What is the initial approach to treating a patient with both myelodysplastic and myeloproliferative features?

Initial Approach to Treating Myelodysplastic/Myeloproliferative Neoplasms

The initial treatment approach for patients with both myelodysplastic and myeloproliferative features should be based on the disease subtype (MD-CMML vs. MP-CMML), blast percentage, and presence of specific genetic abnormalities.

Diagnostic Evaluation

• A comprehensive diagnostic workup is essential and must include:

  • Complete blood count with differential and peripheral blood smear examination 1
  • Bone marrow aspiration and biopsy with iron stain 1
  • Cytogenetic analysis 1
  • Serum erythropoietin level (prior to RBC transfusion) 1
  • Evaluation for PDGFRα/β gene rearrangements, especially in patients with eosinophilia 1
  • JAK2 mutation testing in patients with thrombocytosis 1, 2

• Diagnostic criteria for CMML (the most common MDS/MPN) include:

  • Persistent peripheral blood monocytosis >1×10^9/L 1, 3
  • No Philadelphia chromosome or BCR-ABL1 fusion gene 1, 3
  • No rearrangement of PDGFRα or PDGFRβ 1, 3
  • <20% blasts in peripheral blood and bone marrow 1, 3
  • Evidence of dysplasia in at least one myeloid cell line or presence of clonal cytogenetic/molecular abnormality 1, 3

Classification and Risk Stratification

• MDS/MPN should be classified into subtypes:

  • Myelodysplastic-type CMML (MD-CMML): WBC <13×10^9/L 1, 3
  • Myeloproliferative-type CMML (MP-CMML): WBC ≥13×10^9/L 1, 3
  • Further subclassification based on blast percentage:
    • CMML-0: <2% blasts in peripheral blood and <5% in bone marrow 3
    • CMML-1: 2-4% blasts in peripheral blood and/or 5-9% in bone marrow 3
    • CMML-2: 5-19% blasts in peripheral blood and/or 10-19% in bone marrow 3

• Risk assessment should incorporate:

  • Blast percentage 1
  • Cytogenetic abnormalities 1
  • Number of cytopenias 1
  • Age 1

Initial Treatment Approach

For Myelodysplastic-type CMML (MD-CMML):

• For patients with <10% bone marrow blasts:

  • Supportive care focusing on correction of cytopenias 1
  • Red blood cell transfusions for symptomatic anemia 1
  • Platelet transfusions for severe thrombocytopenia or bleeding 1
  • Consider erythropoiesis-stimulating agents for symptomatic anemia 1

• For patients with ≥10% bone marrow blasts:

  • Supportive care plus hypomethylating agents (5-azacytidine) 1, 4
  • 5-azacytidine has shown efficacy in higher-risk MDS/MPN patients 1, 4

For Myeloproliferative-type CMML (MP-CMML):

• For patients with <10% bone marrow blasts:

  • Cytoreductive therapy with hydroxyurea as the drug of choice 1
  • Target is to control cell proliferation and reduce organomegaly 1

• For patients with ≥10% bone marrow blasts:

  • Polychemotherapy regimens similar to those used for AML 1
  • Consider hypomethylating agents as an alternative in elderly or frail patients 1, 4

Special Considerations:

• For patients with PDGFRβ gene rearrangements:

  • Imatinib mesylate is the treatment of choice 1
  • These patients often show good response to targeted therapy 1

• For patients with JAK2 mutations and significant thrombocytosis:

  • Consider JAK2 inhibitors such as ruxolitinib 2, 5
  • The combination of ruxolitinib and azacytidine has shown promising results with a 57% response rate in MDS/MPN patients 5

• For eligible patients with high-risk disease:

  • Allogeneic stem cell transplantation should be considered as the only potentially curative option 1, 4
  • Important prognostic factors for transplant outcomes include comorbidities, splenomegaly, karyotype alterations, and bone marrow blast percentage 4

Monitoring and Response Assessment

• Regular monitoring of blood counts is essential for all patients 2
• Response should be evaluated using the International Consortium Proposal of response criteria for MDS/MPNs 5
• Patients on cytoreductive therapy should be monitored for potential side effects 2

Common Pitfalls to Avoid

• Failing to exclude reactive monocytosis caused by infection or solid tumors before diagnosing CMML 3
• Not testing for specific genetic abnormalities (PDGFRα/β, JAK2) that may guide targeted therapy 1, 2
• Treating all patients with MDS/MPN as a single entity rather than recognizing the distinct biological and clinical characteristics of subtypes 1, 4
• Overlooking the potential for transformation to acute myeloid leukemia, which requires close monitoring, especially in patients with higher blast percentages 1