Medicine · Hematological Malignancies (Leukemias, Lymphoma, Myeloma, Myeloproliferative)

A 45-year-old man presents with splenomegaly, leukocytosis (WBC 120 × 10⁹/L with basophilia and eosinophilia on differential), low LAP score, and the Philadelphia chromosome is detected by cytogenetics. He is in chronic phase CML. According to current guidelines, what is the first-line treatment?

  • A Second-generation TKI (nilotinib or dasatinib) preferred over imatinib for deeper molecular responses
  • B Hydroxyurea to reduce WBC count followed by allogenic SCT
  • C Imatinib 400 mg daily as first-line TKI
  • D Interferon-alpha as the standard of care
Correct answer: A. Second-generation TKI (nilotinib or dasatinib) preferred over imatinib for deeper molecular responses

Explanation

Both second-generation TKIs (nilotinib and dasatinib) achieve faster and deeper molecular responses (MR4, MR4.5) compared to imatinib in chronic-phase CML, as demonstrated by the ENESTnd (nilotinib) and DASISION (dasatinib) trials. Current NCCN and ELN 2020 guidelines recommend any approved TKI (imatinib, nilotinib, dasatinib, bosutinib) as first-line options. However, in young patients who may aim for treatment-free remission (TFR), second-generation TKIs are preferred due to higher rates of deep molecular remission (MMR and MR4.5). Allogenic SCT is reserved for blast phase or TKI failure.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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