Acute lymphoblastic leukemia
Acute lymphoblastic leukemia is a clonal proliferation of lymphoid precursor blasts that replace the bone marrow, the most common cancer in children, diagnosed when TdT-positive lymphoblasts make up 20% or more of the marrow and classified by flow cytometry immunophenotype and cytogenetics. Treatment is multi-phase chemotherapy (induction, consolidation, CNS prophylaxis, maintenance for up to 2 years), with a tyrosine kinase inhibitor added for Philadelphia-chromosome-positive disease and aggressive tumor lysis prophylaxis at the start of therapy.
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What this article covers
- Overview
Definition: acute lymphoblastic leukemia (ALL) is a clonal, uncontrolled proliferation of an immature lymphoid precursor cell (lymphoblast) that infiltrates and replaces the bone marrow, spills into…
- Epidemiology
Peak incidence in early childhood: ALL is far more common in children than adults; adults account for a minority of cases but have inferior outcomes even with pediatric-style regimens.
- Risk factors
Down syndrome (trisomy 21): the strongest recognized genetic association; ALL is the more likely acute leukemia after age 5, whereas AML predominates before age 5.
- Pathophysiology
Clonal arrest of a lymphoid precursor: an acquired genetic alteration blocks normal maturation of a B- or T-lymphoid progenitor at an immature (blast) stage while allowing unchecked proliferation.
- Clinical features
Marrow-failure triad: fatigue and pallor from anemia, bleeding (gingival, petechiae, epistaxis) from thrombocytopenia, and fever or infection from functional neutropenia, developing over days to weeks.
- Differential diagnosis
Acute myeloid leukemia: also ≥ 20% marrow blasts and marrow failure, but blasts are myeloperoxidase-positive, may show Auer rods, and lack TdT; gingival hyperplasia suggests a monocytic AML subtype (acute myeloid leukemia).
- Diagnosis
Establish the diagnosis by marrow blast percentage plus lineage-defining immunophenotype: the defining threshold is ≥ 20% lymphoblasts in peripheral blood or bone marrow, with the blasts confirmed as…
- Management
Stabilize oncologic emergencies before or alongside induction: treat symptomatic leukostasis (WBC typically 50,000-100,000/mm³) with urgent cytoreduction (induction chemotherapy, leukapheresis, or…
- Complications
Tumor lysis syndrome: hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, and acute kidney injury, most likely with bulky, high-blast-count disease at the start of cytoreductive therapy.
- Prognosis
Age is the dominant prognostic factor: ALL in children is often curable, whereas survival in adults remains inferior despite pediatric-style regimens.
- Prevention
No proven primary prevention: no established modifiable-risk-factor strategy prevents de novo ALL; prevention efforts instead target complications of disease and treatment.
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- Lymphoblastic lymphoma
Lymphoblastic lymphoma is an aggressive precursor lymphoid neoplasm identical to acute lymphoblastic leukemia but presenting as a mass with under 20% marrow blast involvement, classically a T-cell anterior mediastinal mass in an adolescent or young adult male causing respiratory compromise or superior vena cava syndrome. It is diagnosed by biopsy showing TdT-positive lymphoblasts and treated on ALL-type multi-agent chemotherapy protocols with mandatory central nervous system prophylaxis.
- Acute myeloid leukemia
Acute myeloid leukemia is a clonal proliferation of myeloid precursors that fails to differentiate, defined by myeloblasts at or above 20% of the bone marrow or blood, and it presents with cytopenias from marrow replacement plus, in acute promyelocytic leukemia, a coagulopathic emergency. Diagnosis rests on marrow blast count, immunophenotype, and cytogenetic and molecular testing that set both classification and risk, while treatment is intensive induction chemotherapy or ATRA-arsenic trioxide for APL, followed by risk-adapted consolidation.
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Chronic myeloid leukemia is a myeloproliferative neoplasm driven by the Philadelphia chromosome t(9;22), which produces the constitutively active BCR-ABL1 tyrosine kinase and marked, left-shifted granulocytosis with a low leukocyte alkaline phosphatase score. Diagnosis is confirmed by cytogenetics or molecular testing for BCR-ABL1, and a BCR-ABL tyrosine kinase inhibitor such as imatinib is first-line, continued indefinitely with molecular-response monitoring, reserving allogeneic transplant for TKI failure or blast crisis.
- Tumor lysis syndrome (TLS)
Tumor lysis syndrome is a metabolic oncologic emergency in which massive tumor cell breakdown, spontaneous or chemotherapy-induced, releases potassium, phosphate, and nucleic acids into the blood, producing hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia that can precipitate acute kidney injury, arrhythmia, seizure, and death. Risk-stratified prophylaxis with hydration plus allopurinol or rasburicase before chemotherapy, and aggressive correction of electrolytes with renal replacement therapy when needed, are the cornerstones of management.
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Neutropenic fever is an oncologic emergency defined as a single oral temperature of 38.3 C or higher, or 38.0 C sustained for 1 hour, with an ANC of 500/microL or lower, most often during the chemotherapy nadir. Management is empiric antipseudomonal beta-lactam therapy within 60 minutes, with vancomycin, antifungal therapy, and growth factors added only for specific indications.
- Neutropenia
Neutropenia is a reduced absolute neutrophil count that raises infection risk sharply once the count falls below 500/microL, most often from chemotherapy or another marrow-suppressing or idiosyncratic drug. Diagnosis rests on a repeat CBC with differential and smear review followed by a directed search for cause, and management centers on stopping the offending agent, treating any underlying disease, and using G-CSF and neutropenic precautions when the count is low or the patient is febrile.
- Aplastic anemia
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- Chronic lymphocytic leukemia
Chronic lymphocytic leukemia is the most common adult leukemia, a clonal proliferation of mature B lymphocytes usually discovered as incidental lymphocytosis in older adults with smudge cells on smear. Diagnosis rests on absolute B-lymphocytosis with a characteristic flow cytometry immunophenotype, and asymptomatic early-stage disease is observed while symptomatic or progressive disease is treated with targeted agents such as ibrutinib and venetoclax.
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