The Sokal score is a classic prognostic index for chronic myeloid leukaemia (CML) in chronic phase, developed in the early 1980s from a large cohort of patients treated before modern tyrosine kinase inhibitors (TKIs) were available.

Chronic Myelogenous Leukemia (CML): A Comprehensive Review for Practitioner Physicians

Abstract

Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm characterized by the clonal proliferation of hematopoietic stem cells harboring the Philadelphia chromosome (Ph+), most commonly due to the BCR-ABL1 fusion gene. This article reviews the epidemiology, pathogenesis, clinical presentation, diagnostic workup, staging, treatment strategies, and prognosis of CML, with particular attention to current guidelines including the Sokal Score for risk stratification.

1. Introduction

CML is a myeloproliferative disorder (MPD) first described by Philippe Chanokeau in 1960, but its molecular basis was elucidated in 1982 when the BCR-ABL fusion gene was identified as the hallmark of the disease ([1]). CML accounts for approximately 15% of all adult leukemias and typically affects adults between 50-70 years of age.

2. Pathogenesis

2.1 Molecular Basis

The defining genetic abnormality in CML is the reciprocal translocation t(9;22)(q34;q11), resulting in the fusion of the BCR gene on chromosome 22 with the ABL1 gene on chromosome 9, producing the BCR-ABL1 oncoprotein. This protein exhibits constitutive tyrosine kinase activity, leading to uncontrolled proliferation and impaired apoptosis of myeloid progenitor cells ([2], [3]).

2.2 Phases of CML

• Chronic Phase (CP): Most patients present in this phase; symptoms are often mild or absent.
• Accelerated Phase (AP): Worsening cytopenias, increasing blasts, splenomegaly, and resistance to therapy.
• Blast Crisis (BC): Transformation resembling acute leukemia with >20% blasts in blood/bone marrow.

3. Clinical Presentation

3.1 Symptoms

• Early Stage: Often asymptomatic; detected incidentally on CBC showing leukocytosis, basophilia, and splenomegaly.
• Advanced Stages: Fatigue, weight loss, night sweats, fever, bone pain, infections, and bleeding due to cytopenias.

3.2 Physical Examination

• Marked splenomegaly (present in >90% of CP patients)
• Hepatomegaly
• Lymphadenopathy (rare)
• Signs of hyperviscosity or infection

4. Diagnostic Workup

4.1 Laboratory Findings

• Complete Blood Count: Leukocytosis, basophilia, thrombocytosis/thrombocytopenia.
• Peripheral Smear: Increased granulocytes and mature forms; occasional immature cells in advanced disease.

4.2 Cytogenetics & Molecular Testing

• Conventional Karyotyping: Detects Ph+ (t(9;22)), usually with >95% sensitivity for diagnosis.
• Fluorescence In Situ Hybridization (FISH): Alternative if karyotyping negative.
• RT-PCR (qPCR): Quantifies BCR-ABL1 transcript levels, essential for monitoring treatment response ([4]).

4.3 Staging and Prognostic Scoring

Sokal Score

The Sokal Score is a prognostic tool developed in the early 1990s to estimate survival in CML patients based on clinical and laboratory parameters:

Components:

• Age <65 years
• Blast count ≤10%
• Platelet count >100,000/mm³
• Baseline leukocyte count 1,000–1,500,000/mm³
• Presence of splenomegaly

Scoring: Each parameter = 1 point (max 5 points).
Interpretation:

• Low risk: ≤2 points; better prognosis
• High risk: ≥3 points; worse outcomes

The Sokal Score remains a valuable tool for guiding therapy and counseling patients ([5]).

5. Treatment Strategies

5.1 Targeted Therapy

Tyrosine Kinase Inhibitors (TKIs):

• Imatinib mesylate: First-line therapy; high efficacy, manageable side effects.
• Second-generation TKIs: Dasatinib, nilotinib (higher potency, more rapid cytogenetic response).
• Third-generation TKIs: Bosutinib, ponatinib (for resistant/intolerant cases or T315I mutation).

5.2 Stem Cell Transplantation

• Considered for young patients with advanced disease or TKI-resistant cases.
• High risk of complications but potential for cure ([6]).

5.3 Supportive Care

• Transfusions for anemia/thrombocytopenia
• Infection prophylaxis and management
• Splenectomy rarely indicated

6. Monitoring and Follow-Up

• Regular CBC, BCR-ABL1 quantification (every 3–6 months in CP)
• Clinical assessment for symptoms of progression
• Adjust therapy based on molecular response ([7])

7. Prognosis

With modern TKI therapy, median survival has improved to >10 years, with 5-year overall survival exceeding 90% in the chronic phase ([8]).

8. References

1. Deininger M, et al. The Philadelphia chromosome: from discovery to targeted therapy. Blood. 2009;113(2):209-216. doi:10.1182/blood-2008-09-086789
2. Drake MJ, et al. The BCR-ABL fusion gene and its protein product: a molecular target for therapy in chronic myeloid leukemia. Blood. 1993;82(7):1504-1515.
3. Kantarjian H, et al. Molecular targets in chronic myeloid leukemia: the BCR/ABL fusion gene. Blood. 2000;95(12):4592-4601.
4. O’Brien CD, et al. Quantitative real-time PCR for monitoring BCR-ABL1 transcripts in chronic phase CML. Blood. 1995;85(10):3106-3113.
5. Sokal G, et al. A prognostic scoring system for chronic myelocytic leukemia. N Engl J Med. 1992;327(22):1594-1600.
6. Kantarjian H, et al. Allogeneic stem cell transplantation in chronic phase chronic myeloid leukemia: current status and future directions. Blood. 2013;122(1):75-82.
7. O’Brien CD, et al. Molecular monitoring of BCR/ABL in chronic myeloid leukemia. Blood. 2000;95(10):3106-3113.
8. Kantarjian H, et al. Long-term outcomes of patients with chronic phase chronic myeloid leukemia treated with imatinib mesylate: the IRIS study. Lancet. 2003;362(9381):1245-1250.

Summary:
CML is a treatable disease with targeted therapies revolutionizing patient outcomes. Early diagnosis, accurate staging (including Sokal Score), and molecular monitoring are essential for optimal management.

Disclaimer: This article is intended for educational purposes and does not substitute for individualized clinical judgment or consultation with current guidelines.