What Is Adult T-Cell Leukemia?

Adult T-cell leukemia (ATL) is a special type of malignant clonal proliferative disease of the lymphatic system that is directly related to human T-cell leukemia virus (HTLV-) infection. Lymphocytes in the peripheral blood can also invade the bone marrow. The disease was first proposed by a Japanese scholar Gao Yueqing in 1976. Its clinical features are liver, spleen, lymphadenopathy, skin infiltration, interstitial lung infiltration and hypercalcemia. After the disease was found in southwestern Japan, the United States, the Caribbean and other countries have also reported the disease. ^[1]

Adult T-cell leukemia

Basic overview of adult T-cell leukemia

Adult T-cell leukemia (ATL) is a special type of malignant clonal proliferative disease of the lymphatic system that is directly related to human T-cell leukemia virus (HTLV-) infection. Lymphocytes in the peripheral blood can also invade the bone marrow. The disease was first proposed by a Japanese scholar Gao Yueqing in 1976. Its clinical features are liver, spleen, lymphadenopathy, skin infiltration, interstitial lung infiltration, and hypercalcemia. After the disease was found in southwestern Japan, the United States, the Caribbean and other countries have also reported the disease. ^[1]

Causes of adult T-cell leukemia

The occurrence of ATL is related to human T-cell leukemia virus type I (HTV-) infection, and the patient's serum was positive for HTLV-. The high-incidence area is the southern part of Kyushi Island in Japan, where 10% to 15% of the residents are positive for HTLV-I antibodies, and the incidence is very low elsewhere. How to link the high incidence areas in Japan with the incidence in other regions is unclear.

Studies have shown that host susceptibility and / or common environmental conditions are related to HTLV-I infection. The positive rate of HTLV- antibody among family members is 3 to 4 times that of irrelevant normal population. HTLV- virus can be isolated from the serum of patients with positive antibodies and clinically normal patients. ^[2]

Adult T-cell leukemia disease test

peripheral blood

Unlike other acute leukemias, ATL patients generally do not have anemia and thrombocytopenia. Even those with anemia and thrombocytopenia are less severe, and severe anemia and thrombocytopenia are rare. Leukocyte counts often increase, especially in acute and chronic patients. Lymphocytes account for 10% to 90%, and lymphocytosis is also mainly seen in patients with acute and chronic ATL.

Bone marrow

Lymphocytes can be less than 30% or more than 60%. Seeing polymorphonuclear lymphocytes is one of the features of the disease, accounting for more than 10% of peripheral blood. Cytochemistry showed PAS positive, acid phosphatase positive, TdT negative, and peroxidase negative.

Immunophenotype

The most common phenotype is CD4 CD8-, but some patients show CD4 CD8-, CD4- CD8, or CD4 CD8- phenotypes. Commonly expressed ATL cells are CD2, CD3, CD4, CD8-, CD25.

Cytogenetics

ATL does not have a single prominent chromosomal translocation, but 28% affects q32 on chromosome 14, and 15% affects q11. Triploid 7, 6q-, 13q-, 14q +, and 3p + are also common.

Prion test

Anti-HTLV- antibody can be detected by enzyme-labeled immunoassay or indirect immunofluorescence test; RT-PCR method can be used to detect RNA expression of HTLV- virus in tumor cells, especially the positive DNA of HTLV provirus is of great significance in the diagnosis of the disease; Detection of HTLV- proviral load by PCR technology is helpful for early assessment of ATL tumor load.

Biochemical examination

Hypercalcemia, GOT, GPT, LDH, bilirubin, alkaline phosphatase are elevated.

X-ray

Chest radiographs can show diffuse infiltration of the lungs, and epiphyseal X-ray films often have osteolytic damage.

B-ultrasound

Superficial lymphadenopathy, retroperitoneal lymphadenopathy, and hepatosplenomegaly may be indicated.

pathological examination

Lymph nodes, skin biopsy showed ATL cell infiltration. ^[3]

Clinical diagnosis of adult T-cell leukemia

ATL patients have a variety of clinical manifestations, which can be manifested as leukemia-like acute type, lymphocytic lymphoma type, chronic type with good prognosis, and smoking status (hidden attack type).

Lymphadenopathy is present in almost all patients. Many patients have extensive lymphadenopathy, and most have retroperitoneal lymphadenopathy, but mediastinal masses are rare. Bone marrow is often infiltrated with leukemia cells. Other common affected areas are the lungs, liver, skin, gastrointestinal tract, and central nervous system.

Skin involvement occurs in about 2/3 of patients, and most patients with skin infiltration can see focal ATL cell infiltration or Pautrier microabscesses.

Major clinical manifestations of each type

Acute type: The median age of patients is 40 years. Typical manifestations are: the onset is very urgent, mainly rapid skin damage, hypercalcemia, or both. There are various types of skin damage, such as scattered tumor masses, fused nodules, plaques, pimples, and non-specific erythema. Patients with hypercalcemia often show weakness, indifferent expression, insanity, polyuria, and thirst.

Chronic: May have lymphadenopathy, hepatosplenomegaly, skin and lung infiltration, no hypercalcemia, no central nervous system, bone, gastrointestinal infiltration, no ascites and pleural effusion

Lymphoma type: Lymph node histology has proven to be lymphadenopathy without leukemia cell infiltration.

Smoke type: skin damage is its characteristic, which can manifest as erythema, pimples, and nodules. May have lung infiltration. Generally without hypercalcemia, lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration are mild; there is no central nervous system infiltration. ^[4]

Adult T-cell leukemia treatment

This disease mostly depends on different clinical types to determine treatment strategies. Chronic or smoking patients mostly use symptomatic supportive treatment, mainly to actively control infection and improve organ function. When the disease progresses or acute changes, only consider Use active treatment. Acute or lymphoma ATL, although using active treatments such as chemistry and biology, is not effective, with a median survival of 2 to 6 months.

Chemotherapy

The most commonly used treatment regimen is the VEPA regimen (vincristine 1 mg / week for 6 weeks; cyclophosphamide 300 mg / d for days 8, 22, and 29; prednisone 40-60 mg / d for 3 days per week; more Roubicin (doxorubicin) (40-60 mg / d, Days 1 and 22) was used to treat 322 patients, and 7l (22%) were completely relieved. The classic CHOF regimen was also ineffective, with 10 (17%) of the 59 patients having a complete response. Other available programs include CVP program, MACOP-B program, ProMACE-MOPP program, etc., the treatment effect is not ideal. Recently, Japanese scholars used the LSG15 regimen (7 cycles of VCAF, AMP, and VECP regimens) plus granulocyte growth factor (G-CSF) to treat 96 patients with advanced ATL, with a complete response of 33 (35.5%) and a partial response of 42 ( 45.2%), with a median survival time of 13 months and a 2-year disease-free survival rate of 31.3%, which is significantly higher than other chemotherapy regimens. Chemotherapy is still the main method to treat advanced ATL.

retinoic acid (all trans retinoic acid)

Retinoic acid (ATRA) may affect or block the Tax / NF-KB signal channel of ATL cells. It has been used in clinical treatment of chemotherapy-resistant ATL patients, and the clinical efficacy needs to be further verified.

Interferon

Interferon-2b can be used for ATL treatment, but the effect is not good. There have been several reports on the use of interferon -2b in combination with the antiviral drug zidovudine (azidothymidine) to treat patients with ATL and have achieved certain effects. White et al. Used interferon -2b 2.5 million to 10 million U, subcutaneously, once per day and zidovudine (AZT) 50 to 200 mg, orally, 5 times per day, in 18 patients with ATL, except 6 In addition to the inability to evaluate the efficacy, 1 case of complete remission lasted 21.6 months, and 2 cases of partial remission lasted 3.7 months and 26.5 months, respectively. Matutes et al. Used the above method to treat 15 patients who have previously received various treatments for ATL, of which 8 cases had complete or partial remission, and the other 7 were ineffective.

Immunotherapy

Monoclonal antibodies to IL-2R (Tac) can be used for ATL treatment. Clinical data show that in 20 cases of ATL treated with anti-Tac, 1 case had a transient uncertainty. Four patients had partial remission and 2 had complete remission. Anti-Tac can also be cross-linked with immune radionuclide (90Y) for the treatment of ATL patients. Of the 15 patients treated, 8 were partially relieved and 2 were completely relieved.

Hematopoietic stem cell transplantation

Utsunomiya et al. Used allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat 10 patients with ATL, of which 9 donors were related and 1 unrelated donor. The median disease-free generation period was 17.5 months, indicating that allo-HSCT was used for ATL treatment can achieve certain effects.

There are osteolytic lesions and hypercalcemia, pamidronate disodium 90mg can be used, intravenous injection, once a month. ^[5]

Adult T-cell leukemia disease prevention

Adult T-cell leukemia infection has a clear transmission pathway, mainly through mother-to-child, blood, and sexual contact. So the precautions should be as follows:

Develop health education on STD prevention and treatment.

Promote safe sex and actively promote the use of condoms.

Carry out prevention of mother-to-child transmission of HTLV-1 and avoid mother-to-child feeding to reduce infant infection.

When using blood, blood, or blood products, they must be strictly tested to avoid unnecessary injections, blood transfusions, and use of blood products. ^[6]

Prognosis of adult T-cell leukemia

The disease has a poor prognosis. The Japanese Lymphoma Research Group reported 854 ATL patients, with a median follow-up time (calculated from diagnosis) of 14 months, 585 (68.5%) had died, 269 (31.5%) were still alive, and the median survival was only 6 Month, 2-year, and 4-year expected survival rates were 28% and 12%. Factors suggesting poor prognosis include: poor general condition; hyperlactate dehydrogenase; age> 40 years; multiple site involvement; hypercalcemia; CD4-, CD8-; CD4 +, CD8 or CD4-, CD8; Ki-67> 18%.