Infant ALL t(4;11) KMT2A/MLL MCQ — NEET PG Practice Question | NEETPGAI
Infant ALL t(4;11) KMT2A/MLL
medium
microscope Pathology
A 7-month-old infant presents with severe respiratory distress, hepatosplenomegaly, and a white blood cell count of 280,000/µL. Bone marrow aspirate shows 85% lymphoblasts with CD19+, CD22+, TdT+, CD10−, and myeloid antigen co-expression. FISH analysis reveals the translocation marked **A** in the diagram. Which of the following is the most appropriate next step in management for this high-risk patient?
A. Epipodophyllotoxin-based consolidation to minimize long-term toxicity
B. Standard-risk ALL chemotherapy protocol without CNS-directed therapy
C. Observation with supportive care alone, as prognosis is favorable in infants <1 year
D. Allogeneic hematopoietic stem cell transplantation in first complete remission after intensified induction chemotherapy
Explanation
Why allogeneic hematopoietic stem cell transplantation in first complete remission after intensified induction chemotherapy is right
The translocation marked A is t(4;11) KMT2A-AFF1, which defines the highest-risk subset of infant acute lymphoblastic leukemia. According to Robbins Basic Pathology and the INTERFANT-06 protocol, KMT2A-rearranged infant ALL is characterized by profound hyperleukocytosis (WBC >100,000/µL, often >300,000), massive hepatosplenomegaly, CNS involvement risk (~15%), and a dismal 5-year event-free survival of only 30–40%. This patient meets multiple high-risk criteria: age <1 year, WBC >300,000/µL, and confirmed KMT2A rearrangement. Management requires intensified chemotherapy (dexamethasone, vincristine, asparaginase, daunorubicin induction; MARMA-style consolidation with high-dose cytarabine and methotrexate; CNS-directed intrathecal triple therapy) followed by allogeneic HSCT in CR1 for high-risk infants, which is the standard of care per INTERFANT protocols.
Why each distractor is wrong
Observation with supportive care alone, as prognosis is favorable in infants <1 year: KMT2A-rearranged infant ALL is NOT favorable—it is the worst-prognosis pediatric ALL subset with 5-year EFS ~30–40%. Observation alone would be fatal.
Standard-risk ALL chemotherapy protocol without CNS-directed therapy: KMT2A-rearranged infant ALL requires intensified, hybrid ALL/AML-style chemotherapy with mandatory CNS-directed intrathecal triple therapy, not standard-risk protocols. CNS involvement occurs in ~15% at diagnosis and must be prevented.
Epipodophyllotoxin-based consolidation to minimize long-term toxicity: Epipodophyllotoxins (etoposide) should be avoided in KMT2A-rearranged leukemias due to increased risk of secondary therapy-related AML. High-dose cytarabine and methotrexate are preferred.
High-YieldNEET PG
KMT2A-rearranged infant ALL (t(4;11) in ~70–80% of cases) is the highest-risk pediatric ALL subset; management is intensified chemotherapy + allogeneic HSCT in CR1 for high-risk infants, with menin inhibitors emerging as novel salvage options.
