|LETTER TO THE EDITOR - DOCUMENTING A CASE
|Year : 2011 | Volume
| Issue : 3 | Page : 338-340
Adult T-cell leukemia in India: Report of two cases and review of literature
Udupa Karthik1, Prasanth Ganesan1, Tenali Gnana Sagar1, Sanju Cyriac1, Urmila Majhi2
1 Department of Medical Oncology, Cancer Institute, Adyar, Chennai, India
2 Department of Pathology, Cancer Institute, Adyar, Chennai, India
|Date of Web Publication||2-Nov-2011|
Department of Medical Oncology, Cancer institute (WIA), Adyar, Chennai - 600 020
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Karthik U, Ganesan P, Sagar TG, Cyriac S, Majhi U. Adult T-cell leukemia in India: Report of two cases and review of literature. J Can Res Ther 2011;7:338-40
|How to cite this URL:|
Karthik U, Ganesan P, Sagar TG, Cyriac S, Majhi U. Adult T-cell leukemia in India: Report of two cases and review of literature. J Can Res Ther [serial online] 2011 [cited 2019 Sep 21];7:338-40. Available from: http://www.cancerjournal.net/text.asp?2011/7/3/338/86999
Adult T-cell leukemia lymphoma (ATLL) is a rare lymphoproliferative disorder that was first described as a distinct clinical entity in 1977 in Kyoto, Japan.  Human T Lymphotropic Virus type I (HTLV-I) has been implicated in the pathogenesis and hence this condition is mostly reported in areas of the world where the virus is endemic.  About 2% of HTLV-I-infected patients develop ATLL in their lifetime, and >95% of ATLL patients show serologic evidence of HTLV-1. ATLL can present in four forms-acute, lymphomatous, chronic, and smoldering. Of these, the acute leukemic form is the commonest and has a stormy course with a median survival of 6-10 months.  So far, only two cases of ATLL have been reported from India including one from our own center. ,
A 68-year-old man presented with history of skin lesions over chest and groin and gradually worsening breathlessness of 4 months. He was in Eastern Co-operative Oncology Group-Performance Status-3 and had generalized lymphadenopathy, bilateral pleural effusion, pericardial effusion, and hyperpigmented plaques over anterior aspect of chest, back, and groin. Investigations revealed the following: Hemoglobin 129 g/L, white blood cell (WBC) count of 74.9 × 10 9 /L with 80% atypical lymphocytes ("flower cells"; [Figure 1]a), and platelet count of 180 × 10 9 /L. His bone marrow was infiltrated with atypical lymphocytes which were CD2, CD3, CD4, CD5, CD25, CD45 positive, and CD7 and CD8 negative by flow cytometry. Skin biopsy showed lymphomatous infiltration of the dermis [Figure 1]b. HTLV-1 serology by enzyme immune assay was positive. His HIV 1 and 2 serology was negative. Diagnosis of ATLL was made and he received cyclophosphamide, vincristine, and prednisolone (COP) after which there was improvement in performance Status, resolution of effusions, and reduction in skin lesions. He was started on cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy. However, within 2 weeks, lymph nodes and skin lesions reappeared and WBC count increased. He expired within 3 months of diagnosis due to progressive disease.
|Figure 1: Giemsa stained peripheral blood smear showing fl ower cells (a) and skin biopsy (b) from the same patient showing infi ltration by atypical lymphocytes in the dermis with scattered lymphoid cells around blood vessels. The lack of infi ltration in the epidermis is point of differentiation from mycosis fungoides/Sezary syndrome|
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A 51-year-old male presented with worsening fatigue for 1 month. He had generalized lymphadenopathy and hepatomegaly. Investigations revealed the following: Hemoglobin of 98 g/L, WBC count of 46.7 × 10 9 /L (71% atypical lymphocytes), and platelet count of 220 × 10 9 /L. Serum calcium was elevated 14 mg/dL (normal value 8.4-10.2 mg/ dL). Bone marrow was infiltrated with atypical lymphocytes [Figure 2]a which were CD2, CD3, CD4, CD5 positive and CD8 negative by flow cytometry. Cervical lymph node biopsy showed infiltration by high-grade T-cell lymphoma with CD3 being strongly positive [Figure 2]b and c. His HTLV-1 serology was positive by enzyme immune assay and ATLL was diagnosed. He also was negative for HIV serology. Patient completed three courses of CHOP chemotherapy and showed a good response initially with reduction in lymph nodes and WBC count. But after three cycles, there was reappearance of the lymph nodes and rapidly progressing pleural effusion. He died 4 months after diagnosis due to progressive disease.
|Figure 2: Lymph node biopsy (a) shows effacement of the architecture and total replacement by atypical lymphoid cells with scanty cytoplasm, large vesicular nuclei, and prominent nucleoli which are CD3 positive (b). Bone marrow biopsy showing infi ltration by atypical lymphocytes (c)|
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ATLL has been mostly reported from Japan, the Caribbean islands, and parts of South America.  Only few sporadic cases of ATLL are reported from other parts of the world. The low incidence of ATLL in Indian population may be due to the rarity of HTLV-1 infection. There was no detectable HTLV-1 infection among 946 healthy volunteers screened at a single center in North India.  However, an analysis of blood donors from Mumbai showed a 1.9% prevalence of HTLV infection.  A study from South India showed HTLV-1 prevalence of 3.7% among HIV-positive, patients while the rate was 0.3% in the HIV-negative population. 
There were two earlier reports of ATLL from India. , It is interesting to note that three of the four cases of ATLL reported from India is from South India. All four cases of ATLL reported from India presented with leukemic form and survived less than 6 months [Table 1].
HTLV-I is usually transmitted by exposure to blood, through breast milk, or transplacentally.  Both the above cases did not give any history of multiple sexual contacts or prior transfusions.
ATLL is a disease found mostly in adults, and majority (60%) of the cases present in the acute leukemic form with a high number of circulating leukemic cells. This may be associated with hypercalcemia, lymphadenopathy, visceral or leptomeningeal involvement, and opportunistic infection and has a median survival of 6 months. The diagnosis of acute ATLL requires positive HTLV-1 serology, peripheral smear showing 5% or more of atypical cells (flower cells) along with leukemic manifestations.  Most patients with ATLL exhibit phenotype of mature CD4 + T cells and express CD2, CD5, CD25, CD45RO, CD29, T-cell receptor αb, and HLA-DR. Usually, ATLL cells lack CD7 and CD26 and exhibit diminished CD3 expression. The close differential diagnosis of acute ATLL is mycosis fungoides which may have a better prognosis. The lack of epidermotropism on the skin biopsy, the more aggressive behavior of ATLL, associated hypercalcemia, and the demonstration of HTLV-I infection help to differentiate this from mycosis fungoides.
No standard therapy exists for ATLL. Although complete response rates of 30-40% are reported with different combinations of drugs (CHOP, MACOP-B, and PROMACE), no one regimen has been consistently effective.  Responses, when they do occur, are mostly short lasting and patients rapidly relapse and die of progressive disease due to intrinsic chemoresistant nature of the disease. Both our patients received CHOP chemotherapy and had transient responses followed by stormy, fatal progression. Intense combination chemotherapies such as the LSG15 protocol or allogenic bone marrow transplantation are some of the options that are being tried to improve the survival of patients suffering from ATLL.  Another approach is to use a combination of zidovudine and interferon alfa which showed a 5-year survival rate of 46% (compared with 20% with chemotherapy). 
Although ATLL is a rare disease in India, these reports indicate that it must be an important differential diagnosis of aggressive T-cell lymphomas/leukemias. The outcome is poor with conventional chemotherapy and newer therapeutic approaches such as antiviral therapy may be needed.
| > References|| |
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