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.