DISCUSSION
Leukemias constitute one overwhelming branch of the hematologic malignancies and are mainly divided into lymphoblastic/ lymphocytic and myeloblastic/ myelogenous leukemias. CML is one of the MPNs and accounts for 15% of diagnosed cases of leukemia in adults (6). it is characterized by the translocation t(9;22)(q34;q11.2), resulting in the fusion of the Abelson murine leukemia (ABL1 ) gene on chromosome 9 with the breakpoint cluster region (BCR ) gene on chromosome 22 (BCR-ABL1), this rearrangement is known as the Philadelphia chromosome (4,6,7). Most cases of CML are asymptomatic, and the diagnosis is made via a routine complete blood count (CBC), while symptomatic patients may have fatigue, fever, weight loss, anemia, and abdominal discomfort due to splenomegaly (5). Generally, CML can be classified into three phases: chronic phase (CP), accelerated phase (AP), and blast phase (BP) (4). The majority of patients present with CP. GI manifestations of CML is well established in the literature, occurring more commonly in acute leukemias than chronic (5). Reported autopsies showed that the GI tract involvement in leukemias is seen in about 25% (5). Previous studies from the 1960s have described GI involvement in the context of leukemias, stating that the stomach is the most common site of involvement (8). This was further emphasized in recent literature that the most common sites are the stomach, ileum, and proximal colon (5). These leukemic lesions invade mucosa and submucosa and may complicate in ulceration or perforation. Leukemic lesions of the esophagus can be hemorrhagic, ranging from mild petechiae to ulcers and erosions, or can be infiltrative and may cause obstruction or perforation (5). Leukemic infiltration of the lymphoreticular system, particularly liver, spleen, and lymph nodes, is quite common, especially in chronic leukemias. Significant splenomegaly is commonly seen in CML, and to a lesser extent, in chronic lymphocytic leukemia (CLL) and acute leukemias, however, splenic rupture with no history of trauma was recorded in acute leukemias (5). When involving the small and large intestines, leukemic lesions lead to what is called neutropenic enterocolitis or necrotizing colitis, clinically known as typhlitis, which can be hard to distinguish from appendicitis as the case in our patient who was initially suspected to have typhlitis when the CML diagnosis was made. However, typhlitis occurs more frequently with acute leukemias as a complication of neutropenia, which is a cardinal feature, but when typhlitis occurs in chronic leukemias is typically due to chemotherapy and the neutropenia that follows (5) (9). Distinguishing between appendicitis and typhlitis is crucial in leukemic patients as the management is completely different. Wallace et al. described a case of properly diagnosed appendicitis in a 24-year-old CML patient, which occurred three years after being diagnosed, being treated with multiple-agent chemotherapy regimen after the presence of circulating blasts, and finally underwent bone marrow transplant (BMT). The patient was in relapse during his admission for an acute abdomen, which was confirmed to be appendicitis (9). However, our patient presented with abdominal pain, which was found to be due to appendicitis before even establishing a diagnosis of CML. There is paucity in the literature regarding CML per se and GI manifestations. On the other hand, several studies have described the effect of CML treatment on GI tract and other organs (10,11). The oncogene BCR-ABL1 leads to activation of tyrosine kinase, so the mainstay of treatment is tyrosine kinase inhibitors (TKIs) such as imatinib, and more recently, the second-generation TKIs, dasatinib, and nilotinib (6). agents are used first line in the treatment of CML and have been very effective in achieving complete cytogenetic response (CCR), however their adverse events should be considered when initiating treatment and when involving patients with their disease treatment and plan (11). Several case reports described such adverse events, Yassin et al. described a case of hemorrhagic colitis in a patient with CML who was treated with dasatinib 100mg once daily and achieved CCR after 30 months of treatment; however, she complained of watery and bloody diarrhea, she underwent colonoscopy with biopsies that confirmed the diagnosis of cytomegalovirus (CMV) colitis after excluding other possible causes such as clostridium difficile, dasatinib was discontinued, and the patient improved spontaneously within 5 days. The patient was treated with Ganciclovir for 6 weeks, and the follow-up colonoscopy showed a normal mucosa (11,12). Another case report in 2018 by Nacif et al. reported a case of imatinib-induced fulminant hepatitis in a patient treated for CML, the patient had a successful live transplant and was started on dasatinib afterwards with no adverse effects (10).
in conclusion, leukemias whether acute or chronic may manifest in a variety of symptoms and conditions, and patients should be addressed with caution and in a comprehensive approach.