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

A 52-year-old patient with newly diagnosed Philadelphia chromosome-positive ALL is being evaluated for treatment. Per current evidence, which agent should be added to chemotherapy induction?

  • A Imatinib (standard dose 400 mg/day)
  • B Rituximab as the sole targeted therapy
  • C Ponatinib (a third-generation TKI) or dasatinib
  • D Venetoclax plus navitoclax
Correct answer: C. Ponatinib (a third-generation TKI) or dasatinib

Explanation

Ph+ ALL requires a BCR-ABL1 tyrosine kinase inhibitor added to chemotherapy; dasatinib or ponatinib are now preferred over imatinib because dasatinib penetrates the CNS (important given CNS relapse risk in ALL) and ponatinib covers T315I mutations and provides superior MRD negativity rates per GIMEMA and MDACC studies. The HYPER-CVAD plus ponatinib regimen achieves >80% MRD negativity. Imatinib remains an alternative where the others are unavailable. Rituximab is added only when CD20+ (which Ph+ ALL often co-expresses). Venetoclax is being studied in trials but is not standard.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.

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