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__NOTOC__
{{Leukemia}}
'''For patient information click [[Leukemia (patient information)|here]]'''
'''For patient information click [[Leukemia (patient information)|here]]'''
__NOTOC__
{{DiseaseDisorder infobox |
  Name          = Leukemia |
  ICD10          = {{ICD10|C|91||c|81}}-{{ICD10|C|95||c|81}} |
  ICD9          = {{ICD9|208.9}} |
  ICDO          = 9800-9940 |
  Image          = acute_leukemia-ALL.jpg |
  Caption        = A Wright's stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia.|
  OMIM          = |
  MedlinePlus    = |
  eMedicineSubj  = |
  eMedicineTopic = |
  DiseasesDB    = 7431 |
  MeshID        = D007938 |
}}


{{CMG}}; {{AE}} {{SMP}}, {{USAMA}}, {{SSH}}; {{GRR}} {{Nat}}


{{CMG}}
{{SK}} Leukaemia
{{Leukemia}}
{{Editor Join}}


==Overview==
==Overview==
'''Leukemia''' or '''leukaemia''' (Greek leukos, “white”; haima, “blood”) is a [[cancer]] of the [[blood]] or [[bone marrow]] and is characterized by an abnormal proliferation (production by multiplication) of blood [[Cell (biology)|cells]], usually white blood cells ([[leukocytes]]). It is part of the broad group of diseases called [[Hematological malignancy|hematological neoplasms]].
'''Leukemia''' (Greek leukos, “white”; haima, “blood”) can be defined as a group of [[hematopoietic stem cell]] [[malignancies]] due to [[genetic]] abnormalities that may lead to clonal proliferation of these cells. These group of diseases are classified based on the type of [[hematopoietic stem cell]] involved and the duration of the disease. The leukemias are the most common malignancies among children younger than 15 years. Among them, [[ALL|Acute Lymphoblastic Leukemia (ALL)]] is the most common leukemia and accounts for 77% of childhood leukemia. However, [[CLL|Chronic Lymphocytic Leukemia (CLL)]] is the most common form of leukemia in adults, and it accounts for 30% of all leukemias in the United States. The increased rate of proliferation and decreased rate of [[apoptosis]] in this progeny of cells may compromise normal [[bone marrow]] function and ultimately result in marrow failure. Clinical manifestations, diagnosis, laboratory findings, and therapy are different according to the type of malignancy.


==Symptoms==
==Classification==
Damage to the [[bone marrow]], by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood [[platelet]]s, which are important in the [[Coagulation of human blood|blood clotting]] process. This means people with leukemia may become [[purpura|bruised]], [[hemorrhage|bleed]] excessively, or develop pinprick bleeds ([[petechia]]e).


[[White blood cell]]s, which are involved in fighting [[pathogen]]s, may be suppressed or dysfunctional. This could cause the patient's immune system (white blood cells etc.) to start attacking other body cells.
Leukemia may be classified as follows:
<br><br>
{{Family tree/start}}
{{Family tree | | | | | | | | | B01 | | | |B01= Leukemia}}
{{Family tree | | | | |,|-|-|-|-|^|-|-|-|-|.| | }}
{{Family tree | | | | C01 | | | | | | | | C02 |C01= Lymphoid progeny| C02= Myeloid progeny}}
{{Family tree | |,|-|-|^|-|-|.| | | |,|-|-|^|-|-|.| | }}
{{Family tree | D01 | | | | D02 | | D03 | | | | D04 | D01= [[Acute lymphoblastic leukemia]] (ALL) | D02= [[Chronic lymphocytic leukemia]] (CLL) | D03= [[Acute Myeloid Leukemia]] (AML) | D04= [[Chronic myeloid leukemia]] (CML)}}
{{Family tree/end}}
<br><br><br>


Finally, the red blood cell deficiency leads to [[anemia]], which may cause [[dyspnea]]. All symptoms can be attributed to other diseases; for [[diagnosis]], [[blood test]]s and a [[bone marrow examination]] are required.
==Differentiating Leukemia from other Diseases==
Leukemia must be differentiated from various diseases that cause [[weight loss]],  [[night sweats]], [[hepatosplenomegaly]], and palpable [[lymph node]]s, such as [[hairy cell leukaemia|hairy cell leukemia]], prolymphocytic leukemia, [[follicular lymphoma]], and [[mantle cell lymphoma]]. Based on the expression of cell surface markers, the table below differentiates different types of leukemia from other diseases that cause similar clinical presentations:<ref name="H">Hoffbrand V, Moss P. Essential Haematology. John Wiley & Sons; 2011</ref>


Some other related symptoms:
{|
{{div col}}
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
* [[Fever]], [[chills]], [[night sweat]]s and other [[flu]]-like symptoms
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology
* [[Weakness]] and [[fatigue]]
! colspan="4" align="center" style="background:#4479BA; color: #FFFFFF;" + |Clinical Manifestation
* Swollen or bleeding gums
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory Findings
* Neurological symptoms ([[headache]]s)
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Gold standard diagnosis
* [[hepatomegaly|Enlarged liver]] and [[splenomegaly|spleen]]
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
* Frequent [[infection]]
|-
* Bone pain
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Demography
* [[Joint pain]]
! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
* [[Dizziness]]
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Symptoms
* [[Nausea]]
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs
* Swollen [[tonsils]]
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Lab
* [[Diarrhea]]
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
* [[Paleness]]
|-
* [[Malaise]]
! align="center" style="background:#DCDCDC;" + |[[Acute myelogenous leukemia]]<ref name="pmid30410824">{{cite journal |vauthors=Saif A, Kazmi SFA, Naseem R, Shah H, Butt MO |title=Acute Myeloid Leukemia: Is That All There Is? |journal=Cureus |volume=10 |issue=8 |pages=e3198 |date=August 2018 |pmid=30410824 |doi=10.7759/cureus.3198 |url=}}</ref><ref name="pmid23526416">{{cite journal |vauthors=Estey EH |title=Acute myeloid leukemia: 2013 update on risk-stratification and management |journal=Am. J. Hematol. |volume=88 |issue=4 |pages=318–27 |date=April 2013 |pmid=23526416 |doi=10.1002/ajh.23404 |url=}}</ref>
* Unintentional [[Weight_loss#Unintentional_weight_loss | weight loss]]
| align="left" style="background:#F5F5F5;" + |
{{div col end}}
* Clonal proliferation of malignant myeloid blast cells in the [[bone marrow]]
* Genetic abnormalities t(8;21), inv(16), and t(15;17)
| align="left" style="background:#F5F5F5;" + |
* The most common leukemia in adults
* Median age of 63 years old
| align="left" style="background:#F5F5F5;" + |
* [[Smoking]], previous [[chemotherapy]] or [[radiation therapy]], [[myelodysplastic syndrome]], and exposure to the chemical [[benzene]]
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Bleeding]]
| align="left" style="background:#F5F5F5;" + |
* Bone [[tenderness]]
* [[Dyspnea]]
* Leukemia cutis
* Swelling of the [[Gingiva|gums]]
* Chloroma
* Rare LAP
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Leukocytosis]] or [[leukopenia]]
| align="left" style="background:#F5F5F5;" + |
* Leukemic blasts
* Positive [[Auer rod|Auer rods]]
| align="left" style="background:#F5F5F5;" + |
* [[Flow cytometry]] > 20% blasts of [[myeloid]] lineage
| align="left" style="background:#F5F5F5;" + |
* Persistent or frequent [[infections]]
* Fatal within weeks or months if left untreated
* [[Down syndrome]] or [[Bloom syndrome]]
|-
! align="center" style="background:#DCDCDC;" + |[[Acute lymphoblastic leukemia]]<ref name="pmid30302234">{{cite journal |vauthors=Sawalha Y, Advani AS |title=Management of older adults with acute lymphoblastic leukemia: challenges & current approaches |journal=Int J Hematol Oncol |volume=7 |issue=1 |pages=IJH02 |date=March 2018 |pmid=30302234 |pmc=6176956 |doi=10.2217/ijh-2017-0023 |url=}}</ref><ref name="pmid23841506">{{cite journal |vauthors=Portell CA, Advani AS |title=Novel targeted therapies in acute lymphoblastic leukemia |journal=Leuk. Lymphoma |volume=55 |issue=4 |pages=737–48 |date=April 2014 |pmid=23841506 |doi=10.3109/10428194.2013.823493 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Arrest of  [[lymphoblasts]]
* Chromosomal translocations: t(9;22) , t(12;21), t(5;14), t(1;19)
| align="left" style="background:#F5F5F5;" + |
* The most common  cancer in children
*Peak 2-5 years of age
*Boys > girls
| align="left" style="background:#F5F5F5;" + |
* History of [[cancer]]
* History of drug exposure
| align="left" style="background:#F5F5F5;" + |
* Generalized [[weakness]]
* [[Fatigue]]
* [[Bleeding]]
| align="left" style="background:#F5F5F5;" + |
* [[Hepatosplenomegaly]]
* [[Lymphadenopathy|LAP]]
* [[Dyspnea]]
* [[Pallor]]
* [[Papilledema]]
* [[Meningism|Nuchal rigidity]]
* [[Cranial nerve palsy]]
* [[Testicle|Testicular]] enlargement
* [[Mediastinal mass]]
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[Thrombocytopenia]] 
* Normal or slightly increased [[White blood cells|WBC]] counts 
| align="left" style="background:#F5F5F5;" + |
* [[Lymphoblast|Lymphoblasts]]
* Atypical cells
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[CNS]] involvement
|-
! align="center" style="background:#DCDCDC;" + |[[Chronic myelogenous leukemia]]<ref name="pmid25814082">{{cite journal |vauthors=Saußele S, Silver RT |title=Management of chronic myeloid leukemia in blast crisis |journal=Ann. Hematol. |volume=94 Suppl 2 |issue= |pages=S159–65 |date=April 2015 |pmid=25814082 |doi=10.1007/s00277-015-2324-0 |url=}}</ref><ref name="pmid30285354">{{cite journal |vauthors=Eden RE, Coviello JM |title= |journal= |volume= |issue= |pages= |date= |pmid=30285354 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Dysregulated production and uncontrolled proliferation of mature and maturing [[Granulocyte|granulocytes]]
* [[BCR/ABL|BCR-ABL1]] fusion gene
* [[Dominance relationship|Autosomal dominant]] mutation
| align="left" style="background:#F5F5F5;" + |
* Median age 50 years old
| align="center" style="background:#F5F5F5;" + |
| align="left" style="background:#F5F5F5;" + |
* Generalized weakness
* [[Fatigue]]
* [[Satiety|Early satiety]]
* Abdominal fullness
* Bleeding
| align="left" style="background:#F5F5F5;" + |
*Asymptomatic
*[[Blast crisis]]
*Excessive [[Perspiration|sweating]]
* [[Papilledema]]
* [[Tenderness]] over the lower [[sternum]]
* [[Hepatosplenomegaly]]
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[White blood cells|WBC]] > 100,000/microL
* Absolute [[basophilia]] and [[eosinophilia]]
* [[Platelet|Plt]] > 600,000 to 700,000/microL
* Low [[leukocyte alkaline phosphatase]]
* High [[uric acid]]
| align="left" style="background:#F5F5F5;" + |
* All cells of the neutrophilic series, from [[Myeloblast|myeloblasts]] to mature [[Neutrophil|neutrophils]]
* [[Myelocyte]] bulge
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" + |
* Acute [[Gout|gouty arthritis]]
* Venous obstruction
|-
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Demography
! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Lab
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Gold standard diagnosis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
|-
! align="center" style="background:#DCDCDC;" + |'''[[Chronic lymphocytic leukemia]]'''<ref name="pmid266906142">{{cite journal |vauthors=Rai KR, Jain P |title=Chronic lymphocytic leukemia (CLL)-Then and now |journal=Am. J. Hematol. |volume=91 |issue=3 |pages=330–40 |date=March 2016 |pmid=26690614 |doi=10.1002/ajh.24282 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Progressive accumulation of monoclonal [[B cell|B lymphocytes]]
| align="left" style="background:#F5F5F5;" + |
* The most common leukemia in adults in western countries
* M > F
* Median age 70 years old
| align="left" style="background:#F5F5F5;" + |
* Positive family history
* Exposure to [[Herbicide|herbicides]] or [[Insecticide|insecticides]]
| align="left" style="background:#F5F5F5;" + |
* Bleeding
* Abdominal pain
* Generalized [[weakness]]
* [[Anorexia]]
| align="left" style="background:#F5F5F5;" + |
* LAP (Most common sign)
* [[Hepatosplenomegaly]]
* [[Skin lesion|Skin lesions]] (leukemia cutis)
* [[Sleep hyperhidrosis|Night sweats]]
* [[Muscle wasting]]
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[Thrombocytopenia]]
* Absolute [[lymphocytosis]] >5000 cells/μl
* [[Neutropenia]]
* Positive direct Coombs test
* [[Hypogammaglobulinemia]]
* Elevated [[lactate dehydrogenase]] and [[beta-2 microglobulin]]
| align="left" style="background:#F5F5F5;" + |
* Presence of smudge cells
* Monoclonality of [[Light chain|kappa]] and [[Lambda (anatomy)|lambda]] producing [[B cell|B cells]]
* Express [[CD19]], [[CD20]], [[CD23]], and [[CD5]] on the [[cell]] surface
| align="left" style="background:#F5F5F5;" + |
* [[Flow cytometry]] of the [[Venous blood|peripheral blood]]
| align="left" style="background:#F5F5F5;" + |
* Extranodal involvement of [[skin]], [[kidney]], [[lung]], [[Spinal cord|spine]]
* [[Membranoproliferative glomerulonephritis]]
* [[Autoimmune hemolytic anemia]]
|-
! align="center" style="background:#DCDCDC;" + |[[Hairy cell leukemia]]<ref name="pmid29110361">{{cite journal |vauthors=Troussard X, Cornet E |title=Hairy cell leukemia 2018: Update on diagnosis, risk-stratification, and treatment |journal=Am. J. Hematol. |volume=92 |issue=12 |pages=1382–1390 |date=December 2017 |pmid=29110361 |pmc=5698705 |doi=10.1002/ajh.24936 |url=}}</ref><ref name="pmid29118233">{{cite journal |vauthors=Wierda WG, Byrd JC, Abramson JS, Bhat S, Bociek G, Brander D, Brown J, Chanan-Khan A, Coutre SE, Davis RS, Fletcher CD, Hill B, Kahl BS, Kamdar M, Kaplan LD, Khan N, Kipps TJ, Lancet J, Ma S, Malek S, Mosse C, Shadman M, Siddiqi T, Stephens D, Wagner N, Zelenetz AD, Dwyer MA, Sundar H |title=Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology |journal=J Natl Compr Canc Netw |volume=15 |issue=11 |pages=1414–1427 |date=November 2017 |pmid=29118233 |doi=10.6004/jnccn.2017.0165 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Accumulation of small mature [[B cell]] lymphoid cells with abundant [[cytoplasm]] and "hairy" projections
* [[BRAF]] mutation
| align="left" style="background:#F5F5F5;" + |
* Uncommon
* Median age 50 to 55 years old
* M >> F
* More common in Caucasians than Blacks
| align="left" style="background:#F5F5F5;" + |
* Exposures to [[ionizing radiation]], [[Pesticide|pesticides]], and farming
| align="left" style="background:#F5F5F5;" + |
* Generalized weakness
* [[Fatigue]]
* [[Satiety|Early satiety]]
* Abdominal fullness
* Bleeding
| align="left" style="background:#F5F5F5;" + |
* Asymptomatic
* [[Splenomegaly]]
* Spontaneous [[splenic rupture]]
* [[Rash|Skin rash]]
* [[Ascites]]
* [[Pleural effusion]]
| align="left" style="background:#F5F5F5;" + |
* [[Cytopenia]]
* [[Leukocytosis]] in 10 to 20 percent
* [[Azotemia]]
* Abnormal [[liver function tests]]
* [[Hypergammaglobulinemia]]
| align="left" style="background:#F5F5F5;" + |
* [[Pancytopenia]] with [[monocytopenia]] and circulating tumor cells characteristic of HCL
* Dry [[bone marrow]]
| align="left" style="background:#F5F5F5;" + |
* Analysis of [[Venous blood|peripheral blood]] + [[immunophenotyping]] by [[flow cytometry]]
| align="left" style="background:#F5F5F5;" + |
* [[Vasculitis]]
|-
! align="center" style="background:#DCDCDC;" + |Large granular lymphocytic leukemia<ref name="pmid28128670">{{cite journal |vauthors=Matutes E |title=Large granular lymphocytic leukemia. Current diagnostic and therapeutic approaches and novel treatment options |journal=Expert Rev Hematol |volume=10 |issue=3 |pages=251–258 |date=March 2017 |pmid=28128670 |doi=10.1080/17474086.2017.1284585 |url=}}</ref><ref name="pmid28717070">{{cite journal |vauthors=Oshimi K |title=Clinical Features, Pathogenesis, and Treatment of Large Granular Lymphocyte Leukemias |journal=Intern. Med. |volume=56 |issue=14 |pages=1759–1769 |date=2017 |pmid=28717070 |pmc=5548667 |doi=10.2169/internalmedicine.56.8881 |url=}}</ref>​
| align="left" style="background:#F5F5F5;" + |
* Clonal proliferation of [[Cytotoxic T cell|cytotoxic T cells]]
* Dysregulation of [[apoptosis]] through abnormalities in the Fas/Fas ligand pathway
| align="left" style="background:#F5F5F5;" + |
* Rare
* Median age 60 years
* M = F
| align="left" style="background:#F5F5F5;" + |
* Autoimmune diseases
* [[Lymphoproliferative disorders|Lymphoproliferative]] disorders
| align="left" style="background:#F5F5F5;" + |
* Generalized [[weakness]]  
* [[Fatigue]]
| align="left" style="background:#F5F5F5;" + |
* Mostly asymptomatic
| align="left" style="background:#F5F5F5;" + |
* Modest [[lymphocytosis]]
* [[Neutropenia]]
* [[Anemia]]
* [[Thrombocytopenia]]
| align="left" style="background:#F5F5F5;" + |
* Large [[Lymphocyte|lymphocytes]] with a condensed round or oval nucleus, abundant pale basophilic cytoplasm, and small azurophilic granules
| align="left" style="background:#F5F5F5;" + |
* Biopsy and flow cytometry + T-cell receptor gene rearrangement studies
| align="left" style="background:#F5F5F5;" + |
* Recurrent bacterial infection
|-
! align="center" style="background:#DCDCDC;" + |[[Chronic neutrophilic leukemia]]<ref name="pmid29512199">{{cite journal |vauthors=Elliott MA, Tefferi A |title=Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management |journal=Am. J. Hematol. |volume=93 |issue=4 |pages=578–587 |date=August 2018 |pmid=29512199 |doi=10.1002/ajh.24983 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Mature granulocytic proliferation in the blood and [[bone marrow]]
* Point mutations in the [[CSF3R]] gene
| align="left" style="background:#F5F5F5;" + |
* Very rare
* M = F
| align="left" style="background:#F5F5F5;" + |
* [[Multiple myeloma]]
| align="left" style="background:#F5F5F5;" + |
* Generalized [[weakness]]
* [[Fatigue]]
| align="left" style="background:#F5F5F5;" + |
* [[Hepatosplenomegaly]]
* [[Pruritus]]
* [[Gout]]
| align="left" style="background:#F5F5F5;" + |
* Peripheral blood [[neutrophilia]] (> 25 x 10<sup>9</sup>/L) with myeloid precursors (promyelocytes, myelocytes, metamyelocytes)
* Elevated [[leukocyte alkaline phosphatase]]
| align="left" style="background:#F5F5F5;" + |
* Toxic granulation in the [[Neutrophil|neutrophils]]
* Nuclear hypersegmentation
* Increased myeloid:erythroid ratio > 20:1
| align="left" style="background:#F5F5F5;" + |
* [[World Health Organization|WHO]] diagnostic criteria include leukocytosis of ≥ 25 x 109/L
* More than 80% neutrophils,
* Less than 10% circulating neutrophil precursors with blasts
| align="left" style="background:#F5F5F5;" + |
* Poor prognosis
* Absence of the Philadelphia chromosome or a BCR/ABL fusion gene
|-
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Demography
! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Lab
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Gold standard diagnosis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
|-
! align="center" style="background:#DCDCDC;" + |[[Chronic eosinophilic leukemia]]
| align="left" style="background:#F5F5F5;" + |
* There is no known cause for chronic eosinophilic leukemia.
* It hasn't been linked to a specific chromosome or genetic abnormality.
| align="left" style="background:#F5F5F5;" + |
* Unknown
| align="left" style="background:#F5F5F5;" + |
* Unknown
| align="left" style="background:#F5F5F5;" + |
* Constitutional
* [[Rash]]
* [[Rhinitis]]
* [[Gastritis]]
* [[Thromboembolism]]<nowiki/>related
| align="left" style="background:#F5F5F5;" + |
* [[Hypertension]]
* [[Eczema]], [[mucosal]][[ulcers]], [[erythema]]
* [[Angioedema]]


The word leukemia, which means 'white blood,' is derived from the disease's namesake high white blood cell counts that most leukemia patients have before treatment.  The high number of white blood cells are apparent when a blood sample is viewed under a microscope.  Frequently, these extra white blood cells are immature or dysfunctional.  The excessive number of cells can also interfere with the normal function of other cells.
* [[Ataxia]]
* [[Anemia]]
* [[Lymphadenopathy]]
* [[Hepatosplenomegaly]]
| align="left" style="background:#F5F5F5;" + |
*[[Leukocytosis]] with left shift
*[[Eosinophilia]]
*[[Basophilia]]
*[[Monocytosis]]
*[[Anemia]]
*[[Thrombocytopenia]]
*↑ [[B12]] levels
*↑ [[LDH]]


Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called '''aleukemia'''. The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells. However, the leukemic cells are staying in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or lowAleukemia can occur in any of the four major types of leukemia, and is particularly common in [[hairy cell leukemia]].
| align="left" style="background:#F5F5F5;" + |
* Hypercelluar with ↑ [[eosinophilic]]<nowiki/> precursors, ↑ [[eosinophils]], and atypical [[mononuclear cells]]
| align="left" style="background:#F5F5F5;" + |
| align="left" style="background:#F5F5F5;" + |
*[[Heart failure]] [[Lung fibrosis]]
*[[Encephalopathy]]
*Erythema annulare centrifugam
|-
! align="center" style="background:#DCDCDC;" + |[[Chronic monocytic leukemia electrocardiogram|Chronic monocytic leukemia]]
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|-
! align="center" style="background:#DCDCDC;" + |[[Prolymphocytic leukemia]] (PLL)
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! align="center" style="background:#DCDCDC;" + |[[T-cell large granular lymphocyte leukemia|T-cell large granular lymphocytic leukemia]] (TLGL)
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! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Demography
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! align="center" style="background:#4479BA; color: #FFFFFF;" + |Symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs
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! align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Gold standard diagnosis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
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! align="center" style="background:#DCDCDC;" + |[[Aggressive NK-cell leukemia]] (ANKL)
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! align="center" style="background:#DCDCDC;" + |[[Adult T-cell leukemia|Adult T-cell leukemia/lymphoma]] (ATLL)<ref name="wiki1">Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015</ref><ref name="pmid18042693">{{cite journal |vauthors=Matutes E |title=Adult T-cell leukaemia/lymphoma |journal=J. Clin. Pathol. |volume=60 |issue=12 |pages=1373–7 |year=2007 |pmid=18042693 |pmc=2095573 |doi=10.1136/jcp.2007.052456 |url=}}</ref><ref name="wiki">Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015</ref><ref name="pmid20425378">{{cite journal| author=Mahieux R, Gessain A| title=Adult T-cell leukemia/lymphoma and HTLV-1. | journal=Curr Hematol Malig Rep | year= 2007 | volume= 2 | issue= 4 | pages= 257-64 | pmid=20425378 | doi=10.1007/s11899-007-0035-x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20425378  }}</ref><ref name="wiki2">Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015</ref><ref name="pmid180426932">{{cite journal| author=Matutes E| title=Adult T-cell leukaemia/lymphoma. | journal=J Clin Pathol | year= 2007 | volume= 60 | issue= 12 | pages= 1373-7 | pmid=18042693 | doi=10.1136/jcp.2007.052456 | pmc=PMC2095573 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18042693 }}</ref>
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* Adult T-cell leukemia is caused by an infection with [[HTLV]].
* Common [[genetic mutation]]s involved in the development of adult T-cell leukemia can be found [[Adult T-cell leukemia pathophysiology|here]].


==Classification==
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Leukemia is clinically and pathologically subdivided into several large groups. The first division is between its ''[[Acute (medical)|acute]]'' and ''[[chronic (medicine)|chronic]]'' forms:
* The incidence of adult T-cell leukemia increases with age, and the median age at diagnosis is 57 years.
* ''[[Acute leukemia]]'' is characterized by the rapid increase of immature blood cells. This crowding makes the bone marrow unable to produce healthy blood cells. Acute forms of leukemia can occur in children and young adults. (In fact, it is a more common cause of death for children in the [[United States|US]] than any other type of malignant disease). Immediate treatment is required in acute leukemias due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Central nervous system (CNS) involvement is uncommon, although the disease can occasionally cause cranial nerve palsies.
* Males are more commonly affected with adult T-cell leukemia than females.  
* ''[[Chronic leukemia]]'' is distinguished by the excessive build up of relatively mature, but still abnormal, blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy.
* The male to female ratio is approximately 1.4 to 1.
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:* [[Abdominal pain]]
:* [[Constipation]]
:* [[Nausea]] and [[vomiting]]
:* [[Fatigue]]
:* Generalized [[weakness]]
:* [[Cough]]
:* Recurrent [[infection]]s
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:* [[Fever]]
:* [[Weight loss]]
:* Recurrent [[bleeding]]
:* [[Anorexia]]
:* [[Night sweat]]s
:* [[Bone pain]]
:* [[Hypercalcemia]]
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! align="center" style="background:#DCDCDC;" + |[[Sezary syndrome]]<ref name="pmid21883142">{{cite journal |vauthors=Wong HK, Mishra A, Hake T, Porcu P |title=Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome) |journal=Br. J. Haematol. |volume=155 |issue=2 |pages=150–66 |date=October 2011 |pmid=21883142 |pmc=4309373 |doi=10.1111/j.1365-2141.2011.08852.x |url=}}</ref><ref name="pmid27121473">{{cite journal |vauthors=Woollard WJ, Pullabhatla V, Lorenc A, Patel VM, Butler RM, Bayega A, Begum N, Bakr F, Dedhia K, Fisher J, Aguilar-Duran S, Flanagan C, Ghasemi AA, Hoffmann RM, Castillo-Mosquera N, Nuttall EA, Paul A, Roberts CA, Solomonidis EG, Tarrant R, Yoxall A, Beyers CZ, Ferreira S, Tosi I, Simpson MA, de Rinaldis E, Mitchell TJ, Whittaker SJ |title=Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome |journal=Blood |volume=127 |issue=26 |pages=3387–97 |date=June 2016 |pmid=27121473 |doi=10.1182/blood-2016-02-699843 |url=}}</ref><ref name="pmid266071833">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref><ref name="pmid25386354">{{cite journal |vauthors=Horesh N, Horowitz NA |title=Does gender matter in non-hodgkin lymphoma? Differences in epidemiology, clinical behavior, and therapy |journal=Rambam Maimonides Med J |volume=5 |issue=4 |pages=e0038 |date=October 2014 |pmid=25386354 |pmc=4222427 |doi=10.5041/RMMJ.10172 |url=}}</ref><ref name="pmid24421750">{{cite journal |vauthors=Al Hothali GI |title=Review of the treatment of mycosis fungoides and Sézary syndrome: A stage-based approach |journal=Int J Health Sci (Qassim) |volume=7 |issue=2 |pages=220–39 |date=June 2013 |pmid=24421750 |pmc=3883611 |doi= |url=}}</ref><ref name="pmid266071835">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref><ref name="pmid231971992">{{cite journal |vauthors=Yamashita T, Abbade LP, Marques ME, Marques SA |title=Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update |journal=An Bras Dermatol |volume=87 |issue=6 |pages=817–28; quiz 829–30 |date=2012 |pmid=23197199 |pmc=3699909 |doi= |url=}}</ref><ref name="pmid23074497">{{cite journal |vauthors= |title=Extracorporeal photophoresis: an evidence-based analysis |journal=Ont Health Technol Assess Ser |volume=6 |issue=6 |pages=1–82 |date=2006 |pmid=23074497 |pmc=3379535 |doi= |url=}}</ref>
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* The cause of Sezary syndrome has not been identified.
* Sezary syndrome might have one or more of the [[chromosomal]] [[abnormalities]], such as the loss or gain of [[Genetics|genetic]].
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* The prevalence of Sezary syndrome is exact unknown.
*The median age at diagnosis of [[Sézary syndrome]] is 60 years of age.
*Sezary syndrome is more commonly observed among [[Old age|elderly]] [[Patient|patients]].
*[[Male|Males]] are more commonly affected with Sezary syndrome than [[Female|females]](2:1).
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*The majority of sezary syndrome [[Patient|patients]] present with developing [[lymphadenopathy]] and [[erythroderma]] for weeks to months.
*Early clinical features of Sezary syndrome include:
:*Mimic [[psoriasis]]
:*[[Chronic (medical)|Chronic]] [[eczema]]
:*[[Atopic dermatitis (patient information)|Atopic dermatitis]]
:*[[Leprosy]]
:*Lichenoid [[pityriasis]]
*In Sezary syndrome single or multiple [[Lesion|lesions]] (thin [[erythematous]] [[Plaque|plaques]] or flat patch) is a typical [[skin]] involvement  in the [[gluteal]] region or [[Thigh|thighs]]. <ref name="Olsen2015">{{cite journal|last1=Olsen|first1=Elise A.|title=Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma|journal=Dermatologic Clinics|volume=33|issue=4|year=2015|pages=643–654|issn=07338635|doi=10.1016/j.det.2015.06.001}}</ref>
*[[Patient|Patients]] with Sezary syndrome  often have a history of several years of [[Eczema|eczematous]] or [[dermatitis]] [[skin]] [[Lesion|lesions]] before the [[diagnosis]] is finally established.
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* Widespread [[erythema]]
** In Sezary syndrome widespread [[erythema]] can be finely scaly, indurated, or even resemble livido [[reticularis]]
* Indurated
* Resemble livido [[reticularis]]
* [[Erythema]](Not seen in some [[Patient|patients]])
* The severity of [[erythema]] [[body surface area]] (BSA) involved may wax and wane(>80% of BSA)


Additionally, the diseases are subdivided according to which kind of blood cell is affected.  This split divides leukemias into lymphoblastic or ''[[lymphocytic leukemia]]s'' and myeloid or ''[[myelogenous leukemia]]s'':
* Patches and [[Plaque|plaques]] to [[erythroderma]]
* [[Keratosis pilaris]]
* [[Alopecia]] ([[hair loss]])
* [[Ectropion]]
* [[Keratoderma]]
* [[Hypertrophy (medical)|Hypertrophic]] [[Nail (anatomy)|nails]]
* Erosions
* [[Lichenification]]
* [[Trouble]] regulating [[Body Temperature|body temperature]]
* [[Abnormal|Abnormalities]] of [[fingernails]] and [[toenails]]


* In lymphoblastic or ''[[lymphocytic leukemia]]s'', the cancerous change takes place in a type of marrow cell that normally goes on to form [[lymphocyte]]s.
* [[Lymphadenopathy]]
* In myeloid or ''[[myelogenous leukemia]]s'', the cancerous change takes place in a [[myeloid cells|type of marrow cell]] that normally goes on to form red cells, some types of white cells, and [[platelets]].
* [[Viscera|Viscer]]
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! align="center" style="background:#DCDCDC;" + |[[Myelodysplastic syndrome]]
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*Constitutional symptoms
*[[Bleeding]]
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*[[Pallor]]
*[[Petechiae]]
*[[Organomegaly]]
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* [[Pancytopenia]]
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*Hypercellular/ normocellular [[bone marrow]] with [[Dysplastic change|dysplastic]] changes
*Macro-ovalocytes
*Basophilic stippling
*[[Howell-Jolly body]]
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*[[Leukemia]] transformation
*Acquired pseudo-Pelger-Huët anomaly
*Infection
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! align="center" style="background:#DCDCDC;" + |[[Myeloproliferative disorders]]
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! align="center" style="background:#DCDCDC;" + |[[Leukemoid reaction]]
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Combining these two classifications provides a total of four main categories:
==Epidemiology and Demographics==
===Prevalence===


{| class="wikitable"
* In the United States, the age-adjusted [[prevalence]] of leukemia is 75.3 per 100,000 in 2011.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
|+Four major kinds of leukemia
! Cell type !! Acute !! Chronic
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| '''Lymphocytic leukemia''' <br />(or "lymphoblastic") || [[Acute lymphoblastic leukemia]] (ALL) || [[Chronic lymphocytic leukemia]] (CLL)
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| '''Myelogenous leukemia''' <br />(also "myeloid" or "nonlymphocytic") || [[Acute myeloid leukemia|Acute myelogenous leukemia]] (AML) || [[Chronic myelogenous leukemia]] (CML)
|}


Within these main categories, there are typically several subcategories. Finally, [[hairy cell leukemia]] is usually considered to be outside of this classification scheme.
===Incidence===


* ''Acute lymphoblastic leukemia'' (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older.  Standard treatments involve chemotherapy and radiation.  The survival rates vary by age:  85% in children and 50% in adults.<ref>[http://www.accessmedicine.com/content.aspx?aID=65842 Harrison's Principles of Internal Medicine, 16th Edition,] Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.</ref>
* The delay-adjusted [[incidence]] of leukemia in 2011 was estimated as 15.48 per 100,000 individuals in the United States.


* ''Chronic lymphocytic leukemia'' (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children. Two-thirds of affected people are men. The five-year survival rate is 75%.<ref>[http://seer.cancer.gov/statfacts/html/clyl.html Finding Cancer Statistics » Cancer Stat Fact Sheets »Chronic Lymphocytic Leukemia] National Cancer Institute</ref> It is incurable, but there are many effective treatments.  
* In 2011, the age-adjusted incidence of leukemia was 13.66 per 100,000 individuals in the United States.


* ''Acute myelogenous leukemia'' (AML) occurs more commonly in adults than in children, and more commonly in men than women.  AML is treated with chemotherapy.  The five-year survival rate is 40%.<ref>{{cite journal |author=Colvin GA, Elfenbein GJ |title=The latest treatment advances for acute myelogenous leukemia |journal=Med Health R I |volume=86 |issue=8 |pages=243–6 |year=2003 |pmid=14582219 |doi=}}</ref>
===Age===


* ''Chronic myelogenous leukemia'' (CML) occurs mainly in adults. A very small number of children also develop this disease.  Treatment is with [[imatinib]] (Gleevec) or other drugs.  The five-year survival rate is 90%.<ref>[http://www.medscape.com/viewarticle/536049 Patients with Chronic Myelogenous Leukemia Continue to Do Well on Imatinib at 5-Year Follow-Up] Medscape Medical News 2006</ref><ref>[http://professional.cancerconsultants.com/conference_asco_2006.aspx?id=37519 Updated Results of Tyrosine Kinase Inhibitors in CML] ASCO 2006 Conference Summaries</ref>
* The overall age-adjusted incidence of leukemia in the United States between 2007 and 2011 was 13 per 100,000 occurrences. The age-adjusted incidence of leukemia by age category is:
** Under 65 years: 6.5 per 100,000
** 65 and over: 57.9 per 100,000


* ''Hairy cell leukemia'' (HCL) is sometimes considered a subset of CLL, but does not fit neatly into this pattern.  About 80% of affected people are adult men.  There are no reported cases in young children.  HCL is incurable, but easily treatable.  Survival is 96% to 100% at ten years.<ref name="pmid16245328">{{cite journal |author=Else M, Ruchlemer R, Osuji N, ''et al'' |title=Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years |journal=[[Cancer]] |volume=104 |issue=11 |pages=2442–8 |year=2005 |pmid=16245328 |doi=10.1002/cncr.21447}}</ref>
* Shown below is a table depicting the overall age-adjusted incidence of leukemia per 100,000 individuals by age in the United States between 2007 and 2011 for the different types of leukemia.


==Causes and risk factors==
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
There is no single known cause for all of the different types of leukemia. The different leukemias likely have different causes, and very little is certain about what causes them. Researchers have strong suspicions about four possible causes:
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" | || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Acute lymphoblastic leukemia'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" | '''Chronic lymphocytic leukemia'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Acute myeloid leukemia'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Chronic myeloid leukemia'''
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''All ages'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | 1.7 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |4.4|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |3.8 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |1.7
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''<65''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |1.7 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |1.4|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | 1.8 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |0.9
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''≥65''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | 1.6 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |25.2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |17.5|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |6.8
|}


* natural or artificial ionizing radiation
===Gender===
* certain kinds of chemicals
* some viruses
* genetic predispositions


Leukemia, like other cancers, result from [[somatic mutation]]s in the [[DNA]] which activate [[oncogene]]s or deactivate [[tumor suppressor gene]]s, and disrupt the regulation of cell death, differentiation or division.  These mutations may occur spontaneously or as a result of exposure to [[ionizing radiation|radiation]] or [[carcinogen]]ic substances and are likely to be influenced by genetic factors. Cohort and case-control studies have linked exposure to [[petrochemicals]], such as [[benzene]], and hair dyes to the development of some forms of leukemia.
* In the United States, the age-adjusted prevalence of leukemia by gender in 2011 was:
** In males: 92.7 per 100,000
** In females: 60.7 per 100,000
* In the United States, the delay-adjusted incidence of leukemia by gender in 2011 was:
** In males: 19.93 per 100,000 persons
** In females: 11.89 per 100,000 persons


[[virus (biology)|Viruses]] have also been linked to some forms of leukemia. For example, certain cases of ALL are associated with viral infections by either the [[human immunodeficiency virus]] (HIV, responsible for [[AIDS]]) or [[human T-lymphotropic virus]] (HTLV-1 and -2, causing [[adult T-cell leukemia/lymphoma]]).
* In the United States, the age-adjusted incidence of leukemia by gender on 2011 was:
** In males: 17.58 per 100,000 persons
** In females: 10.49 per 100,000 persons


[[Fanconi anemia]] is also a risk factor for developing [[Acute myeloid leukemia|acute myelogenous leukemia]].
* Shown below is an image depicting the delay-adjusted incidence and observed incidence of leukemia by gender and race in the United States between 1975 and 2011. These graphs were gathered from [[SEER]]: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.


Until the cause or causes of leukemia are found, there is no way to prevent the disease. Even when the causes become known, they may prove to be things which are not readily controllable, such as naturally occurring background radiation, and therefore not especially helpful for prevention purposes.
[[Image:Incidence of leukemia by gender and race in USA.PNG|700px|thumb|These graphs are adapted from [[SEER]]: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. - Delay-adjusted [[incidence]] and observed [[incidence]] of leukemia by gender and race in the United States between 1975 and 2011]]


== Treatment options for leukemia by type ==
===Race===
===Hairy Cell Leukemia (HCL)===
[[Hairy cell leukemia]] is an incurable, indolent blood disorder in which mutated, partly matured B cells accumulate in the bone marrow.  Its name is derived from the shape of the cells, which look like they are covered with short, fine, hair-shaped projections.  Unlike any other leukemia, HCL is characterized by ''low'' white blood cell counts.


Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. They engage in "watchful waiting" with routine bloodwork and exams every three to six months to monitor disease progression and identify any new symptoms.
* Shown below is a table depicting the age-adjusted prevalence of leukemia by race in 2011 in the United States.


Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e.g., infection-fighting neutrophil count below 1.0 K/ul), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life.
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" | || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''All Races''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''White''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Black''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Asian/Pacific Islander'''  || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Hispanic'''
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Age-adjusted prevalence'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |75.3 per 100,000|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |83.5 per 100,000|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |45.9 per 100,000|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |41.2 per 100,000|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |57.1 per 100,000
|}


Patients who need treatment, which includes most newly diagnosed HCL cases, usually receive either [[cladribine]] or [[pentostatin]], which are both in a class of chemotherapeutic drugs known as [[purine]] analogs or [[nucleoside]]s. In most cases, one round of treatment will produce a prolonged remission.
* Shown below is an image depicting the incidence of leukemia by race in the United States between 1975 and 2011.


Other treatments include [[rituximab]] infusion or self-injection with [[Interferon-alpha]]. In limited cases, the patient may benefit from [[splenectomy]] (removal of the spleen). These treatments are not typically given as the first treatment for a new patient because their success rates are lower than cladribine or pentostatin.
[[Image:Incidence of leukemia by race in USA.PNG|Incidence of leukemia by race in the United States between 1975 and 2011]]


In the short term, especially when neutrophil counts are low, an immune system hormone called granulocyte colony-stimulating factor may be taken to increase white blood cell counts.  This is believed to help prevent or treat an infection.  Many patients also take [[antibiotics]] until their white blood cell counts have recovered to normal levels.
<small> API: Asian/Pacific Islander; AI/AN: American Indian/ Alaska Native</small>


==References==
==Prognosis==
{{Reflist|2}}
===5-Year Survival===


== Research ==
* Between 2004 and 2010, the 5-year relative survival of patients with leukemia was 60.3%.


Significant research into the causes, diagnosis, treatment, and prognosis of leukemia is being done. Hundreds of [[clinical trials]] are being planned or conducted at any given time. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cure.
* When stratified by age, the 5-year relative survival of patients with leukemia was 68.5% (44.1% for patients <65 and ≥ 65 years of age respectively).


==External links==
* Shown below is a table depicting the 5-year relative survival of patients by the type of leukemia in the United States between 2004 and 2010.
'''Images of leukemias'''
*[http://www.healthsystem.virginia.edu/internet/hematology/HessIDB/stages-of-acute-leukemia.cfm UVA Healthsystem] -- Images of acute leukemias by stage


'''Research organizations'''
{| style="cellpadding=0; cellspacing= 0; width: 800px;"
*[http://www.tacl.us/ The Therapeutic Advances in Childhood Leukemia (TACL) Consortium] -- US research group
|-
*[http://atlasgeneticsoncology.org/Educ/Hempat_e.html "Chromosomes, Leukaemias, Solid Tumors, Hereditary Cancers"] in AtlasGeneticsOncology.
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" | || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Acute lymphoblastic leukemia'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" | '''Chronic lymphocytic leukemia'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Acute myeloid leukemia'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''Chronic myeloid leukemia'''
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''5-year survival'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" | 70% || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |83.5%|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |25.4% || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="center" |59.9%
|}


{{Blood}}
==References==
{{Hematological malignancy histology}}
{{Reflist|2}}
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Latest revision as of 22:30, 29 July 2020

Leukemia Microchapters

Home

Patient Information

Overview

Classification

AML
CML
ALL
CLL

Differentiating Leukemia from other Diseases

Epidemiology and Demographics

Prognosis

For patient information click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2], Usama Talib, BSc, MD [3], Sadaf Sharfaei M.D.[4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Synonyms and keywords: Leukaemia

Overview

Leukemia (Greek leukos, “white”; haima, “blood”) can be defined as a group of hematopoietic stem cell malignancies due to genetic abnormalities that may lead to clonal proliferation of these cells. These group of diseases are classified based on the type of hematopoietic stem cell involved and the duration of the disease. The leukemias are the most common malignancies among children younger than 15 years. Among them, Acute Lymphoblastic Leukemia (ALL) is the most common leukemia and accounts for 77% of childhood leukemia. However, Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia in adults, and it accounts for 30% of all leukemias in the United States. The increased rate of proliferation and decreased rate of apoptosis in this progeny of cells may compromise normal bone marrow function and ultimately result in marrow failure. Clinical manifestations, diagnosis, laboratory findings, and therapy are different according to the type of malignancy.

Classification

Leukemia may be classified as follows:

 
 
 
 
 
 
 
 
Leukemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lymphoid progeny
 
 
 
 
 
 
 
Myeloid progeny
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acute lymphoblastic leukemia (ALL)
 
 
 
Chronic lymphocytic leukemia (CLL)
 
Acute Myeloid Leukemia (AML)
 
 
 
Chronic myeloid leukemia (CML)




Differentiating Leukemia from other Diseases

Leukemia must be differentiated from various diseases that cause weight loss, night sweats, hepatosplenomegaly, and palpable lymph nodes, such as hairy cell leukemia, prolymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma. Based on the expression of cell surface markers, the table below differentiates different types of leukemia from other diseases that cause similar clinical presentations:[1]

Disease Etiology Clinical Manifestation Laboratory Findings Gold standard diagnosis Associated findings
Demography History Symptoms Signs Lab Histopathology
Acute myelogenous leukemia[2][3]
  • Clonal proliferation of malignant myeloid blast cells in the bone marrow
  • Genetic abnormalities t(8;21), inv(16), and t(15;17)
  • The most common leukemia in adults
  • Median age of 63 years old
Acute lymphoblastic leukemia[4][5]
  • Arrest of lymphoblasts
  • Chromosomal translocations: t(9;22) , t(12;21), t(5;14), t(1;19)
  • The most common cancer in children
  • Peak 2-5 years of age
  • Boys > girls
  • History of cancer
  • History of drug exposure
  • CNS involvement
Chronic myelogenous leukemia[6][7]
  • Median age 50 years old
Disease Etiology Demography History Symptoms Signs Lab Histopathology Gold standard diagnosis Associated findings
Chronic lymphocytic leukemia[8]
  • The most common leukemia in adults in western countries
  • M > F
  • Median age 70 years old
Hairy cell leukemia[9][10]
  • Accumulation of small mature B cell lymphoid cells with abundant cytoplasm and "hairy" projections
  • BRAF mutation
  • Uncommon
  • Median age 50 to 55 years old
  • M >> F
  • More common in Caucasians than Blacks
Large granular lymphocytic leukemia[11][12]
  • Rare
  • Median age 60 years
  • M = F
  • Mostly asymptomatic
  • Large lymphocytes with a condensed round or oval nucleus, abundant pale basophilic cytoplasm, and small azurophilic granules
  • Biopsy and flow cytometry + T-cell receptor gene rearrangement studies
  • Recurrent bacterial infection
Chronic neutrophilic leukemia[13]
  • Mature granulocytic proliferation in the blood and bone marrow
  • Point mutations in the CSF3R gene
  • Very rare
  • M = F
  • Toxic granulation in the neutrophils
  • Nuclear hypersegmentation
  • Increased myeloid:erythroid ratio > 20:1
  • WHO diagnostic criteria include leukocytosis of ≥ 25 x 109/L
  • More than 80% neutrophils,
  • Less than 10% circulating neutrophil precursors with blasts
  • Poor prognosis
  • Absence of the Philadelphia chromosome or a BCR/ABL fusion gene
Disease Etiology Demography History Symptoms Signs Lab Histopathology Gold standard diagnosis Associated findings
Chronic eosinophilic leukemia
  • There is no known cause for chronic eosinophilic leukemia.
  • It hasn't been linked to a specific chromosome or genetic abnormality.
  • Unknown
  • Unknown
Chronic monocytic leukemia
Prolymphocytic leukemia (PLL)
T-cell large granular lymphocytic leukemia (TLGL)
Disease Etiology Demography History Symptoms Signs Lab Histopathology Gold standard diagnosis Associated findings
Aggressive NK-cell leukemia (ANKL)
Adult T-cell leukemia/lymphoma (ATLL)[14][15][16][17][18][19]
  • Adult T-cell leukemia is caused by an infection with HTLV.
  • Common genetic mutations involved in the development of adult T-cell leukemia can be found here.
  • The incidence of adult T-cell leukemia increases with age, and the median age at diagnosis is 57 years.
  • Males are more commonly affected with adult T-cell leukemia than females.
  • The male to female ratio is approximately 1.4 to 1.
Sezary syndrome[20][21][22][23][24][25][26][27]
  • The cause of Sezary syndrome has not been identified.
  • Sezary syndrome might have one or more of the chromosomal abnormalities, such as the loss or gain of genetic.
  • The prevalence of Sezary syndrome is exact unknown.
  • The median age at diagnosis of Sézary syndrome is 60 years of age.
  • Sezary syndrome is more commonly observed among elderly patients.
  • Males are more commonly affected with Sezary syndrome than females(2:1).
Myelodysplastic syndrome Biopsy
  • Leukemia transformation
  • Acquired pseudo-Pelger-Huët anomaly
  • Infection
Myeloproliferative disorders
Leukemoid reaction

Epidemiology and Demographics

Prevalence

  • In the United States, the age-adjusted prevalence of leukemia is 75.3 per 100,000 in 2011.[29]

Incidence

  • The delay-adjusted incidence of leukemia in 2011 was estimated as 15.48 per 100,000 individuals in the United States.
  • In 2011, the age-adjusted incidence of leukemia was 13.66 per 100,000 individuals in the United States.

Age

  • The overall age-adjusted incidence of leukemia in the United States between 2007 and 2011 was 13 per 100,000 occurrences. The age-adjusted incidence of leukemia by age category is:
    • Under 65 years: 6.5 per 100,000
    • 65 and over: 57.9 per 100,000
  • Shown below is a table depicting the overall age-adjusted incidence of leukemia per 100,000 individuals by age in the United States between 2007 and 2011 for the different types of leukemia.
Acute lymphoblastic leukemia Chronic lymphocytic leukemia Acute myeloid leukemia Chronic myeloid leukemia
All ages 1.7 4.4 3.8 1.7
<65 1.7 1.4 1.8 0.9
≥65 1.6 25.2 17.5 6.8

Gender

  • In the United States, the age-adjusted prevalence of leukemia by gender in 2011 was:
    • In males: 92.7 per 100,000
    • In females: 60.7 per 100,000
  • In the United States, the delay-adjusted incidence of leukemia by gender in 2011 was:
    • In males: 19.93 per 100,000 persons
    • In females: 11.89 per 100,000 persons
  • In the United States, the age-adjusted incidence of leukemia by gender on 2011 was:
    • In males: 17.58 per 100,000 persons
    • In females: 10.49 per 100,000 persons
  • Shown below is an image depicting the delay-adjusted incidence and observed incidence of leukemia by gender and race in the United States between 1975 and 2011. These graphs were gathered from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.
These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. - Delay-adjusted incidence and observed incidence of leukemia by gender and race in the United States between 1975 and 2011

Race

  • Shown below is a table depicting the age-adjusted prevalence of leukemia by race in 2011 in the United States.
All Races White Black Asian/Pacific Islander Hispanic
Age-adjusted prevalence 75.3 per 100,000 83.5 per 100,000 45.9 per 100,000 41.2 per 100,000 57.1 per 100,000
  • Shown below is an image depicting the incidence of leukemia by race in the United States between 1975 and 2011.

Incidence of leukemia by race in the United States between 1975 and 2011

API: Asian/Pacific Islander; AI/AN: American Indian/ Alaska Native

Prognosis

5-Year Survival

  • Between 2004 and 2010, the 5-year relative survival of patients with leukemia was 60.3%.
  • When stratified by age, the 5-year relative survival of patients with leukemia was 68.5% (44.1% for patients <65 and ≥ 65 years of age respectively).
  • Shown below is a table depicting the 5-year relative survival of patients by the type of leukemia in the United States between 2004 and 2010.
Acute lymphoblastic leukemia Chronic lymphocytic leukemia Acute myeloid leukemia Chronic myeloid leukemia
5-year survival 70% 83.5% 25.4% 59.9%

References

  1. Hoffbrand V, Moss P. Essential Haematology. John Wiley & Sons; 2011
  2. Saif A, Kazmi S, Naseem R, Shah H, Butt MO (August 2018). "Acute Myeloid Leukemia: Is That All There Is?". Cureus. 10 (8): e3198. doi:10.7759/cureus.3198. PMID 30410824. Vancouver style error: initials (help)
  3. Estey EH (April 2013). "Acute myeloid leukemia: 2013 update on risk-stratification and management". Am. J. Hematol. 88 (4): 318–27. doi:10.1002/ajh.23404. PMID 23526416.
  4. Sawalha Y, Advani AS (March 2018). "Management of older adults with acute lymphoblastic leukemia: challenges & current approaches". Int J Hematol Oncol. 7 (1): IJH02. doi:10.2217/ijh-2017-0023. PMC 6176956. PMID 30302234.
  5. Portell CA, Advani AS (April 2014). "Novel targeted therapies in acute lymphoblastic leukemia". Leuk. Lymphoma. 55 (4): 737–48. doi:10.3109/10428194.2013.823493. PMID 23841506.
  6. Saußele S, Silver RT (April 2015). "Management of chronic myeloid leukemia in blast crisis". Ann. Hematol. 94 Suppl 2: S159–65. doi:10.1007/s00277-015-2324-0. PMID 25814082.
  7. Eden RE, Coviello JM. PMID 30285354. Missing or empty |title= (help)
  8. Rai KR, Jain P (March 2016). "Chronic lymphocytic leukemia (CLL)-Then and now". Am. J. Hematol. 91 (3): 330–40. doi:10.1002/ajh.24282. PMID 26690614.
  9. Troussard X, Cornet E (December 2017). "Hairy cell leukemia 2018: Update on diagnosis, risk-stratification, and treatment". Am. J. Hematol. 92 (12): 1382–1390. doi:10.1002/ajh.24936. PMC 5698705. PMID 29110361.
  10. Wierda WG, Byrd JC, Abramson JS, Bhat S, Bociek G, Brander D, Brown J, Chanan-Khan A, Coutre SE, Davis RS, Fletcher CD, Hill B, Kahl BS, Kamdar M, Kaplan LD, Khan N, Kipps TJ, Lancet J, Ma S, Malek S, Mosse C, Shadman M, Siddiqi T, Stephens D, Wagner N, Zelenetz AD, Dwyer MA, Sundar H (November 2017). "Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology". J Natl Compr Canc Netw. 15 (11): 1414–1427. doi:10.6004/jnccn.2017.0165. PMID 29118233.
  11. Matutes E (March 2017). "Large granular lymphocytic leukemia. Current diagnostic and therapeutic approaches and novel treatment options". Expert Rev Hematol. 10 (3): 251–258. doi:10.1080/17474086.2017.1284585. PMID 28128670.
  12. Oshimi K (2017). "Clinical Features, Pathogenesis, and Treatment of Large Granular Lymphocyte Leukemias". Intern. Med. 56 (14): 1759–1769. doi:10.2169/internalmedicine.56.8881. PMC 5548667. PMID 28717070.
  13. Elliott MA, Tefferi A (August 2018). "Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management". Am. J. Hematol. 93 (4): 578–587. doi:10.1002/ajh.24983. PMID 29512199.
  14. Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015
  15. Matutes E (2007). "Adult T-cell leukaemia/lymphoma". J. Clin. Pathol. 60 (12): 1373–7. doi:10.1136/jcp.2007.052456. PMC 2095573. PMID 18042693.
  16. Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015
  17. Mahieux R, Gessain A (2007). "Adult T-cell leukemia/lymphoma and HTLV-1". Curr Hematol Malig Rep. 2 (4): 257–64. doi:10.1007/s11899-007-0035-x. PMID 20425378.
  18. Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015
  19. Matutes E (2007). "Adult T-cell leukaemia/lymphoma". J Clin Pathol. 60 (12): 1373–7. doi:10.1136/jcp.2007.052456. PMC 2095573. PMID 18042693.
  20. Wong HK, Mishra A, Hake T, Porcu P (October 2011). "Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)". Br. J. Haematol. 155 (2): 150–66. doi:10.1111/j.1365-2141.2011.08852.x. PMC 4309373. PMID 21883142.
  21. Woollard WJ, Pullabhatla V, Lorenc A, Patel VM, Butler RM, Bayega A, Begum N, Bakr F, Dedhia K, Fisher J, Aguilar-Duran S, Flanagan C, Ghasemi AA, Hoffmann RM, Castillo-Mosquera N, Nuttall EA, Paul A, Roberts CA, Solomonidis EG, Tarrant R, Yoxall A, Beyers CZ, Ferreira S, Tosi I, Simpson MA, de Rinaldis E, Mitchell TJ, Whittaker SJ (June 2016). "Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome". Blood. 127 (26): 3387–97. doi:10.1182/blood-2016-02-699843. PMID 27121473.
  22. Wilcox RA (January 2016). "Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management". Am. J. Hematol. 91 (1): 151–65. doi:10.1002/ajh.24233. PMC 4715621. PMID 26607183.
  23. Horesh N, Horowitz NA (October 2014). "Does gender matter in non-hodgkin lymphoma? Differences in epidemiology, clinical behavior, and therapy". Rambam Maimonides Med J. 5 (4): e0038. doi:10.5041/RMMJ.10172. PMC 4222427. PMID 25386354.
  24. Al Hothali GI (June 2013). "Review of the treatment of mycosis fungoides and Sézary syndrome: A stage-based approach". Int J Health Sci (Qassim). 7 (2): 220–39. PMC 3883611. PMID 24421750.
  25. Wilcox RA (January 2016). "Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management". Am. J. Hematol. 91 (1): 151–65. doi:10.1002/ajh.24233. PMC 4715621. PMID 26607183.
  26. Yamashita T, Abbade LP, Marques ME, Marques SA (2012). "Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update". An Bras Dermatol. 87 (6): 817–28, quiz 829–30. PMC 3699909. PMID 23197199.
  27. "Extracorporeal photophoresis: an evidence-based analysis". Ont Health Technol Assess Ser. 6 (6): 1–82. 2006. PMC 3379535. PMID 23074497.
  28. Olsen, Elise A. (2015). "Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma". Dermatologic Clinics. 33 (4): 643–654. doi:10.1016/j.det.2015.06.001. ISSN 0733-8635.
  29. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.