T-cell acute lymphoblastic leukemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and Keywords: Cortical T ALL; Lymphomatous T-cell leukemia/lymphoma; Mature T ALL; Pre-T ALL; Precursor T acute lymphoblastic leukemia; Precursor T-cell lymphoblastic leukemia; Pro-T ALL; T-ALL; T-acute lymphoblastic leukemia; T-acute lymphoblastic lymphoma; T-cell leukemia/lymphoma; T-LBL

For patient information click here

Overview

T-cell acute lymphoblastic leukemia (also known as T-ALL) is a type of acute lymphoblastic leukemia (ALL) and a cancer of the lymphocyte-forming cells (lymphoblasts).[1] T-cell acute lymphoblastic leukemia was first described by Nikolaus Friedreich, a German pathologist in 1857.[2] T-cell acute lymphoblastic leukemia accounts for approximately 15 to 25% of acute lymphoblastic leukemias in children and adults and approximately 15% of all acute lymphoblastic leukemias are T cell lymphoblastic leukemias. T-cell acute lymphoblastic leukemia is more commonly observed among patients aged 5 to 10 years old. T-cell acute lymphoblastic leukemia may be classified according to EGIL classification into 4 groups: pro-T cell acute lymphoblastic leukemia, pre-cell acute lymphoblastic leukemia, cortical T cell acute lymphoblastic leukemia, and mature T acute lymphoblastic leukemia. The pathogenesis of T-cell acute lymphoblastic leukemia is characterized by an abnormal production of lymphoblastic cells. T-cell acute lymphoblastic leukemia arises from lymphoblasts, which are precursor white blood cells undergoing hematopoiesis. The molecular pathogenesis of T-cell acute lymphoblastic leukemia is characterized by the positive nuclear staining of TdT, which is a DNA polymerase present in the nucleus of lymphoblasts. On immunohistochemistry, characteristic findings of T-cell acute lymphoblastic leukemia include positive staining for CD8, CD2, CD5, TdT, CD99. Common risk factors in the development of T-cell acute lymphoblastic leukemia, include exposure to radiation, past treatment with chemotherapy, mutations in certain chromosomes or genes, or having certain genetic abnormalities (e.g., Down syndrome, and neurofibromatosis type 1). The majority of patients with T-cell acute lymphoblastic leukemia may be initially asymptomatic. Early clinical features include high grade fever, malaise, and bruising. Common complications of T-cell acute lymphoblastic leukemia, include disseminated intravascular coagulation, infections, posterior reversible encephalopathy syndrome, and leucoencephalopathy. Laboratory findings consistent with the diagnosis of T-cell acute lymphoblastic leukemia may be non-specific such as anemia, thrombocytopenia, and neutropenia. The diagnosis of T-cell acute lymphoblastic leukemia is made with bone marrow biopsy and the following criteria: CD33 and/or CD13 expression, ≥20% bone marrow lymphoblasts, age 1-10 years, and leukoerythroblastosis on peripheral blood smear. Initial medical therapy for T-cell acute lymphoblastic leukemia is with vincristine and dexamethasone. In some cases, it may include an anthracycline (e.g. doxorubicin). Targeted chemotherapy in conjunction with hematopoeitic stem cell transplant is the most common approach to the treatment of T-cell acute lymphoblastic leukemia. Post-treatment follow-up and monitoring may include use of trimethoprim-sulfamethoxazole (TMP-SMZ) to prevent pneumocystis jiroveci pneumonia, and the use of oral nystatin or clotrimazole troches to reduce the risk of oropharyngeal candidiasis.

Historical Perspective

In 1857, T-cell acute lymphoblastic leukemia was first described by the German pathologist Nikolaus Friedreich.[2]

Classification

T-cell acute lymphoblastic leukemia may be classified according to EGIL classification into 4 groups:

T-cell acute lymphoblastic leukemia may also be classified according to molecular translocations into 4 subtypes:

  • t(9;22) / BCR-ABL
  • t(1;19) / E2A-PBX1
  • t(12;21) / ETV-CBFα
  • MLL rearrangement

Pathophysiology

Pathogenesis

The pathogenesis of T-cell acute lymphoblastic leukemia is characterized by an abnormal production of lymphoblastic cells. T-cell acute lymphoblastic leukemia arises from immature T-cells called T-lymphoblasts.

Genetics

Genes associated with the development of T-cell acute lymphoblastic leukemia include:

Gross Pathology

There are no characteristic gross pathology findings associated with T-cell acute lymphoblastic leukemia.

Microscopic Histopathology

On microscopic histopathological analysis, common findings in T-cell acute lymphoblastic leukemia include:

On immunohistopathological analysis, common findings in T-cell acute lymphoblastic leukemia include:

  • Positive CD2
  • Positive CD8
  • Positive CD5
  • Positive TdT
  • Positive CD99

Causes

The most important cause of T-cell acute lymphoblastic leukemia is genetic mutations (e.g., translocations) such as:

Differentiating T-Cell Acute Lymphoblastic Leukemia from Other Diseases

T-cell acute lymphoblastic leukemia must be differentiated from other diseases that cause high-grade fever, fatigue, and anemia such as:

Epidemiology and Demographics

T-cell acute lymphoblastic leukemia accounts for approximately 15 to 25% of acute lymphoblastic leukemias in children and adults.[3] Approximately 15% of all acute lymphoblastic leukemias are T cell.[3]

Age

Gender

Males are more commonly affected with T-cell acute lymphoblastic leukemia than females.

Race

Compared to African-Americans, Caucasians are less likely to develop T-cell acute lymphoblastic leukemia.

Risk Factors

Common risk factors in the development of T-cell acute lymphoblastic leukemia include:[4]

Natural History, Complications and Prognosis

Natural History

The majority of patients with T-cell acute lymphoblastic leukemia may be initially asymptomatic. Early clinical features include fever, malaise, and bruising. If left untreated, the majority of patients with T-cell acute lymphoblastic leukemia may progress to develop acute organ failure and death.

Complications

Common complications of T-cell acute lymphoblastic leukemia include:

Prognosis

The prognosis varies with immunophenotyping; the overall 5-year survival rate of patients with T-cell acute lymphoblastic leukemia ranges between 28% to 90%.

Diagnosis

History & Symptoms

T-cell acute lymphoblastic leukemia is usually asymptomatic. Symptoms of T-cell acute lymphoblastic leukemia may include:[4]

Physical Examination

Patients with T-cell acute lymphoblastic leukemia commonly appear pale, weak, and malnourished.[4] Physical examination may be remarkable for:

Laboratory Findings

Laboratory findings consistent with the diagnosis of T-cell acute lymphoblastic leukemia may include:[4]
Complete Blood Count

Chemistry Panel A chemistry panel in a patient with T-cell acute lymphoblastic leukemia may demonstrate altered concentrations of the following:[4]

Imaging Findings

There are no specific imaging findings associated with T-cell acute lymphoblastic leukemia.

Other Diagnostic Studies

T-cell acute lymphoblastic leukemia may also be diagnosed using the following tests:[4]

  • Bone marrow biopsy
  • Bone marrow is hypercellular, and has an abnormally elevated proportion of lymphoblasts (≥20%)
  • Immunophenotyping
  • Karyotyping
  • t(8;21)(q22;q22)
  • inv(16)(p13q22)
  • t(16;16)(p13;q22)
  • t(15;17)
  • Peripheral blood smear

Treatment

Medical Therapy

  • The mainstay of therapy for T-cell acute lymphoblastic leukemia is gene-targeted chemotherapy.[5]
  • Initial medical therapy for T-cell acute lymphoblastic leukemia is vincristine and dexamethasone. In some cases, treatment may include an anthracycline (e.g., doxorubicin).
  • The table below demonstrates different treatment compounds based on genetic involvement:
Genetic Lesions and Potential Therapeutic Drugs
Adapted from Chiaretti et al[6]
Genes involved Therapeutic compound
TAL1
  • HDAC inhibitors
  • Vorinostat
Notch1
  • γ-secretase inhibitors
ABL1
  • ABL1 kinase inhibitors
  • Imatinib
  • Dasatinib
JAK2
  • JAK2 inhibitors
JAK1
  • Tyrosine kinase inhibitors
  • Erlotinib

Radiation therapy
Cranial and mediastinal radiation therapy may be indicated in patients with T-cell acute lymphoblastic leukemia. Common radiation therapy protocols include:[7]

  • 800 cGy cranial irradiation
  • 500 cGy to non-abdominal bulk disease

Surgery

  • Hematologic transplant is the mainstay of therapy for T-cell acute lymphoblastic leukemia.[5]
  • Targeted chemotherapy in conjunction with hematologic transplant is the most common approach to the treatment of T-cell acute lymphoblastic leukemia.[5]
  • Hematologic transplant can only be performed for patients with T-cell acute lymphoblastic leukemia with the following criteria:

Prevention

Primary Prevention

There are no primary preventive measures available for T-cell acute lymphoblastic leukemia.

  • Once diagnosed and successfully treated, patients with T-cell acute lymphoblastic leukemia should be followed-up periodically.

Secondary Prevention

Secondary preventive measures after diagnosis and treatment of T-cell acute lymphoblastic leukemia include follow-up and monitoring testing to determine the need for:

References

  1. Kim MA, Lee GW, Maeng KY (2005). "An unusual presenting feature of precursor T-cell acute lymphoblastic leukemia/lymphoma.". Ann Hematol. 84 (8): 553–4. PMID 15843931. doi:10.1007/s00277-005-1042-4. 
  2. 2.0 2.1 Nikolaus Friedreich. https://en.wikipedia.org/wiki/Nikolaus_Friedreich Accessed on April 27, 2016
  3. 3.0 3.1 "National Cancer Institute". 
  4. 4.0 4.1 4.2 4.3 4.4 4.5 "National Cancer Institute". 
  5. 5.0 5.1 5.2 Fagioli F, Quarello P, Zecca M, Lanino E, Rognoni C, Balduzzi A, Messina C, Favre C, Foà R, Ripaldi M, Rutella S, Basso G, Prete A, Locatelli F (2013). "Hematopoietic stem cell transplantation for children with high-risk acute lymphoblastic leukemia in first complete remission: a report from the AIEOP registry". Haematologica. 98 (8): 1273–81. PMC 3729909Freely accessible. PMID 23445874. doi:10.3324/haematol.2012.079707. 
  6. Chiaretti S, Foà R (2009). "T-cell acute lymphoblastic leukemia". Haematologica. 94 (2): 160–2. PMC 2635412Freely accessible. PMID 19181788. doi:10.3324/haematol.2008.004150. 
  7. Cherlow JM, Steinherz PG, Sather HN, Gaynon PS, Grossman NJ, Kersey JH, Johnstone HS, Breneman JC, Trigg ME, Hammond GD (1993). "The role of radiation therapy in the treatment of acute lymphoblastic leukemia with lymphomatous presentation: a report from the Childrens Cancer Group". Int. J. Radiat. Oncol. Biol. Phys. 27 (5): 1001–9. PMID 8262820. 

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