Acute Myelogenous Leukemia

Peter Rintels, M.D.

Basic Information

Definition

Acute myelogenous leukemia (AML) is a malignancy of hematopoietic progenitor cells that would normally give rise to mature granulocytes. Strictly speaking, AML is a subset of acute nonlymphocytic leukemia (ANLL), a designation that broadly distinguishes these diseases from the biologically distinct leukemias of lymphocytic origin. ANLL includes leukemias involving the spectrum of myeloid stem cells, including precursors of granulocytes, monocytes, erythrocytes, and megakaryocytes. Acute promyelocytic leukemia is a distinct leukemia syndrome that is part of the ANLL spectrum, but that has very different treatment implications. ANLL is characterized by maturation failure of myeloid progenitors, excessive numbers of immature progenitors (“blasts”), and various degrees of bone marrow failure (neutropenia, thrombocytopenia, anemia).

Synonyms

Acute nonlymphocytic leukemia (ANLL)
Acute myeloid leukemia (AML)

ICD-10CM CODES
C92.60	Acute myeloid leukemia with 11q23-abnormality not having achieved remission
C92.61	Acute myeloid leukemia with 11q23-abnormality in remission
C92.62	Acute myeloid leukemia with 11q23-abnormality in relapse
C92.90	Myeloid leukemia, unspecified, not having achieved remission
C92.91	Myeloid leukemia, unspecified in remission
C92.92	Myeloid leukemia, unspecified in relapse
C92.A0	Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
C92.A1	Acute myeloid leukemia with multilineage dysplasia, in remission
C92.A2	Acute myeloid leukemia with multilineage dysplasia, in relapse
C92.Z0	Other myeloid leukemia not having achieved remission
C92.Z1	Other myeloid leukemia, in remission
C92.Z2	Other myeloid leukemia, in relapse
C92.00	Acute myeloblastic leukemia, not having achieved remission
C92.01	Acute myeloblastic leukemia, in remission
C92.02	Acute myeloblastic leukemia, in relapse

Epidemiology & Demographics

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AML incidence rises with age:
1. •
  
  Incidence 20 to 55 years old: 1 to 3/100,000 persons/year.
2. •
  
  Incidence 65 to 80 years old: 11 to 20/100,000 persons/year.
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Annual incidence is 4 cases/100,000 persons/year.
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Males slightly > females; European ancestry slightly > African ancestry.

Physical Findings & Clinical Presentation

Symptoms/Exam Findings:

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Complications of bone marrow failure:
1. •
  
  Thrombocytopenia-associated bleeding.
2. •
  
  Fatigue and shortness of breath associated with anemia.
3. •
  
  Infection associated with neutropenia.
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Complications of leukocytosis (hyperleukocytic leukemia, WBC >100,000/mcl)
1. •
  
  Retinal hemorrhage with visual symptoms.
2. •
  
  Headache and intracranial bleeding.
3. •
  
  Respiratory symptoms from pulmonary involvement.
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Systemic symptoms
1. •
  
  Fatigue, fever (usually infectious, rarely tumor), bone pain (more common in ALL).
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Hemorrhagic complications of disseminated intravascular coagulation (DIC), especially with APML)
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Physical exam will reflect consequences of cytopenias (bruising from thrombocytopenia, pallor from anemia). Enlarged lymph nodes and enlarged liver and spleen are rare. Exam is often normal.
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Rarely disease will present as skin lesions (leukemia cutis) or mass lesions (granulocytic sarcoma).
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Gum hypertrophy and organ/skin involvement is more common in monocytic leukemia.

Etiology

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Environmental/exposure related: Benzene (best documented), organic solvents (including gasoline), cigarettes smoking (≥20 pack-year 1.34 relative risk), obesity, best documented in women.
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Hereditary disorders: Numerous, including Fanconi anemia, Bloom syndrome, Schwachman Diamond syndrome, Diamond Blackfan anemia, among others.
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Therapy related:
1. •
  
  Alkylator (e.g., melphalan, busulfan, cisplatin) related: typical latency 5 to 7 years, associated with chromosome 5 and 7 abnormalities.
2. •
  
  Topoisomerase II inhibitor (e.g. etoposide, doxorubicin): typical latency 1 to 3 years, associated with 11q23 (mixed lineage leukemia [MLL] gene) rearrangements.
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Radiation exposures (therapeutic—generally low risk), occupational.
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Antecedent hematologic disorders: Myelodysplasia, myeloproliferative disorders, aplastic anemia.

Diagnosis

Differential Diagnosis

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Disorders that can present with circulating blasts or cells with blast like appearance:
1. •
  
  Acute myeloid leukemia/acute lymphocytic leukemia.
2. •
  
  Myelodysplasia (up to 20% circulating blasts, if ≥20% = AML).
3. •
  
  Primary myelofibrosis.
4. •
  
  Chronic myeloid leukemia
5. •
  
  Blastoid variant of mantle cell lymphoma.
6. •
  
  Prolymphocytic leukemia
7. •
  
  Blastic plasmacytoid dendritic cell neoplasm.
8. •
  
  Atypical lymphocytes of Epstein-Barr and cytomegalovirus infection may have blastlike appearance.

Laboratory Tests

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Complete blood counts and blood smear evaluation. Note that morphologic evaluation of blasts may suggest myeloid or lymphoid origin, but flow cytometry or cytochemistries (often faster) are needed to confirm. Auer rods are seen in blasts of myeloid origin.
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LDH is commonly elevated. Other biochemistries to assess organ function (creatinine, liver enzymes) and spontaneous tumor lysis syndrome (uric acid, potassium, phosphate, calcium).
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Coagulation studies to assess DIC. DIC is always present in APML, but can be present in all forms of acute leukemia, especially acute monocytic leukemia.
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HLA typing for possible bone marrow transplant and platelet support.
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Cytochemical stains
1. •
  
  Myeloperoxidase can be performed in minutes, + in myeloid origin leukemia.
2. •
  
  Alpha naphthyl acetate esterase (“nonspecific esterase”) stains mainly monocytic cells.

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Flow cytometry on blood and/or bone marrow (see Table 1)

TABLE1 Flow Cytometry Markers Used For Diagnosis of ANLLAdapted from Doehner H et al, Diagnosis and management of acute myeloid leukemia in adults, recommendations from an international expert panel, on behalf of the European LeukemiaNet, Blood 115: 453-474, 2010.

Precursor stage	CD34, CD38, CD117, CD133, HLA-DR
Granulocytic (myeloid) markers	CD13, CD15 CD16, CD33, CD65, cytoplasmic myeloperoxidase
Monocytic markers	CD11c, CD14, CD64, CD4, CD11b, CD36, NG2 homologue
Megakaryocytic markers	CD41 (glycoprotein IIb/IIIa), CD61 (glycoprotein IIIa), CD42 glycoprotein 1b
Erythroid markers	CD235 (glycophorin A)

•

Cytogenetic studies, ideally on bone marrow, but can be done on peripheral blood. Fluorescence in situ hybridization (FISH) is often used as an adjunct to conventional chromosome analysis.

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Molecular studies to further stratify risk and prognosis, which may affect treatment choices (see Tables 2 and 3). Directing this workup should be done with combined hematology and laboratory expertise and typically will consist of studies for fms-related tyrosine kinase gene (FLT3) mutations, nucleophosmin gene (NPM) mutations, and CCAAT/enhancer binding protein α gene (CEBPA) mutations. Wider molecular panels are increasingly common because of the increasing numbers of potential markers and the potential availability of targeted therapies for FLT3 mutated disease and those with isocitrate dehydrogenase mutations, among others.

TABLE2 Significance of Molecular Abnormalities in Cytogenetically Normal Patients With AMLData from Schlenk RF et al: N Engl J Med 358: 1909-18, 2008, and Green CL et al: J Clin Oncol 28: 2739-47, 2010.

Molecular profile	Patients	4-year overall survival
Mutant CEBPA	67	62%
Mutant NPM, without FLT-3 ITD	150	60%
FLT-3 ITD present	164	24%
FLT-3 ITD absent, wild type NPM, wild type CEBPA (triple negative leukemia)	69	33%
CEBPA, CCAAT/enhancer binding protein α gene; FLT-3 ITD, fms-related tyrosine kinase gene internal tandem duplication; NPM, nucleophosmin gene. Improved prognosis in patients with CEBPA mutations is limited to patients who lack FLT-3 ITD and have biallelic mutations. CEBPA mutations are seen in approximately 6% to 10% of AML cases, NPM mutations in 25% to 35% (more common in cytogenetically normal cases) and FLT-3 ITD in approximately 20% to 30% of cases.

TABLE3 European LeukemiaNet Defined Cytogenetic and Molecular Abnormalities Relevant to Prognosis in AMLAdapted from Doehner H et al, Diagnosis and management of acute myeloid leukemia in adults, recommendations from an international expert panel, on behalf of the European LeukemiaNet, Blood 115: 453-474, 2010.

Favorable	t(8;21)(q22;q22)^∗ inv (16)(p13.1;q22) or t(16;16) (p13.1;q22)^∗ Normal karyotype with mutated NPM1 and absent FLT-3 ITD Normal karyotype and mutated CEBPA
Intermediate-1^†	Normal karyotype and mutated NPM1 and FLT3-ITD Normal karyotype with wild type NPM1 and FLT3-ITD Normal karyotype without FLT3-ITD
Intermediate-2	t(9;11)(p22;q23) Cytogenetic abnormalities not classified as favorable or adverse
Adverse	Complex (3 or more abnormalities, unless associated with a known favorable abnormality), inv(3)(q21;q26.2) or t(3;3)(q21;q26.2); t(6;9)(p23;q34) t(variable;11)(variable;q23) (MLL gene rearrangement), -5 or del (5q); -7; abnormal (17p)

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Formal diagnosis of acute nonlymphocytic leukemia is established if the marrow blast percentage is ≥20%, unless t(8;21), inv(16), t(16;16) or t(15;17) are present, in which case the percentage of blasts may be lower.

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Myeloperoxidase (MPO) staining of 3% of blasts establishes myeloid lineage, but MPO may be negative in some AML cases diagnosed by flow cytometry.

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Specific criteria exist for diagnosing other forms of ANLL, mainly to distinguish it from myelodysplasia. The WHO AML classification is outlined in Table 4.

TABLE4 Classification of Acute Myeloid Leukemia According to the Revised World Health Organization Classification (2016)For AML with recurrent genetic abnormalities, specific genes rearranged follow the chromosome rearrangement. In 2016, the MLL gene has been renamed KMT2A.

Category	Subtype/Definition^∗
AML with recurrent cytogenetic abnormalities	t(8;21)(q22;q22); RUNX1-RUNX1T1^† inv(16)(p13.1q22); CBFB-MYH11^† t(16;16)(p13.1q22); CBFB-MYH11^† t(15;17)(q22;q12); PML-RARA^† (= acute promyelocytic leukemia) t(9;11)(p22;q23); MLLT3-KMT2A t(6;9)(p23;q34); DEK-NUP214 inv(3)(q21q26.2); GATA2, MECOM t(3;3)(q21;q26.2); RPN1-EVI1 t(1;22)(p13q13); RBM15-MKL1 (megakaryoblastic) with mutated NPM1 with biallelic mutations of CEBPA
AML with MDS-related changes	Morphologic features of MDS, or Prior history of MDS or MDS/MPN, or MDS-related karyotype, and None of the recurrent genetic abnormalities above
Therapy-related myeloid neoplasms	Late complications of cytotoxic chemotherapy (alkylating agents, topoisomerase II inhibitors) and/or ionizing radiation therapy^†
AML, not otherwise specified	AML with minimal differentiation AML without maturation AML with maturation Acute myelomonocytic leukemia Acute monoblastic/monocytic leukemia Pure erythroid leukemia Acute megakaryoblastic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis
Myeloid sarcoma
Myeloid proliferations related to Down syndrome	Transient abnormal myelopoiesis Myeloid leukemia associated with Down syndrome
Blastic plasmacytoid dendritic cell neoplasm
Acute leukemia of ambiguous lineage	Acute undifferentiated leukemia Mixed-phenotype acute leukemia with: t(9;22)(q34;q11.2); BCR-ABL1 t(v;11q23); KMT2A rearranged Mixed-phenotype acute leukemia, B/myeloid, NOS Mixed-phenotype acute leukemia, T/myeloid, NOS
Provisional entities	AML with mutated NPM1 AML with mutated CEBPA NK-cell lymphoblastic leukemia/lymphoma
AML, Acute myeloid leukemia; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; NK, natural killer.

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Cytogenetic risk categories in AML are described in Table 3. Bone marrow findings are described in Fig. E1.

FIG.E1

Acute myeloid leukemia with t(8;21)(q22;q22), (AML/ETO).

A, Low-power, Wright-stained bone marrow aspirate smear showing increased blasts associated with differentiating myeloid cells. B, Details illustrating some of the features associated with the leukemia. They include blasts with long thin Auer rods *(top left),* immature cells with abnormal eosinophilic globules *(top and bottom, second from left),* abnormal salmon-colored granulation in the maturing cells, sometimes associated with a basophilic periphery *(top and bottom, fourth from left),* and slightly abnormal features in the mature neutrophils *(far right).* Pseudo–Chédiak-Higashi granules were not seen in this case. C, Biopsy shows the significant degree of maturation that is sometimes seen. In some cases the blast count is less than 20%, but the diagnosis of acute myeloid leukemia still can be made with the cytogenetic finding of t(8;21).

From Hoffman R et al: *Hematology, basic principles and practice,* ed 5, Philadelphia, 2009, Churchill Livingstone.

Imaging Studies

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Imaging studies are typically directed to evaluating specific complaints.
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Echocardiogram or MUGA is usually performed to verify that cardiac function is adequate to tolerate anthracycline (usually daunorubicin) therapy, with left ventricular ejection fraction (LVEF) of >50% typically considered acceptable.

Treatment

Acute General Rx

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Therapy of AML typically has three components:
1. •
  
  Immediate therapy to correct metabolic, infectious, or hyperleukocytic emergencies (if needed). Therapy for AML is always urgent but not always an emergency. However, treatment for APML should be considered a medical emergency to prevent catastrophic bleeding.
2. •
  
  Induction therapy, which is therapy of active disease intended to obtain remission and restore normal bone marrow function. Remission is defined as blasts <5% in the bone marrow, absolute neutrophils (ANC) of >1000/mcl, platelets >100,000/mcl, and transfusion independence. Complete remission with incomplete marrow recovery (CRi) indicates absence of leukemic blasts in the marrow but persistent cytopenias.
3. •
  
  Consolidation therapy, typically some form of intensive chemotherapy or stem cell transplant therapy intended to prevent relapse.
4. •
  
  Hyperleukocytic symptoms are typically seen with WBC >100,000/ml. Leukapheresis requires catheter placement and pheresis but spares tumor lysis. Rapid cytoreduction with chemotherapy (hydroxyurea 3-6 g orally or cytarabine) is often adequate and easier but risks tumor lysis. Optimal management is therefore individualized.
5. •
  
  Tumor lysis syndrome (TLS) is associated with a rise in uric acid, potassium, and serum phosphate, the last causing a reciprocal fall in calcium. The metabolic changes may result in renal failure, cardiac dysrhythmias, muscle spasms (due to low calcium), seizures, and death (a more detailed discussion is in the section on acute lymphocytic leukemia).
6. •
  
  The mainstays of therapy for AML are medications dating from the 1970s—daunorubicin and cytarabine—with few medications having meaningful impact on therapy in the last four decades. In 2017, the U.S. FDA approved four new agents, including three targeted agents, for treatment of AML. The role of these agents and their relation to standard therapy is outlined below.
7. •
  
  Induction chemotherapy typically consists of daunorubicin 60 or 90 mg/m² IV for 3 days and cytarabine (Ara-C) 100 or 200 mg/m²/day as continuous infusion for 7 days (“7+3”). Success rates are 60% to 80% and have been better in recent trials. Other agents that are used include etoposide, idarubicin, fludarabine, and cladribine. Bone marrow examination is usually performed at day 14 of therapy to assess the response.
8. •
  
  Gemtuzumab ozogamicin (GO, Mylotarg) is an antibody-drug conjugate binding an anti-CD33 antibody to the chemotherapeutic agent calicheamicin that was approved in 2017 for therapy of newly diagnosed CD33+ AML. In newly diagnosed AML, the use of low-dose GO when added to standard 7+3 induction had a success rate of 81%, with 2-yr relapse-free survival improving from 22.7% to 50.3% compared with standard therapy alone. The benefit was seen in favorable and intermediate-risk patients.
9. •
  
  Midostaurin was also approved in 2017 for treatment of newly diagnosed AML with mutations in the fms-related tyrosine kinase 3 (FLT3) gene in combination with standard induction therapy. Four-year overall survival was 51.4% in FLT3-positive patients receiving midostaurin vs. 44.3% in the placebo arm, with improved durability of remissions in patients achieving remission. The optimal use of these therapies requires rapid access to genetic data at the time of diagnosis.
  
  Also approved in 2017 was CPX-351, a liposomal formulation of cytarabine and daunorubicin encapsulated in a 5:1 ratio, for patients with AML related to previous therapy (t-AML) or with AML with myelodysplasia-related change (AML-MRC). In a trial of t-AML and AML evolving from myelodysplasia or with WHO-defined myelodysplasia-related cytogenetic changes in patients ages 60 to 75 yr, CPX-351 improved survival to 9.56 months vs. 5.95 months with standard 7+3 induction.
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Consolidation therapy is controversial. For patients managed with chemotherapy, cytarabine 3 g/m² for six doses is commonly used (day 1, 3, 5), but intermediate doses (1000-1500 mg/m²) for six doses appear equally effective and less toxic. Doses above 1000 mg/m² are poorly tolerated in patients over 60 yr because of cerebellar toxicity. Renal insufficiency also increases the risk of cerebellar toxicity from Ara-C, which can be severe.
1. •
  
  For favorable risk disease, consolidation with chemotherapy alone with two to four cycles of intermediate/high-dose cytarabine is typically given, with long-term survival of 60% to 70%.
2. •
  
  For intermediate-risk and unfavorable-risk disease, first-remission allogeneic stem cell marrow transplant is often recommended if a donor is available. If not, chemotherapy consolidation chemotherapy is offered, although the optimal therapy and schedule, especially for unfavorable disease, is uncertain.
3. •
  
  In the trial of GO as initial therapy, GO was also used in consolidation with high-dose cytarabine and daunorubicin.
4. •
  
  The role of autologous bone marrow transplant is controversial, with some evidence of decreased relapse rates after chemotherapy but no clear benefit in overall survival.
5. •
  
  Allogeneic bone marrow transplant is offered to patients with relapsed disease if a second remission can be obtained. It is offered to high-risk patients in first remission if a donor is available.
6. •
  
  Enasidenib, a selective inhibitor of mutated isocitrate dehydrogenase 2 (IDH-2), was approved by the FDA in 2017 for relapsed or refractory AML with IDH-2 mutations. IDH-2 mutations are found in about 12% of AML patients. At a dose of 100 mg orally, the response rate was 40.3%, with 19.3% achieving remission, some durable. Differentiation syndrome can be seen with enasidenib, similar to therapy for APML.
7. •
  
  Relapses after bone marrow transplant can sometimes be managed with donor lymphocyte infusions, adjustment of immune suppression, and chemotherapy (often low intensity). In general, outcomes are poor with posttransplant relapses.
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Treatment of older patients (>60 yr) is problematic, with cure rates of 10% to 15%. Older patients do worse because they are more likely to have high-risk features and less likely to tolerate therapy. Options for these patients include:
1. •
  
  Standard induction therapy is reasonable for patients likely to tolerate it. Even in the absence of cure, quality of life is often excellent in remission. More recent studies suggest that the early death rate (within 30 days of diagnosis) was lower for patients in their 70s and 80s receiving standard induction. There is no standardized approach to evaluating fitness for therapy; one algorithm is at http://www.aml-score.org/.
2. •
  
  Hypomethylating agents—decitabine and azacytidine—may be considered in patients unlikely to tolerate induction therapy. Azacytidine (75 mg/m² daily for 7 days every 28 days) and decitabine (20 mg/m² for 5 days every 28 days) are considered in older patients who are not considered appropriate for induction chemotherapy. Both are outpatient regimens, and decitabine especially is very well tolerated. Recent data with azacytidine suggest benefit in about 20% to 30% lasting 14 to 16 mo in responders, with equivalent results in low blast count (20%-30% in the bone marrow) vs. higher blast count disease.
3. •
  
  Single-agent gemtuzumab ozogamicin is an option for treatment of CD33+ AML in patients considered unfit for induction. The benefit compared to best supportive care (BSC) was mainly seen in patients with CD33 expression of greater than 80% and favorable/intermediate cytogenetics (1 yr survival 22% and 37% respectively, BSC <10%), with no benefit in patients with high-risk cytogenetics.
4. •
  
  Low-dose cytarabine (20 mg/m² twice daily or 40 mg/m² daily for 10 days subcutaneously) has shown survival benefit over hydroxyurea in low-/intermediate- risk patients.
5. •
  
  Oral hydroxyurea dosed to counts and cytopenias.
6. •
  
  Best supportive care.
7. •
  
  Reduced-intensity allogeneic stem cell transplant is an option for patients in remission after standard therapy. A recent meta-analysis of studies including 749 patients over 60 receiving RIT identified a 3-year relapse-free survival of 35%.
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Acute Promyelocytic Leukemia (APML)

APML is a distinct leukemia syndrome with very different treatment implications. Cure rates greater than 95% have been seen in current protocols in the absence of high-risk features. It is associated with t(15;17), which translocates the PML gene to retinoic acid receptor α (PML-RARa). Uncommon variants are t(11;17) and t(5;17).

Risk groups for relapse were defined in studies using retinoic acid and chemotherapy. Patients with presenting WBC >10,000/mcl were considered high risk, patients with WBC <10,000 and platelets >40,000 were considered low risk, and all others were considered intermediate risk. In current protocols, high-risk patients receive some form of intensified therapy.
1. •
  APML is a medical emergency because of the high risk of bleeding complications.
  1. •
    
    All patients with APML have DIC, caused by overexpression of annexin II, (which increases generation of plasmin, degrading fibrin), elastases (which degrade fibrinogen and fibrinolytic inhibitors), and increased endothelial tissue plasminogen activator release.
  2. •
    
    Early death due to hemorrhage is seen in 5% to 17% of newly diagnosed APML patients, usually intracranial or pulmonary. Risk factors include elevated WBC, increased age, and elevated creatinine.
  3. •
    
    Retinoic acid rapidly stabilizes the coagulopathy of APML; consideration should be given to starting this immediately for suspected cases.
  4. •
    
    Cryoprecipitate (usual dose 10 bags) to raise the fibrinogen level to 150 mg/dl and platelet transfusion to raise the count to >50,000//mcl should be given as needed.
  5. •
    
    Unfractionated heparin may paradoxically stop bleeding in APML by inhibiting DIC, but is rarely used in the retinoic acid treatment era.
2. •
  Diagnosis of APML
  1. •
    
    Rapid diagnosis is essential due to treatment implications.
  2. •
    
    Diagnosis by classic APML blast morphology and clinical syndrome (especially DIC with low fibrinogen) is sufficient to justify starting treatment with retinoic acid pending confirmation with molecular studies. Immediate therapy with retinoic acid will rapidly stabilize the coagulopathy and help prevent catastrophic bleeding.
  3. •
    
    Polymerase chain reaction for PML/RARa
  4. •
    
    FISH for t(15;17) or variants
  5. •
    
    Flow cytometry is typically distinct with lack of HLA-DR and CD34; CD13, CD33 and CD64 are usually positive
3. •
  Therapy of APML
  1. •
    
    Emergency measures to stabilize coagulopathy as outlined previously.
  2. •
    
    Patients with WBC ≤10,000 (low/intermediate risk) are treated with retinoic acid and arsenic trioxide (“differentiation therapy”).
  3. •
    
    Therapy of high-risk patients is less well standardized but has included intensification with cytarabine, anthracyclines, and gemtuzumab ozogamicin. A recent trial using arsenic and retinoic acid with GO demonstrated 100% 4-yr survival in high-risk patients after 30 days, emphasizing the importance of preventing early deaths in APML.
  4. •
    
    Maintenance therapy for 2 years is given in some APML protocols.
  5. •
    
    Patients with high-risk disease receive central nervous system prophylaxis with intrathecal chemotherapy.
  6. •
    
    Treatment of relapsed disease typically consists of autologous bone marrow transplant after obtaining second remission.
4. •
  Differentiation syndrome (DS) is a potentially fatal complication of therapy with retinoic acid and arsenic trioxide. It is associated with fever, interstitial pulmonary infiltrates, peripheral edema, pleural and pericardial effusions and renal failure; it is commonly associated with rising WBC seen in patients on differentiation therapy.
  1. •
    
    Therapy for suspected differentiation syndrome is dexamethasone 10 mg/m² every 12 hr. Cytoreductive therapy (hydroxyurea, idarubicin) and stopping retinoic acid and arsenic are appropriate for inadequate response to dexamethasone.
  2. •
    
    Prophylaxis for differentiation syndrome with dexamethasone 2.5 mg/m² every 12 hr has been suggested for WBC >5000 or creatinine >1.4 mg/dl. Hydroxyurea is used to keep the WBC below 10,000/mcl in some protocols.

Pearls & Considerations

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The diagnosis of acute myeloid leukemia or variants is often, but not always, a medical emergency requiring rapid clinical and laboratory assessment by appropriate expertise.
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APML is a distinct clinical entity that has a high cure rate with current protocols, but which requires intensive supportive care at the time of diagnosis.

Ferri – Acute Myelogenous Leukemia