Myeloproliferative neoplasm differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Myeloproliferative disease}}
{{Myeloproliferative disease}}
{{CMG}} {{AE}} {{MJK}}
{{CMG}} {{AE}} {{MJK}} {{shyam}}
==Overview==
==Overview==
Myeloproliferative neoplasm must be differentiated from [[acute lymphoblastic leukemia]], [[acute myelogenous leukemia]], [[chronic myelogenous leukemia]], [[essential thrombocytosis]], [[hypereosinophilic syndrome]], [[non-Hodgkin lymphoma]], [[primary myelofibrosis]], secondary thrombocytosis, [[splenomegaly]], [[systemic mastocytosis]], and [[waldenstrom macroglobulinemia]].<ref>{{Cite journal
Myeloproliferative neoplasm must be differentiated from [[acute lymphoblastic leukemia]], [[acute myelogenous leukemia]], [[chronic myelogenous leukemia]], [[essential thrombocytosis]], [[hypereosinophilic syndrome]], [[non-Hodgkin lymphoma]], [[primary myelofibrosis]], secondary thrombocytosis, [[splenomegaly]], [[systemic mastocytosis]], and [[waldenstrom macroglobulinemia]].
| author = [[James W. Vardiman]], [[Nancy Lee Harris]] & [[Richard D. Brunning]]
 
| title = The World Health Organization (WHO) classification of the myeloid neoplasms
| journal = [[Blood]]
| volume = 100
| issue = 7
| pages = 2292–2302
| year = 2002
| month = October
| doi = 10.1182/blood-2002-04-1199
| pmid = 12239137
}}</ref>
<ref>{{Cite journal
| author = [[A. Tefferi]], [[L. A. Solberg]] & [[M. N. Silverstein]]
| title = A clinical update in polycythemia vera and essential thrombocythemia
| journal = [[The American journal of medicine]]
| volume = 109
| issue = 2
| pages = 141–149
| year = 2000
| month = August
| pmid = 10967156
}}</ref>
==Differentiating Myeloproliferative neoplasm from other Diseases==
==Differentiating Myeloproliferative neoplasm from other Diseases==
Myeloproliferative neoplasm must be differentiated from:<ref>{{Cite journal
 
| author = [[James W. Vardiman]], [[Nancy Lee Harris]] & [[Richard D. Brunning]]
{| class="wikitable"
| title = The World Health Organization (WHO) classification of the myeloid neoplasms
!Characteristic
| journal = [[Blood]]
!Causes
| volume = 100
!Laboratory abnormalities
| issue = 7
!Physical examination
| pages = 2292–2302
!Therapy
| year = 2002
!Other associations
| month = October
|-
| doi = 10.1182/blood-2002-04-1199
|Myelodysplastic syndrome
| pmid = 12239137
|
}}</ref>
* Prior exposure to alkylating agents
<ref>{{Cite journal
* Prior exposure to topoisomerase II inhibitors
| author = [[A. Tefferi]], [[L. A. Solberg]] & [[M. N. Silverstein]]
* Age-related changes in hematopoietic stem cells
| title = A clinical update in polycythemia vera and essential thrombocythemia
* Deletion of chromosome 5q or 7
| journal = [[The American journal of medicine]]
* Gain of chromosome 8
| volume = 109
|
| issue = 2
* Dysplasia in at least 10% of cells of at least 1 cell line
  | pages = 141–149
* Low [[white blood cell]] count
| year = 2000
* [[Anemia]]
| month = August
* [[Neutropenia]]
| pmid = 10967156
* [[Thrombocytopenia]]  
}}</ref>
|
*[[Acute lymphoblastic leukemia]]
* [[Mucosal bleeding]]
*[[Acute myelogenous leukemia]]
* Petechiae
*[[Chronic myelogenous leukemia]]
* Ecchymoses
*[[Essential thrombocytosis]]
* Evidence of infection
*[[Hypereosinophilic syndrome]]
* Pallor
*[[Non-Hodgkin lymphoma]]
|
*[[Primary myelofibrosis]]
* Lenalidomide
*Secondary thrombocytosis
* Decitabine
*[[Splenomegaly]]
* Azacitidine
*[[Systemic mastocytosis]]
* Erythropoiesis-stimulating agents (ESAs)
*[[Waldenstrom macroglobulinemia]]
* Granulocyte colony-stimulating factor (G-CSF)
* Transfusion support
|
Age-related changes in the bone marrow contribute to myelodysplastic syndrome
|-
|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
* Bruising
|
* Cytarabine
* Anthracycline
* Enasidenib
* Liposomal daunorubicin plus cytarabine
* Gemtuzumab ozogamycin
* Midostaurin
* [[Stem cell transplant]]
|
* Variable prognosis based on cytogenetic and molecular profile
* Four new FDA-approved therapies became available in 2017
|-
|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==
{{Reflist|2}}
{{Reflist|2}}

Revision as of 03:19, 10 June 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2] Shyam Patel [3]

Overview

Myeloproliferative neoplasm must be differentiated from acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, essential thrombocytosis, hypereosinophilic syndrome, non-Hodgkin lymphoma, primary myelofibrosis, secondary thrombocytosis, splenomegaly, systemic mastocytosis, and waldenstrom macroglobulinemia.

Differentiating Myeloproliferative neoplasm from other Diseases

Characteristic Causes Laboratory abnormalities Physical examination Therapy Other associations
Myelodysplastic syndrome
  • Prior exposure to alkylating agents
  • Prior exposure to topoisomerase II inhibitors
  • Age-related changes in hematopoietic stem cells
  • Deletion of chromosome 5q or 7
  • Gain of chromosome 8
  • Lenalidomide
  • Decitabine
  • Azacitidine
  • Erythropoiesis-stimulating agents (ESAs)
  • Granulocyte colony-stimulating factor (G-CSF)
  • Transfusion support

Age-related changes in the bone marrow contribute to myelodysplastic syndrome

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
  • Bruising
  • Cytarabine
  • Anthracycline
  • Enasidenib
  • Liposomal daunorubicin plus cytarabine
  • Gemtuzumab ozogamycin
  • Midostaurin
  • Stem cell transplant
  • Variable prognosis based on cytogenetic and molecular profile
  • Four new FDA-approved therapies became available in 2017
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)[2]
  • 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[3]
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[5]
  • 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[6]
  • 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. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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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