ALL Flashcards
What is acute lymphoblastic leukemia (ALL)?
A malignant proliferation of lymphoid precursor cells (lymphoblasts) in the bone marrow, blood, and other tissues.
What are the two main subtypes of ALL?
B-cell ALL (most common).
T-cell ALL.
What age groups are most affected by ALL?
Most common cancer in children (peak incidence: 2–5 years).
Smaller peak in adults, particularly >50 years.
Name some risk factors for ALL.
Genetic predisposition (e.g., Down syndrome, Klinefelter syndrome).
Prior chemotherapy or radiation therapy.
Exposure to high doses of ionizing radiation.
Certain infections (e.g., Epstein-Barr virus in some cases of T-cell ALL).
What is the underlying pathophysiology of ALL?
Genetic mutations in lymphoid precursor cells result in uncontrolled proliferation and a failure to mature, crowding out normal hematopoiesis.
What cytogenetic abnormalities are associated with ALL?
t(9;22): Philadelphia chromosome (BCR-ABL1 fusion, poor prognosis).
t(12;21): ETV6-RUNX1 fusion (common in children, good prognosis).
t(4;11): MLL rearrangement (poor prognosis, common in infants).
What are the common symptoms of ALL?
Symptoms of bone marrow failure: Fatigue, pallor, infections, bleeding/bruising.
Organ infiltration: Bone pain, lymphadenopathy, hepatosplenomegaly, testicular swelling.
CNS involvement: Headache, vomiting, cranial nerve palsies.
What are B-symptoms in ALL?
Fever, night sweats, and unintentional weight loss.
How does T-cell ALL often present?
With a mediastinal mass, causing symptoms like cough, dyspnea, or superior vena cava syndrome.
What are the key diagnostic steps for ALL?
Complete blood count (CBC) with peripheral smear: Blasts, anemia, thrombocytopenia, leukopenia, or leukocytosis.
Bone marrow biopsy: Hypercellular marrow with >20% lymphoblasts (diagnostic).
Immunophenotyping/flow cytometry: Identifies B-cell or T-cell lineage.
What markers are used to identify B-cell ALL?
CD19, CD20, CD22, CD79a.
What markers are used to identify T-cell ALL?
CD3, CD4, CD8, CD7.
What cytogenetic studies are critical in ALL?
Fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) for specific chromosomal translocations like t(9;22).
How is CNS involvement diagnosed in ALL?
Lumbar puncture with cerebrospinal fluid (CSF) analysis for blasts.
What are the key phases of ALL treatment?
Induction therapy: Achieve remission by eradicating detectable leukemia.
Consolidation therapy: Eliminate residual disease and prevent relapse.
Maintenance therapy: Prolong remission and eradicate minimal residual disease.
CNS prophylaxis: Prevent CNS relapse using intrathecal chemotherapy or cranial irradiation.
What drugs are commonly used in the treatment of ALL?
Chemotherapy: Vincristine, prednisone, asparaginase, anthracyclines.
Tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome-positive ALL (e.g., imatinib).
Methotrexate and cytarabine for CNS prophylaxis.
When is hematopoietic stem cell transplantation (HSCT) considered?
For high-risk or relapsed ALL.
What supportive therapies are needed during ALL treatment?
Blood product transfusions for anemia and thrombocytopenia.
Prophylactic antibiotics and antifungals to prevent infections.
Allopurinol or rasburicase for tumor lysis syndrome.
What factors influence the prognosis of ALL?
Age: Better prognosis in children; worse in adults and infants.
Cytogenetics: Good prognosis with t(12;21), poor with t(9;22).
White blood cell count at diagnosis: Higher counts indicate poorer outcomes.
Response to induction therapy: Minimal residual disease (MRD) negativity indicates better prognosis.
What are common complications of ALL and its treatment?
Infection: Due to neutropenia and immunosuppression.
Tumor lysis syndrome: Hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia.
CNS relapse: Neurological deficits due to leukemic infiltration.
Long-term: Secondary malignancies, cardiotoxicity (anthracyclines), growth retardation (cranial irradiation).
What is the mechanism of action of vincristine?
Vincristine binds to tubulin and inhibits microtubule formation, preventing mitotic spindle assembly and arresting cell division at metaphase.
What is the mechanism of action of anthracyclines (e.g., doxorubicin, daunorubicin)?
Intercalate into DNA, inhibiting topoisomerase II and preventing DNA replication.
Generate free radicals, causing oxidative damage to DNA and cell membranes.
How does asparaginase work in ALL?
Asparaginase depletes asparagine, an amino acid essential for leukemic cell survival, leading to apoptosis.
What is the mechanism of action of methotrexate?
Methotrexate inhibits dihydrofolate reductase, blocking folate metabolism and DNA synthesis, particularly in rapidly dividing cells.
How does cytarabine (Ara-C) work?
Cytarabine is a nucleoside analog that inhibits DNA polymerase, halting DNA synthesis and repair in dividing cells.
What is the mechanism of action of imatinib in Philadelphia chromosome-positive ALL?
Imatinib selectively inhibits BCR-ABL tyrosine kinase, preventing phosphorylation of proteins needed for leukemic cell proliferation and survival.
Why is methotrexate used intrathecally in ALL?
Methotrexate penetrates the cerebrospinal fluid (CSF), preventing or treating leukemic infiltration of the CNS.
How does allopurinol prevent tumor lysis syndrome in ALL?
Allopurinol inhibits xanthine oxidase, reducing uric acid formation from purine breakdown during cell lysis.
What is the mechanism of action of rasburicase in tumor lysis syndrome?
Rasburicase catalyzes the conversion of uric acid to allantoin, a more soluble compound, rapidly reducing serum uric acid levels.
Why are glucocorticoids (e.g., prednisone, dexamethasone) used in ALL?
Glucocorticoids induce apoptosis in lymphoid cells by binding to glucocorticoid receptors and altering gene transcription.
