br Discussion Appendicitis is seen in the

Discussion Appendicitis is seen in the general population with a lifetime cumulative incidence rate of 9% [7]. Our calculated incidence rate of appendicitis in the setting of acute leukemia (1.9%) correlates with the reported incidence of 0.5–4.4% [1]. Leukemic involvement of the gastrointestinal tract as well as the treatment thereof can compromise the structural integrity of the intestinal wall [5]. Moreover, atypical presentations of appendicitis are common in immunocompromised patients due to underlying malignancy and ongoing chemotherapy. Early symptoms such as nausea, vomiting, abdominal pain, and diarrhea are non-specific and may be attributed to chemotherapy side effects delaying accurate diagnosis [8]. In addition, typhlitis often mimics the classic presentation of appendicitis, and therefore imaging must be performed to distinguish these entities as their management approaches differ. 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 GDC-0994 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 cycle 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.