Primary laboratory markers
The first step in the patient evaluation algorithm is the assessment of standard blood parameters.
The complete blood count (CBC) shows signs of suppressed normal hematopoiesis, manifesting as decreased red blood cells, hemoglobin, hematocrit, and platelets. Quantitative changes in leukocytes are highly variable: the patient may present with marked leukocytosis, leukopenia, or a normal leukocyte count. A specific qualitative marker is the presence of blasts in the blood smear, though they are not always detected. The «leukemic hiatus» (hiatus leukaemicus) phenomenon is characteristic — a condition where only immature blasts and fully mature cells are present in the blood, while intermediate maturing forms (myelocytes, metamyelocytes) are completely absent.
In the blood chemistry panel, an elevated lactate dehydrogenase (LDH) level is a classic sign. Additionally, markers indicating liver and kidney dysfunction may be registered.
Bone marrow examination
Bone marrow analysis is the primary and mandatory criterion for confirming the diagnosis.
The diagnosis of acute leukemia is established if the cytological examination (myelogram) reveals more than 25% blast cells in the aspirate. In acute lymphoblastic leukemia (ALL), this figure often exceeds 90%. The smear also shows overall hypercellularity and profound suppression of healthy hematopoietic lineages.
The technique for material collection strictly depends on the child's age:
- In infants under one year of age, a puncture of the tibial tuberosity or calcaneus is performed.
- In children over 1 year of age, the material is obtained via an iliac bone puncture.
Refining typing and staging
To select the treatment protocol, it is necessary to precisely determine the nature and characteristics of the tumor cells.
- Cytochemical examination: helps differentiate the blast type using specific stains (for glycogen, myeloperoxidase, acid phosphatase, Sudan black).
- Immunophenotyping: classifies the blast population (e.g., distinguishing T- and B-lymphoblasts or various types of myeloblasts) and determines their exact stage of maturation.
- Cerebrospinal fluid (CSF) analysis: is mandatory to rule out central nervous system involvement. It evaluates cellularity and the presence of blasts.
Genetic risk stratification
Molecular genetic and cytogenetic analyses of blast cells are necessary for prognosis estimation. The study evaluates structural and quantitative chromosomal abnormalities, as well as the DNA index (the ratio of DNA in tumor cells versus healthy cells).
Prognostic factors in ALL:
- Unfavorable: presence of the Philadelphia chromosome t[9;22], as well as translocations t[1;19] or t[4;11].
- Favorable: a DNA index exceeding 1.16 and the detection of the t[12;21] translocation.
In acute myeloid leukemia (AML), chromosomal aberrations are statistically detected much more frequently.
Instrumental methods and therapy monitoring
Instrumental diagnostics aim to detect extramedullary lesions and assess internal organ involvement:
- Ultrasound: examination of lymph nodes, kidneys, pelvic organs, abdominal cavity, and testes.
- Radiological imaging (CT, radiography): evaluation of the osteoarticular system and chest organs.
- Neuroimaging (CT, MRI): examination of the spinal cord and brain to confirm or rule out neuroleukemia.
- ECG and Echocardiography: performed initially and dynamically to monitor therapy cardiotoxicity.
At the end of the primary treatment course, a critical step is monitoring minimal residual disease (MRD) — the pool of remaining leukemic cells that can trigger a relapse. PCR, flow cytometry, and cytogenetic tests are used for its detection.
Differential diagnosis
The clinical presentation of acute leukemias requires ruling out a number of other conditions.
- Leukemoid reactions. May accompany severe infections (sepsis, pneumonia, infectious mononucleosis, tuberculosis, cat-scratch disease, enteroviral infections), systemic juvenile idiopathic arthritis (sJIA), or solid tumors. Key distinction: marked hyperleukocytosis is present in the peripheral blood, but the blast count in the bone marrow remains within the physiological norm.
- Cytopenia and bone marrow failure syndromes. Must be differentiated from agranulocytosis, immune thrombocytopenic purpura (ITP), and aplastic anemia.
- Autoimmune pathologies. Include systemic connective tissue diseases.
- Myelodysplastic syndrome (MDS). Differentiated primarily from AML. Both diseases are pathogenetically linked to a mutation of the progenitor cell. However, in MDS, the tumor clone retains its ability to differentiate into mature cells. The prognosis for MDS is serious: in a significant number of patients, it transforms into acute myeloid leukemia over time.
To memorize unfavorable genetic markers of ALL, focus on the number "1" combined with nine and four: t[1;19], t[4;11], and t[9;22] are high-risk signals.
Class and exam questions
What is the difference between acute leukemia and a leukemoid reaction?
In a leukemoid reaction, sharp hyperleukocytosis is observed in the blood against the background of infections or autoimmune processes, but the blast count in the bone marrow does not exceed the normal limit. In leukemia, the myelogram always shows more than 25% blast cells.
Why is a lumbar puncture necessary when leukemia is suspected?
Cerebrospinal fluid (CSF) analysis is strictly mandatory to detect extramedullary lesions, specifically neuroleukemia, which determines further therapeutic tactics.
What is a “leukemic gap”?
This is a phenomenon in the peripheral blood where only the most immature cells (blasts) and fully mature cells are found, while intermediate stages of their maturation are completely absent.
How does MDS differ from acute myeloid leukemia?
Unlike AML, in myelodysplastic syndrome, the tumor cell clone still retains the ability to mature into normal mature forms, although MDS frequently transforms into leukemia over time.
What else to study on this topic
- Specificity of cytochemical reactions (markers for glycogen, myeloperoxidase, acid phosphatase)
- Principles of immunophenotyping: differentiation of T- and B-lymphoblasts
- Minimal residual disease (MRD): PCR and flow cytometry methods
- Differential diagnosis with aplastic anemia and ITP
Master the entire topic in the Pediatrics course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Diagnosis of Acute Leukemias" and 3,738 more pages of the subject
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- AI tutor answers questions on the topic anytime
- 71 video lessons on the subject
Other topics in "Chapter 10. Diseases of the Blood and Blood-Forming Organs"
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