Myeloproliferative neoplasm differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Myeloproliferative disease}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Myeloproliferative_neoplasm]]
{{CMG}} {{AE}} {{HMHJ}} {{ZAS}} {{MJK}} {{shyam}}
{{CMG}} {{AE}} {{HMHJ}} {{ZAS}} {{MJK}} {{shyam}}
==Overview==
==Overview==
Myeloproliferative neoplasm must be differentiated from [[myelodysplastic syndrome]], [[acute myelogenous leukemia]], [[acute lymphoblastic leukemia, [[Waldenstrom's macroglobulinemia]], and [[lymphoproliferative disorder]]. Each of these conditions has unique set of causes, laboratory abnormalities, physical exam findings, and therapies.
Myeloproliferative neoplasm must be differentiated from [[myelodysplastic syndrome]], [[acute myelogenous leukemia]], [[acute lymphoblastic leukemia]], [[Waldenstrom's macroglobulinemia]], and [[lymphoproliferative disorder]]. Each of these conditions has a unique set of causes, laboratory abnormalities, physical exam findings, and investigations.
==Differentiating Myelodysplastic Syndrome==
 
==Differentiating Myeloproliferative Neoplasm from other Diseases==
'''ABBREVIATIONS'''
'''ABBREVIATIONS'''


'''N/A''': Not available, '''NL''': Normal, '''FISH''': Fluorescence in situ hybridization, '''PCR''': Polymerase chain reaction, '''LDH''': Lactate dehydrogenase, '''PUD''': Peptic ulcer disease, '''EPO''': Erythropoietin, '''LFTs''': Liver function tests, '''RFTs''': Renal function tests, '''LAP''': Leukocyte alkaline phosphatase, '''LAD''': Leukocyte alkaline dehydrgenase, '''WBCs''': White blood cells.  
'''EPO''': Erythropoietin, '''FISH''': Fluorescence in situ hybridization, '''Hb''': Hemoglobin, '''LAD''': Leukocyte alkaline dehydrgenase, '''LAP''': Leukocyte alkaline phosphatase, '''LDH''': Lactate dehydrogenase, '''LFTs''': Liver function tests, '''NL''': Normal, '''PCR''': Polymerase chain reaction, '''Plt''': Platelet, '''PUD''': Peptic ulcer disease, '''RFTs''': Renal function tests, '''WBCs''': White blood cells.  
{| class="wikitable"
{| class="wikitable"
! colspan="2" rowspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! colspan="2" rowspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
Line 31: Line 32:
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
|-
|-
! colspan="2" |[[Chronic myeloid leukemia]]<br>([[CML]]), [[BCR/ABL|BCR-ABL1]]+<ref name="pmid9012696">{{cite journal |vauthors=Savage DG, Szydlo RM, Goldman JM |title=Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period |journal=Br. J. Haematol. |volume=96 |issue=1 |pages=111–6 |date=January 1997 |pmid=9012696 |doi= |url=}}</ref><ref name="pmid26434969">{{cite journal |vauthors=Thompson PA, Kantarjian HM, Cortes JE |title=Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015 |journal=Mayo Clin. Proc. |volume=90 |issue=10 |pages=1440–54 |date=October 2015 |pmid=26434969 |pmc=5656269 |doi=10.1016/j.mayocp.2015.08.010 |url=}}</ref>
! colspan="2" |[[Chronic myeloid leukemia]]<br>([[CML]])<ref name="pmid9012696">{{cite journal |vauthors=Savage DG, Szydlo RM, Goldman JM |title=Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period |journal=Br. J. Haematol. |volume=96 |issue=1 |pages=111–6 |date=January 1997 |pmid=9012696 |doi= |url=}}</ref><ref name="pmid26434969">{{cite journal |vauthors=Thompson PA, Kantarjian HM, Cortes JE |title=Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015 |journal=Mayo Clin. Proc. |volume=90 |issue=10 |pages=1440–54 |date=October 2015 |pmid=26434969 |pmc=5656269 |doi=10.1016/j.mayocp.2015.08.010 |url=}}</ref>
|
|
* Asymptomatic
* Asymptomatic
Line 64: Line 65:
* Classic [[myelocyte]] bulge
* Classic [[myelocyte]] bulge
* [[thrombocytopenia]] indicates advanced stage
* [[thrombocytopenia]] indicates advanced stage
|-
! colspan="2" |[[Chronic neutrophilic leukemia]] ([[CNL]])<ref name="pmid29440636">{{cite journal |vauthors=Szuber N, Tefferi A |title=Chronic neutrophilic leukemia: new science and new diagnostic criteria |journal=Blood Cancer J |volume=8 |issue=2 |pages=19 |date=February 2018 |pmid=29440636 |pmc=5811432 |doi=10.1038/s41408-018-0049-8 |url=}}</ref><ref name="pmid28028025">{{cite journal |vauthors=Maxson JE, Tyner JW |title=Genomics of chronic neutrophilic leukemia |journal=Blood |volume=129 |issue=6 |pages=715–722 |date=February 2017 |pmid=28028025 |pmc=5301820 |doi=10.1182/blood-2016-10-695981 |url=}}</ref><ref name="pmid26366092">{{cite journal |vauthors=Menezes J, Cigudosa JC |title=Chronic neutrophilic leukemia: a clinical perspective |journal=Onco Targets Ther |volume=8 |issue= |pages=2383–90 |date=2015 |pmid=26366092 |pmc=4562747 |doi=10.2147/OTT.S49688 |url=}}</ref>
|
* Asymptomatic
* Constitutional symptoms
* [[Bleeding]]
* [[Infection]]
|
* [[Splenomegaly]]
* [[Heptomegaly]]
* [[Purpura]]
* [[Anemia]] related
|↑
|Minimal
| +
|NL
|NL
|NL
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Uniforme and intense hypercellularity with minimal to none [[fibrosis]]
* [[Neutrophil]] toxic granulations and [[Dohle bodies]]
|
* [[FISH]]
* Imaging for [[hepatosplenomegaly]]
* ↑  [[LDH]]
* ↑ [[B12]] levels
|
* Associationed with [[polycythemia vera]] and [[plasma cell disorders]]
* [[Leukocytosis]] with<br>[[chronic]] [[neutrophilia]]
|-
|-
! colspan="2" |[[Polycythemia vera]]<br>([[PV]])<ref name="pmid29194068">{{cite journal |vauthors=Vannucchi AM, Guglielmelli P, Tefferi A |title=Polycythemia vera and essential thrombocythemia: algorithmic approach |journal=Curr. Opin. Hematol. |volume=25 |issue=2 |pages=112–119 |date=March 2018 |pmid=29194068 |doi=10.1097/MOH.0000000000000402 |url=}}</ref><ref name="pmid30252337">{{cite journal |vauthors=Pillai AA, Babiker HM |title= |journal= |volume= |issue= |pages= |date= |pmid=30252337 |doi= |url=}}</ref><ref name="pmid30281843">{{cite journal |vauthors=Tefferi A, Barbui T |title=Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management |journal=Am. J. Hematol. |volume=94 |issue=1 |pages=133–143 |date=January 2019 |pmid=30281843 |doi=10.1002/ajh.25303 |url=}}</ref><ref name="pmid28028026">{{cite journal |vauthors=Rumi E, Cazzola M |title=Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms |journal=Blood |volume=129 |issue=6 |pages=680–692 |date=February 2017 |pmid=28028026 |pmc=5335805 |doi=10.1182/blood-2016-10-695957 |url=}}</ref>
! colspan="2" |[[Polycythemia vera]]<br>([[PV]])<ref name="pmid29194068">{{cite journal |vauthors=Vannucchi AM, Guglielmelli P, Tefferi A |title=Polycythemia vera and essential thrombocythemia: algorithmic approach |journal=Curr. Opin. Hematol. |volume=25 |issue=2 |pages=112–119 |date=March 2018 |pmid=29194068 |doi=10.1097/MOH.0000000000000402 |url=}}</ref><ref name="pmid30252337">{{cite journal |vauthors=Pillai AA, Babiker HM |title= |journal= |volume= |issue= |pages= |date= |pmid=30252337 |doi= |url=}}</ref><ref name="pmid30281843">{{cite journal |vauthors=Tefferi A, Barbui T |title=Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management |journal=Am. J. Hematol. |volume=94 |issue=1 |pages=133–143 |date=January 2019 |pmid=30281843 |doi=10.1002/ajh.25303 |url=}}</ref><ref name="pmid28028026">{{cite journal |vauthors=Rumi E, Cazzola M |title=Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms |journal=Blood |volume=129 |issue=6 |pages=680–692 |date=February 2017 |pmid=28028026 |pmc=5335805 |doi=10.1182/blood-2016-10-695957 |url=}}</ref>
Line 240: Line 210:
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! rowspan="4" |[[Myelodysplastic]]<br>/[[Myeloproliferative neoplasm|myeloproliferative<br>neoplasms]] (MDS/MPN)
![[Chronic myelomonocytic leukemia]] (CMML)<ref name="pmid27185207">{{cite journal |vauthors=Patnaik MM, Tefferi A |title=Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=6 |pages=631–42 |date=June 2016 |pmid=27185207 |doi=10.1002/ajh.24396 |url=}}</ref>
: <ref name="pmid22615103">{{cite journal |vauthors=Parikh SA, Tefferi A |title=Chronic myelomonocytic leukemia: 2012 update on diagnosis, risk stratification, and management |journal=Am. J. Hematol. |volume=87 |issue=6 |pages=610–9 |date=June 2012 |pmid=22615103 |doi=10.1002/ajh.23203 |url=}}</ref><ref name="pmid25869097">{{cite journal |vauthors=Benton CB, Nazha A, Pemmaraju N, Garcia-Manero G |title=Chronic myelomonocytic leukemia: Forefront of the field in 2015 |journal=Crit. Rev. Oncol. Hematol. |volume=95 |issue=2 |pages=222–42 |date=August 2015 |pmid=25869097 |pmc=4859155 |doi=10.1016/j.critrevonc.2015.03.002 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Bleeding]]
* [[Infections]]
* [[Bone]] [[pain]]
* [[Leukemia Cutis]]
|
* [[Organomegaly]]
* [[Bruising]]
|↑
| < 20%
|
|NL
|[[Eosinophilia|↑]]
|↑↑
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* [[Myelodysplastic]] and [[myeloproliferative]] feature
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* ↑ [[LDH]]
|
* Overlapping of both, [[MDS]] and [[MPN]]
* Absolute [[monocytosis]] > 1 × 10<sup>9</sup>/L (defining feature)
* MD-CMML:[[WBC]] ≤ 13 × 10<sup>9</sup>/L (FAB)
*  MP-CMML:[[WBC]] > 13 × 10<sup>9</sup>/L (FAB)
|-
![[Atypical chronic myeloid leukemia]] (aCML), [[BCR/ABL|BCR-ABL]]1-<ref name="pmid26637732">{{cite journal |vauthors=Dao KH, Tyner JW |title=What's different about atypical CML and chronic neutrophilic leukemia? |journal=Hematology Am Soc Hematol Educ Program |volume=2015 |issue= |pages=264–71 |date=2015 |pmid=26637732 |pmc=5266507 |doi=10.1182/asheducation-2015.1.264 |url=}}</ref><ref name="pmid22289493">{{cite journal |vauthors=Muramatsu H, Makishima H, Maciejewski JP |title=Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions |journal=Semin. Oncol. |volume=39 |issue=1 |pages=67–73 |date=February 2012 |pmid=22289493 |pmc=3523950 |doi=10.1053/j.seminoncol.2011.11.004 |url=}}</ref>
|
*Asymptomatic
* Constitutional
* [[Hyperviscosity|Hyperviscosity]]  and/or [[anemia]] related
* [[Bleeding|Bleeding]]
* [[Infection|Infection]]
|
* [[Splenomegaly]]  (46–76%)
* [[Purpura]]
* [[Anemia]] related
* [[Priapism]]
|↑
|<20%
| +
|<2% of WBCs
|N/A
|N/A
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Granulocytic [[hyperplasia]] with prominent [[dysplasia]]
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
|
* Granulocytic [[dysplasia]] is prominent
* Absence of ''[[BCR/ABL|BCR-ABL]]'' or ''PDGFRA'', [[PDGFRB|''PDGFRB'',]] or ''[[FGFR1]]'' rearrangements
* [[WBC]] > 13 × 10<sup>9</sup>/L
|-
![[Juvenile myelomonocytic leukemia (patient information)|Juvenile myelomonocytic leukemia (]]JMML)<ref name="pmid9226148">{{cite journal |vauthors=Aricò M, Biondi A, Pui CH |title=Juvenile myelomonocytic leukemia |journal=Blood |volume=90 |issue=2 |pages=479–88 |date=July 1997 |pmid=9226148 |doi= |url=}}</ref><ref name="pmid80255132">{{cite journal |vauthors=Hasle H |title=Myelodysplastic syndromes in childhood--classification, epidemiology, and treatment |journal=Leuk. Lymphoma |volume=13 |issue=1-2 |pages=11–26 |date=March 1994 |pmid=8025513 |doi=10.3109/10428199409051647 |url=}}</ref>
|
* [[Infections]]
* [[Anemia]] related
|
* [[Hepatosplenomegaly]]
* [[Lymphadenopathy]]
* [[Rash]]
|[[Leukocytosis|↑]]
|↑
|N/A
|N/A
|N/A
|[[Monocytosis|↑]]
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Hypercelluar with  ↑ [[myeloid cells]] in stages of maturation
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* [[Flow cytometry|↓]] [[Serum]] [[Iron]]
* [[Flow cytometry|↑]] [[Vitamin B12|B12]] levels
|
* Polyclonal [[hypergammaglobulinemia]]
|-
![[MDS]]/[[MPN]] with ring sideroblasts and [[thrombocytosis]] (MDS/MPN-RS-T)<ref name="pmid28188970">{{cite journal |vauthors=Patnaik MM, Tefferi A |title=Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T): 2017 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=92 |issue=3 |pages=297–310 |date=March 2017 |pmid=28188970 |doi=10.1002/ajh.24637 |url=}}</ref><ref name="pmid30186759">{{cite journal |vauthors=Alshaban A, Padilla O, Philipovskiy A, Corral J, McAlice M, Gaur S |title=Lenalidomide induced durable remission in a patient with MDS/MPN-with ring sideroblasts and thrombocytosis with associated 5q- syndrome |journal=Leuk Res Rep |volume=10 |issue= |pages=37–40 |date=2018 |pmid=30186759 |doi=10.1016/j.lrr.2018.08.001 |url=}}</ref><ref name="pmid30524760">{{cite journal |vauthors=Bouchla A, Papageorgiou SG, Tsakiraki Z, Glezou E, Pavlidis G, Stavroulaki G, Bazani E, Foukas P, Pappa V |title=Plasmablastic Lymphoma in an Immunocompetent Patient with MDS/MPN with Ring Sideroblasts and Thrombocytosis-A Case Report |journal=Case Rep Hematol |volume=2018 |issue= |pages=2525070 |date=2018 |pmid=30524760 |pmc=6247723 |doi=10.1155/2018/2525070 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Thrombosis]]
|
* Variable
|NL or ↑
|NL
| -
|NL
|N/A
|N/A
|[[Anemia|↓]]
|[[Thrombocytosis|↑]]
|
* Hypercellularity with [[dyserythropoiesis]] and increased [[megakaryocytes]]
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* ↑ [[Serum]] [[Iron]]
|
* Large atypical [[megakaryocytes]]
* Ringed [[sideroblasts]]
* [[SF3B1]] [[mutation]]
|-
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Sign
! style="background:#4479BA; color: #FFFFFF;" align="center" + |WBC
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Blasts
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Left<br>shift
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Baso-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Eosino-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Hb
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Plt
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bone marrow biopsy
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! colspan="2" |[[Chronic neutrophilic leukemia]] ([[CNL]])<ref name="pmid29440636">{{cite journal |vauthors=Szuber N, Tefferi A |title=Chronic neutrophilic leukemia: new science and new diagnostic criteria |journal=Blood Cancer J |volume=8 |issue=2 |pages=19 |date=February 2018 |pmid=29440636 |pmc=5811432 |doi=10.1038/s41408-018-0049-8 |url=}}</ref><ref name="pmid28028025">{{cite journal |vauthors=Maxson JE, Tyner JW |title=Genomics of chronic neutrophilic leukemia |journal=Blood |volume=129 |issue=6 |pages=715–722 |date=February 2017 |pmid=28028025 |pmc=5301820 |doi=10.1182/blood-2016-10-695981 |url=}}</ref><ref name="pmid26366092">{{cite journal |vauthors=Menezes J, Cigudosa JC |title=Chronic neutrophilic leukemia: a clinical perspective |journal=Onco Targets Ther |volume=8 |issue= |pages=2383–90 |date=2015 |pmid=26366092 |pmc=4562747 |doi=10.2147/OTT.S49688 |url=}}</ref>
|
* Asymptomatic
* Constitutional symptoms
* [[Bleeding]]
* [[Infection]]
|
* [[Splenomegaly]]
* [[Heptomegaly]]
* [[Purpura]]
* [[Anemia]] related
|↑
|Minimal
| +
|NL
|NL
|NL
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Uniforme and intense hypercellularity with minimal to none [[fibrosis]]
* [[Neutrophil]] toxic granulations and [[Dohle bodies]]
|
* [[FISH]]
* Imaging for [[hepatosplenomegaly]]
* ↑  [[LDH]]
* ↑ [[B12]] levels
|
* Associationed with [[polycythemia vera]] and [[plasma cell disorders]]
* [[Leukocytosis]] with<br>[[chronic]] [[neutrophilia]]
|-
|-
! colspan="2" |[[Chronic eosinophilic leukemia]],<br>not otherwise specified<br>(NOS)<ref name="pmid27512192">{{cite journal |vauthors=Vidyadharan S, Joseph B, Nair SP |title=Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations |journal=Indian J Dermatol |volume=61 |issue=4 |pages=437–9 |date=2016 |pmid=27512192 |pmc=4966405 |doi=10.4103/0019-5154.185716 |url=}}</ref><ref name="pmid29892549">{{cite journal |vauthors=Hofmans M, Delie A, Vandepoele K, Van Roy N, Van der Meulen J, Philippé J, Moors I |title=A case of chronic eosinophilic leukemia with secondary transformation to acute myeloid leukemia |journal=Leuk Res Rep |volume=9 |issue= |pages=45–47 |date=2018 |pmid=29892549 |pmc=5993353 |doi=10.1016/j.lrr.2018.04.001 |url=}}</ref><ref name="pmid23662039">{{cite journal |vauthors=Yamada Y, Rothenberg ME, Cancelas JA |title=Current concepts on the pathogenesis of the hypereosinophilic syndrome/chronic eosinophilic leukemia |journal=Transl Oncogenomics |volume=1 |issue= |pages=53–63 |date=2006 |pmid=23662039 |pmc=3642145 |doi= |url=}}</ref><ref name="pmid27722133">{{cite journal |vauthors=Kim TH, Gu HJ, Lee WI, Lee J, Yoon HJ, Park TS |title=Chronic eosinophilic leukemia with FIP1L1-PDGFRA rearrangement |journal=Blood Res |volume=51 |issue=3 |pages=204–206 |date=September 2016 |pmid=27722133 |doi=10.5045/br.2016.51.3.204 |url=}}</ref>
! colspan="2" |[[Chronic eosinophilic leukemia]],<br>not otherwise specified<br>(NOS)<ref name="pmid27512192">{{cite journal |vauthors=Vidyadharan S, Joseph B, Nair SP |title=Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations |journal=Indian J Dermatol |volume=61 |issue=4 |pages=437–9 |date=2016 |pmid=27512192 |pmc=4966405 |doi=10.4103/0019-5154.185716 |url=}}</ref><ref name="pmid29892549">{{cite journal |vauthors=Hofmans M, Delie A, Vandepoele K, Van Roy N, Van der Meulen J, Philippé J, Moors I |title=A case of chronic eosinophilic leukemia with secondary transformation to acute myeloid leukemia |journal=Leuk Res Rep |volume=9 |issue= |pages=45–47 |date=2018 |pmid=29892549 |pmc=5993353 |doi=10.1016/j.lrr.2018.04.001 |url=}}</ref><ref name="pmid23662039">{{cite journal |vauthors=Yamada Y, Rothenberg ME, Cancelas JA |title=Current concepts on the pathogenesis of the hypereosinophilic syndrome/chronic eosinophilic leukemia |journal=Transl Oncogenomics |volume=1 |issue= |pages=53–63 |date=2006 |pmid=23662039 |pmc=3642145 |doi= |url=}}</ref><ref name="pmid27722133">{{cite journal |vauthors=Kim TH, Gu HJ, Lee WI, Lee J, Yoon HJ, Park TS |title=Chronic eosinophilic leukemia with FIP1L1-PDGFRA rearrangement |journal=Blood Res |volume=51 |issue=3 |pages=204–206 |date=September 2016 |pmid=27722133 |doi=10.5045/br.2016.51.3.204 |url=}}</ref>
Line 576: Line 713:
* TdT expression positive
* TdT expression positive
* May develop [[chronic myelomonocytic leukemia]] (CMML)
* May develop [[chronic myelomonocytic leukemia]] (CMML)
|-
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Sign
! style="background:#4479BA; color: #FFFFFF;" align="center" + |WBC
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Blasts
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Left<br>shift
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Baso-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Eosino-<br>phils
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mono-<br>cytes
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Hb
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Plt
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bone marrow biopsy
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other investigations
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Other features
|-
! rowspan="4" |[[Myelodysplastic]]<br>/[[Myeloproliferative neoplasm|myeloproliferative<br>neoplasms]] (MDS/MPN)
![[Chronic myelomonocytic leukemia]] (CMML)<ref name="pmid27185207">{{cite journal |vauthors=Patnaik MM, Tefferi A |title=Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=6 |pages=631–42 |date=June 2016 |pmid=27185207 |doi=10.1002/ajh.24396 |url=}}</ref>
: <ref name="pmid22615103">{{cite journal |vauthors=Parikh SA, Tefferi A |title=Chronic myelomonocytic leukemia: 2012 update on diagnosis, risk stratification, and management |journal=Am. J. Hematol. |volume=87 |issue=6 |pages=610–9 |date=June 2012 |pmid=22615103 |doi=10.1002/ajh.23203 |url=}}</ref><ref name="pmid25869097">{{cite journal |vauthors=Benton CB, Nazha A, Pemmaraju N, Garcia-Manero G |title=Chronic myelomonocytic leukemia: Forefront of the field in 2015 |journal=Crit. Rev. Oncol. Hematol. |volume=95 |issue=2 |pages=222–42 |date=August 2015 |pmid=25869097 |pmc=4859155 |doi=10.1016/j.critrevonc.2015.03.002 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Bleeding]]
* [[Infections]]
* [[Bone]] [[pain]]
* [[Leukemia Cutis]]
|
* [[Organomegaly]]
* [[Bruising]]
|↑
| < 20%
|
|NL
|[[Eosinophilia|↑]]
|↑↑
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* [[Myelodysplastic]] and [[myeloproliferative]] feature
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* ↑ [[LDH]]
|
* Overlapping of both, [[MDS]] and [[MPN]]
* Absolute [[monocytosis]] > 1 × 10<sup>9</sup>/L (defining feature)
* MD-CMML:[[WBC]] ≤ 13 × 10<sup>9</sup>/L (FAB)
*  MP-CMML:[[WBC]] > 13 × 10<sup>9</sup>/L (FAB)
|-
![[Atypical chronic myeloid leukemia]] (aCML), [[BCR/ABL|BCR-ABL]]1-<ref name="pmid26637732">{{cite journal |vauthors=Dao KH, Tyner JW |title=What's different about atypical CML and chronic neutrophilic leukemia? |journal=Hematology Am Soc Hematol Educ Program |volume=2015 |issue= |pages=264–71 |date=2015 |pmid=26637732 |pmc=5266507 |doi=10.1182/asheducation-2015.1.264 |url=}}</ref><ref name="pmid22289493">{{cite journal |vauthors=Muramatsu H, Makishima H, Maciejewski JP |title=Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions |journal=Semin. Oncol. |volume=39 |issue=1 |pages=67–73 |date=February 2012 |pmid=22289493 |pmc=3523950 |doi=10.1053/j.seminoncol.2011.11.004 |url=}}</ref>
|
*Asymptomatic
* Constitutional
* [[Hyperviscosity|Hyperviscosity]]  and/or [[anemia]] related
* [[Bleeding|Bleeding]]
* [[Infection|Infection]]
|
* [[Splenomegaly]]  (46–76%)
* [[Purpura]]
* [[Anemia]] related
* [[Priapism]]
|↑
|<20%
| +
|<2% of WBCs
|N/A
|N/A
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Granulocytic [[hyperplasia]] with prominent [[dysplasia]]
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
|
* Granulocytic [[dysplasia]] is prominent
* Absence of ''[[BCR/ABL|BCR-ABL]]'' or ''PDGFRA'', [[PDGFRB|''PDGFRB'',]] or ''[[FGFR1]]'' rearrangements
* [[WBC]] > 13 × 10<sup>9</sup>/L
|-
![[Juvenile myelomonocytic leukemia (patient information)|Juvenile myelomonocytic leukemia (]]JMML)<ref name="pmid9226148">{{cite journal |vauthors=Aricò M, Biondi A, Pui CH |title=Juvenile myelomonocytic leukemia |journal=Blood |volume=90 |issue=2 |pages=479–88 |date=July 1997 |pmid=9226148 |doi= |url=}}</ref><ref name="pmid80255132">{{cite journal |vauthors=Hasle H |title=Myelodysplastic syndromes in childhood--classification, epidemiology, and treatment |journal=Leuk. Lymphoma |volume=13 |issue=1-2 |pages=11–26 |date=March 1994 |pmid=8025513 |doi=10.3109/10428199409051647 |url=}}</ref>
|
* [[Infections]]
* [[Anemia]] related
|
* [[Hepatosplenomegaly]]
* [[Lymphadenopathy]]
* [[Rash]]
|[[Leukocytosis|↑]]
|↑
|N/A
|N/A
|N/A
|[[Monocytosis|↑]]
|[[Anemia|↓]]
|[[Thrombocytopenia|↓]]
|
* Hypercelluar with  ↑ [[myeloid cells]] in stages of maturation
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* [[Flow cytometry|↓]] [[Serum]] [[Iron]]
* [[Flow cytometry|↑]] [[Vitamin B12|B12]] levels
|
* Polyclonal [[hypergammaglobulinemia]]
|-
![[MDS]]/[[MPN]] with ring sideroblasts and [[thrombocytosis]] (MDS/MPN-RS-T)<ref name="pmid28188970">{{cite journal |vauthors=Patnaik MM, Tefferi A |title=Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T): 2017 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=92 |issue=3 |pages=297–310 |date=March 2017 |pmid=28188970 |doi=10.1002/ajh.24637 |url=}}</ref><ref name="pmid30186759">{{cite journal |vauthors=Alshaban A, Padilla O, Philipovskiy A, Corral J, McAlice M, Gaur S |title=Lenalidomide induced durable remission in a patient with MDS/MPN-with ring sideroblasts and thrombocytosis with associated 5q- syndrome |journal=Leuk Res Rep |volume=10 |issue= |pages=37–40 |date=2018 |pmid=30186759 |doi=10.1016/j.lrr.2018.08.001 |url=}}</ref><ref name="pmid30524760">{{cite journal |vauthors=Bouchla A, Papageorgiou SG, Tsakiraki Z, Glezou E, Pavlidis G, Stavroulaki G, Bazani E, Foukas P, Pappa V |title=Plasmablastic Lymphoma in an Immunocompetent Patient with MDS/MPN with Ring Sideroblasts and Thrombocytosis-A Case Report |journal=Case Rep Hematol |volume=2018 |issue= |pages=2525070 |date=2018 |pmid=30524760 |pmc=6247723 |doi=10.1155/2018/2525070 |url=}}</ref>
|
* Constitutional
* [[Anemia]] related
* [[Thrombosis]]
|
* Variable
|NL or ↑
|NL
| -
|NL
|N/A
|N/A
|[[Anemia|↓]]
|[[Thrombocytosis|↑]]
|
* Hypercellularity with [[dyserythropoiesis]] and increased [[megakaryocytes]]
|
* [[Cytogenetic analysis]]
* [[Flow cytometry]]
* ↑ [[Serum]] [[Iron]]
|
* Large atypical [[megakaryocytes]]
* Ringed [[sideroblasts]]
* [[SF3B1]] [[mutation]]
|-
|-
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease
Line 833: Line 834:
!Characteristic
!Characteristic
!Causes
!Causes
!Physical examination
!Laboratory abnormalities
!Laboratory abnormalities
!Physical examination
!Therapy
!Therapy
!Other associations
!Other associations
|-
|-
|Myeloproliferative neoplasm
!Myeloproliferative neoplasm
|
|
* ''JAK2'' mutation
* ''JAK2'' mutation
Line 847: Line 848:
* ''SETBP1'' mutation
* ''SETBP1'' mutation
* ''PDGFRA'' or ''PDGFRB'' rearrangement
* ''PDGFRA'' or ''PDGFRB'' rearrangement
|
* Splenomegaly
* Hepatomegaly
* Evidence of infection
* Pallor
|
|
* Elevated hemoglobin
* Elevated hemoglobin
Line 853: Line 859:
* Elevated [[eosinophil]] and/or [[neutrophil]] count
* Elevated [[eosinophil]] and/or [[neutrophil]] count
* Bone marrow fibrosis
* Bone marrow fibrosis
|
* Splenomegaly
* Hepatomegaly
* Evidence of infection
* Pallor
|
|
* Ruxolitinib
* Ruxolitinib
Line 868: Line 869:
* Variable features based on the subtype of myeloproliferative neoplasm
* Variable features based on the subtype of myeloproliferative neoplasm
|-
|-
|Myelodysplastic syndrome
!Myelodysplastic syndrome
|
|
* Prior exposure to alkylating agents
* Prior exposure to alkylating agents
Line 875: Line 876:
* Deletion of chromosome 5q or 7
* Deletion of chromosome 5q or 7
* Gain of chromosome 8
* Gain of chromosome 8
|
* [[Mucosal bleeding]]
* Petechiae
* Ecchymoses
* Evidence of infection
* Pallor
|
|
* Dysplasia in at least 10% of cells of at least 1 cell line
* Dysplasia in at least 10% of cells of at least 1 cell line
Line 881: Line 888:
* [[Neutropenia]]
* [[Neutropenia]]
* [[Thrombocytopenia]]  
* [[Thrombocytopenia]]  
|
* [[Mucosal bleeding]]
* Petechiae
* Ecchymoses
* Evidence of infection
* Pallor
|
|
* Lenalidomide
* Lenalidomide
Line 898: Line 899:
* Age-related changes in the bone marrow contribute to myelodysplastic syndrome
* Age-related changes in the bone marrow contribute to myelodysplastic syndrome
|-
|-
|Acute myeloid leukemia  
!Acute myeloid leukemia  
|
|
* Chromosomal instability
* Chromosomal instability
Line 906: Line 907:
* Prior exposure to topoisomerase II inhibitors
* Prior exposure to topoisomerase II inhibitors
* Germline ''RUNX1'' mutation
* Germline ''RUNX1'' mutation
|
* Pyrexia
* Evidence of infection
* Pallor
* Mucosal bleeding
* Bruising
|
|
* [[Anemia]]
* [[Anemia]]
Line 916: Line 923:
* Low calcium
* 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>
* 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
* Cytarabine
Line 934: Line 935:
* Four new FDA-approved therapies became available in 2017
* Four new FDA-approved therapies became available in 2017
|-
|-
|Acute lymphoblastic leukemia
!Acute lymphoblastic leukemia
|
|
* Chromosomal instability
* Chromosomal instability
* Sporadic mutations
* Sporadic mutations
|
* Neurologic deficits
* Pallor
* Lymphadenopathy
|
|
* [[Anemia]]
* [[Anemia]]
Line 948: Line 953:
* Low calcium
* Low calcium
* Greater than 20% lymphoblasts on bone marrow aspirate
* 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>
* 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>
Line 965: Line 966:
* 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>
* 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>
|-
|-
|Waldenstrom's macroglobulinemia
!Waldenstrom's macroglobulinemia
|
|
* ''MYD88'' mutation
* ''MYD88'' mutation
* Lymphoplasmacytic cell proliferation
* Lymphoplasmacytic cell proliferation
|
* Elevated [[immunoglobulin M]] (IgM) [[paraprotein]]
* Presence of M-spike on protein electrophoresis
* Elevated serum free light chains (''kappa'' and ''lambda'')
* Increased serum viscosity
|
|
* Hepatomegaly
* Hepatomegaly
Line 980: Line 976:
* Decreased visual acuity
* Decreased visual acuity
* Headache  
* Headache  
|
* Elevated [[immunoglobulin M]] (IgM) [[paraprotein]]
* Presence of M-spike on protein electrophoresis
* Elevated serum free light chains (''kappa'' and ''lambda'')
* Increased serum viscosity
|
|
* [[Rituximab]]
* [[Rituximab]]
Line 989: Line 990:
* Typically does not require [[stem cell transplant]]
* Typically does not require [[stem cell transplant]]
|-
|-
|[[Lymphoproliferative disorder]]<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>
![[Lymphoproliferative disorder]]<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>
|
|
* [[Epstein-Barr virus]] (EBV)
* [[Epstein-Barr virus]] (EBV)
Line 998: Line 999:
* Sporadic mutations
* Sporadic mutations
* Rheumatologic disease
* Rheumatologic disease
|
* [[Lymph node enlargement]]
* [[Splenomegaly]]
* [[Hepatomegaly]]
|
|
* Elevated lymphocyte count with presence of clonality
* Elevated lymphocyte count with presence of clonality
Line 1,003: Line 1,008:
* Thrombocytopenia  
* Thrombocytopenia  
* Neutropenia
* Neutropenia
|
* [[Lymph node enlargement]]
* [[Splenomegaly]]
* [[Hepatomegaly]]
|
|
* Variable based on the etiology
* Variable based on the etiology
Line 1,018: Line 1,019:
|}
|}
==References==
==References==
{{Reflist|2}}
{{reflist|2}}
[[Category:Hematology]]  
[[Category:Up-To-Date]]
 
[[Category:Medicine]]
[[Category: Disease]]
 
{{WH}}
{{WS}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Differential diagnosis]]

Latest revision as of 20:15, 6 March 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2] Zahir Ali Shaikh, MD[3] Mohamad Alkateb, MBBCh [4] Shyam Patel [5]

Overview

Myeloproliferative neoplasm must be differentiated from myelodysplastic syndrome, acute myelogenous leukemia, acute lymphoblastic leukemia, Waldenstrom's macroglobulinemia, and lymphoproliferative disorder. Each of these conditions has a unique set of causes, laboratory abnormalities, physical exam findings, and investigations.

Differentiating Myeloproliferative Neoplasm from other Diseases

ABBREVIATIONS

EPO: Erythropoietin, FISH: Fluorescence in situ hybridization, Hb: Hemoglobin, LAD: Leukocyte alkaline dehydrgenase, LAP: Leukocyte alkaline phosphatase, LDH: Lactate dehydrogenase, LFTs: Liver function tests, NL: Normal, PCR: Polymerase chain reaction, Plt: Platelet, PUD: Peptic ulcer disease, RFTs: Renal function tests, WBCs: White blood cells.

Disease Clinical manifestations Diagnosis Other features
Symptoms Signs CBC & Peripheral smear Bone marrow biopsy Other investigations
WBCs Hb Plt
WBC Blasts Left
shift 		Baso-
phils 		Eosino-
phils 		Mono-
cytes
Chronic myeloid leukemia
(CML)[1][2] 		↑ <2% + ↑ ↑ ↑ ↓ NL
Polycythemia vera
(PV)[3][4][5][6]
  • Constitutional
 NL or ↑ None - ↑ or ↓ NL or ↑ NL ↑↑ NL
  • Hypercellularity for age with tri-lineage growth
Primary myelofibrosis (PMF)[7][8][9][10] ↓ Erythroblasts - Absent NL NL ↓ ↓
  • Variable with fibrosis or hypercellularity
Essential thrombocythemia (ET)[11][12][13]

NL or ↑

None

-

↓ or absent

NL

NL

↓

↑↑

  • Normal/Hypercellular
Disease Symptoms Sign WBC Blasts Left
shift 		Baso-
phils 		Eosino-
phils 		Mono-
cytes 		Hb Plt Bone marrow biopsy Other investigations Other features
Myelodysplastic
/myeloproliferative
neoplasms (MDS/MPN) 		Chronic myelomonocytic leukemia (CMML)[14]
[15][16]
 ↑ < 20% NL ↑ ↑↑ ↓ ↓
  • Overlapping of both, MDS and MPN
  • Absolute monocytosis > 1 × 109/L (defining feature)
  • MD-CMML:WBC ≤ 13 × 109/L (FAB)
  •  MP-CMML:WBC > 13 × 109/L (FAB)
Atypical chronic myeloid leukemia (aCML), BCR-ABL1-[17][18] ↑ <20% + <2% of WBCs N/A N/A ↓ ↓
Juvenile myelomonocytic leukemia (JMML)[19][20] ↑ ↑ N/A N/A N/A ↑ ↓ ↓
MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)[21][22][23]
  • Variable
 NL or ↑ NL - NL N/A N/A ↓ ↑
Disease Symptoms Sign WBC Blasts Left
shift 		Baso-
phils 		Eosino-
phils 		Mono-
cytes 		Hb Plt Bone marrow biopsy Other investigations Other features
Chronic neutrophilic leukemia (CNL)[24][25][26] ↑ Minimal + NL NL NL ↓ ↓
Chronic eosinophilic leukemia,
not otherwise specified
(NOS)[27][28][29][30] 		↑ Present + ↑ ↑↑ ↑ ↓ ↓
MPN,
unclassifiable 		↑ Variable ± ↑ or ↓ ↑ or ↓ ↑ or ↓ ↓ ↑
Mastocytosis[31][32][33][34]
  • Constitutional
 ↑ None - NL ↑ NL ↓ ↓ or ↑
Myeloid/lymphoid neoplasms
with eosinophilia and rearrangement
of PDGFRA, PDGFRB, or FGFR1,
or with PCM1-JAK2[35][36][37][38] 		↑ NL - NL ↑ ↑ NL ↓
  • FISH shows t(8;13) and t(8;22)
Disease Symptoms Sign WBC Blasts Left
shift 		Baso-
phils 		Eosino-
phils 		Mono-
cytes 		Hb Plt Bone marrow biopsy Other investigations Other features
B-lymphoblastic leukemia/lymphoma[39][40] NL or ↑ >25% N/A ↑ or ↓ ↑ or ↓ ↑ or ↓ ↓ ↓
Myelodysplastic syndromes
(MDS)[41][42] 		↓ Variable - ↓ ↓ ↓ ↓ ↓
  • Leukemia transformation
  • Acquired pseudo-Pelger-Huët anomaly
Acute myeloid leukemia (AML)
and related neoplasms[43][44] 		NL or ↑ ↑ N/A ↑ or ↓ ↑ or ↓ ↑ or ↓ ↓ ↓

with dysplasia

Blastic plasmacytoid
dendritic cell neoplasm[45][46][47][48] 		NL ↑ NL NL NL ↓ ↓
Disease Symptoms Sign WBC Blasts Left
shift 		Baso-
phils 		Eosino-
phils 		Mono-
cytes 		Hb Plt Bone marrow biopsy Other investigations Other features
T-lymphoblastic leukemia/
lymphoma
T-lymphoblastic leukemia/
lymphoma[49][50][51] 		↑ >25% blasts (Leukemia)

<25% blasts (Lymphoma)

± ↑ or ↓ ↑ or ↓ ↑ or ↓ ↓ ↓
  • Hypercelluarity with increased T cells precursors
Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph[52] ↑ ↑ ± ↑ or ↓ ↑ or ↓ ↑ or ↓ ↓ ↓
  • N/A
Provisional entity: Early T-cell precursor lymphoblastic leukemia[53][54] ↑ ↑ ± ↑ or ↓ ↑ or ↓ ↑ or ↓ ↓ ↓
  • Hypercelluarity with increased T cells precursors

Differentiating Myeloproliferative neoplasm from other Diseases

Characteristic Causes Physical examination Laboratory abnormalities Therapy Other associations
Myeloproliferative neoplasm
  • JAK2 mutation
  • CALR mutation
  • MPL mutation
  • BCR-ABL translocation
  • CSF3R mutation
  • SETBP1 mutation
  • PDGFRA or PDGFRB rearrangement
  • Splenomegaly
  • Hepatomegaly
  • Evidence of infection
  • Pallor
  • Ruxolitinib
  • Hydroxyurea
  • Anagrelide
  • Imatinib
  • Midostaurin
  • Stem cell transplant
  • Variable features based on the subtype of myeloproliferative neoplasm
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
  • Stem cell transplant for high-risk myelodysplastic syndrome
  • 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
  • Neurologic deficits
  • Pallor
  • Lymphadenopathy
  • Anemia
  • Thrombocytopenia
  • Neutropenia
  • Elevated LDH
  • Elevated uric acid
  • Elevated phosphorus
  • Elevated potassium
  • Low calcium
  • Greater than 20% lymphoblasts on bone marrow aspirate
  • HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)[56]
  • 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[57]
Waldenstrom's macroglobulinemia
  • MYD88 mutation
  • Lymphoplasmacytic cell proliferation
  • Hepatomegaly
  • Splenomegaly
  • Retinal vascular dilation and thrombosis
  • Decreased visual acuity
  • Headache
  • Elevated immunoglobulin M (IgM) paraprotein
  • Presence of M-spike on protein electrophoresis
  • Elevated serum free light chains (kappa and lambda)
  • Increased serum viscosity
  • MYD88 mutation testing is standard-of-care
  • Plasmapheresis should be initiated if symptoms of hyperviscosity are present
  • Typically does not require stem cell transplant
Lymphoproliferative disorder[58]
  • Elevated lymphocyte count with presence of clonality
  • Anemia
  • Thrombocytopenia
  • Neutropenia
  • Variable based on the etiology
  • Cytotoxic chemotherapy
  • Antiviral agents
  • Biologic therapy with anti-CD20 monoclonal antibodies
  • Tapering immunosuppressive medications (for post-transplant lymphoproliferative disorder)
  • Can be due to a variety of causes
  • Variable prognosis

References

  1. ↑ Savage DG, Szydlo RM, Goldman JM (January 1997). "Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period". Br. J. Haematol. 96 (1): 111–6. PMID 9012696.
  2. ↑ Thompson PA, Kantarjian HM, Cortes JE (October 2015). "Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015". Mayo Clin. Proc. 90 (10): 1440–54. doi:10.1016/j.mayocp.2015.08.010. PMC 5656269. PMID 26434969.
  3. ↑ Vannucchi AM, Guglielmelli P, Tefferi A (March 2018). "Polycythemia vera and essential thrombocythemia: algorithmic approach". Curr. Opin. Hematol. 25 (2): 112–119. doi:10.1097/MOH.0000000000000402. PMID 29194068.
  4. ↑ Pillai AA, Babiker HM. PMID 30252337. Missing or empty |title= (help)
  5. ↑ Tefferi A, Barbui T (January 2019). "Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management". Am. J. Hematol. 94 (1): 133–143. doi:10.1002/ajh.25303. PMID 30281843.
  6. ↑ Rumi E, Cazzola M (February 2017). "Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms". Blood. 129 (6): 680–692. doi:10.1182/blood-2016-10-695957. PMC 5335805. PMID 28028026.
  7. ↑ Cervantes F, Correa JG, Hernandez-Boluda JC (May 2016). "Alleviating anemia and thrombocytopenia in myelofibrosis patients". Expert Rev Hematol. 9 (5): 489–96. doi:10.1586/17474086.2016.1154452. PMID 26891375.
  8. ↑ Hoffman, Ronald (2018). Hematology : basic principles and practice. Philadelphia, PA: Elsevier. ISBN 9780323357623.
  9. ↑ Michiels JJ, Bernema Z, Van Bockstaele D, De Raeve H, Schroyens W (March 2007). "Current diagnostic criteria for the chronic myeloproliferative disorders (MPD) essential thrombocythemia (ET), polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF)". Pathol. Biol. 55 (2): 92–104. doi:10.1016/j.patbio.2006.06.002. PMID 16919893.
  10. ↑ Hoffman, Ronald (2018). Hematology : basic principles and practice. Philadelphia, PA: Elsevier. ISBN 9780323357623.
  11. ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID http://dx.doi.org/10.1182/blood-2007-04-083501 Check |pmid= value (help).
  12. ↑ Daniel A. Arber, Attilio Orazi, Robert Hasserjian, Jurgen Thiele, Michael J. Borowitz, Michelle M. Le Beau, Clara D. Bloomfield, Mario Cazzola & James W. Vardiman (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. PMID 27069254. Unknown parameter |month= ignored (help)
  13. ↑ A. Tefferi, R. Fonseca, D. L. Pereira & H. C. Hoagland (2001). "A long-term retrospective study of young women with essential thrombocythemia". Mayo Clinic proceedings. 76 (1): 22–28. doi:10.4065/76.1.22. PMID 11155408. Unknown parameter |month= ignored (help)
  14. ↑ Patnaik MM, Tefferi A (June 2016). "Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management". Am. J. Hematol. 91 (6): 631–42. doi:10.1002/ajh.24396. PMID 27185207.
  15. ↑ Parikh SA, Tefferi A (June 2012). "Chronic myelomonocytic leukemia: 2012 update on diagnosis, risk stratification, and management". Am. J. Hematol. 87 (6): 610–9. doi:10.1002/ajh.23203. PMID 22615103.
  16. ↑ Benton CB, Nazha A, Pemmaraju N, Garcia-Manero G (August 2015). "Chronic myelomonocytic leukemia: Forefront of the field in 2015". Crit. Rev. Oncol. Hematol. 95 (2): 222–42. doi:10.1016/j.critrevonc.2015.03.002. PMC 4859155. PMID 25869097.
  17. ↑ Dao KH, Tyner JW (2015). "What's different about atypical CML and chronic neutrophilic leukemia?". Hematology Am Soc Hematol Educ Program. 2015: 264–71. doi:10.1182/asheducation-2015.1.264. PMC 5266507. PMID 26637732.
  18. ↑ Muramatsu H, Makishima H, Maciejewski JP (February 2012). "Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions". Semin. Oncol. 39 (1): 67–73. doi:10.1053/j.seminoncol.2011.11.004. PMC 3523950. PMID 22289493.
  19. ↑ Aricò M, Biondi A, Pui CH (July 1997). "Juvenile myelomonocytic leukemia". Blood. 90 (2): 479–88. PMID 9226148.
  20. ↑ Hasle H (March 1994). "Myelodysplastic syndromes in childhood--classification, epidemiology, and treatment". Leuk. Lymphoma. 13 (1–2): 11–26. doi:10.3109/10428199409051647. PMID 8025513.
  21. ↑ Patnaik MM, Tefferi A (March 2017). "Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T): 2017 update on diagnosis, risk-stratification, and management". Am. J. Hematol. 92 (3): 297–310. doi:10.1002/ajh.24637. PMID 28188970.
  22. ↑ Alshaban A, Padilla O, Philipovskiy A, Corral J, McAlice M, Gaur S (2018). "Lenalidomide induced durable remission in a patient with MDS/MPN-with ring sideroblasts and thrombocytosis with associated 5q- syndrome". Leuk Res Rep. 10: 37–40. doi:10.1016/j.lrr.2018.08.001. PMID 30186759.
  23. ↑ Bouchla A, Papageorgiou SG, Tsakiraki Z, Glezou E, Pavlidis G, Stavroulaki G, Bazani E, Foukas P, Pappa V (2018). "Plasmablastic Lymphoma in an Immunocompetent Patient with MDS/MPN with Ring Sideroblasts and Thrombocytosis-A Case Report". Case Rep Hematol. 2018: 2525070. doi:10.1155/2018/2525070. PMC 6247723. PMID 30524760.
  24. ↑ Szuber N, Tefferi A (February 2018). "Chronic neutrophilic leukemia: new science and new diagnostic criteria". Blood Cancer J. 8 (2): 19. doi:10.1038/s41408-018-0049-8. PMC 5811432. PMID 29440636.
  25. ↑ Maxson JE, Tyner JW (February 2017). "Genomics of chronic neutrophilic leukemia". Blood. 129 (6): 715–722. doi:10.1182/blood-2016-10-695981. PMC 5301820. PMID 28028025.
  26. ↑ Menezes J, Cigudosa JC (2015). "Chronic neutrophilic leukemia: a clinical perspective". Onco Targets Ther. 8: 2383–90. doi:10.2147/OTT.S49688. PMC 4562747. PMID 26366092.
  27. ↑ Vidyadharan S, Joseph B, Nair SP (2016). "Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations". Indian J Dermatol. 61 (4): 437–9. doi:10.4103/0019-5154.185716. PMC 4966405. PMID 27512192.
  28. ↑ Hofmans M, Delie A, Vandepoele K, Van Roy N, Van der Meulen J, Philippé J, Moors I (2018). "A case of chronic eosinophilic leukemia with secondary transformation to acute myeloid leukemia". Leuk Res Rep. 9: 45–47. doi:10.1016/j.lrr.2018.04.001. PMC 5993353. PMID 29892549.
  29. ↑ Yamada Y, Rothenberg ME, Cancelas JA (2006). "Current concepts on the pathogenesis of the hypereosinophilic syndrome/chronic eosinophilic leukemia". Transl Oncogenomics. 1: 53–63. PMC 3642145. PMID 23662039.
  30. ↑ Kim TH, Gu HJ, Lee WI, Lee J, Yoon HJ, Park TS (September 2016). "Chronic eosinophilic leukemia with FIP1L1-PDGFRA rearrangement". Blood Res. 51 (3): 204–206. doi:10.5045/br.2016.51.3.204. PMID 27722133.
  31. ↑ Carter MC, Metcalfe DD, Komarow HD (February 2014). "Mastocytosis". Immunol Allergy Clin North Am. 34 (1): 181–96. doi:10.1016/j.iac.2013.09.001. PMC 3863935. PMID 24262698.
  32. ↑ Macri A, Cook C. PMID 29494109. Missing or empty |title= (help)
  33. ↑ Lladó AC, Mihon CE, Silva M, Galzerano A (2014). "Systemic mastocytosis - a diagnostic challenge". Rev Bras Hematol Hemoter. 36 (3): 226–9. doi:10.1016/j.bjhh.2014.03.003. PMC 4109736. PMID 25031064.
  34. ↑ Valent P, Akin C, Metcalfe DD (March 2017). "Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts". Blood. 129 (11): 1420–1427. doi:10.1182/blood-2016-09-731893. PMC 5356454. PMID 28031180.
  35. ↑ Kumar, Kirthi R.; Chen, Weina; Koduru, Prasad R.; Luu, Hung S. (2015). "Myeloid and Lymphoid Neoplasm With Abnormalities of FGFR1 Presenting With Trilineage Blasts and RUNX1 Rearrangement". American Journal of Clinical Pathology. 143 (5): 738–748. doi:10.1309/AJCPUD6W1JLQQMNA. ISSN 1943-7722.
  36. ↑ Paolo Strati, Guilin Tang, Dzifa Y. Duose, Saradhi Mallampati, Rajyalakshmi Luthra, Keyur P. Patel, Mohammad Hussaini, Abu-Sayeef Mirza, Rami S. Komrokji, Stephen Oh, John Mascarenhas, Vesna Najfeld, Vivek Subbiah, Hagop Kantarjian, Guillermo Garcia-Manero, Srdan Verstovsek & Naval Daver (2018). "Myeloid/lymphoid neoplasms with FGFR1 rearrangement". Leukemia & lymphoma. 59 (7): 1672–1676. doi:10.1080/10428194.2017.1397663. PMID 29119847. Unknown parameter |month= ignored (help)
  37. ↑ Ximena Montenegro-Garreaud, Roberto N. Miranda, Alexandra Reynolds, Guilin Tang, Sa A. Wang, Mariko Yabe, Wei Wang, Lianghua Fang, Carlos E. Bueso-Ramos, Pei Lin, L. Jeffrey Medeiros & Xinyan Lu (2017). "Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase". Human pathology. 65: 147–156. doi:10.1016/j.humpath.2017.05.008. PMID 28551329. Unknown parameter |month= ignored (help)
  38. ↑ Paola Villafuerte-Gutierrez, Montserrat Lopez Rubio, Pilar Herrera & Eva Arranz (2018). "A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation". Case reports in hematology. 2018: 5724960. doi:10.1155/2018/5724960. PMID 30647980.
  39. ↑ Kamiya-Matsuoka C, Garciarena P, Amin HM, Tremont-Lukats IW, de Groot JF (December 2013). "B lymphoblastic leukemia/lymphoma presenting as seventh cranial nerve palsy". Neurol Clin Pract. 3 (6): 532–534. doi:10.1212/CPJ.0b013e3182a78ef0. PMC 6082360. PMID 30107017.
  40. ↑ Zhang X, Rastogi P, Shah B, Zhang L (September 2017). "B lymphoblastic leukemia/lymphoma: new insights into genetics, molecular aberrations, subclassification and targeted therapy". Oncotarget. 8 (39): 66728–66741. doi:10.18632/oncotarget.19271. PMC 5630450. PMID 29029550.
  41. ↑ Germing U, Kobbe G, Haas R, Gattermann N (November 2013). "Myelodysplastic syndromes: diagnosis, prognosis, and treatment". Dtsch Arztebl Int. 110 (46): 783–90. doi:10.3238/arztebl.2013.0783. PMC 3855821. PMID 24300826.
  42. ↑ Gangat N, Patnaik MM, Tefferi A (January 2016). "Myelodysplastic syndromes: Contemporary review and how we treat". Am. J. Hematol. 91 (1): 76–89. doi:10.1002/ajh.24253. PMID 26769228.
  43. ↑ Islam A, Catovsky D, Goldman JM, Galton DA (September 1985). "Bone marrow biopsy changes in acute myeloid leukaemia. I: Observations before chemotherapy". Histopathology. 9 (9): 939–57. PMID 3864727.
  44. ↑ Orazi A (2007). "Histopathology in the diagnosis and classification of acute myeloid leukemia, myelodysplastic syndromes, and myelodysplastic/myeloproliferative diseases". Pathobiology. 74 (2): 97–114. doi:10.1159/000101709. PMID 17587881.
  45. ↑ F. Julia, T. Petrella, M. Beylot-Barry, M. Bagot, D. Lipsker, L. Machet, P. Joly, O. Dereure, M. Wetterwald, M. d'Incan, F. Grange, J. Cornillon, G. Tertian, E. Maubec, P. Saiag, S. Barete, I. Templier, F. Aubin & S. Dalle (2013). "Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients". The British journal of dermatology. 169 (3): 579–586. doi:10.1111/bjd.12412. PMID 23646868. Unknown parameter |month= ignored (help)
  46. ↑ Livio Pagano, Caterina Giovanna Valentini, Alessandro Pulsoni, Simona Fisogni, Paola Carluccio, Francesco Mannelli, Monia Lunghi, Gianmatteo Pica, Francesco Onida, Chiara Cattaneo, Pier Paolo Piccaluga, Eros Di Bona, Elisabetta Todisco, Pellegrino Musto, Antonio Spadea, Alfonso D'Arco, Stefano Pileri, Giuseppe Leone, Sergio Amadori & Fabio Facchetti (2013). "Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study". Haematologica. 98 (2): 239–246. doi:10.3324/haematol.2012.072645. PMID 23065521. Unknown parameter |month= ignored (help)
  47. ↑ Joseph D. Khoury (2018). "Blastic Plasmacytoid Dendritic Cell Neoplasm". Current hematologic malignancy reports. 13 (6): 477–483. doi:10.1007/s11899-018-0489-z. PMID 30350260. Unknown parameter |month= ignored (help)
  48. ↑ Shinichiro Sukegawa, Mamiko Sakata-Yanagimoto, Ryota Matsuoka, Haruka Momose, Yusuke Kiyoki, Masayuki Noguchi, Naoya Nakamura, Rei Watanabe, Manabu Fujimoto, Yasuhisa Yokoyama, Hidekazu Nishikii, Takayasu Kato, Manabu Kusakabe, Naoki Kurita, Naoshi Obara, Yuichi Hasegawa & Shigeru Chiba (2018). "[Blastic plasmacytoid dendritic cell neoplasm accompanied by chronic myelomonocytic leukemia successfully treated with azacitidine]". [[[Rinsho ketsueki] The Japanese journal of clinical hematology]]. 59 (12): 2567–2573. doi:10.11406/rinketsu.59.2567. PMID 30626790.
  49. ↑ You MJ, Medeiros LJ, Hsi ED (September 2015). "T-lymphoblastic leukemia/lymphoma". Am. J. Clin. Pathol. 144 (3): 411–22. doi:10.1309/AJCPMF03LVSBLHPJ. PMID 26276771.
  50. ↑ Patel KJ, Latif SU, de Calaca WM (March 2009). "An unusual presentation of precursor T cell lymphoblastic leukemia/lymphoma with cholestatic jaundice: case report". J Hematol Oncol. 2: 12. doi:10.1186/1756-8722-2-12. PMC 2663564. PMID 19284608.
  51. ↑ Elreda L, Sandhu M, Sun X, Bekele W, Cohen AJ, Shah M (2014). "T-cell lymphoblastic leukemia/lymphoma: relapse 16 years after first remission". Case Rep Hematol. 2014: 359158. doi:10.1155/2014/359158. PMC 4005062. PMID 24822133.
  52. ↑ Sedick Q, Alotaibi S, Alshieban S, Naheet KB, Elyamany G (2017). "Natural Killer Cell Lymphoblastic Leukaemia/Lymphoma: Case Report and Review of the Recent Literature". Case Rep Oncol. 10 (2): 588–595. doi:10.1159/000477843. PMID 28868017.
  53. ↑ Jain N, Lamb AV, O'Brien S, Ravandi F, Konopleva M, Jabbour E, Zuo Z, Jorgensen J, Lin P, Pierce S, Thomas D, Rytting M, Borthakur G, Kadia T, Cortes J, Kantarjian HM, Khoury JD (April 2016). "Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype". Blood. 127 (15): 1863–9. doi:10.1182/blood-2015-08-661702. PMC 4915808. PMID 26747249.
  54. ↑ Haydu JE, Ferrando AA (July 2013). "Early T-cell precursor acute lymphoblastic leukaemia". Curr. Opin. Hematol. 20 (4): 369–73. doi:10.1097/MOH.0b013e3283623c61. PMC 3886681. PMID 23695450.
  55. ↑ 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.
  56. ↑ 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.
  57. ↑ 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.
  58. ↑ 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.
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