A 35-year-old man presents with fever, bone pain, and fatigue. CBC shows WBC 45,000/µL with 80% blasts; blasts are MPO-negative, PAS-positive, and express CD10, CD19, CD22. Cytogenetics reveal t(9;22)(q34;q11). The prognosis of this B-ALL is primarily determined by:

• A Age >30 years at diagnosis
• B High WBC count at presentation
• C PAS positivity on cytochemistry
• D Presence of Philadelphia chromosome (BCR-ABL1 fusion) ✓

Explanation

Philadelphia chromosome-positive ALL (Ph+ ALL, BCR-ABL1) is the single most important adverse prognostic factor in adult B-ALL, historically associated with very poor outcomes (5-year OS <20% with chemotherapy alone). The addition of tyrosine kinase inhibitors (imatinib, dasatinib, ponatinib) has dramatically improved outcomes but Ph+ ALL still requires allogeneic stem cell transplantation in CR1. High WBC and age are also adverse factors but BCR-ABL1 takes precedence as the defining high-risk molecular marker.

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

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Written and medically reviewed by the StethoPrep medical team.