Efficacy and safety of fostamatinib in refractory immune thrombocytopenia: a meta-analysis from randomized controlled trials.

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated disease that results in low platelet counts. Despite appropriate treatment, many patients continue to experience refractory disease. Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, has emerged as a promising option for refractory ITP. OBJECTIVE: This meta-analysis aims to evaluate the efficacy and safety of fostamatinib compared to conventional therapy in adults aged ≥ 18 years with refractory ITP. MATERIALS AND METHODS: Literature search was conducted in PubMed, Scopus, Embase, and clinicaltrials.gov databases from inception to March 31, 2024. Randomized controlled trials (RCTs) assessing the safety and efficacy of fostamatinib in adults with refractory ITP were included. Data extraction, risk of bias assessment, and statistical analysis were performed following PRISMA guideline. RESULTS: A total of 495 articles were screened, with three RCTs meeting the inclusion criteria. Fostamatinib therapy demonstrated superior efficacy in achieving stable platelet response by week 24 (ORR 0.80; 95%CI 0.72-0.88), platelet count ≥ 50,000/µL at weeks 12 (ORR 0.80; 95%CI 0.72-0.90) and week 24 (ORR 0.82; 95%CI 0.72-0.90). Additionally, fostamatinib improves platelet counts in subjects with a baseline count of < 15,000/µL. The Number Needed to Treat (NNT) was calculated as 10. Adverse effects include diarrhea (RR 2.32; 95%CI 1.11-4.84), hypertension (RR 2.33; 95%CI 1.00-5.43), and abnormal liver function tests (RR 4.18; 95% CI 1.00-17.48). Interestingly, the occurrences of nausea (RR 1.77; 95% CI 0.33-9.67) and rash (RR 2.28; 95% CI 0.50-10.29) did not achieve statistical significance. CONCLUSION: This meta-analysis provides robust evidence supporting the efficacy of fostamatinib in improving platelet counts and achieving therapeutic goals in adults with refractory ITP. However, fostamatinib's safety profile warrants consideration due to higher rates of diarrhea, hypertension, and abnormal liver function tests.

Concomitant L248V With E225V Mutation in the BCR-ABL Gene Associated With Rapid Chronic Myeloid Leukemia Lymphoid Blast Crisis.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome (Ph), resulting from the t(9;22)(q34;q11.2) translocation. Imatinib, a tyrosine kinase inhibitor (TKI), has revolutionized the treatment of CML. However, despite the initial response, some patients may progress to an advanced stage, such as a blast crisis. We report a 40-year-old female who presented with CML chronic phase (CP) taking imatinib 400 mg/day and achieved a complete hematological response (CHR) after one month of treatment. She achieved a suboptimal response in the third month (BCR-ABL positive 10.29% IS). However, five months into therapy, she developed a sudden lymphoid blast crisis with chromosomal aberrations involving chromosomes 10 and 12. Molecular analysis detected concomitant L248V with partial exon 4 deletion and E225V mutations within the BCR-ABL1 fusion gene. The patient received intensive chemotherapy and dasatinib. We report the first case of concomitant mutation of L248V with partial exon 4 deletion and E255V on BCR-ABL1 gene mutation, which contributes to a sudden precursor B-cell lymphoid blast crisis.

First Case Report of Deferiprone-Induced Anaphylactic Reaction.

A 56-year-old Thai male, known for allergies to penicillin, sulfa, and lincosamide, presented with hyperferritinemia. Upon initiating deferiprone therapy, the patient experienced recurrent episodes of dyspnea, culminating in anaphylactic shock. Treatment included subcutaneous epinephrine, intravenous chlorpheniramine, and hydrocortisone, which led to symptom resolution. This case constitutes the first case report of deferiprone-associated anaphylactic reactions.

Erlotinib-associated interstitial pneumonitis with successful readministration.

INTRODUCTION: Erlotinib is the main stay treatment of non-small cell lung cancer (NSCLC) in recent years. Though, interstitial lung disease following erlotinib use is rarely develop, it is a fatal adverse event if not immediately treat. CASE REPORT: We report the first case of erlotinib-induced interstitial pneumonitis with successful readministration. A Thai 64-year-old male patient with NSCLC, information includes patient presentation, laboratory findings, chest x-ray, computed tomography (CT) of chest, corticosteroid dose and duration. MANAGEMENT & OUTCOME: The patient readministrated erlotinib after developed interstitial pneumonitis 3 weeks without developing second adverse event. Evaluation of disease after 2 months of treatment is stable disease per RECIST v1.1. DISCUSSION: We assumed that the mechanism for interstitial pneumonitis are diverse and some mechanism is not related with drug directly but rather transient condition and the drug can be readministrated without developing second adverse event. This could lead to change in practice of erlotinib readministration in the future.

ChAdOx1 nCoV-19 vaccine-associated thrombocytopenia: three cases of immune thrombocytopenia after 107 720 doses of ChAdOx1 vaccination in Thailand.

We reported three cases of immune thrombocytopenia (ITP) that developed within 6 weeks after ChAdOx1 nCoV-19 vaccination. Antiplatelet factor 4 antibodies were undetectable in all three cases. Therefore, vaccine-induced immune thrombotic thrombocytopenia was very unlikely. Other potential causes of thrombocytopenia were excluded. Their clinical presentations, severity of thrombocytopenia and outcomes were varied. Only one ITP case, an 80-year-old man, received ITP treatments and achieved complete response after 2 weeks of eltrombopag. An 84-year-old man had spontaneous complete remission, and a 55-year-old woman had partial platelet recovery without ITP treatments. Among 107 720 Thais administered the ChAdOx1 vaccine between 16 March and 10 May 2021, these three ITP cases resulted in an estimated risk of ITP of at least one per 36 000 doses, which was approximately similar to the risk of ITP after measles-mumps-rubella immunization. This raises the concern of an increased risk of ITP after ChAdOx1 vaccination.