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Acute myeloid leukaemia
Acute myeloid leukaemia auer rods
Acute myeloid leukaemia bone marrow biopsy under a microscope
Synonyms
Synonyms
Various; see text
MeSH D015470
ICD-9

205.0

ICD-10

C92.0

ICD-O

9861/3

MSR

Medscape Reference
Adult Ped. myelocytic APL
Overview
Presentation
DDx
Workup
Treatment
Medication
Overview
Presentation
DDx
Workup
Treatment
Medication
Overview
Presentation
DDx
Workup
Treatment
Medication
MedlinePlus

000542

Patient.co.uk

Professional Reference
Patient Reference

OMIM

602439

Wikipedia

Acute myeloid leukaemia

Acute myeloid leukaemias are a family of rapidly-progressing (hence acute) malignancies that arise from the myeloid lineage cells of the bone marrow. They can be classified according to the cell variety that is affected (which is called the French-American-British [FAB] system), the genetic abnormalities found in the malignant cells (which are present only in a limited number of cases) or a newer system created by the World Health Organization (WHO). It can also be classified as primary or secondary. Primary means that there were no preceding treatments or diseases that are likely to have caused it. The 5-year survival rate overall for AML is about 25% in Australia and while this has improved since the 1980s (when it was about 10%) most of this improvement can be traced back to improvements in supportive care rather than the development of new therapies.[1][2] This survival rate, however, is highly dependent on the age of the patient: at ages of less than 50 the 5-year survival rate was about 66% in Australia during the time period of 2006-2010, whereas in those aged >70 the 5-year survival rate was about 2.5%.[1]


NamingEdit

Synonyms for acute myeloid leukaemia are usually variants, affecting the last two words to its name. 

2nd word synonyms 3rd word synonyms
Myelogenous Leukemia
Nonlymphoblastic
Nonlymphocytic

e.g., acute myelogenous leukemia, acute myeloid leukemia, etc.

ClassificationEdit

The WHO classifies acute myeloid leukaemias (AMLs) as:[3][4]

Acute myeloid leukaemia and related neoplasms
Acute myeloid leukaemia with recurrent genetic abnormalities

AML with t(8;21)(q22;q22); RUNX1-RUNX1T1

AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

APL with t(15;17)(q22;q12); PML-RARA

AML with t(9;11)(p22;q23); MLLT3-MLL

AML with t(6;9)(p23;q34); DEK-NUP214

AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1

AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1

Provisional entity: AML with mutated NPM1

Provisional entity: AML with mutated CEBPA

Acute myeloid leukaemia, not otherwise specified

AML with minimal differentiation (M1)

AML without maturation (M2)

AML with maturation (M2)

Acute myelomonocytic leukaemia

Acute monoblastic/monocytic leukaemia (M4)

Acute erythroid leukaemia (M5)

Pure erythroid leukaemia (M6)

Erythroleukaemia, erythroid/myeloid (M6)

Acute megakaryoblastic leukaemia (M7)

Acute basophilic leukaemia

Acute panmyelosis with myelofibrosis

Myeloid proliferations related to Down syndrome
Transient abnormal myelopoiesis

Myeloid leukaemia associated with Down syndrome

Secondary acute myeloid leukaemia

[note 1]

AML associated with myelodysplastic syndromes

Therapy-related myeloid neoplasms

Others

[note 2]

Myeloid sarcoma

Blastic plasmacytoid dendritic cell neoplasm

French-American-British (FAB) system:[4]

Type Variant name
M0 Undifferentiated acute myeloblastic leukaemia
M1 Acute myeloblastic leukaemia with minimal maturation
M2 Acute myeloblastic leukaemia with maturation
M3 Acute promyelocytic leukaemia
M4 Acute myelomonocytic leukaemia
M4eos Acute myelomonocytic leukaemia with eosinophilia
M5 Acute monocytic leukaemia
M6 Acute erythroid leukaemia
M7 Acute megakaryocytic leukaemia

Signs and symptomsEdit

Its signs and symptoms are almost identical to those of other leukaemias and include:[5]

  • Signs of bone marrow failure, such as signs of cytopenias including (with the first letter of the cytopenial cause in brackets[note 3]): fatigue (A), lethargy (A), dyspnoea (A), myocardial infarction (rare, more frequent in the elderly; A), infections (L), fever (L) and bleeds (T)
  • Signs of leukaemic cell infiltration of the tissues, including: liver (leading to hepatomegaly), spleen (leading to splenomegaly), gums (leading to gingivitis) and skin (leading to lesions)

DiagnosisEdit

As with other leukaemias the diagnosis is performed via blood tests, bone marrow aspiration and biopsy, imaging and analysis of the genetic abnormalities in the affected cells.[6]

TreatmentEdit

The treatment for most types of AML (except the PML-RARA [APL] variant) has not changed significantly over the past several decades and induction therapy usually consists of an antimetabolite (most commonly cytarabine, but also cladribine or clofarabine) and an anthracycline/anthracenedione (such as daunorubicin, idarubicin or mitoxantrone).[7]

Previously untreated AMLEdit

The most commonly used induction regimen is the "7 and 3" regimen which consists of seven days of continuous IV infusion of cytarabine (usually at doses of 100-200 mg/m2/d, although higher doses of 2-3 g/m2/d are sometimes used and given over 12 hours each day) and three days of treatments with daunorubicin/idarubicin (usually at 45-90 mg/m2/d or 12 mg/m2/d, respectively).[7] A remission with this regimen is attainable in about 60-70% of adult patients with AML.[8] In cases of resistance to cytarabine clofarabine may be used in its place.[9]

Consolidation therapy usually consists of 3 hour long, 12 hourly infusions of high dose (3 g/m2/d) cytarabine, with or without an allogenic (for intermediate/high-risk patients) or autologous (for low-risk patients) haematopoietic stem cell transplant.[7]

Post-consolidation therapy can be given after consolidation therapy, but is almost only ever used in Europe, and consists of histamine dihydrochloride and low-dose interleukin-2.[10][11][12]

Relapsed or refractory diseaseEdit

These patients may benefit from clofarabine, cladribine, etoposide, mitoxantrone or fludarabine-based regimens, although response rates tend to be fairly low, especially if first remission was short-lived (<2 years).[2][7] Examples of such regimens include:

  • Fludarabine, cytarabine, idarubicin, filgrastim (FLAG-IDA)
  • Cladribine, cytarabine, mitoxantrone and filgrastim (CLAG-M). 
  • Mitoxantrone, etoposide and cytarabine (MEC)

Alternatively an allogenic haematopoietic stem cell transplant may be used, or an experimental therapy.[13]

Other therapies, including investigation onesEdit

A monoclonal antibody-drug conjugate called gemtuzumab ozogamicin has been used in the treatment of AML, but it was taken off the market due to concerns over unacceptable hepatotoxicity.[14] Despite this recent systematic reviews and meta-analyses have found its safety to be acceptable and its efficacy to be clinically-relevant.[15]

External linksEdit

NotesEdit

  1. Not a term used in the actual classification, this is a division I have added
  2. Also not used in the original classification
  3. A: anaemia, L: leucopenia, N: neutropenia and T: thrombocytopenia

Reference listEdit

  1. 1.0 1.1 Australian Institute of Health and Welfare (AIHW) (2012). Cancer survival and prevalence in Australia: period estimates from 1982 to 2010 (PDF). Canberra, Australia: AIHW. p. 30. ISBN 978-1-74249-338-1. 
  2. 2.0 2.1 Ferrara, F; Schiffer, CA (9 February 2013). "Acute myeloid leukaemia in adults.". Lancet 381 (9865): 484–95. PMID 23399072. doi:10.1016/S0140-6736(12)61727-9. 
  3. Vardiman, JW; Thiele, J; Arber, DA; Brunning, RD; Borowitz, MJ; Porwit, A; Harris, NL; Le Beau, MM; Hellström-Lindberg, E; Tefferi, A; Bloomfield, CD (30 July 2009). "The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes.". Blood 114 (5): 937–51. PMID 19357394. doi:10.1182/blood-2009-03-209262. 
  4. 4.0 4.1 Seiter, K (24 July 2013). Anand, J; Braden, CD; Harris, JE, ed. "Acute Myeloid Leukemia Staging". Medscape Reference. New York, USA: WebMD. Retrieved 6 December 2014. 
  5. Seiter, K (15 August 2014). Adoo, CS; Talavera, F; Sacher, RA; Besa, EC, ed. "Acute Myelogenous Leukemia Clinical Presentation". Medscape Reference. New York, USA: WebMD. Retrieved 6 December 2014. 
  6. Seiter, K (15 August 2014). Adoo, CS; Talavera, F; Sacher, RA; Besa, EC, ed. "Acute Myelogenous Leukemia Workup". Medscape Reference. New York, USA: WebMD. Retrieved 6 December 2014. 
  7. 7.0 7.1 7.2 7.3 Seiter, K (7 August 2013). Talavera, F; Braden, CD; Harris, JE, ed. "Acute Myeloid Leukemia Treatment Protocols". Medscape Reference. New York, USA: WebMD. Retrieved 6 December 2014. 
  8. Seiter, K (15 August 2014). Adoo, CS; Talavera, F; Sacher, RA; Besa, EC, ed. "Acute Myelogenous Leukemia". Medscape Reference. New York, USA: WebMD. Retrieved 10 December 2014. 
  9. Fozza, C (22 October 2014). "The role of Clofarabine in the treatment of adults with acute myeloid leukemia.". Critical Reviews in Oncology/Hematology. PMID 25457773. doi:10.1016/j.critrevonc.2014.10.009. 
  10. "Ceplene : EPAR - Product Information". European Medicines Agency. Solna, Sweden: Meda AB. 10 April 2014. Retrieved 5 December 2014. 
  11. Yang, LP; Perry, CM (1 January 2011). "Histamine dihydrochloride: in the management of acute myeloid leukaemia.". Drugs 71 (1): 109–22. PMID 21175244. doi:10.2165/11206410-000000000-00000. 
  12. Schlenk, RF (November 2014). "Post-remission therapy for acute myeloid leukemia.". Haematologica 99 (11): 1663–1670. PMC 4222459. PMID 25420282. doi:10.3324/haematol.2014.114611. 
  13. Longo, DL; Fauci, AS; Kasper, DL; Hauser, SL; Jameson, JL; Loscalzo, J, ed. (2012). "Chapter 109. Acute and Chronic Myeloid Leukemia". Harrison's Principles of Internal Medicine, 18e. New York, USA: McGraw-Hill. ISBN 978-0-07174889-6. 
  14. Brayfield, A, ed. (23 September 2011). "Gemtuzumab Ozogamicin". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 16 December 2014. 
  15. Hills, RK; Castaigne, S; Appelbaum, FR; Delaunay, J; Petersdorf, S; Othus, M; Estey, EH; Dombret, H; Chevret, S; Ifrah, N; Cahn, JY; Récher, C; Chilton, L; Moorman, AV; Burnett, AK (August 2014). "Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials.". The Lancet. Oncology 15 (9): 986–96. PMID 25008258. doi:10.1016/S1470-2045(14)70281-5. 

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