Rushwalton8786

Childhood acute myeloid leukemia (AML) harboring core binding factor (CBF)-associated translocations are considered as a favorable cytogenetic subgroup. The 2 major subtypes of CBF-AML include t(8;21) and inversion of chromosome 16, accounting for ∼25% of patients. Because of expensive and toxic treatment, which may require hospitalization during the entire course of induction chemotherapy, most of the centers in Pakistan neither workup for this low-risk entity nor offer curative treatment. Therefore, we adopted an approach of screening AML cases for the presence of CBF with the rationale of offering curative treatment to this subgroup. Data of 244 cases were reviewed, and translocations were found in 72 (34%) patients among them, 59 (82%) had t(8;21) and 13 (18%) showed inversion of chromosome 16. The event-free survival with and without abandonment was 36% and 40%, respectively. Among 44 patients who completed treatment, 26 (59%) are leukemia-free, while 18 (41%) relapsed. None of the relapsed patients received salvage chemotherapy or hematopoietic stem cell transplant. Treatment-related mortality and abandonment was found in 24% and 10% of patients, respectively. The frequency of CBF-AML is higher in our study; however, poor outcome demands holistic measures in supportive care to improve the survival.Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by variable and diverse symptoms including the classic triad of hemolytic anemia, thrombosis, and bone marrow failure. It is a disorder primarily seen in the adult population. The authors report a unique case of an 8-year-old girl diagnosed with PNH after initially presenting with a febrile illness and acute kidney injury. Though rare in children, PNH should remain in the differential diagnosis of a child presenting with acute kidney injury. The disease has serious long-term complications, mandating timely diagnosis and appropriate therapy.Liver abscesses are poorly known in sickle cell disease. We report here multiple liver abscesses occurring in a 17-year-old patient with hemoglobin SC disease. A Fusobacterium nucleatum was identified on cyst puncture. Such complications have been described in only 11 children and young adults with hemoglobin SS/Sβ-thalassemia diseases. Fusobacterium species are the most frequent pathogens reported and require anaerobic culture to be identified.Infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have historically poor outcomes despite maximal intensification of chemotherapy. Chimeric antigen receptor (CAR) T-cell therapy has revolutionized our approach to pediatric patients with relapsed/refractory ALL. Unfortunately, infants were excluded from early CAR T-cell trials due to concerns regarding the feasibility of T-cell collection and expansion. Here, we report the use of tisagenlecleucel in an infant with chemotherapy-refractory KMT2A-rearranged ALL. While CAR T-cell therapy was not curative for this patient, collection and expansion of T-cells proved feasible despite prior chemotherapy, he achieved minimal residual disease negative remission with excellent quality of life, and it facilitated a delay in hematopoietic stem cell transplantation.Hereditary thrombotic thrombocytopenic purpura is an ultra-rare disorder caused by biallelic mutations in the ADAMTS13 gene. Idasanutlin clinical trial Because it can be difficult to diagnose, plasma ADAMTS13 activity assessment should be considered in patients with thrombocytopenia, anemia, and schistocytes on peripheral blood smear. We present the diagnostic evaluation of a patient with hereditary thrombotic thrombocytopenic purpura. Genetic testing revealed one known pathogenic mutation and one novel mutation of ADAMTS13 classified as likely pathogenic on the basis of parental genetic testing and in silico analyses. We further discuss off-label use of prophylactic plasma-derived Factor VIII (Koate-DVI) and the benefit of rare disease registries.Tumor cell expression of major histocompatibility complex (MHC) class I is required for antigen presentation and adaptive immune recognition. Absent or diminished MHC class I expression is thought to contribute to immunotherapeutic resistance in some epithelial tumors but has not been previously studied in cervical and vulvar carcinoma. Given that anti-programmed cell death 1 (PD-1) checkpoint inhibition is deployed for programmed cell death ligand 1 (PD-L1)-positive recurrent and metastatic cervical squamous carcinomas, identifying tumors with loss of MHC class I is of clinical interest to optimize the selection of immunotherapeutic candidates. Immunohistochemistry for PD-L1 and MHC class I combined A, B, and C heavy chains (MHC class I) was assessed in 58 human papillomavirus-associated cervical and vulvar lesions, including 27 squamous intraepithelial lesions (SILs) and 31 invasive squamous cell carcinoma (SCC). Although 84% of SCC and 22% of SIL were PD-L1-positive, 35.5% (11/31) of SCC and 18.5% (5/27) of SIL also showed clonal or complete loss of MHC class I. Loss of MHC class I expression was more common in PD-L1-positive (10/26, 38%) versus PD-L1-negative SCC (1/5, 20%). In summary, over one third of human papillomavirus-associated cervical and vulvar SCC show clonal or complete loss of MHC class I expression, including many PD-L1-positive cases. This suggests that the efficacy of checkpoint inhibitors targeting the PD-1/PD-L1 axis may be limited in a subset of cervical and vulvar squamous neoplasms due to an impaired ability to engage with the adaptive immune system related to loss of MHC class I expression.The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma using immunohistochemistry is improving. However, immunohistochemical markers with high sensitivity and specificity have yet to be identified. In this study, we investigated the utility of sex-determining region Y box 6 (SOX6) as a novel immunohistochemical marker, identified by analyzing previous gene expression data. Immunohistochemically, SOX6 expression was present in 53 of 54 (98%) cases of epithelioid mesothelioma, compared with its expression in only 5 of 69 (7%) cases of lung adenocarcinoma. The sensitivity and specificity of SOX6 expression for differentiating epithelioid mesothelioma and lung adenocarcinoma were 98% and 93%, respectively. SOX6 expression showed similar sensitivity and far better specificity than those of calretinin or podoplanin (D2-40). In addition, SOX6 expression was more sensitive than Wilms' tumor 1 expression. The combination of SOX6 with other markers showed comparable or better sensitivity and specificity relative to other combinations.