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]

Synonyms and keywords: Leukaemia

Overview

Leukemia (Greek leukos, “white”; haima, “blood”) could 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 type of hematopoietic stem cell involvement and duration of disease. The leukemias are the most common malignancies among children younger than 15 years. Among them, ALL is the most common leukemia accounts for 77% of childhood leukemia. However, CLL is the most common form of leukemia in adults, 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 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 leukaemia, prolymphocytic leukaemia, 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						Histopathology	Imaging	Gold standard diagnosis	Associated findings
		Demography	History	Symptoms				Signs
				Constitutional symptoms	Weight	Bleeding	Abdominal Pain	Vital sign	Jaundice	LAP	Hepatosplenomegaly	Other	CBC	BMP	LFT	PT/PTT	ALP	U/A
Acute myelogenous leukemia (AML)	Mutation of myeloblast	More in congenital disorders such as Down syndrome, Bloom syndrome	pre-existing hematological disorder Exposure to alkylating agents or ionizing radiation or benzene and other aromatic hydrocarbons	Fatigue		+	+	Fever				Bone tenderness Dyspnea	↓ Hb, ↓ Plt						Immature Myeloblasts Positive Aur rods		Flow cytometry	Persistent or frequent infections
Acute lymphoblastic leukemia	Arrest of lymphoblasts. Chromosomal translocations involved 9 and 22, t(9;22) (q34;q11.2) BCR-ABL1 12 and 21, t(12;21)(p13;q22) TEL-AML1 5 and 14, t(5;14)(q31;q32)IL3-IGH 1 and 19 t(1;19)(q23;p13.3) TCF3-PBX1		History of cancer History of drug exposure	Generalised weakness and fatigue Frequent or unexplained fever and infections Weight loss and/or loss of appetite Excessive bruising, bleeding from wounds, nosebleeds, petechiae, bone pain, joint pains and dyspnea.				Lymphadenopathy Hepato-splenomegaly Stridor Pallor Petechiae Bruising Papilledema Nuchar rigidity Cranial nerve palsy Testicular enlargement					Eosinophilia Lymphocytosis Decreased erythrocytes production Thrombocytopenia. Chemistry panels with altered levels of uric acid, creatinine, blood urea nitrogen, potassium, phosphate, calcium, bilirubin, hepatic transaminases and ferritin. A spinal tap will tell if the spinal column and brain has been invaded.
Chronic myelogenous leukemia	Myeloproliferative expansion of pluripotent stem cells. Philadelphia chromosome resulting from the reciprocal t(9;22)(q34;q11.2) Resulting in a derivative 9q+ and a small 22q-. results in a BCR-ABL fusion gene Ativates numerous downstream targets including c-myc Akt Jun,			Insidious in onset Nonspecific symptoms of fatigue and weight loss. Early satiety and decreased food intake due to splenic compression of stomach Low-grade fever and excessive sweating				Splenomegaly Correlates with granulocyte counts Findings of leukostasis and hyperviscosity. Funduscopy may show papilledema, venous obstruction, and hemorrhages.					WBC counts, exceeding 300,000-600,000 cells/μL Elevated alkaline phosphatase (ALP) Philadelphia (Ph1) chromosome\
CLL	Clonal B cells arrested in the B-cell differentiation pathway, Genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. SF3B1 gene located on chromosome 2 FBXW7 gene located on chromosome 4 MYD88 gene located on chromosome 3 TP53 gene located on chromosome 7 NOTCH1 gene located on chromosome 9 ATM gene located on chromosome 11 CHD2 gene located on chromosome 15		Review family history for members with positive history of the disease Review occupational history related to farming Review any exposure to herbicides or insecticides	Fever Recurrent bleeding Weight loss Muscle wasting Generalized weakness Anorexia Night sweats Abdominal pain Recurrent infections				Skin pallor Palpable cervical lymph nodes Hepatomegaly.					Monoclonality of kappa and lambda producing B cells Presence of smudge cells CBC Absolute lymphocytosis (>5000 cells/μl) Decreased hemoglobin concentration Decreased platelets count Express CD19, CD20, CD23, and CD5 on the cell surface
Hairy cell leukemia
Mast cell leukemia
Large granular lymphocytic leukemia​
Chronic neutrophilic leukemia
Chronic eosinophilic leukemia
Chronic monocytic leukemia
Prolymphocytic leukemia (PLL)
T-cell large granular lymphocytic leukemia (TLGL)
Aggressive NK-cell leukemia (ANKL)
Adult T-cell leukemia/lymphoma (ATLL)
Sezary syndrome
Myelodysplastic syndrome
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 to be 15.48 per 100,000 persons in the United States.

• In 2011, the age-adjusted incidence of leukemia was 13.66 per 100,000 persons in the United States.

Age

• The overall age-adjusted incidence of leukemia in the United States between 2007 and 2011 is 13 per 100,000, 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 is:
  • 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 is:
  • 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 is:
  • 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 are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.

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% and 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%