Leukemia (Blood Cancer)

Bharat R Agarwal
ALL - Diagnosis
On clinical suspicion, a variety of tests are done: blood tests, bone marrow aspiration & biopsy, monoclonal antibody tests, immunophenotyping etc.

However, primary diagnosis is made by bone marrow examination. By definition, the presence of 30% or more blasts in the marrow is diagnostic of acute leukemia.

The distinction between ALL and AML is made primarily by morphology of blasts in the marrow and the characteristic pattern of staining with cytochemical stains. Morphologically, the lymphoblasts are smaller than the myeloblasts and do not stain with cytochemical stains except with PAS.

The essential laboratory work up is:
- Hb, total and differential WBC count
- Bone marrow aspirate
- Chest-X ray (mediastinal mass)
- Uric acid and electrolytes: Na, K, Ca, PO4
- LDH/ Renal function tests/ Liver function tests
- Diagnostic lumbar puncture

During this period, it is important to monitor and maintain the WBC count (ANC) between 1000 to 1500 or as mentioned in the protocol sheet. It is also important to monitor for clinical signs of relapse like persistent unexplained fever, hepatosplenomegaly, lymphadenopathy, testicular enlargement or new CNS deficits as well as suspicious peripheral blood values.

The French-American-British classification system divides AML into 7 types -

M1 - Acute myeloblastic leukemia without maturation
M2 - Acute myeloblastic leukemia with maturation
M3 - Acute promyelocytic leukemia
M4 - Acute myelomonocytic leukemia
M5 - Acute monocytic leukemia
M6 - Acute erythroleukemia
M7 - Acute megakaryocytic leukemia

M0 category is not officially recognized as part of AML as it lacks definitive myeloid differentiation by morphology or conventional cytochemistry but shows evidence of AML by ultrastructural or immunophenotyping.

Identification of AML subtypes is important because several new drugs have more activity against some variety of AML as against others. Also, prognosis and some clinical features may differ considerably among various AML sub-types.

On clinical suspicion, a complete hemogram and peripheral smear examination should be done which may aide in suspicion of leukemia in most cases. Peripheral WBC count may be increased, decreased or normal with equal frequency. Granulocytopenia is common. Thrombocytopenia, with a platelet count < 20,000/ul is also common. Hematocrit is generally low.

Bone marrow aspiration and examination is usually diagnostic. Bone marrow biopsy may be required to assess cellularity. AML is diagnosed when bone marrow has more than 30% blasts. The bone marrow aspirate is stained with special histochemical stains to distinguish between AML and ALL and to confirm their diagnosis. The stains most commonly used include myeloperoxidase, PAS, Sudan Black B and esterase. (ALL stains with only PAS).

Bone marrow aspirate should also be sent for karyotyping and immunophenotyping as it helps in both type-classification and prognosis.

AML can also be diagnosed by biopsy of a chloroma. In addition, base line biochemical profile, X-Ray chest, coagulation screen and CSF examination are required.

Hematologic Features
- Blood counts: Leukocytosis (usually <50x109/L); monocytosis in the peripheral blood, which exceeds 5x109/L, thrombocytopenia; presence of nucleated red cell on blood smear, and circulating immature myeloid cells and a few blasts.
- Bone marrow reveals increased cellularity with increased myeloid series, monocytes comprise 5-10% of myeloid cells with some blasts.
- Sixty-eight percent of JMML cases lack cytogenetic abnormality: Monosomy 7 is seen in 6%.
- Erythropoiesis of fetal characteristics: Increased fetal hemoglobin level (> 10%), decreased HbA2, increased levels of G6PD, phosphoglycerate kinase, and enolase in red blood cells, decreased I antigen expression

Immunologic abnormalities:
- Increased immunoglobulin levels
- Increased incidence of ANA positivity
- Vitamin B12 levels are elevated
- Lysozyme levels are increased in 70% of patients

Clinical Criteria for Diagnosis of Juvenile Myelomonocytic Leukemia:
- Hepatosplenomegaly
- Lymphadenopathy
- Pallor
- Skin rash
- Absence of t(9;22)
- Bone marrow blasts less than 20%
- Peripheral blood monocytosis greater than 1x109/l and at least two of the following:
- Spontaneous in vitro growth of granulocyte macrophage progenitors (CFU-GM)
- HbF elevated for age
- Peripheral blood myeloid precursors
- Leukocyte count greater than 10x109/L
- Chromosome abnormalities

Leukemia (Blood Cancer) Leukemia (Blood Cancer) 02/02/2001
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