyte count and alanine aminotransferase (ALT) worsened by 50% and mucositis risk increased nearly threefold. Logistic regression showed increased baseline serum creatinine, decreased baseline albumin, and 24 h infusion duration as factors associated with delayed elimination, while Chinese ethnicity was associated with reduced odd of delayed elimination. These findings support a population-tailored threshold to better guide supportive management and highlight key predictors that can inform future pharmacokinetic modeling for optimized HDMTX therapy.

Ganesh Kasinathan, Jameela Sathar. Blood Res -0001;0:. https://doi.org/10.5045/br.2021.2021165

Hyperhemolysis syndrome (HS) is characterized by the occurrence of severe anemia with post‐transfusion hemoglobin and hematocrit levels being markedly lower than those present prior to transfusion. A high index of suspicion of HS in a multi‐transfused thalassemia patient allows prompt institution of therapy resulting in improved survival outcome.

Coexistent myelodysplastic syndrome and acute megakaryoblastic leukemia is an aggressive disease which often do not respond to standard chemotherapy due to the various molecular and cytogenetic abnormalities. Understanding of the molecular pathogenesis may lead to better therapeutic modalities as current conventional therapies are largely ineffective.

Although the patient with very severe aplastic anemia might be a fit elderly receiving standard therapy, there are factors which contribute to an adverse outcome such as severity of pancytopenia, absence of minor paroxysmal nocturnal hemoglobinuria clone and infective complications of therapy.

Hyperhemolysis syndrome (HS) should be considered in a multiply transfused thalassemia patient. HS in this patient was attributed to a combination of factors including multiple transfusions, presence of anti-Cw, macrophage hyperactivity, hypersplenism and suppression of erythropoiesis.

Introduction: Autoimmune hemolytic anaemia (AIHA) is a heterogenous disorder characterised by the presence of IgG or IgM pathological autoantibodies that target antigens of erythrocytes resulting in active hemolysis. Case presentation: A 40-year-old gentleman presented to a medical centre with chest pain and right sided hemiparesis for a week. He was pale and jaundiced. The power of the right upper and lower limbs was 3/5. His spleen was palpable. His complete blood count revealed macrocytic anaemia of 7.6 g/dL. The brain Magnetic Resonance Imaging (MRI) showed left fronto-parietal infarction. The right cardiac and left carotid angiogram revealed thromboses involving the right coronary and left internal carotid artery respectively. At the cardiology department, he was transfused with two units of red blood cells without his anemia being investigated and a stent was deployed to the left internal carotid artery. He was referred to the hematology department in which his peripheral blood smear revealed hemolysis and his direct antiglobulin test was positive. He responded to a course of steroids and direct oral anticoagulation and is in complete remission for the past 18 months. Conclusion: It is always imperative to investigate the cause of anaemia and consider hemolysis in a patient presenting with multiple unexplained thromboses.