Acute Myeloid Leukemia
Acute Myeloid Leukemia: Excerpt from The 5-Minute Pediatric Consult
David T. Teachey, MDTammy I. Kang, MD (4th Edition)
Acute Myeloid Leukemia - BASICS
Acute Myeloid Leukemia - description
- Acute myeloid leukemia (AML) is a block in differentiation and an unregulated proliferation of myeloid progenitor cells.
- Classified according to the World Health Organization (WHO) Classification (1999)
- Formerly classified by French-American-British (FAB) Classification
- WHO classification based on genetic alterations, whereas FAB based on morphology
Acute Myeloid Leukemia - epidemiology
- 7th most common pediatric malignancy
- Leukemia in 1st 4 weeks of life is usually AML
- Ratio of AML to acute lymphoblastic leukemia (ALL) throughout childhood is 1:4.
- Boys and girls are equally affected.
Acute Myeloid Leukemia - incidence
- Incidence peaks at 2 years and again at 16 years of age.
- 500 children/year in the US
Acute Myeloid Leukemia - risk factors
Acute Myeloid Leukemia - genetics
- Only 20–30% of pediatric blasts have a normal karyotype, vs. 40–50% in adults.
- 60% of abnormal karyotypes fall into known subgroups
- Translocations or duplications of the MLL gene at 11q23 and monosomy 7 are found in many cases of therapy-induced AML and carry a poor prognosis.
- Translocations t(8;21), t(15;17), and inv(16) carry a better prognosis.
Acute Myeloid Leukemia - pathophysiology
- Principal defect is a block in the differentiation of primitive myeloid precursor cells
- 2 predominant mechanisms have been identified:
- Defect at the level of transcriptional activation
- Defects in the signaling pathway of hematopoietic growth factors. The proto-oncogene Ras is mutated in up to 1/3 of patients with AML.
Acute Myeloid Leukemia - etiology
- Exact cause unknown
- Acquired risk factors:
- Exposure to benzene
- Exposure to ionizing radiation
- Therapy induced, from chemotherapy for a prior malignancy
- Alkylating agents such as cyclophosphamide, nitrogen mustard, chlorambucil, and melphalan (typically presents several years after therapy)
- Epipodophyllotoxins such as VP16, VM26 (typically occurs within 2 years after therapy and is characterized by rearrangements involving 11q23)
- Certain congenital syndromes that carry an increased risk of AML:
- Fanconi anemia
- Bloom syndrome
- Neurofibromatosis type I
- Down syndrome
- Severe congenital anemia (i.e., Kostmann disease treated with granulocyte colony-stimulating factor)
- Diamond Blackfan anemia
- Paroxysmal nocturnal hemoglobinemia
- Li-Fraumeni syndrome
Acute Myeloid Leukemia - DIAGNOSIS
Acute Myeloid Leukemia - signs & symptoms
Acute Myeloid Leukemia - history
Children with AML can present with very few symptoms or with life-threatening sepsis or hemorrhage. Common symptoms include the following:
- Fever: 30–40%
- Pallor: 25%
- Weight loss/anorexia: 22%
- Fatigue: 19%
- Bleeding (i.e., cutaneous, mucosal, menorrhagia): 33%
- Bone or joint pain: 18%
Acute Myeloid Leukemia - physical exam
- Signs of anemia:
- Pallor, fatigue, headache, dyspnea, systolic flow murmur
- Signs of thrombocytopenia:
- Petechiae, bruising, epistaxis, gingival bleeding
- Signs of infection:
- Fever
- Lingering bacterial infections of lung, sinuses, gingiva, perirectal area, skin
- Other exam findings:
- Hepatomegaly
- Splenomegaly
- Lymphadenopathy
- Gingival hyperplasia
- Papilledema, cranial nerve palsies (rare)
- Colorless or slightly purple subcutaneous nodules: “Blueberry muffin” lesions of leukemia cutis (more commonly seen in neonates)
Acute Myeloid Leukemia - tests
Techniques such as fluorescence in situ hybridization, Southern blotting, and reverse transcriptase–polymerase chain reaction are becoming necessary diagnostic tools for AML.
Acute Myeloid Leukemia - lab
- CBC:
- Anemia, thrombocytopenia, elevated or low total WBC peripheral smear
- Myeloblasts may be seen.
- Prothrombin time (PT)/partial thromboplastin time (PTT) fibrin spit products:
- Elevated in some cases, especially with acute promyelocytic leukemia (M3)
- Can have severe, life-threatening disseminated intravascular coagulation (DIC)
- Electrolytes (abnormalities associated with tumor lysis syndrome):
- Hyperkalemia
- Hypocalcemia
- Hyperphosphatemia
- Hyperuricemia
- CSF analysis for cell count and cytology:
- >5 WBC/mm3 is suggestive of CNS disease.
- 5–15% of cases have CNS involvement at diagnosis.
Acute Myeloid Leukemia - diag proced-surgery
Bone marrow aspirate:
- >20% myeloblasts is diagnostic.
- Confirm with immunophenotyping and cytochemistry
Acute Myeloid Leukemia - pathological findings
- Immunophenotyping:
- Blasts positive for myeloid-associated surface antigens (CD11b, CD13, CD14, CD15, CD33, or CD36) in 90% of cases
- Lymphoid markers: T and B cells may be present in 30–60% of pediatric patients.
- CD41, CD42, and CD61 (megakaryocytic)
- Morphology:
- Large blasts with low nuclear/cytoplasmic ratio
- Multiple nucleoli and cytoplasmic granules
- Cytochemistry:
- Blasts are positive for myeloperoxidase and Sudan black and usually negative for periodic acid-Schiff (PAS) and terminal deoxynucleotide transferase (TdT).
Acute Myeloid Leukemia - differencial diagnosis
- Myeloid blast crisis of chronic myeloid leukemia (Philadelphia chromosome–positive)
- ALL
- Leukemoid reaction
- Exaggerated leukocytosis
Acute Myeloid Leukemia - TREATMENT
Acute Myeloid Leukemia - initial stabilization
Children with suspected AML should have immediate evaluation with physical exam, history, and laboratory data including CBC, PT/PTT, electrolytes, calcium, phosphorus, uric acid, and creatinine.
Acute Myeloid Leukemia - general measures
- Hydration, alkalization, and allopurinol during induction
- Rasburicase should be considered in patients with marked elevations in uric acid and renal compromise (contraindicated in patients with G6PD deficiency).
- Blood product support:
- Avoid products from family members, due to the possibility of allogeneic bone marrow transplant.
- Broad-spectrum antibiotics and antifungal therapy for fever and neutropenia
- Prophylactic trimethoprim/sulfamethoxazole for Pneumocystis infection
- Nystatin/fluconazole for fungal prophylaxis
Acute Myeloid Leukemia - special therapy
Allogeneic bone marrow transplant may be the best treatment for AML in 1st remission.
Acute Myeloid Leukemia - medication
- Patients are treated with 6–9 months of intensive chemotherapy given in cycles.
- The most effective drugs for remission induction in AML are anthracyclines (e.g., doxorubicin, daunomycin, and mitoxantrone) and cytarabine (Ara-C).
- Etoposide (VP-16), gemtuzumab (anti-CD33 monoclonal antibody), dexamethasone, l-asparaginase, and 6-thioguanine are added in some regimens (remission rate is ~70–85%).
- High rate of remission induction with all-trans-retinoic acid in acute promyelocytic leukemia
- Intrathecal Ara-C for CNS prophylaxis
Acute Myeloid Leukemia - FOLLOW UP
Acute Myeloid Leukemia - prognosis
- 85% achieve remission with intensive chemotherapy.
- ~30–50% achieve long-term survival (>5 years after diagnosis).
- Factors associated with low remission induction rate (poor prognosis):
- WBC count >100,000/mm3
- Monosomy 7
- Secondary AML or prior myelodysplastic syndrome
- FLT3 mutation
Acute Myeloid Leukemia - complications
- Bleeding (usually secondary to thrombocytopenia)
- DIC occurs in some types of AML, including acute promyelocytic leukemia (M3).
- Treat aggressively with fresh frozen plasma and platelet transfusions.
- Infection:
- 40% of patients are febrile at diagnosis.
- Empiric antibiotic therapy must be started after blood cultures are obtained.
- Leukostasis:
- Intravascular clumping of blasts causing hypoxia, infarction, and hemorrhage
- Usually with WBC >200,000/mm3
- Brain and lung are commonly affected organs.
- Leukopheresis or exchange transfusion may be indicated for patients who are symptomatic with extremely high blast counts.
- Tumor lysis syndrome:
- Refers to the metabolic consequences from the release of cellular contents of dying leukemic cells
- Hyperuricemia can lead to renal failure.
- Hyperkalemia, hyperphosphatemia, and secondary hypocalcemia can be life threatening.
- Patients should be hydrated with fluid containing bicarbonate and given allopurinol.
Acute Myeloid Leukemia - patient monitoring
- Blood counts monthly for 1st year, every 4 months for the 2nd year, and every 6 months thereafter
- Liver and kidney function tests every 3–6 months
- Cardiac function should be checked every 12 months.
- Endocrine function should be tested in pubertal children.
Acute Myeloid Leukemia - bibliography
- Hastle H, Niemeyer CM, Chessells JM. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative disease. Leukemia. 2003;17:277–282.
- Hurwitz CA, Mounce KG, Grier HE. Treatment of patients with AML: Review of clinical trials of past decade. J Pediatr Hematol Oncol. 1995;17:185–197.
- Kersey JH. Fifty years of studies of biology and therapy of childhood leukemia. Blood. 1997;90:4243–4251.
- Kottaridis PD, Gale RE, Linch DC. Prognostic implication of the presence of FLT3 mutations in patients with acute myeloid leukemia. Leuk Lymphoma. 2003;44:905–913.
- Langmuir P, Aplenc R, Lange B. Acute myeloid leukemia in children. Best Pract Res Clin Haematol. 2001;14:77–93.
- Woods W. Curing childhood acute myeloid leukemia (AML) at the half-way point: Promises to keep and miles to go before we sleep. Pediatr Blood Cancer. 2006;46;565–569.
Acute Myeloid Leukemia - CODES
Acute Myeloid Leukemia - icd9
205.0 Myeloid leukemia
Acute Myeloid Leukemia - FAQ
- Q: Is an indwelling line required for therapy?
- A: Always
- Q: Are repeated hospitalizations likely?
- A: Repeated hospitalizations are needed for chemotherapy and infectious complications.
- Q: Can the child go to school?
- A: May be able to go intermittently during therapy
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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