Adult T-cell leukemia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response. Development of adult T-cell leukemia is the result of multiple genetic mutations, induced by an infection with human T‐cell lymphotropic virus (HTLV). On gross pathology, skin nodules, maculopapular eruption, and erythema are characteristic skin findings of adult T-cell leukemia. On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include pleomorphic, medium sized lymphocytes with a polylobulated nucleus and agranular cytoplasm. Based on both the clinical presentation and lab values, adult T-cell leukemia may be classified into either an acute variant, chronic variant, smoldering variant, or an adult T-cell lymphoma variant. The majority of adult T-cell leukemia cases are reported in Japan, the Caribbean, South America, and Africa. The natural history of adult T-cell leukemia varies between the different sub-types of the disease. Common complications of adult T-cell leukemia include cardiac arrhythmias, opportunistic infections, and bone fractures. The prognosis varies between the sub-types of adult T-cell leukemia. Acute and lymphomatous sub-types have a poor prognosis; whereas chronic and smoldering sub-types have a good prognosis. The optimal therapy for adult T-cell leukemia depends on the clinical variant of the disease. Chronic and smoldering adult T-cell leukemia patients are usually managed by either observation, skin directed therapies, or a combination of zidovudine and interferon therapy. Acute adult T-cell leukemia patients are usually managed by either chemotherapy, supportive care, allogeneic stem cell transplant, or a combination of zidovudine and interferon therapy. The first line chemotherapeutic regimens used for the initial management of adult T-cell leukemia include CHOP, CHOEP, or Dose-adjusted EPOCH. Second line chemotherapeutic agents might be DHAP, ESHAP, GDP, GemOx, or ICE. Surgery is not the first-line treatment option for patients with adult T-cell leukemia. Splenectomy is usually reserved for certain cases of adult T-cell leukemia. No preventive vaccine against HTLV-1 is currently available.
Historical Perspective
Adult T-cell leukemia was first discovered in 1977 by Dr. K. Takatsuki, a Japanese physician. The association between HTLV infection and adult T-cell leukemia was made in 1981.
Classification
Based on both the clinical presentation and laboratory findings, adult T-cell leukemia may be classified into either an acute variant, chronic variant, smoldering variant, or an adult T-cell lymphoma variant.
Pathophysiology
Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response. Development of adult T-cell leukemia is the result of multiple genetic mutations induced by an infection with human T‐cell lymphotropic virus (HTLV). On gross pathology, skin nodules, maculopapular eruption, and erythema are characteristic skin findings of adult T-cell leukemia. On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include pleomorphic, medium sized lymphocytes with a polylobulated nucleus and agranular cytoplasm.
Causes
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.
Differentiating Adult T-cell leukemia from other Diseases
Adult T-cell leukemia must be differentiated from other 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.
Epidemiology and Demographics
The majority of adult T-cell leukemia cases are reported in Japan, the Caribbean, South America, and Africa. In southern Japan, the age-adjusted incidence rate of adult T-cell leukemia is approximately 6.6 per 100,000 individuals. 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. Adult T-cell leukemia usually affects individuals of the African American, Latin American, and Asian race. Caucasian individuals are less likely to develop adult T-cell leukemia.
Risk Factors
Common risk factors in the development of adult T-cell leukemia among HTLV carriers are vertical transmission of HTLV infection during labor, male sex, and specific human leukocyte antigens such as HLA-A 26, HLA-B 4002, and HLA-B 4801.
Screening
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for adult T-cell leukemia.
Natural History, Complications and Prognosis
The natural history of adult T-cell leukemia varies between the different sub-types of the disease. Common complications of adult T-cell leukemia include cardiac arrhythmias, opportunistic infections , and bone fractures. The prognosis varies between the sub-types of adult T-cell leukemia. Acute and lymphomatous sub-types have a poor prognosis; whereas chronic and smouldering sub-types have a good prognosis.
Diagnosis
Diagnostic Study of Choice
There is no single diagnostic study of choice for the diagnosis of adult T-cell leukemia. However, adult T-cell leukemia can be diagnosed based on clinical manifestation and laboratory findings confirming characteristic histopathology and HTLV-1 infection.
History and Symptoms
Symptoms of adult T-cell leukemia include fatigue, fever, night sweats, constipation, and recurrent infections.
Physical Examination
Patients with adult T-cell leukemia usually appear lethargic and fatigued. Physical examination of patients with adult T-cell leukemia is usually remarkable for maculopapular rash, skin ulceration, and splenomegaly.
Laboratory Findings
Laboratory findings consistent with the diagnosis of adult T-cell leukemia include abnormal anemia, thrombocytopenia, and elevated lymphocyte count. Hypercalcemia is a key feature among patients with adult T-cell leukemia.
Electrocardiogram
There are no ECG findings associated with adult T-cell leukemia. However, electrocardiogram might be helpful in detecting complications of adult T-cell leukemia such as cardiac arrhythmias due to hypercalcemia. To view the electrocardiogram findings in hypercalcemia, click here.
X-ray
There are no x-ray findings associated with adult T-cell leukemia. However, an x-ray may be helpful in the diagnosis of complications of adult T-cell leukemia, which include bone fractures and lytic lesions.
Echocardiography and Ultrasound
There are no echocardiography findings associated with adult T-cell leukemia. Findings on an ultrasound suggestive of adult T-cell leukemia include hepatomegaly, splenomegaly and lymphadenopathy.
CT Scan
Thoracic CT scan may be helpful in the diagnosis of adult T-cell leukemia. Findings on CT scan suggestive of pulmonary infiltration by adult T-cell leukemia cells include thickening of the bronchovascular bundles, consolidation in the peripheral lung parenchyma, and ground-glass attenuations. Findings on abdominal CT scan suggestive of adult T-cell leukemia cells include hepatomegaly and splenomegaly.
MRI
There are no MRI findings associated with adult T-cell leukemia.
Other Imaging Findings
There are no other imaging findings associated with adult T-cell leukemia.
Other Diagnostic Studies
Other diagnostic studies for adult T-cell leukemia include skin biopsy, bone marrow biopsy, and fluorescent in-situ hybridization.
Treatment
Medical Therapy
The optimal therapy for adult T-cell leukemia depends on the clinical variant of the disease. Chronic and smoldering adult T-cell leukemia patients are usually managed by either observation, skin directed therapies, or a combination of zidovudine and interferon therapy. Acute adult T-cell leukemia patients are usually managed by either chemotherapy, supportive care, allogeneic stem cell transplant, or a combination of zidovudine and interferon therapy. The first line chemotherapeutic regimens used for the initial management of adult T-cell leukemia include CHOP, CHOEP, or Dose-adjusted EPOCH. Second line chemotherapeutic agents might be DHAP, ESHAP, GDP, GemOx, or ICE.
Interventions
The mainstay of treatment for Adult T-cell leukemia is medical therapy. There are no recommended therapeutic interventions for the management of Adult T-cell leukemia.
Surgery
Surgery is not the first-line treatment option for patients with adult T-cell leukemia. Splenectomy is usually reserved for certain cases of adult T-cell leukemia.
Primary Prevention
Primary prevention of adult-T cell leukemia is aimed at preventing the vertical and person-person transmission of HTLV virus. No preventive vaccine against HTLV-1 is currently available.
Secondary Prevention
There are no established measures for the secondary prevention of Adult T-cell leukemia.