How to manage a 7-year-old patient with Acute Myeloid Leukemia (AML) and Juvenile Idiopathic Arthritis (JIA) who is currently on azacitidine, venetoclax, and midostaurin for AML, after discontinuing sulfasalazine and steroids?

Management of AML with FLT3 Mutation and History of JIA in a 7-Year-Old Patient

The current treatment regimen of azacitidine, venetoclax, and midostaurin is appropriate for this 7-year-old patient with AML harboring FLT3-TKD mutation, and the discontinuation of sulfasalazine and steroids was necessary to prioritize AML treatment.

Current Treatment Analysis

• The patient is currently receiving a combination of azacitidine and venetoclax, which has been completed for 7 days (until 2/10/25), with midostaurin added on 3/10/25 1
• Midostaurin is specifically indicated for FLT3-mutated AML, targeting the FLT3-TKD mutation identified in this patient 2
• The discontinuation of sulfasalazine (23/9/25) and oral prednisolone (30/9/25) was appropriate to avoid potential drug interactions and immunosuppression complications during AML treatment 1

Treatment Rationale for AML with FLT3 Mutation

• For FLT3-mutated AML, midostaurin is recommended to be added to standard treatment regimens, as it specifically targets the FLT3 mutation 1
• The combination of azacitidine and FLT3 inhibitors has demonstrated efficacy in FLT3-positive AML, with reported CR/CRi rates of 67% in clinical studies 1
• Recent evidence shows that venetoclax combined with azacitidine is highly effective in AML, with median overall survival of 14.7 months versus 9.6 months with azacitidine alone 3
• For pediatric patients with AML, intensive anthracycline and cytarabine-based therapy is typically recommended, but the current regimen may be appropriate considering the patient's specific molecular profile 1

Management of KMT2A::GAS7 Fusion

• The KMT2A rearrangement (KMT2A::GAS7 fusion) identified in this patient is particularly relevant, as recent evidence shows excellent response rates with the combination of azacitidine, venetoclax, and menin inhibitors in KMT2A-rearranged AML 4
• In a recent study of KMT2A-rearranged AML, the combination of azacitidine and venetoclax achieved a 100% overall response rate with 88.9% composite complete remission 4
• While the current regimen does not include a menin inhibitor, the azacitidine-venetoclax combination still provides a strong foundation for treating KMT2A-rearranged AML 4, 5

Monitoring and Potential Complications

• Close monitoring for differentiation syndrome is essential, particularly with the use of FLT3 inhibitors, which may be managed with corticosteroids and hydroxyurea if it occurs 1
• Regular assessment for hyperleukocytosis is important, as it can lead to hemorrhagic events, tumor lysis syndrome, and infections; hydroxyurea may be used if WBC counts exceed 100 × 10^9/L 1
• Careful monitoring of hematologic parameters is crucial, as prolonged Grade 4 neutropenia and thrombocytopenia have been reported in pediatric patients receiving midostaurin in combination with chemotherapy 2
• Midostaurin may cause QT interval prolongation, requiring ECG monitoring 2

Management of Juvenile Idiopathic Arthritis

• The patient's JIA symptoms had improved with sulfasalazine after failing methotrexate and hydroxychloroquine 1
• Currently, JIA management should be deferred while focusing on AML treatment, as the leukemia poses the more immediate life-threatening condition 1
• After achieving remission of AML, JIA treatment can be reconsidered, potentially with agents that have less bone marrow suppression 1
• The development of pancytopenia while on JIA treatment was likely related to the underlying AML rather than medication toxicity 1

Follow-up and Response Assessment

• Bone marrow evaluation should be performed 14-21 days after starting therapy to assess response 1
• For patients achieving complete remission, consideration for allogeneic stem cell transplantation should be evaluated, especially given the high-risk molecular features (KMT2A rearrangement and FLT3 mutation) 1
• Measurable residual disease (MRD) assessment is important for determining prognosis and guiding subsequent treatment decisions 5
• If the patient responds well to the current regimen, maintenance therapy with midostaurin could be considered, although its benefit after chemotherapy consolidation remains unclear 1

Treatment Adjustments if Needed

• If the patient fails to respond to the current regimen, alternative options include:
  • Intensive induction chemotherapy with cytarabine and anthracycline if the patient's condition permits 1
  • Clinical trial enrollment, particularly those investigating novel agents for FLT3-mutated or KMT2A-rearranged AML 1
  • Consideration of allogeneic stem cell transplantation once remission is achieved 1
• For refractory disease, combination approaches such as adding targeted therapies to the current regimen may be considered 5

The current treatment approach with azacitidine, venetoclax, and midostaurin represents an appropriate strategy for this pediatric patient with AML harboring FLT3-TKD mutation and KMT2A rearrangement, while temporarily deferring JIA management until AML is controlled.