Treatment of ALL with Aberrant Myeloid Expression
Treat ALL with aberrant myeloid expression using standard ALL-directed multiagent chemotherapy regimens, not AML protocols, as the aberrant myeloid markers do not change the fundamental lymphoid nature of the disease or alter treatment approach. 1
Core Treatment Principles
The presence of aberrant myeloid antigen expression on lymphoblasts is a relatively common immunophenotypic finding in ALL but does not constitute mixed phenotype acute leukemia (MPAL) and does not warrant AML-directed therapy. 1, 2
Standard Induction Approach
For adults <65 years with B-cell ALL and aberrant myeloid markers:
Initiate intensive multiagent induction with the 4-drug backbone: vincristine, anthracycline (daunorubicin or doxorubicin), corticosteroid (dexamethasone or prednisone), and L-asparaginase 1, 2
High-intensity regimen options include CALGB 9111, ECOG 1910, or dose-adjusted Hyper-CVAD 1, 2
Moderate-intensity alternatives include modified DFCI 91-01, GMALL, GRAALL, or EWALL regimens 1, 2
Add rituximab to GMALL if CD20-positive disease is present 1, 2
Critical Treatment Components
CNS prophylaxis is mandatory from induction start:
Triple intrathecal therapy (methotrexate, cytarabine, hydrocortisone) is preferred over methotrexate alone 2, 3
Prophylactic cranial irradiation is not recommended with effective systemic and intrathecal therapy 2
Dexamethasone provides superior CNS penetration compared to prednisone, reducing CNS relapse risk, though it carries higher risks of induction mortality, neuropsychiatric events, and myopathy 2
MRD-Directed Treatment Intensification
MRD assessment after induction is mandatory and determines subsequent therapy: 1, 2, 3
MRD-negative patients: Proceed with standard consolidation and maintenance 2
MRD-positive or rising MRD: Add blinatumomab or inotuzumab ozogamicin before consolidation 2, 3
Blinatumomab achieves 88% complete MRD response in patients with MRD ≥10⁻³ 2
Risk Stratification and Transplant Consideration
High-risk features requiring treatment intensification include: 2, 3
- Age ≥35 years
- WBC >30 × 10⁹/L
- Time to complete remission >4 weeks
- Poor-risk cytogenetics
- MRD ≥0.01% at end of induction
For high-risk patients, consider allogeneic hematopoietic cell transplantation in first complete remission after achieving MRD negativity 1, 2, 3
Treatment for Older Adults (≥65 years)
For patients ≥65 years or those with substantial comorbidities: 1
- Low-intensity options: Vincristine and prednisone, or POMP
- Moderate-intensity options: ALLOLD07, EWALL, GMALL, GRAALL, or modified DFCI 91-01
- Inotuzumab ozogamicin monotherapy (category 2B) per ALLIANCE A041703 1
- Dose modifications required for systemic therapy agents as needed 1
Common Pitfalls to Avoid
Do not treat as AML based solely on aberrant myeloid marker expression—this is a critical error that leads to inappropriate therapy selection 1, 2
Do not delay MRD assessment as this guides treatment intensification decisions 2, 3
Do not omit CNS prophylaxis during induction—this must begin immediately 2, 3
Do not use chronologic age alone to determine treatment intensity; assess performance status, comorbidities, and end-organ function 1, 2
Do not proceed to allogeneic transplant with MRD-positive status without attempting additional therapy to achieve MRD negativity 3