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==Overview==
==Overview==
Acute myeloid leukemia must be differentiated from other diseases such as [[acute lymphoblastic leukemia]], [[chronic myeloid leukemia]], [[agranulocytosis]], [[aplastic anemia]] and [[lymphoma]].
The differential diagnosis of acute myeloid leukemia includes a variety of other hematologic malignancies, specifically acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Each of these conditions has distinct causes and therapies. There is some overlap between the causes and laboratory abnormalities amongst these diseases.  


==Differentiating from other Diseases in Adults==
==Differentiating from other Diseases in Adults==
Acute myeloid leukemia should be differentiated from the following hematological disorders:
Acute myeloid leukemia can be distinguished from other types of AML based on a variety of features.
* [[Acute lymphoblastic leukemia]]
* [[Chronic myelogenous leukemia]]
* [[Agranulocytosis]]
* [[Aplastic anemia]]
* [[Lymphoma]]
* [[Myelodysplastic syndrome]]
* [[Myeloproliferative disorders]]


==Differentiating from other Diseases in Children==
{| class="wikitable"
Acute myeloid leukemia should be differentiated from the following hematological disorders:<ref name=AML>{{cite web | title = National Cancer Institute| url =http://www.cancer.gov/types/leukemia/patient/child-aml-treatment-pdq }}</ref>
!Characteristic
* [[Chronic myelogenous leukemia]]
!Causes
* [[Juvenile myelomonocytic leukemia]]
!Laboratory abnormalities
* [[Myelodysplastic syndromes]]
!Physical examination
!Therapy
!Other associations
|-
|Acute myeloid leukemia
|
* Chromosomal instability
* Sporadic mutations
* Prior exposure to benzene
* Prior exposure to alkylating agents
* Prior exposure to topoisomerase II inhibitors
* Germline ''RUNX1'' mutation
|
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Neutropenia]]
* Elevated LDH
* Elevated uric acid
* Elevated phosphorus
* Elevated potassium
* Low calcium
* Greater than 20% myeloblasts on bone marrow aspirate<ref name="pmid27895058">{{cite journal| author=Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al.| title=Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | journal=Blood | year= 2017 | volume= 129 | issue= 4 | pages= 424-447 | pmid=27895058 | doi=10.1182/blood-2016-08-733196 | pmc=5291965 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27895058  }} </ref>
|
* Pyrexia
* Evidence of infection
* Pallor
* Mucosal bleeding (less common than in acute promyelocytic leukemia)
* Bruising (less common than in acute promyelocytic leukemia)
|
* Cytarabine
* Anthracycline
* Enasidenib
* Liposomal daunorubicin plus cytarabine
* Gemtuzumab ozogamycin
* Midostaurin
* Enasidenib
* Ivosidenib
* [[Stem cell transplant]]
|
* Variable prognosis based on cytogenetic and molecular profile
* Four new FDA-approved therapies became available in 2017
|-
|Acute promyelocytic leukemia
|
* Prior exposure to alkylating agents
* Prior exposure to topoisomerase II inhibitors
* Translocation between chromosomes 15 and 17
* Creation of PML-RAR''alpha'' gene product
* Differentiation block in myeloid cells
|
* Low [[white blood cell]] count (typically)
* [[Anemia]]
* [[Neutropenia]]
* [[Thrombocytopenia]]
* Low [[fibrinogen]]
* Elevated prothrombin time (PT)
* Elevated partial thromboplastin time (PTT)
|
* [[Mucosal bleeding]]
* Petechiae
* Ecchymoses
* Evidence of infection
* Pallor
* [[Thrombosis]]
|
* All-''trans'' retinoic acid (ATRA)
* Arsenic trioxide
* [[Cytarabine]]
* [[Anthracycline]]
|
* Presence of Auer rods in promyelocytes
* High risk for early death from hemorrhagic complications<ref name="pmid21993679">{{cite journal| author=McClellan JS, Kohrt HE, Coutre S, Gotlib JR, Majeti R, Alizadeh AA et al.| title=Treatment advances have not improved the early death rate in acute promyelocytic leukemia. | journal=Haematologica | year= 2012 | volume= 97 | issue= 1 | pages= 133-6 | pmid=21993679 | doi=10.3324/haematol.2011.046490 | pmc=3248942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21993679  }} </ref>
|-
|Acute lymphoblastic leukemia
|
* Chromosomal instability
* Sporadic mutations
|
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Neutropenia]]
* Elevated LDH
* Elevated uric acid
* Elevated phosphorus
* Elevated potassium
* Low calcium
* Greater than 20% lymphoblasts on bone marrow aspirate
|
* Neurologic deficits
* Pallor
* Lymphadenopathy
|
* HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)<ref name="pmid28665419">{{cite journal| author=Terwilliger T, Abdul-Hay M| title=Acute lymphoblastic leukemia: a comprehensive review and 2017 update. | journal=Blood Cancer J | year= 2017 | volume= 7 | issue= 6 | pages= e577 | pmid=28665419 | doi=10.1038/bcj.2017.53 | pmc=5520400 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28665419  }} </ref>
* R-HyperCVAD (inclusion of rituximab)
* Peg-asparaginase
* Intrathecal methotrexate
* Intrathecal cytarabine
* Blinatumomab (bispecific T cell engager)
* Inotuzumab ozogamycin (anti-CD22 antibody)
* Tisagenlecleucel (chimeric antigen receptor T (CAR-T) cell therapy)
* [[Stem cell transplant]]
|
* Sanctuary sites include the central nervous system (CNS) and testes<ref name="pmid23523389">{{cite journal| author=Inaba H, Greaves M, Mullighan CG| title=Acute lymphoblastic leukaemia. | journal=Lancet | year= 2013 | volume= 381 | issue= 9881 | pages= 1943-55 | pmid=23523389 | doi=10.1016/S0140-6736(12)62187-4 | pmc=3816716 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23523389  }} </ref>
|-
|Chronic myeloid leukemia
|
* Translocation between chromosomes 9 and 22
* Creation of BCR-Abl gene product
|
* Elevated [[white blood cell]] count
* Presence of [[white blood cell]] precursors at various stages of maturation
* Presence of excess metamyelocytes, basophils, eosinophils, and band cells
|
* Splenomegaly
* Abdominal tenderness
* Pallor
* Evidence of infection
|
* [[Imatinib]]
* [[Nilotinib]]
* [[Dasatinib]]
* [[Bosutinib]]
* [[Ponatinib]]
* [[Omacetaxine]]<ref name="pmid24516334">{{cite journal| author=Chen Y, Li S| title=Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue=  | pages= 177-86 | pmid=24516334 | doi=10.2147/OTT.S41786 | pmc=3916637 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24516334  }} </ref>
|
* High response rate to tyrosine kinase inhibitors
* Risk for development of T315I kinase domain mutation
* Typically does not require [[stem cell transplant]]
* Three phases include chronic, accelerated, and blast phase
|-
|-
|[[Chronic lymphocytic leukemia]]<ref name="pmid28102226">{{cite journal| author=Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG et al.| title=Chronic lymphocytic leukaemia. | journal=Nat Rev Dis Primers | year= 2017 | volume= 3 | issue=  | pages= 16096 | pmid=28102226 | doi=10.1038/nrdp.2016.96 | pmc=5336551 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28102226  }} </ref>
|
* Chromosomal instability
* Sporadic mutations
* Infections
|
* Elevated absolute lymphocyte count (in all stages)
* Presence of >5000 clonal B cells per microliter in peripheral blood
* Anemia (in Rai stage III)
* Thrombocytopenia (in Rai stage IV)
|
* [[Lymph node enlargement]] in Rai stage I
* [[Splenomegaly]] in Rai stage II
* [[Hepatomegaly]] in Rai stage II
* [[Pallor]]
* [[Bleeding]]
|
* Fludarabine
* Cyclophosphamide
* Rituximab
* Obinutuzumab<ref name="pmid28182141">{{cite journal| author=Al-Sawaf O, Fischer K, Engelke A, Pflug N, Hallek M, Goede V| title=Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy. | journal=Drug Des Devel Ther | year= 2017 | volume= 11 | issue=  | pages= 295-304 | pmid=28182141 | doi=10.2147/DDDT.S104869 | pmc=5279834 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28182141  }} </ref>
* Ofatumumab
* Ibrutinib
* Venetoclax
|
* Associated with [[autoimmune hemolytic anemia]], which occurs in 10-25% of patients with CLL
* Associated with [[immune thrombocytopenia purpura]]
* Associated with [[pure red cell aplasia]]
* Treatment with corticosteroids or anti-leukemic therapy will correct the autoimmune complications of CLL
|}


==References==
==References==

Revision as of 01:10, 26 October 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Carlos A Lopez, M.D. [3]

Overview

The differential diagnosis of acute myeloid leukemia includes a variety of other hematologic malignancies, specifically acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Each of these conditions has distinct causes and therapies. There is some overlap between the causes and laboratory abnormalities amongst these diseases.

Differentiating from other Diseases in Adults

Acute myeloid leukemia can be distinguished from other types of AML based on a variety of features.

Characteristic Causes Laboratory abnormalities Physical examination Therapy Other associations
Acute myeloid leukemia
  • Chromosomal instability
  • Sporadic mutations
  • Prior exposure to benzene
  • Prior exposure to alkylating agents
  • Prior exposure to topoisomerase II inhibitors
  • Germline RUNX1 mutation
  • Pyrexia
  • Evidence of infection
  • Pallor
  • Mucosal bleeding (less common than in acute promyelocytic leukemia)
  • Bruising (less common than in acute promyelocytic leukemia)
  • Cytarabine
  • Anthracycline
  • Enasidenib
  • Liposomal daunorubicin plus cytarabine
  • Gemtuzumab ozogamycin
  • Midostaurin
  • Enasidenib
  • Ivosidenib
  • Stem cell transplant
  • Variable prognosis based on cytogenetic and molecular profile
  • Four new FDA-approved therapies became available in 2017
Acute promyelocytic leukemia
  • Prior exposure to alkylating agents
  • Prior exposure to topoisomerase II inhibitors
  • Translocation between chromosomes 15 and 17
  • Creation of PML-RARalpha gene product
  • Differentiation block in myeloid cells
  • Presence of Auer rods in promyelocytes
  • High risk for early death from hemorrhagic complications[2]
Acute lymphoblastic leukemia
  • Chromosomal instability
  • Sporadic mutations
  • Anemia
  • Thrombocytopenia
  • Neutropenia
  • Elevated LDH
  • Elevated uric acid
  • Elevated phosphorus
  • Elevated potassium
  • Low calcium
  • Greater than 20% lymphoblasts on bone marrow aspirate
  • Neurologic deficits
  • Pallor
  • Lymphadenopathy
  • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)[3]
  • R-HyperCVAD (inclusion of rituximab)
  • Peg-asparaginase
  • Intrathecal methotrexate
  • Intrathecal cytarabine
  • Blinatumomab (bispecific T cell engager)
  • Inotuzumab ozogamycin (anti-CD22 antibody)
  • Tisagenlecleucel (chimeric antigen receptor T (CAR-T) cell therapy)
  • Stem cell transplant
  • Sanctuary sites include the central nervous system (CNS) and testes[4]
Chronic myeloid leukemia
  • Translocation between chromosomes 9 and 22
  • Creation of BCR-Abl gene product
  • Elevated white blood cell count
  • Presence of white blood cell precursors at various stages of maturation
  • Presence of excess metamyelocytes, basophils, eosinophils, and band cells
  • Splenomegaly
  • Abdominal tenderness
  • Pallor
  • Evidence of infection
  • High response rate to tyrosine kinase inhibitors
  • Risk for development of T315I kinase domain mutation
  • Typically does not require stem cell transplant
  • Three phases include chronic, accelerated, and blast phase
Chronic lymphocytic leukemia[6]
  • Chromosomal instability
  • Sporadic mutations
  • Infections
  • Elevated absolute lymphocyte count (in all stages)
  • Presence of >5000 clonal B cells per microliter in peripheral blood
  • Anemia (in Rai stage III)
  • Thrombocytopenia (in Rai stage IV)
  • Fludarabine
  • Cyclophosphamide
  • Rituximab
  • Obinutuzumab[7]
  • Ofatumumab
  • Ibrutinib
  • Venetoclax

References

  1. ↑ Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T; et al. (2017). "Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel". Blood. 129 (4): 424–447. doi:10.1182/blood-2016-08-733196. PMC 5291965. PMID 27895058.
  2. ↑ McClellan JS, Kohrt HE, Coutre S, Gotlib JR, Majeti R, Alizadeh AA; et al. (2012). "Treatment advances have not improved the early death rate in acute promyelocytic leukemia". Haematologica. 97 (1): 133–6. doi:10.3324/haematol.2011.046490. PMC 3248942. PMID 21993679.
  3. ↑ Terwilliger T, Abdul-Hay M (2017). "Acute lymphoblastic leukemia: a comprehensive review and 2017 update". Blood Cancer J. 7 (6): e577. doi:10.1038/bcj.2017.53. PMC 5520400. PMID 28665419.
  4. ↑ Inaba H, Greaves M, Mullighan CG (2013). "Acute lymphoblastic leukaemia". Lancet. 381 (9881): 1943–55. doi:10.1016/S0140-6736(12)62187-4. PMC 3816716. PMID 23523389.
  5. ↑ Chen Y, Li S (2014). "Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia". Onco Targets Ther. 7: 177–86. doi:10.2147/OTT.S41786. PMC 3916637. PMID 24516334.
  6. ↑ Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG; et al. (2017). "Chronic lymphocytic leukaemia". Nat Rev Dis Primers. 3: 16096. doi:10.1038/nrdp.2016.96. PMC 5336551. PMID 28102226.
  7. ↑ Al-Sawaf O, Fischer K, Engelke A, Pflug N, Hallek M, Goede V (2017). "Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy". Drug Des Devel Ther. 11: 295–304. doi:10.2147/DDDT.S104869. PMC 5279834. PMID 28182141.

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