Abdominal pain in January, the cause is this common blood disease

Preface

Chronic myeloid leukemia (CML) is a chronic myeloproliferative tumor (MPN).

Derived from hematopoietic stem cell clonal abnormalities
.
Has a specific Ph chromosome and/or BCR-ABL1 fusion gene
.
The incidence of CML worldwide is 1 to 2 cases per 100,000 people, accounting for 15% to 25%
of all leukemias.
It can be divided into three stages: initially the occult chronic phase (CP) and then progression to accelerated phase (AP) or blast phase (BP).

Most patients are diagnosed in the chronic phase, and a few patients present first with blast phase
.

Case history

The patient is an elderly man who was admitted to surgery
for one month due to abdominal pain.
Blood routine examination showed a significant increase in the number of white blood cells, an increase in the number of basophils, moderate anemia, and a marked increase in the number of platelets
.

Scatterplot shows naïve granulocytosis
.

Push the film retest, it can be seen that the number of white blood cells is significantly increased, and the original cells are 9%:

Visible at all stages of naïve granulocytes:

Basophils 17%, a significantly increased number of platelets:

Issue a prompt report:

Other tests:

Bone marrow was sent for examination, and it can be seen that hyperplasia is significantly active, and the blasts are 15%:

Basophils 13%:

Consider chronic myeloid leukemia-accelerated phase:

Test case studies

Flow cytometry showed 14.
68% abnormal myeloid blasts with an increased
proportion of granulocytes.

Biopsy considers chronic myeloid leukemia (fibrosis grade 3).

BCR-ABL1 (P210) fusion gene positive
.

Karyotypes: 46, XY, t(9; 22; 11)(q34； q11.
2；q13)

The BCR-ABL1 fusion gene is the golden marker for the diagnosis of CML, and can be diagnosed by combining clinical manifestations and blood and bone marrow images
.
Post-diagnosis staging is critical to determine prognosis and treatment planning
.
Stages of domestic diagnostic criteria CML:

Chronic phase (1) 10% blasts in peripheral blood or bone marrow<; (2) The criteria
for diagnosing accelerated or blast phase are not met.

Accelerated phase meets any of the following: (1) 10%-19% of blasts in peripheral blood or bone marrow; (2) Peripheral blood basophils ≧20%; (3) persistent thrombocytopenia (PLT< 100×109/L) or increased (PLT>1000×109/L) not related to treatment; (4) Other clonal chromosomal abnormalities based on Ph+ cells during treatment; (5) Progressive enlargement of the spleen or increased blood count
.

Blasts meet any of the following: (1) 20% blasts in peripheral blood or bone marrow ≧; (2) Bone marrow biopsy blast agglomeration; (3) Extramedullary blast infiltration
.

Clinical case studies

The patient had abdominal pain without obvious predisposition before one month, the pain was intermittent, paroxysmal and exacerbated, no fever, no bloating, no jaundice, no low back pain, no frequent and urgent
urination.
Self-medication at home is less effective
.
For further diagnosis and treatment, come to the hospital
.
Since the onset of the patient, the general condition can be, the mind is clear, the spirit can be, the diet and sleep are average, there is no obvious abnormality in urine and urine, and there is no obvious change
in weight.
The cause of abdominal pain is to be investigated and admitted to hospital
.

Differential diagnosis: 1.
acute pancreatitis, 2.
acute gastritis, 3.
urinary stones, 4.
intussusception
.
Improve blood routine, urine routine, electrocardiogram, CT examination for further diagnosis
.

Blood routine examination showed significant increase in white blood cells and
platelets.
CT of the abdomen shows splenomegaly
.
Physical examination: normal body temperature and blood pressure, rhythmic rhythm, no obvious murmur, no percussion pain in the liver and kidney area, negative mobile dullness, soft abdomen, no gastrointestinal type and peristaltic waves, lower abdominal distension, percussion sound, pubic symphysis can reach the inferior edge of the spleen, tenderness, normal limb movement
.
Patients with leukocytosis, thrombocytosis, anemia with giant spleen, preliminary consideration of myeloproliferative tumors
.
Hyperleukocyte and splenomegaly for no apparent reason are the most prominent signs
of CML.
It is necessary to complete bone marrow aspiration, biopsy, genetics, flow cytometry and other examinations to confirm the diagnosis
.

Differential diagnosis:

1.
Leukemia-like reaction Almost all white blood cells have a good cause of increased peripheral blood leukocytes and the appearance of naïve cells
.
It is more common in infection, after major surgery, severe burns, allergic reactions, advanced cancer, etc
.

2.
Other types of MPN slow granules (CML), primary bone fiber (PMF), essential thrombocytosis (ET), true red (PV) are the main types of MPN, all of which can appear splenomegaly, peripheral blood leukocytes, and even naïve cells, bone marrow is often multilineage hyperplasia
.

3.
Ph chromosome-negative chronic myeloid tumors Slow mesogranules (CNL), slow granules (CMML), atypical slow granules (aCML), juvenile slow granules (JMML), etc.
are all Ph chromosome negative related diseases
.

Bone marrow cell morphology examination does not exclude chronic myeloid leukemia-accelerated phase, the proportion of blasts is 15%, flow cytometry can show 14.
68% abnormal myeloid blasts, BCR-ABL1 (P210) fusion gene positive, JAK-2 gene negative, comprehensive consideration is chronic myeloid leukemia-accelerated stage
.

Test case summary

Since the era of TKI (tyrosine kinase inhibitor) therapy, chronic CML of formidable malignancies has been transformed into chronic disease
.
However, TKI is still poorly effective in patients in the accelerated stage
.

The WHO2016 revision proposes that although CML-AP has become rare in the era of TKI (tyrosine kinase inhibitor) therapy, the definition of accelerated phase has not been widely recognized
.
Diagnostic criteria are based on haematology, cell morphology, genetic parameters plus cytogenetic evolution and tentative response to anti-KTI therapy
.

The fifth edition of the WHO (2022) refines the risk factors for chronic myeloid leukemia and cancels the accelerated period
.
Resistance due to ABL1 kinase mutations and/or other cytogenetic abnormalities and the development of blast phases represent key disease attributes
.
Therefore, the accelerated phase is omitted from the current classification in favor of highlighting high-risk features
associated with chronic phase progression and resistance to TKI.

Clinical case summary

Chronic myeloid leukemia is divided into chronic, accelerated and blast phases
.
The accelerated phase can last from a few months to years, often with fever, weakness, progressive weight loss, bone pain, and gradual anemia and bleeding
.
Persistent or progressive enlargement
of the spleen.

The treatment of chronic myeloid leukemia should focus on the early stage of chronic phase, avoid disease transformation, and strive for remission
at the cytogenetic and molecular biological level.
Once it enters the accelerated or blast phase, the prognosis is poor
.
Mutations in the BCR-ABL1 kinase region were refined to understand whether tyrosine kinase inhibitor resistance was present
.

If tyrosine kinase inhibitors have not been used in the past, additional doses of first- or second-generation tyrosine kinase inhibitors can be considered to achieve remission followed by allogeneic hematopoietic stem cell transplantation
.
The patients were negative for MPLW515 mutant gene, negative for CALR1 and type 2 genes, and negative for JAK2V617F gene, which further supported the diagnosis of
chronic myeloid leukemia.
BCR-ABL1 kinase region mutation test negative, treated with second-generation tyrosine kinase inhibitor flumatinib and well
tolerated.
Regular outpatient review, blood routine results after two months:

【References】

[1] Criteria for the diagnosis and efficacy of hematological diseases/Shen Ti Zhao Yongqiang, eds.
4th edition.
Beijing: People's Medical Publishing House, 2018

[2] Atlas of Clinical Laboratory Diagnostics/Wang Jianzhong, editor-in-chief.
Beijing: People's Medical Publishing House, 2012

[3] Chronic myeloid tumor diagnostics/Lu Xingguo, editor-in-chief.
Beijing: People's Medical Publishing House, 2013

[4] Hematology/Zhang Zhinan Hao Yushu, eds.
2nd ed.
Beijing: People's Medical Publishing House, 2011