Erythroleukemia: Difference between revisions

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   MeshID        = D004915 |
   MeshID        = D004915 |
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{{SI}}
{{SI}}
{{CMG}};  {{AE}}{{MA}} [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu]
{{CMG}};  {{AE}}{{MA}} [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu]
 
{{SK}}Pure erythroid leukemia,  FAB ( French-American-British)  M6, acute erythroid leukemia, Di Guglielmo’s disease  
{{SK}}Pure erythroid leukemia,  FAB ( French-American-British)  M6, acute erythroid leukemia, Di Guglielmo’s disease  


==Overview==
==Overview==
 
Erythroleukemia was first discovered by M. Copelli, in 1912. In 1917, Di Guglielmo, Italian [[Hematology|hematologist]], described [[leukemic]] nature of the erythroleukemia. Erythroleukemia accounts for < 5 % of [[acute myeloid leukemia|acute myeloid leukemia (AML)]]. Erythroleukemia may be classified into 2 groups: [[De novo]] cases of erythroleukemia and secondary erythroleukemia. Erythroleukemia may be classified according to previous version [[World Health Organization|WHO]] into 2 sub-types : The [[erythroid]]/[[myeloid]] type and the pure type. Erythroleukemia is the [[neoplastic]] proliferation of [[myeloid]] and [[erythroid]] precursors of [[bone marrow]] [[Hematopoietic stem cell|hematopoietic stem cells]]. A pure [[erythroid]] proliferation may also occur. The [[erythroblasts]] do not [[Staining|stain]] with [[myeloperoxidase|myeloperoxidase (MPO)]]. [[Marker|Markers]] of [[myeloid]] lineage can not be expressed on the [[erythroblasts]]. [[Leukemia|Leukemic]] [[Cell (biology)|cells]] are positive for [[myeloid]] [[Marker|markers]] such as [[CD117]], [[CD13]], [[CD33]], and[[myeloperoxidase|myeloperoxidase (MPO)]]. [[Megakaryocyte|Megakaryocytes]] [[Antigen|antigens]] can be positive in some cases of erythroleukemia, such as CD41 and [[CD61]]. Erythroleukemia may be caused by [[translocation]] t(1;16) generating the [[fusion gene]] [[NFIA]]/[[CBFA2T3]]. Erythroleukemia must be differentiated from [[MDS]] with [[erythroid]] predominance, other types of [[AML]] with increased [[erythroid]] precursors, [[AML]] with [[myelodysplasia]]-related changes. Non-[[Cancer|neoplastic]] disorders that can cause [[erythroid]] predominance in the [[bone marrow]] such as [[megaloblastic anemia]] due to [[vitamin B12]] or [[folate]] deficiency, heavy metal [[intoxication]] such as [[arsenic]], drug effects (such as [[antineoplastic agents]] or [[chloramphenicol]]) are other [[Differential diagnosis|differential diagnoses]]. The [[incidence]] of erythroleukemia is approximately 0.077 per 100,000 individuals worldwide. Erythroleukemia commonly affects individuals older than 50 years of age with a [[median]] age of 65. There is no racial predilection to erythroleukemia. Men are more commonly affected by erythroleukemia than women. The [[male]] to [[female]] ratio is approximately 2 to 1. There are no established [[Risk factor|risk factors]] for [[de novo]] cases of erythroleukemia. The most potent [[risk factor]] in the development of [[secondary]] erythroleukemia is previous [[myelodysplastic syndrome|myelodysplastic syndrome (MDS)]]. There is insufficient evidence to recommend routine [[screening]] for erythroleukemia. If left untreated, [[Patient|patients]] with erythroleukemia may progress to develop [[bleeding]] due to [[disseminated intravascular coagulation|disseminated intravascular coagulation (DIC)]]. Common [[Complication (medicine)|complications]] of erythroleukemia include [[infection]] and [[bleeding]]. [[Therapy]] related [[Complication (medicine)|complications]] are [[rash]], [[Cardiomyopathy|cardiomyopathy]] and [[cerebellar]] [[toxicity]]''.'' [[Prognosis]] is generally poor. [[Median]] survival ranges from 3 - 9 months after the initial [[diagnosis]]. A high [[proerythroblast]]/[[myeloblast]] ratio correlates with worse outcome. The [[diagnosis]] of erythroleukemia is based on the 2016 version of [[World Health Organization|WHO]] [[classification]] for [[AML]]. History and [[Symptom|symptoms]] include [[fatigue]], [[Malaise]], [[bone pain]], [[abdominal pain]], [[weight loss]], [[Easy bruising]], [[Fever]], and [[Dyspnea]]. [[Patient|Patients]] with erythroleukemia usually appear [[anemic]].  [[Physical examination]] of [[Patient|patients]] with erythroleukemia may include [[Ecchymoses]] or [[petechiae]], [[Hepatomegaly]], [[Splenomegaly]], [[Lymphadenopathy]], and [[headache]]. [[Medical laboratory|Laboratory]] findings include [[Pancytopenia]], few [[peripheral blood]] [[blast|blasts]], [[Dysplasia]] in [[bone marrow]] and [[peripheral blood]], [[Dysplasia|dysplastic]] [[PAS stain|PAS]] positive [[erythroblasts]] with overexpression of the [[multidrug resistance|multidrug resistance (MDR)]] [[gene]] product [[P-glycoprotein]], and high frequency of [[mutations]], especially of [[TP53]]. [[Electrocardiogram]] is useful for the assessment of [[QT interval]] prior to starting [[chemotherapy]]. An [[x-ray]] may be helpful in the [[diagnosis]] of [[Complication (medicine)|complications]] of erythroleukemia management which include [[infection]], volume overload. [[Chest X-ray|Chest x-ray]] is also useful for [[venous]] [[catheter]] placement for [[chemotherapy]]. An [[echocardiogram]] is helpful for assessing [[cardiac]] function ([[ejection fraction]]) in [[Patient|patients]] with [[acute myeloid leukemia]] before and after receiving [[anthracycline]] [[chemotherapy]]. An [[ultrasound]] is useful for the [[diagnosis]] of [[lower extremity]] [[thrombosis]], which commonly occurs in [[Patient|patients]] with [[acute myeloid leukemia]]. [[Abdominal]] and [[chest]] [[Computed tomography|CT scan]] may be helpful in the [[diagnosis]] of [[acute myeloid leukemia]]. Findings on [[CT scan]] suggestive of [[acute myeloid leukemia]] include [[lymphadenopathy]], [[hepatomegaly]], [[splenomegaly]] and [[pulmonary embolism]] because of [[Deep vein thrombosis|deep venous thrombosis]]. [[Brain]] [[MRI]] is helpful in the [[diagnosis]] of [[CNS]] [[bleeding]] in [[acute myeloid leukemia|acute myeloid leukemia (AML)]]. There are no other [[imaging]] findings associated with erythroleukemia. Other [[Diagnosis|diagnostic]] studies include [[cytogenetics]] and [[flow cytometry]]. [[Pharmacology|Pharmacologic]] [[Medicine|medical]] [[therapy]] is recommended for [[Patient|patients]] with erythroleukemia who are not candidates for intensive [[chemotherapy]] or [[Allogeneic|allogenic]] [[hematopoietic stem cell]] [[Organ transplant|transplantation]]. [[Pharmacology|Pharmacologic]] [[Medicine|medical]] [[Therapy|therapies]] for erythroleukemia include hypomethylating agents (HMA) such as [[Azacytidine|azacitidine]] and [[Decitabine]]. [[Surgery|Surgical]] interventions include [[Allogeneic|allogenic]] [[hematopoietic stem cell]] [[Organ transplant|transplantation]] (Allo-SCT). There are no established measures for the [[Prevention (medical)|primary prevention]] of erythroleukemia. Effective measures for the [[Prevention (medical)|secondary prevention]] of erythroleukemia include maintenance of [[Remission (medicine)|remission]] treatment post-[[Organ transplant|transplant]].
==Historical Perspective==
==Historical Perspective==
Erythroleukemia was first discovered by M. Copelli, in 1912.<ref name="pmid21091147">{{cite journal |vauthors=Santos FP, Bueso-Ramos CE, Ravandi F |title=Acute erythroleukemia: diagnosis and management |journal=Expert Rev Hematol |volume=3 |issue=6 |pages=705–18 |date=December 2010 |pmid=21091147 |doi=10.1586/ehm.10.62 |url=}}</ref>  
* Erythroleukemia was first discovered by M. Copelli, in 1912.<ref name="pmid21091147">{{cite journal |vauthors=Santos FP, Bueso-Ramos CE, Ravandi F |title=Acute erythroleukemia: diagnosis and management |journal=Expert Rev Hematol |volume=3 |issue=6 |pages=705–18 |date=December 2010 |pmid=21091147 |doi=10.1586/ehm.10.62 |url=}}</ref>
 
In 1917, Di Guglielmo, Italian hematologist, described leukemic nature of the erythroleukemia.
 
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
 
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
 
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
 
There have been several outbreaks of [disease name], including -----.
 
In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
 
The first known case of acute erythroid leukemia was described in 1912 by M. Copelli under the name ''erythromatosis''. In 1917, Italian hematologist Giovanni Di Guglielmo (1886–1962), expanded on the description, coining the name "eritroleucemia" (Italian for ''erythroleukemia''). Di Guglielmo was the first to recognize the leukemic nature of the condition, and it is sometimes referred to as Di Guglielmo's syndrome in recognition of his work.
 
Chris Squire, bassist from the progressive rock group Yes, died from complications related to acute erythroid leukemia on June 27, 2015
 
'''ure erythroid leukemia (FAB M6)''' — Pure erythroid leukemia (equivalent to FAB M6, acute erythroid leukemia, erythroleukemia, or Di Guglielmo’s disease) accounts for <5 percent of AML. The erythroblasts do not express markers of myeloid lineage and do not stain with MPO [22]. They may express CD117 and do react with antibodies to hemoglobin A and glycophorin. In prior versions of the WHO classification system, two types of this leukemia were recognized, the erythroid/myeloid type and the "pure" type [39], and a diagnosis of AML, erythroid/myeloidcould be made if erythroid precursors accounted for more than 50 percent of the cells in the bone marrow and the blasts accounted for 20 percent or more of the non-erythroid cells. In the 2016 revision of the WHO classification, a diagnosis of acute leukemia requires blasts to account for 20 percent or more of the bone marrow cellularity irrespective of the number of erythroid precursors. Entities with less than 20 percent blasts have been reclassified as other forms of AML or MDS [3].
 
A diagnosis of pure erythroid leukemia is made in patients without exposure to cytotoxic agents and without AML-associated recurrent genetic abnormalities in whom erythroblasts account for >80 percent of the marrow cells. The erythroblasts are primarily at the pronormoblast stage and may have vacuolization in the cytoplasm surrounding the nucleus. This has been referred to as a "pearl necklace," and should not be confused with the vacuolated cells seen in Burkitt leukemia/lymphoma.


The "erythroid/myeloid type" was previously defined as those with erythroid precursors accounting for >50 percent of the nucleated marrow elements and myeloblasts accounting for >20 percent of the nonerythroid forms (picture 14). Evaluation of myeloblasts in such cases now considers the percentage of total nucleated cells and does not limit the percentage to nonerythroid forms. These cases are classified as MDS or as a non-erythroid subtype of AML, not otherwise specified depending upon the percentage of myeloblasts, identification of cytogenetic abnormalities, and the presence of dysplasia.
* In 1917, Di Guglielmo, Italian [[Hematology|hematologist]], described [[leukemic]] nature of the erythroleukemia. [[Erythroblasts]] may have [[vacuolization]] in the [[cytoplasm]] surrounding the [[nucleus]] (pearl necklace).  


==Classification==
==Classification==
Erythroleukemia accounts for <5 percent of AML( acute myeloid leukemia). Erythroleukemia may be classified according to previous version WHO into 2 subtypes : The erythroid/myeloid type and the pure type.
* Erythroleukemia accounts for < 5 % of [[acute myeloid leukemia|acute myeloid leukemia (AML)]].  
 
* Erythroleukemia may be classified into 2 groups: [[De novo]] cases of erythroleukemia and secondary erythroleukemia.  
Diagnosis of erythroid/myeloid type, base on previous version  WHO:
* Erythroleukemia may be classified according to previous version [[World Health Organization|WHO]] into 2 sub-types : The [[erythroid]]/[[myeloid]] type and the pure type.<ref name="pmid12752097">{{cite journal |vauthors=Forestier E, Heim S, Blennow E, Borgström G, Holmgren G, Heinonen K, Johannsson J, Kerndrup G, Andersen MK, Lundin C, Nordgren A, Rosenquist R, Swolin B, Johansson B |title=Cytogenetic abnormalities in childhood acute myeloid leukaemia: a Nordic series comprising all children enrolled in the NOPHO-93-AML trial between 1993 and 2001 |journal=Br. J. Haematol. |volume=121 |issue=4 |pages=566–77 |date=May 2003 |pmid=12752097 |doi= |url=}}</ref>
* Erythroid precursors more than 50 percent of the cells in bone marrow and,
* The blasts compromise 20 percent or more of the non-erythroid cells
2016 version of WHO calcification for AML (erythroid/myeloid type) :
* 20 percent or more blasts in bone marrow irrespective of the number of erythroid precursors
Diagnosis of pure erythroid leukemia:
* Erythroblasts ( at the stage of pronormoblast >80 percent of the marrow cells in patients without exposure to cytotoxic agent and without AML genetic abnormalities. Erythroblasts may have vacuolization in the cytoplasm arrounding the nucleus ( pearl necklace).  
 
*  
 
OR
 
Erythroleukemia may be classified into 2 groups. De novo cases of erythroleukemia and secondary Erythroleukemia. De novo cases are not associated with any risk factors. The most common predisposing factors in secondary acute erythroleukemia are as follows:based on [classification method 1], [classification method 2], and [classification method 3].
[Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].
 
OR
 
Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.
 
OR
 
If the staging system involves specific and characteristic findings and features:
According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].


OR
* [[Diagnosis]] of [[erythroid]]/[[myeloid]] type, based on previous version [[WHO]]:


The staging of [malignancy name] is based on the [staging system].
** [[Erythroid]] precursors more than 50% of the cells in [[bone marrow]]
** The [[blast]]<nowiki/>[[blast|s]] comprise of 20% or more of the non-[[erythroid]] [[Cell (biology)|cells]]
'''2016 version of [[World Health Organization|WHO]] [[classification]] for [[AML]] ([[erythroid]]/[[myeloid]] type) :'''
* 20% or more [[blast|blasts]] in [[Bone marrow|bo]]<nowiki/>[[Bone marrow|ne marrow]] irrespective of the number of [[erythroid]] precursors


OR
* [[Diagnosis]] of pure [[erythroid]] [[leukemia]]:


There is no established system for the staging of [malignancy name].
** [[Erythroblasts]] (at the stage of [[Proerythroblast|pronormoblast]] > 80% of the [[Bone marrow|marrow]] [[Cell (biology)|cells]] in [[Patient|patients]] without exposure to [[cytotoxic]] agent and without [[AML]] [[genetic]] abnormalities). [[Erythroblasts]] may have [[vacuolization]] in the [[cytoplasm]] surrounding the [[nucleus]] (pearl necklace).


==Pathophysiology==
==Pathophysiology==
Erythroleukemia is a neoplastic proliferation of myeloid and erythroid precursors of bone marrow hematopoietic stem cells. Erythroleukemia is accounting for 3–5% of all AML cases.<ref name="pmid210911472">{{cite journal |vauthors=Santos FP, Bueso-Ramos CE, Ravandi F |title=Acute erythroleukemia: diagnosis and management |journal=Expert Rev Hematol |volume=3 |issue=6 |pages=705–18 |date=December 2010 |pmid=21091147 |doi=10.1586/ehm.10.62 |url=}}</ref> A pure erythroid proliferation on rare occasion may occur.  The erythroblasts do not stain with MPO ( myeloperoxidase). Markers of myeloid lineage can not be expressed on the erythroblasts.
* Erythroleukemia is the [[neoplastic]] proliferation of [[myeloid]] and [[erythroid]] precursors of [[bone marrow]] [[Hematopoietic stem cell|hematopoietic stem cells]].  
 
* Erythroleukemia accounts for 3 - 5% of all [[AML]] cases.<ref name="pmid210911472">{{cite journal |vauthors=Santos FP, Bueso-Ramos CE, Ravandi F |title=Acute erythroleukemia: diagnosis and management |journal=Expert Rev Hematol |volume=3 |issue=6 |pages=705–18 |date=December 2010 |pmid=21091147 |doi=10.1586/ehm.10.62 |url=}}</ref>  
'''Gross pathology:'''  
* A pure [[erythroid]] proliferation may also occur.   
* The [[erythroblasts]] do not [[Staining|stain]] with [[myeloperoxidase|myeloperoxidase (MPO)]].  
* [[Marker|Markers]] of [[myeloid]] lineage can not be expressed on the [[erythroblasts]].
'''Microscopic Examanination:'''
* [[Erythroblasts]] may have [[vacuolization]] in the [[cytoplasm]] surrounding the [[nucleus]] (pearl necklace). 
'''Immunohistochemistry'''


'''Microscopic examanination:'''
[[Leukemia|Leukemic]] [[Cell (biology)|cells]] are positive for [[myeloid]] [[Marker|markers]] such as:<ref name="pmid2386768">{{cite journal |vauthors=Cuneo A, Van Orshoven A, Michaux JL, Boogaerts M, Louwagie A, Doyen C, Dal Cin P, Fagioli F, Castoldi G, Van den Berghe H |title=Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types |journal=Br. J. Haematol. |volume=75 |issue=3 |pages=346–54 |date=July 1990 |pmid=2386768 |doi= |url=}}</ref>
 
* [[CD117]]
Erythroblasts may have vacuolization in the cytoplasm arrounding the nucleus ( pearl necklace). 
* [[CD13]]
 
* [[CD33]]
'''Immunohistochemistry'''   
* [[myeloperoxidase|Myeloperoxidase (MPO)]]
 
[[Megakaryocyte|Megakaryocytes]] [[Antigen|antigens]] can be positive in some cases of erythroleukemia, such as:
and should not be confused with the vacuolated cells seen in Burkitt leukemia/lymphoma.
* CD41
 
* [[CD61]]
The "erythroid/myeloid type" was previously defined as those with erythroid precursors accounting for >50 percent of the nucleated marrow elements and myeloblasts accounting for >20 percent of the nonerythroid forms (picture 14). Evaluation of myeloblasts in such cases now considers the percentage of total nucleated cells and does not limit the percentage to nonerythroid forms. These cases are classified as MDS or as a non-erythroid subtype of AML, not otherwise specified depending upon the percentage of myeloblasts, identification of cytogenetic abnormalities, and the presence of dysplasia.
 
The exact pathogenesis of [disease name] is not fully understood.
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Causes==
==Causes==
Erythroleukemia may be caused by translocation t(1;16) generating the fusion gene NFIA/CBFA2T3. <ref name="pmid23032695">{{cite journal |vauthors=Micci F, Thorsen J, Panagopoulos I, Nyquist KB, Zeller B, Tierens A, Heim S |title=High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24) |journal=Leukemia |volume=27 |issue=4 |pages=980–2 |date=April 2013 |pmid=23032695 |pmc=3626019 |doi=10.1038/leu.2012.266 |url=}}</ref>
Erythroleukemia may be caused by [[translocation]] t(1;16) generating the [[fusion gene]] [[NFIA]]/[[CBFA2T3]].<ref name="pmid23032695">{{cite journal |vauthors=Micci F, Thorsen J, Panagopoulos I, Nyquist KB, Zeller B, Tierens A, Heim S |title=High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24) |journal=Leukemia |volume=27 |issue=4 |pages=980–2 |date=April 2013 |pmid=23032695 |pmc=3626019 |doi=10.1038/leu.2012.266 |url=}}</ref>


==Differentiating ((Page name)) from Other Diseases==
==Differentiating Erythroleukemia from Other Diseases==
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
* Erythroleukemia must be differentiated from [[MDS]] with [[erythroid]] predominance, other types of [[AML]] with increased [[erythroid]] precursors, [[AML]] with [[myelodysplasia]]-related changes.  
 
* Non-[[Cancer|neoplastic]] disorders that can cause [[erythroid]] predominance in the [[bone marrow]] such as [[megaloblastic anemia]] due to [[vitamin B12]] or [[folate]] deficiency, heavy metal [[intoxication]] such as [[arsenic]], drug effects (such as [[antineoplastic agents]] or [[chloramphenicol]]) are other [[Differential diagnosis|differential diagnoses]].<ref name="pmid208070442">{{cite journal |vauthors=Zuo Z, Polski JM, Kasyan A, Medeiros LJ |title=Acute erythroid leukemia |journal=Arch. Pathol. Lab. Med. |volume=134 |issue=9 |pages=1261–70 |date=September 2010 |pmid=20807044 |doi=10.1043/2009-0350-RA.1 |url=}}</ref>
OR
 
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence of erythroleukemia is approximately 0.077 per 100,000 individuals worldwide. <ref name="pmid11477115">{{cite journal |vauthors=Wells AW, Bown N, Reid MM, Hamilton PJ, Jackson GH, Taylor PR |title=Erythroleukaemia in the north of England: a population based study |journal=J. Clin. Pathol. |volume=54 |issue=8 |pages=608–12 |date=August 2001 |pmid=11477115 |pmc=1731487 |doi= |url=}}</ref>
* The [[incidence]] of erythroleukemia is approximately 0.077 per 100,000 individuals worldwide.<ref name="pmid11477115">{{cite journal |vauthors=Wells AW, Bown N, Reid MM, Hamilton PJ, Jackson GH, Taylor PR |title=Erythroleukaemia in the north of England: a population based study |journal=J. Clin. Pathol. |volume=54 |issue=8 |pages=608–12 |date=August 2001 |pmid=11477115 |pmc=1731487 |doi= |url=}}</ref>


Erythroleukemia commonly affects individuals older than 50 years of age with a median age of 65. <ref name="pmid210911473">{{cite journal |vauthors=Santos FP, Bueso-Ramos CE, Ravandi F |title=Acute erythroleukemia: diagnosis and management |journal=Expert Rev Hematol |volume=3 |issue=6 |pages=705–18 |date=December 2010 |pmid=21091147 |doi=10.1586/ehm.10.62 |url=}}</ref>
* Erythroleukemia commonly affects individuals older than 50 years of age with a [[median]] age of 65.<ref name="pmid210911473">{{cite journal |vauthors=Santos FP, Bueso-Ramos CE, Ravandi F |title=Acute erythroleukemia: diagnosis and management |journal=Expert Rev Hematol |volume=3 |issue=6 |pages=705–18 |date=December 2010 |pmid=21091147 |doi=10.1586/ehm.10.62 |url=}}</ref>


There is no racial predilection to Erythroleukemia.   
* There is no racial predilection to erythroleukemia.   


Men are slightlly more affected by Erythroleukemia than women.  
* Men are more commonly affected by erythroleukemia than women. The [[male]] to [[female]] ratio is approximately 2 to 1.  




==Risk Factors==
* There are no established [[Risk factor|risk factors]] for [[de novo]] cases of erythroleukemia.


==Risk Factors==
* The most potent [[risk factor]] in the development of [[secondary]] erythroleukemia is previous [[myelodysplastic syndrome|myelodysplastic syndrome (MDS)]].<ref name="pmid1486289">{{cite journal |vauthors=Atkinson J, Hrisinko MA, Weil SC |title=Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature |journal=Blood Rev. |volume=6 |issue=4 |pages=204–14 |date=December 1992 |pmid=1486289 |doi= |url=}}</ref>
There are no established risk factors for de novo cases of erythroleukemia.  


The most potent risk factor in the development of secondary Erythroleukemia is previous MDS ( myelodysplastic syndrome). <ref name="pmid1486289">{{cite journal |vauthors=Atkinson J, Hrisinko MA, Weil SC |title=Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature |journal=Blood Rev. |volume=6 |issue=4 |pages=204–14 |date=December 1992 |pmid=1486289 |doi= |url=}}</ref>
* Other [[Risk factor|risk factors]] include:


Other risk factors include: 
** [[Ionizing radiation]] such as [[Thorium dioxide]] [[Suspension (chemistry)|suspension]] ([[Thorotrast]])  
* Ionizing radiation such as Thorium dioxide suspension (Thorotrast)  
** Previous use of [[chemotherapy]] [[drugs]] such as [[Alkylating agent|alkylating agents]]
* Previous use of chemotherapy drugs such as alkylating agents  
** [[Familial]] erythroleukemia, [[Dominance relationship|autosomal dominant]] [[Disorder (medicine)|disorder]]    
* Famillial erythroleukemia, autosomal dominant disorder   


==Screening==
==Screening==
There is insufficient evidence to recommend routine screening for Erythroleukemia.  
There is insufficient evidence to recommend routine [[screening]] for erythroleukemia.  


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, patients with Erythroleukemia may progress to develop bleeding due to [[disseminated intravascular coagulation]].  
* If left untreated, [[Patient|patients]] with erythroleukemia may progress to develop [[bleeding]] due to [[disseminated intravascular coagulation|disseminated intravascular coagulation (DIC)]].  


Common complications of erythroleukemia include infection and bleeding. Therapy related complications are rash, c''ardiomyopathy and cerebellar toxicity.''
* Common [[Complication (medicine)|complications]] of erythroleukemia include [[infection]] and [[bleeding]]. [[Therapy]] related [[Complication (medicine)|complications]] are [[rash]], [[Cardiomyopathy|cardiomyopathy]] and [[cerebellar]] [[toxicity]]''.''


Prognosis is generally poor. 3-9 months after initial diagnosis is medican survival range. <ref name="pmid28420120">{{cite journal |vauthors=Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, Pinto R, Maurillo L, Wetzel J, Musto P, Van De Loosdrecht AA, Costa MJ, Esteves S, Burgstaller S, Stauder R, Autzinger EM, Lang A, Krippl P, Geissler D, Falantes JF, Pedro C, Bargay J, Deben G, Garrido A, Bonanad S, Diez-Campelo M, Thepot S, Ades L, Sperr WR, Valent P, Fenaux P, Sekeres MA, Greil R, Pleyer L |title=Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study |journal=Int J Mol Sci |volume=18 |issue=4 |pages= |date=April 2017 |pmid=28420120 |pmc=5412421 |doi=10.3390/ijms18040837 |url=}}</ref> A high proerythroblast/myeloblast ratio correlates with worse outcome.<ref name="pmid17852448">{{cite journal |vauthors=Srinivas U, Kumar R, Pati H, Saxena R, Tyagi S |title=Sub classification and clinico-hematological correlation of 40 cases of acute erythroleukemia - can proerythroblast/myeloblast and proerythroblast/total erythroid cell ratios help subclassify? |journal=Hematology |volume=12 |issue=5 |pages=381–5 |date=October 2007 |pmid=17852448 |doi=10.1080/10245330701393816 |url=}}</ref>
* [[Prognosis]] is generally poor.  
* [[Median]] survival ranges from 3 - 9 months after the initial [[diagnosis]].<ref name="pmid28420120">{{cite journal |vauthors=Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, Pinto R, Maurillo L, Wetzel J, Musto P, Van De Loosdrecht AA, Costa MJ, Esteves S, Burgstaller S, Stauder R, Autzinger EM, Lang A, Krippl P, Geissler D, Falantes JF, Pedro C, Bargay J, Deben G, Garrido A, Bonanad S, Diez-Campelo M, Thepot S, Ades L, Sperr WR, Valent P, Fenaux P, Sekeres MA, Greil R, Pleyer L |title=Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study |journal=Int J Mol Sci |volume=18 |issue=4 |pages= |date=April 2017 |pmid=28420120 |pmc=5412421 |doi=10.3390/ijms18040837 |url=}}</ref>  
* A high [[proerythroblast]]/[[myeloblast]] ratio correlates with worse outcome.<ref name="pmid17852448">{{cite journal |vauthors=Srinivas U, Kumar R, Pati H, Saxena R, Tyagi S |title=Sub classification and clinico-hematological correlation of 40 cases of acute erythroleukemia - can proerythroblast/myeloblast and proerythroblast/total erythroid cell ratios help subclassify? |journal=Hematology |volume=12 |issue=5 |pages=381–5 |date=October 2007 |pmid=17852448 |doi=10.1080/10245330701393816 |url=}}</ref>


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===


===== Bone marrow biopsy =====
===== Bone Marrow Biopsy =====
The diagnosis of Erythroleukemia is based on 2016 version of WHO classification for AML:  
The [[diagnosis]] of erythroleukemia is based on the 2016 version of [[World Health Organization|WHO]] [[classification]] for [[AML]]:  
* AML (erythroid/myeloid type): 20 percent or more blasts in bone marrow irrespective of the number of erythroid precursors
* [[AML]] ([[erythroid]]/[[myeloid]] type): 20% or more [[blast|blasts]] in th<nowiki/>e [[bone marrow]] irrespective of the number of [[erythroid]] precursors
* Pure erythroid leukemia: Erythroblasts, at the stage of pronormoblast, more than 80 percent of the marrow cells in patients without exposure to cytotoxic agent and without AML genetic abnormalities. Erythroblasts may have vacuolization in the cytoplasm arrounding the nucleus ( pearl necklace).
* Pure [[erythroid]] [[leukemia]]: [[Erythroblasts]], at the stage of [[pronormoblast]], more than 80% of the [[marrow]] [[Cells (biology)|cells]] in [[Patient|patients]] without exposure to [[cytotoxic]] agent and without [[AML]] [[Genetics|genetic]] abnormalities. [[Erythroblasts]] may have [[vacuolization]] in the [[cytoplasm]] surrounding the [[nucleus]] (pearl necklace).


===History and Symptoms===
===History and Symptoms===
* Fatigue
* [[Fatigue]]
* Malaise
* [[Malaise]]
 
* [[Bone pain]]
* Fatigue
* [[Abdominal pain]]
* Malaise
* [[Weight loss]]
* Bone pain
* [[Easy bruising]]
* Abdominal pain
* [[Fever]]
* Weight loss
* [[Dyspnea]]
* Easy bruising
Less common [[Symptom|symptoms]] of erythroleukemia include diffuse [[joint pain]].
* Fever
* Dyspnea
Less common symptoms of Erythroleukemia include diffuse joint pain


===Physical Examination===
===Physical Examination===
Patients with Erythroleukemia usually appear anemic. Physical examination of patients with Erythroleukemia may include:<ref name="pmid20807044">{{cite journal |vauthors=Zuo Z, Polski JM, Kasyan A, Medeiros LJ |title=Acute erythroid leukemia |journal=Arch. Pathol. Lab. Med. |volume=134 |issue=9 |pages=1261–70 |date=September 2010 |pmid=20807044 |doi=10.1043/2009-0350-RA.1 |url=}}</ref>
[[Patient|Patients]] with erythroleukemia usually appear [[anemic]]. [[Physical examination]] of [[Patient|patients]] with erythroleukemia may include:<ref name="pmid20807044">{{cite journal |vauthors=Zuo Z, Polski JM, Kasyan A, Medeiros LJ |title=Acute erythroid leukemia |journal=Arch. Pathol. Lab. Med. |volume=134 |issue=9 |pages=1261–70 |date=September 2010 |pmid=20807044 |doi=10.1043/2009-0350-RA.1 |url=}}</ref>
* Ecchymoses or petechiae
* [[Ecchymoses]] or [[petechiae]]
* Hepatomegaly  
* [[Hepatomegaly]]
* Splenomegaly  
* [[Splenomegaly]]
* Lymphadenopathy
* [[Lymphadenopathy]]
* Headache
* [[Headache]]


===Laboratory Findings===
===Laboratory Findings===
* Pancytopenia<ref name="pmid26293512">{{cite journal |vauthors=Peng J, Hasserjian RP, Tang G, Patel KP, Goswami M, Jabbour EJ, Garcia-Manero G, Medeiros LJ, Wang SA |title=Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response |journal=Leuk. Lymphoma |volume=57 |issue=4 |pages=812–9 |date=2016 |pmid=26293512 |doi=10.3109/10428194.2015.1079318 |url=}}</ref>
* [[Pancytopenia]]<ref name="pmid26293512">{{cite journal |vauthors=Peng J, Hasserjian RP, Tang G, Patel KP, Goswami M, Jabbour EJ, Garcia-Manero G, Medeiros LJ, Wang SA |title=Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response |journal=Leuk. Lymphoma |volume=57 |issue=4 |pages=812–9 |date=2016 |pmid=26293512 |doi=10.3109/10428194.2015.1079318 |url=}}</ref>
* Few peripheral blood blasts<ref name="pmid16337853">{{cite journal |vauthors=Lessard M, Struski S, Leymarie V, Flandrin G, Lafage-Pochitaloff M, Mozziconacci MJ, Talmant P, Bastard C, Charrin C, Baranger L, Hélias C, Cornillet-Lefebvre P, Mugneret F, Cabrol C, Pagès MP, Fert-Ferret D, Nguyen-Khac F, Quilichini B, Barin C, Berger R |title=Cytogenetic study of 75 erythroleukemias |journal=Cancer Genet. Cytogenet. |volume=163 |issue=2 |pages=113–22 |date=December 2005 |pmid=16337853 |doi=10.1016/j.cancergencyto.2005.05.006 |url=}}</ref>
* Few [[peripheral blood]] [[blast]]<nowiki/>[[blast|s]]<ref name="pmid16337853">{{cite journal |vauthors=Lessard M, Struski S, Leymarie V, Flandrin G, Lafage-Pochitaloff M, Mozziconacci MJ, Talmant P, Bastard C, Charrin C, Baranger L, Hélias C, Cornillet-Lefebvre P, Mugneret F, Cabrol C, Pagès MP, Fert-Ferret D, Nguyen-Khac F, Quilichini B, Barin C, Berger R |title=Cytogenetic study of 75 erythroleukemias |journal=Cancer Genet. Cytogenet. |volume=163 |issue=2 |pages=113–22 |date=December 2005 |pmid=16337853 |doi=10.1016/j.cancergencyto.2005.05.006 |url=}}</ref>
* Dysplasia in bone marrow and peripheral blood
* [[Dysplasia]] in [[bone marrow]] and [[peripheral blood]]
* Dysplastic PAS positive erythroblasts with overexpression of the multidrug resistance (MDR) gene product P-glycoprotein
* [[Dysplasia|Dysplastic]] [[PAS stain|PAS]] positive [[erythroblasts]] with overexpression of the [[multidrug resistance|multidrug resistance (MDR)]] [[gene]] product [[P-glycoprotein]]
* High freqiency of mutations, especially of TP53<ref name="pmid23648669">{{cite journal |vauthors=Grossmann V, Bacher U, Haferlach C, Schnittger S, Pötzinger F, Weissmann S, Roller A, Eder C, Fasan A, Zenger M, Staller M, Kern W, Kohlmann A, Haferlach T |title=Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics |journal=Leukemia |volume=27 |issue=9 |pages=1940–3 |date=September 2013 |pmid=23648669 |doi=10.1038/leu.2013.144 |url=}}</ref>
* High frequency of [[mutations]], especially of [[TP53]]<ref name="pmid23648669">{{cite journal |vauthors=Grossmann V, Bacher U, Haferlach C, Schnittger S, Pötzinger F, Weissmann S, Roller A, Eder C, Fasan A, Zenger M, Staller M, Kern W, Kohlmann A, Haferlach T |title=Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics |journal=Leukemia |volume=27 |issue=9 |pages=1940–3 |date=September 2013 |pmid=23648669 |doi=10.1038/leu.2013.144 |url=}}</ref>


===Electrocardiogram===
===Electrocardiogram===
Electrocardiogram is useful for assessment of QT interval prior to starting chemptherapy. It is also useful for assessing arrhythmias induced by anthracycline chemotherapy. <ref name="pmid25616318">{{cite journal| author=Hefti E, Blanco JG| title=Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and Down Syndrome: A Literature Review. | journal=Cardiovasc Toxicol | year= 2016 | volume= 16 | issue= 1 | pages= 5-13 | pmid=25616318 | doi=10.1007/s12012-015-9307-1 | pmc=4514565 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25616318  }}</ref>For more information, click [[Acute myeloid leukemia electrocardiogram|here]].  
* [[Electrocardiogram]] is useful for the assessment of [[QT interval]] prior to starting [[chemotherapy]].
* It is also useful for assessing [[arrhythmias]] induced by [[anthracycline]] [[chemotherapy]].<ref name="pmid25616318">{{cite journal| author=Hefti E, Blanco JG| title=Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and Down Syndrome: A Literature Review. | journal=Cardiovasc Toxicol | year= 2016 | volume= 16 | issue= 1 | pages= 5-13 | pmid=25616318 | doi=10.1007/s12012-015-9307-1 | pmc=4514565 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25616318  }}</ref>  
* For more information, click [[Acute myeloid leukemia electrocardiogram|here]].  


===X-ray===
===X-ray===
An x-ray may be helpful in the diagnosis of complications of Erythroleukemia management which include infection, volume overload. Chest x-ray is also useful for venous catheter placement for chemotherapy.  
* An [[x-ray]] may be helpful in the [[diagnosis]] of [[Complication (medicine)|complications]] of erythroleukemia management which include [[infection]], volume overload.
* [[Chest X-ray|Chest x-ray]] is also useful for [[venous]] [[catheter]] placement for [[chemotherapy]].  


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
An echocardiogram is helpful for assessing cardiac function ( ejection fraction) in patients with acute myeloid leukemia before and after receiving anthracycline chemotherapy. <ref name="pmid24947931">{{cite journal |vauthors=Armenian SH, Gelehrter SK, Vase T, Venkatramani R, Landier W, Wilson KD, Herrera C, Reichman L, Menteer JD, Mascarenhas L, Freyer DR, Venkataraman K, Bhatia S |title=Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors |journal=Clin. Cancer Res. |volume=20 |issue=24 |pages=6314–23 |date=December 2014 |pmid=24947931 |pmc=4268342 |doi=10.1158/1078-0432.CCR-13-3490 |url=}}</ref>
* An [[echocardiogram]] is helpful for assessing [[cardiac]] function ([[ejection fraction]]) in [[Patient|patients]] with [[acute myeloid leukemia]] before and after receiving [[anthracycline]] [[chemotherapy]]. <ref name="pmid24947931">{{cite journal |vauthors=Armenian SH, Gelehrter SK, Vase T, Venkatramani R, Landier W, Wilson KD, Herrera C, Reichman L, Menteer JD, Mascarenhas L, Freyer DR, Venkataraman K, Bhatia S |title=Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors |journal=Clin. Cancer Res. |volume=20 |issue=24 |pages=6314–23 |date=December 2014 |pmid=24947931 |pmc=4268342 |doi=10.1158/1078-0432.CCR-13-3490 |url=}}</ref>


An ultrasound is useful for diagnosis of lower extremity thrombosis, which commonly occurs in patients with acute myeloid leukemia.<ref name="pmid20124617">{{cite journal |vauthors=Oehadian A, Iqbal M, Sumantri R |title=Deep vein thrombosis in acute myelogenous leukemia |journal=Acta Med Indones |volume=41 |issue=4 |pages=200–4 |date=October 2009 |pmid=20124617 |doi= |url=}}</ref>
* An [[ultrasound]] is useful for the [[diagnosis]] of [[lower extremity]] [[thrombosis]], which commonly occurs in [[Patient|patients]] with [[acute myeloid leukemia]].<ref name="pmid20124617">{{cite journal |vauthors=Oehadian A, Iqbal M, Sumantri R |title=Deep vein thrombosis in acute myelogenous leukemia |journal=Acta Med Indones |volume=41 |issue=4 |pages=200–4 |date=October 2009 |pmid=20124617 |doi= |url=}}</ref>


===CT scan===
===CT scan===
Abdominal and chest CT scan may be helpful in the diagnosis of acute myeloid leukemia. Findings on CT scan suggestive of of acute myeloid leukemia include lymphadenopathy, hepatomegaly, splenomegaly and pulmonary embolism because of deep venous thrombosis. <ref name="pmid27642861">{{cite journal |vauthors=Vallipuram J, Dhalla S, Bell CM, Dresser L, Han H, Husain S, Minden MD, Paul NS, So M, Steinberg M, Vallipuram M, Wong G, Morris AM |title=Chest CT scans are frequently abnormal in asymptomatic patients with newly diagnosed acute myeloid leukemia |journal=Leuk. Lymphoma |volume=58 |issue=4 |pages=834–841 |date=April 2017 |pmid=27642861 |doi=10.1080/10428194.2016.1213825 |url=}}</ref>
* [[Abdominal]] and [[chest]] [[Computed tomography|CT scan]] may be helpful in the [[diagnosis]] of [[acute myeloid leukemia]].  
* Findings on [[CT scan]] suggestive of [[acute myeloid leukemia]] include [[lymphadenopathy]], [[hepatomegaly]], [[splenomegaly]] and [[pulmonary embolism]] because of [[Deep vein thrombosis|deep venous thrombosis]].<ref name="pmid27642861">{{cite journal |vauthors=Vallipuram J, Dhalla S, Bell CM, Dresser L, Han H, Husain S, Minden MD, Paul NS, So M, Steinberg M, Vallipuram M, Wong G, Morris AM |title=Chest CT scans are frequently abnormal in asymptomatic patients with newly diagnosed acute myeloid leukemia |journal=Leuk. Lymphoma |volume=58 |issue=4 |pages=834–841 |date=April 2017 |pmid=27642861 |doi=10.1080/10428194.2016.1213825 |url=}}</ref>


Non contrast brain CT scan is useful to rule out CNS bleed.<ref name="pmid22931433">{{cite journal |vauthors=Chen CY, Tai CH, Cheng A, Wu HC, Tsay W, Liu JH, Chen PY, Huang SY, Yao M, Tang JL, Tien HF |title=Intracranial hemorrhage in adult patients with hematological malignancies |journal=BMC Med |volume=10 |issue= |pages=97 |date=August 2012 |pmid=22931433 |pmc=3482556 |doi=10.1186/1741-7015-10-97 |url=}}</ref>
* Non [[contrast]] [[brain]] [[CT scan]] is useful to rule out [[CNS]] [[Bleeding|bleed]].<ref name="pmid22931433">{{cite journal |vauthors=Chen CY, Tai CH, Cheng A, Wu HC, Tsay W, Liu JH, Chen PY, Huang SY, Yao M, Tang JL, Tien HF |title=Intracranial hemorrhage in adult patients with hematological malignancies |journal=BMC Med |volume=10 |issue= |pages=97 |date=August 2012 |pmid=22931433 |pmc=3482556 |doi=10.1186/1741-7015-10-97 |url=}}</ref>


===MRI===
===MRI===
Brain MRI is helpful in the diagnosis of CNS bleeding in acute myeloid leukemia. <ref name="pmid26239467">{{cite journal |vauthors=Cervantes GM, Cayci Z |title=Intracranial CNS Manifestations of Myeloid Sarcoma in Patients with Acute Myeloid Leukemia: Review of the Literature and Three Case Reports from the Author's Institution |journal=J Clin Med |volume=4 |issue=5 |pages=1102–12 |date=May 2015 |pmid=26239467 |pmc=4470219 |doi=10.3390/jcm4051102 |url=}}</ref>
[[Brain]] [[MRI]] is helpful in the [[diagnosis]] of [[CNS]] [[bleeding]] in [[acute myeloid leukemia|acute myeloid leukemia (AML)]].<ref name="pmid26239467">{{cite journal |vauthors=Cervantes GM, Cayci Z |title=Intracranial CNS Manifestations of Myeloid Sarcoma in Patients with Acute Myeloid Leukemia: Review of the Literature and Three Case Reports from the Author's Institution |journal=J Clin Med |volume=4 |issue=5 |pages=1102–12 |date=May 2015 |pmid=26239467 |pmc=4470219 |doi=10.3390/jcm4051102 |url=}}</ref>


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with Erythroleukemia.  
There are no other [[imaging]] findings associated with erythroleukemia.  


===Other Diagnostic Studies===
===Other Diagnostic Studies===


===== Flow cytometry: =====
===== Flow Cytometry: =====
The myeloid blasts are often postive for myeloid marker such as CD117, CD13, CD33 and MPO.<ref name="pmid21393910">{{cite journal |vauthors=Sharma A, Buxi G, Walia R, Yadav RB, Sharma S |title=Childhood acute erythroleukemia diagnosis by flow cytometry |journal=Indian J Pathol Microbiol |volume=54 |issue=1 |pages=173–5 |date=2011 |pmid=21393910 |doi=10.4103/0377-4929.77395 |url=}}</ref>
* The [[myeloid]] [[blast|blasts]] are often postive for [[myeloid]] [[marker]] such as [[CD117]], [[CD13]], [[CD33]] and [[Myeloperoxidase|MPO]].<ref name="pmid21393910">{{cite journal |vauthors=Sharma A, Buxi G, Walia R, Yadav RB, Sharma S |title=Childhood acute erythroleukemia diagnosis by flow cytometry |journal=Indian J Pathol Microbiol |volume=54 |issue=1 |pages=173–5 |date=2011 |pmid=21393910 |doi=10.4103/0377-4929.77395 |url=}}</ref>


The erythroblasts lack myeloid antigens. They are postive for glycophorin A.
* The [[erythroblasts]] lack [[myeloid]] [[Antigen|antigens]]. They are postive for [[glycophorin A]].


===== Cytogenetics: =====
===== Cytogenetics: =====
Loss of all or part of the long arm (q) of chromosomes 5 and/or 7. <ref name="pmid14862892">{{cite journal |vauthors=Atkinson J, Hrisinko MA, Weil SC |title=Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature |journal=Blood Rev. |volume=6 |issue=4 |pages=204–14 |date=December 1992 |pmid=1486289 |doi= |url=}}</ref>
* Loss of all or part of the long arm (q) of [[Chromosome|chromosomes]] 5 and/or 7. <ref name="pmid14862892">{{cite journal |vauthors=Atkinson J, Hrisinko MA, Weil SC |title=Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature |journal=Blood Rev. |volume=6 |issue=4 |pages=204–14 |date=December 1992 |pmid=1486289 |doi= |url=}}</ref>


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
Pharmacologic medical therapy is recommended among patients with Erythroleukemia who are not candidate for intensive chemotherapy or allogenic hematopoietic stem cell transplantation. <ref name="pmid284201202">{{cite journal |vauthors=Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, Pinto R, Maurillo L, Wetzel J, Musto P, Van De Loosdrecht AA, Costa MJ, Esteves S, Burgstaller S, Stauder R, Autzinger EM, Lang A, Krippl P, Geissler D, Falantes JF, Pedro C, Bargay J, Deben G, Garrido A, Bonanad S, Diez-Campelo M, Thepot S, Ades L, Sperr WR, Valent P, Fenaux P, Sekeres MA, Greil R, Pleyer L |title=Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study |journal=Int J Mol Sci |volume=18 |issue=4 |pages= |date=April 2017 |pmid=28420120 |pmc=5412421 |doi=10.3390/ijms18040837 |url=}}</ref>
* [[Pharmacology|Pharmacologic]] [[Medicine|medical]] [[therapy]] is recommended for [[Patient|patients]] with erythroleukemia who are not candidates for intensive [[chemotherapy]] or [[Allogeneic|allogenic]] [[hematopoietic stem cell]] [[Organ transplant|transplantation]].<ref name="pmid284201202">{{cite journal |vauthors=Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, Pinto R, Maurillo L, Wetzel J, Musto P, Van De Loosdrecht AA, Costa MJ, Esteves S, Burgstaller S, Stauder R, Autzinger EM, Lang A, Krippl P, Geissler D, Falantes JF, Pedro C, Bargay J, Deben G, Garrido A, Bonanad S, Diez-Campelo M, Thepot S, Ades L, Sperr WR, Valent P, Fenaux P, Sekeres MA, Greil R, Pleyer L |title=Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study |journal=Int J Mol Sci |volume=18 |issue=4 |pages= |date=April 2017 |pmid=28420120 |pmc=5412421 |doi=10.3390/ijms18040837 |url=}}</ref>


Pharmacologic medical therapies for Erythroleukemia include hyypomethylating agents ( HMA) such as:<ref name="pmid20026804">{{cite journal |vauthors=Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR |title=Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia |journal=J. Clin. Oncol. |volume=28 |issue=4 |pages=562–9 |date=February 2010 |pmid=20026804 |doi=10.1200/JCO.2009.23.8329 |url=}}</ref>
* [[Pharmacology|Pharmacologic]] [[Medicine|medical]] [[Therapy|therapies]] for erythroleukemia include hypomethylating agents (HMA) such as:<ref name="pmid20026804">{{cite journal |vauthors=Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR |title=Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia |journal=J. Clin. Oncol. |volume=28 |issue=4 |pages=562–9 |date=February 2010 |pmid=20026804 |doi=10.1200/JCO.2009.23.8329 |url=}}</ref>
* Azacitidine
 
* Decitabine
** [[Azacytidine|Azacitidine]]
For more information about acute myeloid leukemia medical therapy, click [[Acute myeloid leukemia medical therapy|here]].
** [[Decitabine]]
For more information about [[Acute myeloid leukemia|acute myeloid leukemia (AML)]] [[Medicine|medical]] [[therapy]], click [[Acute myeloid leukemia medical therapy|here]].


===Surgery===
===Surgery===
* Allo-SCT ( Allogenic hematopoietic stem cell transplantation)<ref name="pmid284201202" />
* Allo-SCT ([[Allogeneic|Allogenic]] [[hematopoietic stem cell]] [[Organ transplant|transplantation]])<ref name="pmid284201202" />
 
.


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of Erythroleukemia.  
There are no established measures for the [[Prevention (medical)|primary prevention]] of erythroleukemia.  


===Secondary Prevention===
===Secondary Prevention===
Effective measures for the secondary prevention of Erythroleukemia include maintenance of remission treatment posttransplant.<ref name="pmid21897227">{{cite journal |vauthors=Oran B, de Lima M |title=Prevention and treatment of acute myeloid leukemia relapse after allogeneic stem cell transplantation |journal=Curr. Opin. Hematol. |volume=18 |issue=6 |pages=388–94 |date=November 2011 |pmid=21897227 |doi=10.1097/MOH.0b013e32834b6158 |url=}}</ref>  
Effective measures for the [[Prevention (medical)|secondary prevention]] of erythroleukemia include maintenance of [[Remission (medicine)|remission]] treatment post-[[Organ transplant|transplant]].<ref name="pmid21897227">{{cite journal |vauthors=Oran B, de Lima M |title=Prevention and treatment of acute myeloid leukemia relapse after allogeneic stem cell transplantation |journal=Curr. Opin. Hematol. |volume=18 |issue=6 |pages=388–94 |date=November 2011 |pmid=21897227 |doi=10.1097/MOH.0b013e32834b6158 |url=}}</ref>  


==References==
==References==

Latest revision as of 14:31, 8 May 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2] [3] [4] Synonyms and keywords:Pure erythroid leukemia, FAB ( French-American-British) M6, acute erythroid leukemia, Di Guglielmo’s disease

Overview

Erythroleukemia was first discovered by M. Copelli, in 1912. In 1917, Di Guglielmo, Italian hematologist, described leukemic nature of the erythroleukemia. Erythroleukemia accounts for < 5 % of acute myeloid leukemia (AML). Erythroleukemia may be classified into 2 groups: De novo cases of erythroleukemia and secondary erythroleukemia. Erythroleukemia may be classified according to previous version WHO into 2 sub-types : The erythroid/myeloid type and the pure type. Erythroleukemia is the neoplastic proliferation of myeloid and erythroid precursors of bone marrow hematopoietic stem cells. A pure erythroid proliferation may also occur. The erythroblasts do not stain with myeloperoxidase (MPO). Markers of myeloid lineage can not be expressed on the erythroblasts. Leukemic cells are positive for myeloid markers such as CD117, CD13, CD33, andmyeloperoxidase (MPO). Megakaryocytes antigens can be positive in some cases of erythroleukemia, such as CD41 and CD61. Erythroleukemia may be caused by translocation t(1;16) generating the fusion gene NFIA/CBFA2T3. Erythroleukemia must be differentiated from MDS with erythroid predominance, other types of AML with increased erythroid precursors, AML with myelodysplasia-related changes. Non-neoplastic disorders that can cause erythroid predominance in the bone marrow such as megaloblastic anemia due to vitamin B12 or folate deficiency, heavy metal intoxication such as arsenic, drug effects (such as antineoplastic agents or chloramphenicol) are other differential diagnoses. The incidence of erythroleukemia is approximately 0.077 per 100,000 individuals worldwide. Erythroleukemia commonly affects individuals older than 50 years of age with a median age of 65. There is no racial predilection to erythroleukemia. Men are more commonly affected by erythroleukemia than women. The male to female ratio is approximately 2 to 1. There are no established risk factors for de novo cases of erythroleukemia. The most potent risk factor in the development of secondary erythroleukemia is previous myelodysplastic syndrome (MDS). There is insufficient evidence to recommend routine screening for erythroleukemia. If left untreated, patients with erythroleukemia may progress to develop bleeding due to disseminated intravascular coagulation (DIC). Common complications of erythroleukemia include infection and bleeding. Therapy related complications are rash, cardiomyopathy and cerebellar toxicity. Prognosis is generally poor. Median survival ranges from 3 - 9 months after the initial diagnosis. A high proerythroblast/myeloblast ratio correlates with worse outcome. The diagnosis of erythroleukemia is based on the 2016 version of WHO classification for AML. History and symptoms include fatigue, Malaise, bone pain, abdominal pain, weight loss, Easy bruising, Fever, and Dyspnea. Patients with erythroleukemia usually appear anemic. Physical examination of patients with erythroleukemia may include Ecchymoses or petechiae, Hepatomegaly, Splenomegaly, Lymphadenopathy, and headache. Laboratory findings include Pancytopenia, few peripheral blood blasts, Dysplasia in bone marrow and peripheral blood, dysplastic PAS positive erythroblasts with overexpression of the multidrug resistance (MDR) gene product P-glycoprotein, and high frequency of mutations, especially of TP53. Electrocardiogram is useful for the assessment of QT interval prior to starting chemotherapy. An x-ray may be helpful in the diagnosis of complications of erythroleukemia management which include infection, volume overload. Chest x-ray is also useful for venous catheter placement for chemotherapy. An echocardiogram is helpful for assessing cardiac function (ejection fraction) in patients with acute myeloid leukemia before and after receiving anthracycline chemotherapy. An ultrasound is useful for the diagnosis of lower extremity thrombosis, which commonly occurs in patients with acute myeloid leukemia. Abdominal and chest CT scan may be helpful in the diagnosis of acute myeloid leukemia. Findings on CT scan suggestive of acute myeloid leukemia include lymphadenopathy, hepatomegaly, splenomegaly and pulmonary embolism because of deep venous thrombosis. Brain MRI is helpful in the diagnosis of CNS bleeding in acute myeloid leukemia (AML). There are no other imaging findings associated with erythroleukemia. Other diagnostic studies include cytogenetics and flow cytometry. Pharmacologic medical therapy is recommended for patients with erythroleukemia who are not candidates for intensive chemotherapy or allogenic hematopoietic stem cell transplantation. Pharmacologic medical therapies for erythroleukemia include hypomethylating agents (HMA) such as azacitidine and Decitabine. Surgical interventions include allogenic hematopoietic stem cell transplantation (Allo-SCT). There are no established measures for the primary prevention of erythroleukemia. Effective measures for the secondary prevention of erythroleukemia include maintenance of remission treatment post-transplant.

Historical Perspective

  • Erythroleukemia was first discovered by M. Copelli, in 1912.[1]

Classification

  • Erythroleukemia accounts for < 5 % of acute myeloid leukemia (AML).
  • Erythroleukemia may be classified into 2 groups: De novo cases of erythroleukemia and secondary erythroleukemia.
  • Erythroleukemia may be classified according to previous version WHO into 2 sub-types : The erythroid/myeloid type and the pure type.[2]

2016 version of WHO classification for AML (erythroid/myeloid type) :

Pathophysiology

Microscopic Examanination:

Immunohistochemistry

Leukemic cells are positive for myeloid markers such as:[4]

Megakaryocytes antigens can be positive in some cases of erythroleukemia, such as:

Causes

Erythroleukemia may be caused by translocation t(1;16) generating the fusion gene NFIA/CBFA2T3.[5]

Differentiating Erythroleukemia from Other Diseases

Epidemiology and Demographics

  • The incidence of erythroleukemia is approximately 0.077 per 100,000 individuals worldwide.[7]
  • Erythroleukemia commonly affects individuals older than 50 years of age with a median age of 65.[8]
  • There is no racial predilection to erythroleukemia.
  • Men are more commonly affected by erythroleukemia than women. The male to female ratio is approximately 2 to 1.


Risk Factors

Screening

There is insufficient evidence to recommend routine screening for erythroleukemia.

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Study of Choice

Bone Marrow Biopsy

The diagnosis of erythroleukemia is based on the 2016 version of WHO classification for AML:

History and Symptoms

Less common symptoms of erythroleukemia include diffuse joint pain.

Physical Examination

Patients with erythroleukemia usually appear anemic. Physical examination of patients with erythroleukemia may include:[12]

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT scan

MRI

Brain MRI is helpful in the diagnosis of CNS bleeding in acute myeloid leukemia (AML).[21]

Other Imaging Findings

There are no other imaging findings associated with erythroleukemia.

Other Diagnostic Studies

Flow Cytometry:
Cytogenetics:

Treatment

Medical Therapy

For more information about acute myeloid leukemia (AML) medical therapy, click here.

Surgery

Primary Prevention

There are no established measures for the primary prevention of erythroleukemia.

Secondary Prevention

Effective measures for the secondary prevention of erythroleukemia include maintenance of remission treatment post-transplant.[26]

References

  1. ↑ Santos FP, Bueso-Ramos CE, Ravandi F (December 2010). "Acute erythroleukemia: diagnosis and management". Expert Rev Hematol. 3 (6): 705–18. doi:10.1586/ehm.10.62. PMID 21091147.
  2. ↑ Forestier E, Heim S, Blennow E, Borgström G, Holmgren G, Heinonen K, Johannsson J, Kerndrup G, Andersen MK, Lundin C, Nordgren A, Rosenquist R, Swolin B, Johansson B (May 2003). "Cytogenetic abnormalities in childhood acute myeloid leukaemia: a Nordic series comprising all children enrolled in the NOPHO-93-AML trial between 1993 and 2001". Br. J. Haematol. 121 (4): 566–77. PMID 12752097.
  3. ↑ Santos FP, Bueso-Ramos CE, Ravandi F (December 2010). "Acute erythroleukemia: diagnosis and management". Expert Rev Hematol. 3 (6): 705–18. doi:10.1586/ehm.10.62. PMID 21091147.
  4. ↑ Cuneo A, Van Orshoven A, Michaux JL, Boogaerts M, Louwagie A, Doyen C, Dal Cin P, Fagioli F, Castoldi G, Van den Berghe H (July 1990). "Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types". Br. J. Haematol. 75 (3): 346–54. PMID 2386768.
  5. ↑ Micci F, Thorsen J, Panagopoulos I, Nyquist KB, Zeller B, Tierens A, Heim S (April 2013). "High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24)". Leukemia. 27 (4): 980–2. doi:10.1038/leu.2012.266. PMC 3626019. PMID 23032695.
  6. ↑ Zuo Z, Polski JM, Kasyan A, Medeiros LJ (September 2010). "Acute erythroid leukemia". Arch. Pathol. Lab. Med. 134 (9): 1261–70. doi:10.1043/2009-0350-RA.1. PMID 20807044.
  7. ↑ Wells AW, Bown N, Reid MM, Hamilton PJ, Jackson GH, Taylor PR (August 2001). "Erythroleukaemia in the north of England: a population based study". J. Clin. Pathol. 54 (8): 608–12. PMC 1731487. PMID 11477115.
  8. ↑ Santos FP, Bueso-Ramos CE, Ravandi F (December 2010). "Acute erythroleukemia: diagnosis and management". Expert Rev Hematol. 3 (6): 705–18. doi:10.1586/ehm.10.62. PMID 21091147.
  9. ↑ Atkinson J, Hrisinko MA, Weil SC (December 1992). "Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature". Blood Rev. 6 (4): 204–14. PMID 1486289.
  10. ↑ Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, Pinto R, Maurillo L, Wetzel J, Musto P, Van De Loosdrecht AA, Costa MJ, Esteves S, Burgstaller S, Stauder R, Autzinger EM, Lang A, Krippl P, Geissler D, Falantes JF, Pedro C, Bargay J, Deben G, Garrido A, Bonanad S, Diez-Campelo M, Thepot S, Ades L, Sperr WR, Valent P, Fenaux P, Sekeres MA, Greil R, Pleyer L (April 2017). "Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study". Int J Mol Sci. 18 (4). doi:10.3390/ijms18040837. PMC 5412421. PMID 28420120.
  11. ↑ Srinivas U, Kumar R, Pati H, Saxena R, Tyagi S (October 2007). "Sub classification and clinico-hematological correlation of 40 cases of acute erythroleukemia - can proerythroblast/myeloblast and proerythroblast/total erythroid cell ratios help subclassify?". Hematology. 12 (5): 381–5. doi:10.1080/10245330701393816. PMID 17852448.
  12. ↑ Zuo Z, Polski JM, Kasyan A, Medeiros LJ (September 2010). "Acute erythroid leukemia". Arch. Pathol. Lab. Med. 134 (9): 1261–70. doi:10.1043/2009-0350-RA.1. PMID 20807044.
  13. ↑ Peng J, Hasserjian RP, Tang G, Patel KP, Goswami M, Jabbour EJ, Garcia-Manero G, Medeiros LJ, Wang SA (2016). "Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response". Leuk. Lymphoma. 57 (4): 812–9. doi:10.3109/10428194.2015.1079318. PMID 26293512.
  14. ↑ Lessard M, Struski S, Leymarie V, Flandrin G, Lafage-Pochitaloff M, Mozziconacci MJ, Talmant P, Bastard C, Charrin C, Baranger L, Hélias C, Cornillet-Lefebvre P, Mugneret F, Cabrol C, Pagès MP, Fert-Ferret D, Nguyen-Khac F, Quilichini B, Barin C, Berger R (December 2005). "Cytogenetic study of 75 erythroleukemias". Cancer Genet. Cytogenet. 163 (2): 113–22. doi:10.1016/j.cancergencyto.2005.05.006. PMID 16337853.
  15. ↑ Grossmann V, Bacher U, Haferlach C, Schnittger S, Pötzinger F, Weissmann S, Roller A, Eder C, Fasan A, Zenger M, Staller M, Kern W, Kohlmann A, Haferlach T (September 2013). "Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics". Leukemia. 27 (9): 1940–3. doi:10.1038/leu.2013.144. PMID 23648669.
  16. ↑ Hefti E, Blanco JG (2016). "Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and Down Syndrome: A Literature Review". Cardiovasc Toxicol. 16 (1): 5–13. doi:10.1007/s12012-015-9307-1. PMC 4514565. PMID 25616318.
  17. ↑ Armenian SH, Gelehrter SK, Vase T, Venkatramani R, Landier W, Wilson KD, Herrera C, Reichman L, Menteer JD, Mascarenhas L, Freyer DR, Venkataraman K, Bhatia S (December 2014). "Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors". Clin. Cancer Res. 20 (24): 6314–23. doi:10.1158/1078-0432.CCR-13-3490. PMC 4268342. PMID 24947931.
  18. ↑ Oehadian A, Iqbal M, Sumantri R (October 2009). "Deep vein thrombosis in acute myelogenous leukemia". Acta Med Indones. 41 (4): 200–4. PMID 20124617.
  19. ↑ Vallipuram J, Dhalla S, Bell CM, Dresser L, Han H, Husain S, Minden MD, Paul NS, So M, Steinberg M, Vallipuram M, Wong G, Morris AM (April 2017). "Chest CT scans are frequently abnormal in asymptomatic patients with newly diagnosed acute myeloid leukemia". Leuk. Lymphoma. 58 (4): 834–841. doi:10.1080/10428194.2016.1213825. PMID 27642861.
  20. ↑ Chen CY, Tai CH, Cheng A, Wu HC, Tsay W, Liu JH, Chen PY, Huang SY, Yao M, Tang JL, Tien HF (August 2012). "Intracranial hemorrhage in adult patients with hematological malignancies". BMC Med. 10: 97. doi:10.1186/1741-7015-10-97. PMC 3482556. PMID 22931433.
  21. ↑ Cervantes GM, Cayci Z (May 2015). "Intracranial CNS Manifestations of Myeloid Sarcoma in Patients with Acute Myeloid Leukemia: Review of the Literature and Three Case Reports from the Author's Institution". J Clin Med. 4 (5): 1102–12. doi:10.3390/jcm4051102. PMC 4470219. PMID 26239467.
  22. ↑ Sharma A, Buxi G, Walia R, Yadav RB, Sharma S (2011). "Childhood acute erythroleukemia diagnosis by flow cytometry". Indian J Pathol Microbiol. 54 (1): 173–5. doi:10.4103/0377-4929.77395. PMID 21393910.
  23. ↑ Atkinson J, Hrisinko MA, Weil SC (December 1992). "Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature". Blood Rev. 6 (4): 204–14. PMID 1486289.
  24. ↑ 24.0 24.1 Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, Pinto R, Maurillo L, Wetzel J, Musto P, Van De Loosdrecht AA, Costa MJ, Esteves S, Burgstaller S, Stauder R, Autzinger EM, Lang A, Krippl P, Geissler D, Falantes JF, Pedro C, Bargay J, Deben G, Garrido A, Bonanad S, Diez-Campelo M, Thepot S, Ades L, Sperr WR, Valent P, Fenaux P, Sekeres MA, Greil R, Pleyer L (April 2017). "Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study". Int J Mol Sci. 18 (4). doi:10.3390/ijms18040837. PMC 5412421. PMID 28420120.
  25. ↑ Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR (February 2010). "Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia". J. Clin. Oncol. 28 (4): 562–9. doi:10.1200/JCO.2009.23.8329. PMID 20026804.
  26. ↑ Oran B, de Lima M (November 2011). "Prevention and treatment of acute myeloid leukemia relapse after allogeneic stem cell transplantation". Curr. Opin. Hematol. 18 (6): 388–94. doi:10.1097/MOH.0b013e32834b6158. PMID 21897227.


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