The malignant clone arises from hematopoietic progenitors in the bone marrow or lymphatic system – ⬆️of immature nonfunctioning leukemic cells
ALL
accumulation of immature lymphoblasts in the bone marrow
Seen in ~50% of elderly B-ALL patients
Philadelphia chromosome-positive (Ph+ ALL, BCR/ABL)
⬆️ALL risk in some chromosomal disorders:
Down syndrome: ↑ALL in childhood, ↑AML in adulthood
Common CBC abnormalities in ALL
Anemia (Hb <7–8 g/dL in ~1/3 of adults)
Thrombocytopenia (critical <20 ×10⁹/L in ~20%)
Neutropenia (<0.5 ×10⁹/L in ~20%) → ↑infection risk
Confirm leukemia, distinguish ALL vs AML, assess immunologic, cytogenetic, molecular markers
BONE MARROW EXAMINATION
BMA findings in ALL
usually heavily packed with blasts (>90% in ~70% of cases)
normal hematopoiesis greatly reduced or absent
biopsy shows hypercellularity, replacement of fat, sometimes fibrosis
Routine for ALL
LUMBAR PUNCTURE AND CNS EVALUATION
CNS leukemia if ≥5 cells/μL or blasts in CSF
either before therapy or after remission to avoid iatrogenic seeding
Residual leukemia undetectable by microscopy
MINIMAL RESIDUAL DISEASE (MRD)
flow cytometry, PCR for Ig/TCR rearrangements, fusion genes (BCR-ABL, MLL-AF4)
Strongest predictor of disease free survival (DFS) and overall survival
molecular complete remission (mCR)
Most important prognostic factor
MRD during therapy
Leukemic cells not detectable by light microscopy (<5% blast cells in bone marrow [BM])
COMPLETE hematologic
remission (CHR)
Patient in complete remission, MRD not detectable, ≤0.01% = ≤1 leukemia cell in 10,000 BM cells
Complete molecular
remission/MRD negativity
Patient in complete hematologic remission, but not in molecular complete remission >0.01%
Molecular failure/MRD
positivity
Patient still in complete remission, had prior
molecular complete remission, leukemic blast cells in BM not detectable (<5%)
Molecular relapse/MRD
positivity
>5% blast cells in BM/blood
Hematologic relapse
Reduce tumor burden, prevent TLS, allow supportive care
Pre-phase therapy
Glucocorticoids (prednisone 20–60 mg/d or dexamethasone 6–16 mg/d, IV/PO) ± vincristine/cyclophosphamide, 5–7 days
Achieve complete remission (CR) or molecular CR
Induction therapy
Vincristine, glucocorticoids, anthracyclines ± cyclophosphamide/cytarabine; L-asparaginase (pegylated for longer effect), dexamethasone preferred for CNS penetration
Eliminate residual leukemia, reach sanctuary sites (CNS, testes)
Post-remission consolidation
6–8 cycles, often HD methotrexate (1–5 g/m²) ± HD cytarabine (1–3 g/m²)
Prevent relapse
Maintenance therapy
6-mercaptopurine + methotrexate ± intrathecal therapy; duration 2–2.5 years for B-ALL/T-ALL; TKI added for Ph+ ALL
Prevent CNS leukemia and peripheral spread
CNS Prophylaxis / Treatment
Intrathecal chemotherapy: methotrexate ± cytarabine ± glucocorticoids
Systemic HD therapy: HD methotrexate or cytarabine
Cranial radiation therapy (CRT): 18–24 Gy in 12 fractions
For high-risk patients or MRD-positive in first CR; all relapsed patients
Stem Cell Transplantation (SCT)
Immunotherapies
Rituximab CD20
Inotuzumab ozogamicin CD22
Blinatumomab CD19/CD3 bispecific
CAR-T cells CD19
Viral infections associated with ALL
HTLV
EBV