Leukemia

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Patient Information
Overview
Classification AML CML ALL CLL
Differentiating Leukemia from other Diseases
Epidemiology and Demographics
Prognosis

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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:

Disease	Etiology	Clinical Manifestation				Laboratory Findings		Gold standard diagnosis	Associated findings
		Demography	History	Symptoms	Signs	Lab	Histopathology
Acute myelogenous leukemia	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	Smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene	Fatigue Bleeding	Bone tenderness Dyspnea Leukemia cutis Swelling of the gums Chloroma Rare LAP	Anemia Thrombocytopenia Leukocytosis or leukopenia	Leukemic blasts Positive Auer rods	Flow cytometry > 20% blasts of myeloid lineage	Persistent or frequent infections Fatal within weeks or months if left untreated Down syndrome or Bloom syndrome
Acute lymphoblastic leukemia	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	Generalized weakness Fatigue Bleeding	Hepatosplenomegaly LAP Dyspnea Pallor Papilledema Nuchal rigidity Cranial nerve palsy Testicular enlargement Mediastinal mass	Anemia Thrombocytopenia Normal or slightly increased WBC counts	Lymphoblasts Atypical cells	Bone marrow biopsy	CNS involvement
Chronic myelogenous leukemia	Dysregulated production and uncontrolled proliferation of mature and maturing granulocytes BCR-ABL1 fusion gene Autosomal dominant mutation	Median age 50 years old		Generalized weakness Fatigue Early satiety Abdominal fullness Bleeding	Asymptomatic Blast crisis Excessive sweating Papilledema Tenderness over the lower sternum Hepatosplenomegaly	Anemia WBC > 100,000/microL Absolute basophilia and eosinophilia Plt > 600,000 to 700,000/microL Low leukocyte alkaline phosphatase High uric acid	All cells of the neutrophilic series, from myeloblasts to mature neutrophils Myelocyte bulge	Bone marrow biopsy	Acute gouty arthritis Venous obstruction
Disease	Etiology	Demography	History	Symptoms	Signs	Lab	Histopathology	Gold standard diagnosis	Associated findings
Chronic lymphocytic leukemia	Progressive accumulation of monoclonal B lymphocytes	The most common leukemia in adults in western countries M > F Median age 70 years old	Positive family history Exposure to herbicides or insecticides	Bleeding Abdominal pain Generalized weakness Anorexia	LAP (Most common sign) Hepatosplenomegaly Skin lesions (leukemia cutis) Night sweats Muscle wasting	Anemia Thrombocytopenia Absolute lymphocytosis >5000 cells/μl Neutropenia Positive direct Coombs test Hypogammaglobulinemia Elevated lactate dehydrogenase and beta-2 microglobulin	Presence of smudge cells Monoclonality of kappa and lambda producing B cells Express CD19, CD20, CD23, and CD5 on the cell surface	Flow cytometry of the peripheral blood	Extranodal involvement of skin, kidney, lung, spine Membranoproliferative glomerulonephritis Autoimmune hemolytic anemia
Hairy cell leukemia	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	Exposures to ionizing radiation, pesticides, and farming	Generalized weakness Fatigue Early satiety Abdominal fullness Bleeding	Asymptomatic Splenomegaly Spontaneous splenic rupture Skin rash Ascites Pleural effusion	Cytopenia Leukocytosis in 10 to 20 percent Azotemia Abnormal liver function tests Hypergammaglobulinemia	Pancytopenia with monocytopenia and circulating tumor cells characteristic of HCL Dry bone marrow	Analysis of peripheral blood + immunophenotyping by flow cytometry	Vasculitis
Large granular lymphocytic leukemia​	Clonal proliferation of cytotoxic T cells Dysregulation of apoptosis through abnormalities in the Fas/Fas ligand pathway	Rare Median age 60 years M = F	Autoimmune diseases Lymphoproliferative disorders	Generalized weakness Fatigue	Mostly asymptomatic	Modest lymphocytosis Neutropenia Anemia Thrombocytopenia	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	Mature granulocytic proliferation in the blood and bone marrow Point mutations in the CSF3R gene	Very rare M = F	Multiple myeloma	Generalized weakness Fatigue	Hepatosplenomegaly Pruritus Gout	Peripheral blood neutrophilia (> 25 x 109/L) with myeloid precursors (promyelocytes, myelocytes, metamyelocytes) Elevated leukocyte alkaline phosphatase	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	Constitutional Rash Rhinitis Gastritis Thromboembolismrelated	Hypertension Eczema, mucosalulcers, erythema Angioedema Ataxia Anemia Lymphadenopathy Hepatosplenomegaly	Leukocytosis with left shift Eosinophilia Basophilia Monocytosis Anemia Thrombocytopenia ↑ B12 levels ↑ LDH	Hypercelluar with ↑ eosinophilic precursors, ↑ eosinophils, and atypical mononuclear cells		Heart failure Lung fibrosis Encephalopathy Erythema annulare centrifugam
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)	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.	Abdominal pain Constipation Nausea and vomiting Fatigue Generalized weakness Cough Recurrent infections	Fever Weight loss Recurrent bleeding Anorexia Night sweats Bone pain Hypercalcemia
Sezary syndrome	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).	The majority of sezary syndrome patients present with developing lymphadenopathy and erythroderma for weeks to months. Early clinical features of Sezary syndrome include: Mimic psoriasis Chronic eczema Atopic dermatitis Leprosy Lichenoid pityriasis In Sezary syndrome single or multiple lesions (thin erythematous plaques or flat patch) is a typical skin involvement in the gluteal region or thighs. Patients with Sezary syndrome often have a history of several years of eczematous or dermatitis skin lesions before the diagnosis is finally established.	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 patients) The severity of erythema body surface area (BSA) involved may wax and wane(>80% of BSA) Patches and plaques to erythroderma Keratosis pilaris Alopecia (hair loss) Ectropion Keratoderma Hypertrophic nails Erosions Lichenification Trouble regulating body temperature Abnormalities of fingernails and toenails Lymphadenopathy Viscer
Myelodysplastic syndrome				Constitutional symptoms Bleeding	Pallor Petechiae Organomegaly	Pancytopenia	Hypercellular/ normocellular bone marrow with dysplastic changes Macro-ovalocytes Basophilic stippling Howell-Jolly body	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.

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.

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%