Sokal Score For Chronic Myeloid Leukemia (CML)

Sokal index explained

The Sokal index offers a survival prognosis of patients with chronic myeloid leukemia (CML) based on patient age, spleen size determination and two simple laboratory results (platelet count and percentage of myeloblasts).

The following explains the choice of the 4 independent prognostic factors:

■ Patient age – reflects the fact that elder patients are more susceptible to develop CML and have an adverse outcome;

■ Spleen size – measured in centimetres to identify and quantify splenomegaly;

■ Platelet count measured in x 10⁹/L – high platelet count is associated with higher risk of adverse outcome;

■ Myeloblasts percentage* – reflects the amount of immature blood cells.

*This is the peripheral blood blast laboratory test that is obtained through flow cytometry and hematologic counting.

The formula used is:

Sokal Score = Exp (0.0116 x (Age in years – 43.4)) + (0.0345 x (Spleen size in cm – 7.51)) + (0.188 x ((Platelets in 10⁹/L / 700)² – 0.563)) + (0.0887 x (Blasts in % – 2.10))

The main criticism of the Sokal Index refers to it not being up to date with new treatment methods, such as interferon- alpha based treatments. At the time of the study, the main compound used was busulfan and tyrosine kinase inhibitors were yet to be introduced as a treatment, thus survival rates tend to be lower.

More recent CML survival prognostic tools are the Hasford score from 1990s and the EUTOS (European Treatment and Outcome Study) from the 2000s. The former is deemed to identify with greater specificity lower risk patients.

Result interpretation

The Sokal index stratifies prognosis in chronic myeloid leukemia (CML) into three risk groups, each with a designated 2-year survival rate and a median survival time, as summarized below:

In the original study, in the low risk group, the subsequent risk averages less than 20% per year whilst in the high risk group, the adverse outcome risk is of about 35% per year.

About the study

The score was created by Sokal et al. after a 1984 study which involved 813 patients with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia (CGL).

Several prognostic determinants were analysed. Multivariate regression analysis found that some prognostic factors such as haematocrit, had little prediction value, whilst others: spleen size and percentage of circulating blasts, had significant prognostic value.

It was also found that although platelet count did not influence survival significantly when below 700 X 10⁹ /litre, at higher values, was a relevant unfavourable factor.

The Cox model was then generated with four variables: percent blasts, spleen size, platelet count, and age. This provided a useful representation of risk status in the study sample.

The study identified three risk groups, as described in the above section “Result interpretation”.

CML guidelines

Leukemia can be of myeloid or lymphocytic type and each of these can be acute or chronic, meaning that in total, there are four main types of leukemia:

■ Acute myeloid leukemia (AML);

■ Chronic myeloid leukemia (CML);

■ Acute lymphocytic leukemia (ALL);

■ Chronic lymphocytic leukemia (CLL).

The differences between the four are in terms of progression rate and malignancy localization.

Around 95% of cases of myeloid leukemia are caused by a genetic defect between chromosomes 9 and 2, also known as the Philadelphia chromosome.

Some sources now say that the cause of leukemia is a combination of environmental and genetic factors that end up affecting the normal development of white blood cells.

CML makes up around 15 to 20% of cases of adult leukemia but tends to have a higher incidence in older patients. The condition is lethal and the only curative option is allogeneic bone marrow transplantation, which is possible in around 35% of cases (due to limiting factors).

Typical symptoms include:

■ Swollen lymph nodes;

■ Bruising easily;

■ Bleeding;

■ Fatigue;

■ Weight loss;

■ Predisposition to infections;

■ Spleno- and hepato – megaly.

Diagnosis is a combination of laboratory blood tests, physical examination of lymph nodes, tumoral markers and specific biopsy.

Original study

Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, Tso CY, Braun TJ, Clarkson BD, Cervantes F, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood. 1984; 63(4):789-99.

Validation

Thomas M, Irving J, Lennard A, Proctor S, and Taylor P. Validation of the Hasford score in a demographic study in chronic granulocytic leukaemia. J Clin Pathol. 2001; 54(6): 491–493.