Myeloproliferative neoplasm medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Myeloproliferative disease}}
{{Myeloproliferative disease}}
{{CMG}} {{AE}} {{MJK}}
{{CMG}} {{AE}} {{MJK}} {{shyam}}
==Overview==
==Overview==
The mainstay of therapy for myeloproliferative neoplasm is [[chemotherapy]], [[aspirin]], and palliative care. Treatment is directed at reducing the excessive numbers of blood cells.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19</ref>
Medical therapy for myeloproliferative neoplasm is based on the specific subtype of myeloproliferative neoplasm. The mainstay of therapy for myeloproliferative neoplasm is [[chemotherapy]], [[cytoreduction]], [[aspirin]], and palliative care. Treatment is directed at reducing the excessive numbers of blood cells.
 
==Medical Therapy==
==Medical Therapy==
Medical therapy for myeloproliferative neoplasm is based on the specific subtype of myeloproliferative neoplasm.
Treatment varies for each of the eight subtypes of myeloproliferative neoplasm. The treatment recommendations are based on guidelines by the National Comprehensive Cancer Network.


===Polycythemia vera===
===[[Polycythemia vera]]<ref name="pmidPMID28982745">{{cite journal| author=Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT et al.| title=NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018. | journal=J Natl Compr Canc Netw | year= 2017 | volume= 15 | issue= 10 | pages= 1193-1207 | pmid=PMID28982745 | doi=10.6004/jnccn.2017.0157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28982745  }} </ref>===


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Primary myelofibrosis
Ruxolitinib
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits JAK2 (tyrosine kinase inhibitor)
| style="padding: 5px 5px; background: #F5F5F5;" |
10mg PO twice daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Weight gain, zoster, non-melanoma skin cancers, cytopenias
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Phlebotomy
| style="padding: 5px 5px; background: #F5F5F5;" |
Mechanically removes red blood cells from circulation
| style="padding: 5px 5px; background: #F5F5F5;" |
*Induction: 450cc blood removal daily until hematocrit < 45%
*Maintenance: One session every 2 months, with goal hematocrit < 45%
| style="padding: 5px 5px; background: #F5F5F5;" |
Iron deficiency anemia, fatigue, vasovagal episodes, pain at phlebotomy site
|}
 
===[[Essential thrombocythemia]]<ref name="pmidPMID28982745">{{cite journal| author=Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT et al.| title=NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018. | journal=J Natl Compr Canc Netw | year= 2017 | volume= 15 | issue= 10 | pages= 1193-1207 | pmid=PMID28982745 | doi=10.6004/jnccn.2017.0157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28982745  }} </ref>===
Treatment of essential thrombocythemia is based on risk assessment and prognostication:
 
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
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! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Prognostic Group}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Defining Features}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Therapy}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Very low risk<ref name="pmid29321520">{{cite journal| author=Tefferi A, Vannucchi AM, Barbui T| title=Essential thrombocythemia treatment algorithm 2018. | journal=Blood Cancer J | year= 2018 | volume= 8 | issue= 1 | pages= 2 | pmid=29321520 | doi=10.1038/s41408-017-0041-8 | pmc=5802626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29321520  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
* No history of thrombosis
* Age < 60
* ''JAK2'' or ''MPL'' wild-type
| style="padding: 5px 5px; background: #F5F5F5;" |
* Observation
''or''
* Aspirin once daily
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Low risk<ref name="pmid29321520">{{cite journal| author=Tefferi A, Vannucchi AM, Barbui T| title=Essential thrombocythemia treatment algorithm 2018. | journal=Blood Cancer J | year= 2018 | volume= 8 | issue= 1 | pages= 2 | pmid=29321520 | doi=10.1038/s41408-017-0041-8 | pmc=5802626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29321520  }} </ref>
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* No history of thrombosis
* Age < 60
* ''JAK2'' or ''MPL'' mutation present
| style="padding: 5px 5px; background: #F5F5F5;" |
* Aspirin once daily
''or''
* Aspirin twice daily
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Intermediate risk<ref name="pmid29321520">{{cite journal| author=Tefferi A, Vannucchi AM, Barbui T| title=Essential thrombocythemia treatment algorithm 2018. | journal=Blood Cancer J | year= 2018 | volume= 8 | issue= 1 | pages= 2 | pmid=29321520 | doi=10.1038/s41408-017-0041-8 | pmc=5802626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29321520  }} </ref>
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* No history of thrombosis
* Age > 60
* ''JAK2'' or ''MPL'' wild-type
| style="padding: 5px 5px; background: #F5F5F5;" |
* Aspirin once daily ''plus'' hydroxyurea
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
High risk<ref name="pmid29321520">{{cite journal| author=Tefferi A, Vannucchi AM, Barbui T| title=Essential thrombocythemia treatment algorithm 2018. | journal=Blood Cancer J | year= 2018 | volume= 8 | issue= 1 | pages= 2 | pmid=29321520 | doi=10.1038/s41408-017-0041-8 | pmc=5802626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29321520  }} </ref>
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* History of thrombosis, ''or''
* Age > 60 with ''JAK2'' or ''MPL'' mutation present
| style="padding: 5px 5px; background: #F5F5F5;" |
* Aspirin twice daily ''plus'' hydroxyurea
''or''
* Hydroxyurea, ''plus'' systemic anticoagulation
|-
|}
 
 
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|valign=top|
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Therapy}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Mechanism of Action}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Dosing}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Adverse Effects}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Anagrelide
| style="padding: 5px 5px; background: #F5F5F5;" |
*Inhibits phosphodiesterase 3 (PDE-3)
*Inhibits release of arachidonic acid from phospholipase A2
*Disrupts maturation of megakaryocytes
| style="padding: 5px 5px; background: #F5F5F5;" |
0.5mg PO every 6 hours or 1mg every 12 hours
| style="padding: 5px 5px; background: #F5F5F5;" |
Headache, palpitations, diarrhea, edema, nausea
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Hydroxyurea
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits ribonucleotide reductase
| style="padding: 5px 5px; background: #F5F5F5;" |
20mg/kg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Anemia, thrombocytopenia, ulcerations, secondary cancers
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Aspirin
| style="padding: 5px 5px; background: #F5F5F5;" |
Irreversibly inhibits cyclooxygenase-1 and -2 (COX-1 and COX-2)
| style="padding: 5px 5px; background: #F5F5F5;" |
81mg PO twice daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Mucosal bleeding
Gastrointestinal bleeding
|-
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Ruxolitinib
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| style="padding: 5px 5px; background: #F5F5F5;" |
Megakaryocyte
Inhibits JAK2 (tyrosine kinase inhibitor)
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
''Major criteria'':
10mg PO twice daily
*Presence of megakaryocyte proliferation and atypia with reticulin fibrosis
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*Not meeting criteria for other myeloproliferative neoplasms
Weight gain, zoster, non-melanoma skin cancers, cytopenias
*Presence of ''JAK2'', ''CALR'', or ''MPL'' mutation
''Minor criteria'':
*Anemia
*White blood cell count >11,000 per microliter.
*Palpable splenomegaly
*Elevated LDH
*Leukoerythroblastic smear
Diagnosis requires meeting all major criteria and at least 1 minor criterion.
|-
|-
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Chronic myeloid leukemia
Plateletpheresis
| style="padding: 5px 5px; background: #F5F5F5;" |
Mechanically removes platelets from circulation
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Common myeloid progenitor
Daily until platelet count returns to normal range
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Presence of BCR-ABL translocation (chromosomes 9 and 22)
Hypotension, thrombocytopenia
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Chronic neutrophilic leukemia
Pegylated interferon ''alpha'' 2a
| style="padding: 5px 5px; background: #F5F5F5;" |
Immunomodulatory agent; anti-angiogenic agent
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Neutrophil
45mcg/week
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Peripheral blood white blood cell count > 25,000 per microliter with rare myeloblasts and no dysgranulopoiesis
Hypotension, infusion reaction
*Bone marrow hypercellularity with increased granulocytes and normal maturation and <5% myeloblasts
|-
*Not meeting criteria for other myeloproliferative neoplasms
|}
*Absence of genetic rearrangements of ''PDGFRA'', ''PDGFRB'', ''FGFR1'', or ''PCM1-JAK2''
 
*Presence of ''CSF3R'' ''T618I'' or other characteristic mutation
===[[Primary myelofibrosis]]<ref name="pmidPMID28982745">{{cite journal| author=Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT et al.| title=NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018. | journal=J Natl Compr Canc Netw | year= 2017 | volume= 15 | issue= 10 | pages= 1193-1207 | pmid=PMID28982745 | doi=10.6004/jnccn.2017.0157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28982745  }} </ref>===
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
|valign=top|
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Therapy}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Mechanism of Action}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Dosing}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Adverse Effects}}
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Chronic eosinophilic leukemia
Hydroxyurea
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits ribonucleotide reductase
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Eosinophil
20mg/kg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
No formal W.H.O. criteria
Anemia, thrombocytopenia, ulcerations, secondary cancers
*Typically associated with >1,500 eosinophils per microliter in peripheral blood
*Typically associated with rearrangements of ''PDGFRA'', ''PDGFRB'', ''FGFR1'', ''JAK2''
|-
|-
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| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Myeloproliferative neoplasm, unclassifiable
Ruxolitinib
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Variable
Inhibits JAK2 (tyrosine kinase inhibitor)
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Not meeting criteria for other subcategories
10mg PO twice daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Weight gain, zoster, non-melanoma skin cancers, cytopenias
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Mastocytosis
Radiation therapy
| style="padding: 5px 5px; background: #F5F5F5;" |
Unknown mechanism
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Mast cell
0.5 Gy to spleen 5 days weekly
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
''Major criteria'':
Fatigue, secondary cancers, nausea, cytopenias
*Dense multifocal aggregates of >15 mast cells in bone marrow or other organ
''Minor criteria'':
*Presence of ''c-kit'' ''D816V''mutation
*Expression of CD2, CD25, or both on mast cells
*Serum tryptase level >20ng/ml when patient is at baseline health
*Atypical morphology or spindles in >25% of mast cells in bone marrow or other organ
Diagnosis requires meeting the one major plus one minor criterion, or 3 minor criteria.
|}
|}


===[[Chronic myeloid leukemia]]<ref name="pmidPMID27956535">{{cite journal| author=Pallera A, Altman JK, Berman E, Abboud CN, Bhatnagar B, Curtin P et al.| title=NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017. | journal=J Natl Compr Canc Netw | year= 2016 | volume= 14 | issue= 12 | pages= 1505-1512 | pmid=PMID27956535 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27956535  }} </ref>===
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
|valign=top|
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Therapy}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Mechanism of Action}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Dosing}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Adverse Effects}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Imatinib
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits BCR-ABL tyrosine kinase
| style="padding: 5px 5px; background: #F5F5F5;" |
400mg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Edema, periorbital swelling, nausea, anasarca
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Dasatinib
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits BCR-ABL tyrosine kinase
| style="padding: 5px 5px; background: #F5F5F5;" |
100mg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Pleural effusions, edema, periorbital swelling, facial edema
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Nilotinib
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits BCR-ABL tyrosine kinase
| style="padding: 5px 5px; background: #F5F5F5;" |
400mg PO twice daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Occlusive arterial disease, peripheral vascular disease, cytopenias, nausea
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Bosutinib
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits BCR-ABL tyrosine kinase
| style="padding: 5px 5px; background: #F5F5F5;" |
400mg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Edema, chest pain, fatigue, diarrhea
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Ponatinib
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits BCR-ABL tyrosine kinase; effective against the ''T315I'' kinase domain mutation in BCR-ABL
| style="padding: 5px 5px; background: #F5F5F5;" |
45mg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Hypertension, arterial ischemia, fatigue, constipation
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
Omacetaxine
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits protein synthesis
| style="padding: 5px 5px; background: #F5F5F5;" |
*Induction: 1.25mg/m2 subQ twice daily for 14 days of a 28-day cycle
*Maintenance: 1.25mg/m2 subQ twice daily for 7 days of a 28-day cycle
| style="padding: 5px 5px; background: #F5F5F5;" |
Peripheral edema, fatigue, nausea, thrombocytopenia
|-
|}
===[[Chronic neutrophilic leukemia]]<ref name="pmidPMID28982745">{{cite journal| author=Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT et al.| title=NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018. | journal=J Natl Compr Canc Netw | year= 2017 | volume= 15 | issue= 10 | pages= 1193-1207 | pmid=PMID28982745 | doi=10.6004/jnccn.2017.0157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28982745  }} </ref>===
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
|valign=top|
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Therapy}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Mechanism of Action}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Dosing}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Adverse Effects}}
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Hydroxyurea
| style="padding: 5px 5px; background: #F5F5F5;" |
Inhibits ribonucleotide reductase
| style="padding: 5px 5px; background: #F5F5F5;" |
20mg/kg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Anemia, thrombocytopenia, ulcerations, secondary cancers
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Pegylated interferon ''alpha'' 2a
| style="padding: 5px 5px; background: #F5F5F5;" |
Immunomodulatory agent; anti-angiogenic agent
| style="padding: 5px 5px; background: #F5F5F5;" |
45mcg/week
| style="padding: 5px 5px; background: #F5F5F5;" |
Hypotension, infusion reaction
|-
|}
===[[Chronic eosinophilic leukemia]]<ref name="pmidPMID28982745">{{cite journal| author=Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT et al.| title=NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018. | journal=J Natl Compr Canc Netw | year= 2017 | volume= 15 | issue= 10 | pages= 1193-1207 | pmid=PMID28982745 | doi=10.6004/jnccn.2017.0157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28982745  }} </ref>===
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
|valign=top|
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Therapy}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Mechanism of Action}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Dosing}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Adverse Effects}}
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Imatinib<ref name="pmid28254862">{{cite journal| author=Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O et al.| title=Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future. | journal=Cancer Res | year= 2017 | volume= 77 | issue= 6 | pages= 1261-1270 | pmid=28254862 | doi=10.1158/0008-5472.CAN-16-2234 | pmc=5354959 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28254862  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
Tyrosine kinase inhibitor that inhibits wild-type ''c-kit''; not effective for ''c-kit'' ''D816V'' mutation
| style="padding: 5px 5px; background: #F5F5F5;" |
400mg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Edema, periorbital swelling, nausea, anasarca
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Corticosteroids
| style="padding: 5px 5px; background: #F5F5F5;" |
Immunosuppressive agent; inhibits IL-2 and COX2
| style="padding: 5px 5px; background: #F5F5F5;" |
Variable; typical dose is 1mg/kg/day
| style="padding: 5px 5px; background: #F5F5F5;" |
Infections, cataract, glaucoma, bone loss, muscular atrophy
|-
|}
===[[Systemic mastocytosis]]===
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
|valign=top|
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Therapy}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Mechanism of Action}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Dosing}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Adverse Effects}}
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| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Imatinib<ref name="pmid28254862">{{cite journal| author=Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O et al.| title=Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future. | journal=Cancer Res | year= 2017 | volume= 77 | issue= 6 | pages= 1261-1270 | pmid=28254862 | doi=10.1158/0008-5472.CAN-16-2234 | pmc=5354959 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28254862  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
Tyrosine kinase inhibitor that inhibits wild-type ''c-kit''; not effective for ''c-kit'' ''D816V'' mutation
| style="padding: 5px 5px; background: #F5F5F5;" |
400mg PO daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Edema, periorbital swelling, nausea, anasarca
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
Midostaurin<ref name="pmid28254862">{{cite journal| author=Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O et al.| title=Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future. | journal=Cancer Res | year= 2017 | volume= 77 | issue= 6 | pages= 1261-1270 | pmid=28254862 | doi=10.1158/0008-5472.CAN-16-2234 | pmc=5354959 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28254862  }} </ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
Tyrosine kinase inhibitor that inhibits wild-type ''c-kit'' and mutant ''c-kit'' ''D816V''
| style="padding: 5px 5px; background: #F5F5F5;" |
10mg PO twice daily
| style="padding: 5px 5px; background: #F5F5F5;" |
Nausea, hypocalcemia, mucositis, headache, epistaxis, hypernatremia
|-
|}


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Latest revision as of 04:07, 15 July 2018

Myeloproliferative Neoplasm Microchapters

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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

Medical therapy for myeloproliferative neoplasm is based on the specific subtype of myeloproliferative neoplasm. The mainstay of therapy for myeloproliferative neoplasm is chemotherapy, cytoreduction, aspirin, and palliative care. Treatment is directed at reducing the excessive numbers of blood cells.

Medical Therapy

Treatment varies for each of the eight subtypes of myeloproliferative neoplasm. The treatment recommendations are based on guidelines by the National Comprehensive Cancer Network.

Polycythemia vera[1]
Therapy Mechanism of Action Dosing Adverse Effects

Aspirin

Irreversibly inhibits cyclooxygenase-1 and -2 (COX-1 and COX-2)

81mg PO daily

Mucosal bleeding Gastrointestinal bleeding

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Ruxolitinib

Inhibits JAK2 (tyrosine kinase inhibitor)

10mg PO twice daily

Weight gain, zoster, non-melanoma skin cancers, cytopenias

Phlebotomy

Mechanically removes red blood cells from circulation

  • Induction: 450cc blood removal daily until hematocrit < 45%
  • Maintenance: One session every 2 months, with goal hematocrit < 45%

Iron deficiency anemia, fatigue, vasovagal episodes, pain at phlebotomy site

Essential thrombocythemia[1]

Treatment of essential thrombocythemia is based on risk assessment and prognostication:

Prognostic Group Defining Features Therapy

Very low risk[2]

  • No history of thrombosis
  • Age < 60
  • JAK2 or MPL wild-type
  • Observation

or

  • Aspirin once daily

Low risk[2]

  • No history of thrombosis
  • Age < 60
  • JAK2 or MPL mutation present
  • Aspirin once daily

or

  • Aspirin twice daily

Intermediate risk[2]

  • No history of thrombosis
  • Age > 60
  • JAK2 or MPL wild-type
  • Aspirin once daily plus hydroxyurea

High risk[2]

  • History of thrombosis, or
  • Age > 60 with JAK2 or MPL mutation present
  • Aspirin twice daily plus hydroxyurea

or

  • Hydroxyurea, plus systemic anticoagulation
Therapy Mechanism of Action Dosing Adverse Effects

Anagrelide

  • Inhibits phosphodiesterase 3 (PDE-3)
  • Inhibits release of arachidonic acid from phospholipase A2
  • Disrupts maturation of megakaryocytes

0.5mg PO every 6 hours or 1mg every 12 hours

Headache, palpitations, diarrhea, edema, nausea

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Aspirin

Irreversibly inhibits cyclooxygenase-1 and -2 (COX-1 and COX-2)

81mg PO twice daily

Mucosal bleeding Gastrointestinal bleeding

Ruxolitinib

Inhibits JAK2 (tyrosine kinase inhibitor)

10mg PO twice daily

Weight gain, zoster, non-melanoma skin cancers, cytopenias

Plateletpheresis

Mechanically removes platelets from circulation

Daily until platelet count returns to normal range

Hypotension, thrombocytopenia

Pegylated interferon alpha 2a

Immunomodulatory agent; anti-angiogenic agent

45mcg/week

Hypotension, infusion reaction

Primary myelofibrosis[1]
Therapy Mechanism of Action Dosing Adverse Effects

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Ruxolitinib

Inhibits JAK2 (tyrosine kinase inhibitor)

10mg PO twice daily

Weight gain, zoster, non-melanoma skin cancers, cytopenias

Radiation therapy

Unknown mechanism

0.5 Gy to spleen 5 days weekly

Fatigue, secondary cancers, nausea, cytopenias

Chronic myeloid leukemia[3]
Therapy Mechanism of Action Dosing Adverse Effects

Imatinib

Inhibits BCR-ABL tyrosine kinase

400mg PO daily

Edema, periorbital swelling, nausea, anasarca

Dasatinib

Inhibits BCR-ABL tyrosine kinase

100mg PO daily

Pleural effusions, edema, periorbital swelling, facial edema

Nilotinib

Inhibits BCR-ABL tyrosine kinase

400mg PO twice daily

Occlusive arterial disease, peripheral vascular disease, cytopenias, nausea

Bosutinib

Inhibits BCR-ABL tyrosine kinase

400mg PO daily

Edema, chest pain, fatigue, diarrhea

Ponatinib

Inhibits BCR-ABL tyrosine kinase; effective against the T315I kinase domain mutation in BCR-ABL

45mg PO daily

Hypertension, arterial ischemia, fatigue, constipation

Omacetaxine

Inhibits protein synthesis

  • Induction: 1.25mg/m2 subQ twice daily for 14 days of a 28-day cycle
  • Maintenance: 1.25mg/m2 subQ twice daily for 7 days of a 28-day cycle

Peripheral edema, fatigue, nausea, thrombocytopenia

Chronic neutrophilic leukemia[1]
Therapy Mechanism of Action Dosing Adverse Effects

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Pegylated interferon alpha 2a

Immunomodulatory agent; anti-angiogenic agent

45mcg/week

Hypotension, infusion reaction

Chronic eosinophilic leukemia[1]
Therapy Mechanism of Action Dosing Adverse Effects

Imatinib[4]

Tyrosine kinase inhibitor that inhibits wild-type c-kit; not effective for c-kit D816V mutation

400mg PO daily

Edema, periorbital swelling, nausea, anasarca

Corticosteroids

Immunosuppressive agent; inhibits IL-2 and COX2

Variable; typical dose is 1mg/kg/day

Infections, cataract, glaucoma, bone loss, muscular atrophy

Systemic mastocytosis
Therapy Mechanism of Action Dosing Adverse Effects

Imatinib[4]

Tyrosine kinase inhibitor that inhibits wild-type c-kit; not effective for c-kit D816V mutation

400mg PO daily

Edema, periorbital swelling, nausea, anasarca

Midostaurin[4]

Tyrosine kinase inhibitor that inhibits wild-type c-kit and mutant c-kit D816V

10mg PO twice daily

Nausea, hypocalcemia, mucositis, headache, epistaxis, hypernatremia

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Mesa RA, Jamieson C, Bhatia R, Deininger MW, Fletcher CD, Gerds AT; et al. (2017). "NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018". J Natl Compr Canc Netw. 15 (10): 1193–1207. doi:10.6004/jnccn.2017.0157. PMID PMID28982745 Check |pmid= value (help).
  2. ↑ 2.0 2.1 2.2 2.3 Tefferi A, Vannucchi AM, Barbui T (2018). "Essential thrombocythemia treatment algorithm 2018". Blood Cancer J. 8 (1): 2. doi:10.1038/s41408-017-0041-8. PMC 5802626. PMID 29321520.
  3. ↑ Pallera A, Altman JK, Berman E, Abboud CN, Bhatnagar B, Curtin P; et al. (2016). "NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017". J Natl Compr Canc Netw. 14 (12): 1505–1512. PMID PMID27956535 Check |pmid= value (help).
  4. ↑ 4.0 4.1 4.2 Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O; et al. (2017). "Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future". Cancer Res. 77 (6): 1261–1270. doi:10.1158/0008-5472.CAN-16-2234. PMC 5354959. PMID 28254862.

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