buy continine Although successful conservative management ha

Although successful conservative management has been reported [9], the majority require surgical intervention to avoid devastating complications [1,10]. Several groups have demonstrated safety and efficacy of surgical intervention [1,4,10] and operative management may also shorten the length of hospital stay compared to nonoperative management [10]. In our cohort, all three patients were operated upon emergently and all of them including the patient with appendiceal perforation and leukemic infiltration tolerated surgery well. For the treating clinician, the bigger conundrum is the need to suspend chemotherapeutic treatment during life-threatening infections such as appendicitis, while weighing in a heightened risk for uncontrolled leukemic cell proliferation. Alternatively, other anti-leukemic agents such as decitabine have been demonstrated to be effective and well-tolerated in adults with myelodysplastic syndrome, high risk AML, as well as those ineligible for standard chemotherapy due to extensive comorbidities such as the elderly [11–13]. Decitabine (5-aza-2′-deoxycytidine) is a cytosine nucleoside analog that after phosphorylation directly incorporates into DNA resulting in inhibition of DNA methyltransferases. The resulting DNA hypomethylation causes reversal of abnormal epigenetic silencing of genes critical to normal cellular differentiation, proliferation, and normal cellular life processes such as apoptosis [14]. It has minimal toxicity and hence is favored in patients who are unable to tolerate standard chemotherapeutic regimens [11]. Our third patient was enrolled in a trial utilizing a short five-day course of decitabine prior to intensive chemotherapy with cytarabine, daunorubicin and etoposide. She achieved and remained in remission with one buy continine of decitabine and one dose of cytarabine without significant hematologic toxicities despite considerable delay in resumption of chemotherapy due to overwhelming infection. Low-dose decitabine (20mg/m2/day for 10 days given every 4 weeks) has demonstrated promising results in children with very high risk relapsed/ refractory AML in whom other treatment options had been exhausted. Three out of eight patients had a complete response, with best responses noted after a median of 2.5 cycles. Despite significant comorbidities, decitabine monotherapy demonstrated minimal toxicity [15]. Recently, sequential treatment with decitabine and cytarabine was found to be more effective than cytarabine alone in xenograft models of childhood AML [16].
Conflicts of interests
Introduction Runx1 is an important transcription factor for myeloid development [1,2]. Impairments in Runx1 function lead to a block in myeloid differentiation and can drive leukemogenesis [3]. Clinically, germline mutations in the RUNX1 gene cause an autosomal dominant familial platelet disorder (FPD) with propensity to transform into myeloid malignancies such as myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) [4–8]. Although rare, enhanced awareness of RUNX1 mutations has led to increased reports in recent literature, suggesting that the disease is actually more common than once thought.[9] Germline mutations in RUNX1 have important clinical implications and knowledge about such mutations is critical.
Case report We report a case of an 18 year-old Caucasian male who was found to have thrombocytopenia at birth, with a platelet count of 58,000/mm3. Bone marrow biopsy was first performed in 1993, at 13 months of age, and showed 70–80% cellular marrow with occasional megakaryocytes and no evidence of dysplastic changes or increased monocytes. There was no history of thrombocytopenia or bleeding tendency in his family. Throughout childhood, his platelet counts averaged between 90,000 and 120,000/mm3. He had a lifelong history of easy bruising, however had no major bleeding episodes. He underwent several operations including spinal fusion surgery for scoliosis, later requiring revision, and a tonsillectomy with adenoidectomy. He received pre- and post-operative platelet transfusions as well as intravenous aminocaproic acid for his spinal operations without significant bleeding. He also had history of several infections, including lower extremity cellulitis, periorbital cellulitis, and a perirectal abscess. The patient was otherwise developmentally and phenotypically normal and was of normal intelligence. In 2007, the patient was noted to have a mild normocytic anemia with hemoglobin and hematocrit of 10g/dL and 30%. Four years later, at 18 years of age, the patient developed a mild leukopenia (3200/mm3), as well as worsening of his baseline thrombocytopenia to around 60,000/mm3. Bone marrow biopsy revealed 65–70% cellular marrow with 10% myeloblasts aberrantly expressing CD7, dysplastic erythroid progenitors and megakaryocytes, increased monocytes (25%), increased eosinophils, and no fibrosis. Cytogenetic analysis revealed normal male karyotype. FISH was negative for AML1-ETO (RUNX1-RUNX1T1) gene fusion and CBFB gene rearrangements. Molecular studies for CEBPA, c-MPL, FLT3, and NPM1 gene mutations were negative. The bone marrow pathology was interpreted as a high grade MDS (RAEB-1, Intermediate-2 IPSS risk). Although there were some features of CMML in the bone marrow, the patient did not have an elevated number of peripheral blood monocytes to meet criteria for this diagnosis.