Epidemiologic Notes and Reports Adult T-Cell Leukemia/Lymphoma Associated With Human T-Lymphotropic Virus Type I (HTLV-I) Infection -- North Carolina

A case of adult T-cell leukemia/lymphoma (ATL) associated with human T-lymphotropic virus type I (HTLV-I) has been reported from North Carolina. The patient, a black adult male, developed jaundice in December 1986, after several weeks of anorexia, fatigue, and fever.

When admitted to the hospital, he had an enlarged liver, a serum bilirubin level of 15.5 mg/dL, and an SGOT level of 279 IU/L, but serologic tests for hepatitis B markers and hepatitis A antibody were negative. Ultrasound examination revealed no evidence of intra- or extra-hepatic obstruction. He was thought to have alcoholic hepatitis. During the next week, he became pancytopenic, and bone marrow biopsy revealed hypocellularity of all cell lines but no malignant infiltrates. He was given transfusions of red blood cells and platelets and was discharged in February 1987, despite continued clinical and laboratory abnormalities. The diagnosis upon discharge was resolving hepatitis.

In March 1987, the patient returned to the hospital because of abdominal pain, nausea, vomiting, and somnolence. Laboratory studies revealed a leukocytosis with abnormal lymphocytes, a calcium level of 20.5 mg/dL, and an amylase level of 1,209 IU/L. He was thought to have ATL with hypercalcemia and consequent acute pancreatitis. His condition deteriorated despite chemotherapy and treatment for hypercalcemia, and he died on March 22. Autopsy revealed leukemic infiltrates in the spleen, bone marrow, and kidneys. When peripheral blood mononuclear cells obtained before the patient's death were subjected to flow cytometric analysis, 95% of the cells were of the CD4+ (T-helper cell) phenotype. Antibodies against HTLV-I were detected in several serum samples by radioimmunoassay and by Western blot. HTLV-I was isolated from the man's peripheral blood lymphocytes.

The patient had served in the U.S. Army in South Vietnam, Korea, and Germany and had gone to North Carolina after discharge. He was divorced at the time of his illness. He had used intravenous drugs and had shared needles with a woman with whom he had had sexual contact for 2 years before his illness. He had never had a blood transfusion.

Serum specimens were obtained from 28 family members and sexual contacts of the patient. Five of these persons had antibodies against HTLV-I. They comprised the woman with whom the patient had had sexual contact and had shared needles, this woman's former husband, another former female sexual partner of the patient, the patient's sister, and the sister's daughter. None of these persons had lived outside the United States or had received blood transfusions, and none other than the woman with whom the index patient had shared needles were known to have used intravenous drugs.

A serosurvey of 245 attendees at sexually transmitted disease and family planning clinics in the county in which the patient had resided revealed no persons seropositive for antibody against HTLV-I. Reported by: JB Weinberg, MD, DL Blazey, MD, PhD, TJ Matthews, PhD, BF Haynes, MD, TJ Palker, PhD, Veterans Administration and Duke Univ Medical Center, Durham; RA Spiegel, DVM, MPH, RA Meriwether, MD, JN MacCormack, MD, MPH, State Epidemiologist, North Carolina Dept of Human Resources. M Robert-Guroff, PhD, M Popovic, MD, Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health. Div of Field Svcs, Epidemiology Program Office; Div of Viral Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: HTLV-I, the first human retrovirus to be discovered, was first isolated and reported in the United States in 1980 (1) and in Japan in 1981 (2). Infection with HTLV-I, like infection with other retroviruses, probably occurs for life and can be inferred when antibody against HTLV-I is detected in the serum. Studies of HTLV-I antibody indicate that the virus is endemic in southern Japan (3), in the Caribbean (4), and in Africa (5,6).

HTLV-I infection in the United States appears to be rare. Although little serologic data exist, prevalence of infection is thought to be highest among blacks living in the Southeast (7). A prevalence rate of 30% has been found among black intravenous drug abusers in New Jersey, and a rate of 49% has been found in a similar group in New Orleans (8). It is possible that prevalence of infection is increasing in this risk group.

ATL is usually a highly aggressive non-Hodgkin's lymphoma with no characteristic histologic appearance except for a diffuse pattern and a mature T-cell phenotype. Circulating lymphocytes with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that HTLV-I causes ATL. This evidence includes the frequent isolation of HTLV-I from patients with this disease and the detection of HTLV-I proviral genome in ATL leukemic cells (9). ATL is frequently accompanied by visceral involvement, hypercalcemia, lytic bone lesions, and skin lesions (10). Most patients die within 1 year of diagnosis.

ATL is relatively uncommon among those infected with HTLV-I. The overall incidence of ATL is estimated at about 1 per 1,500 adult HTLV-I carriers per year (11,12). Those cases that have been reported have occurred mostly among persons from the Caribbean or blacks from the Southeast (National Institutes of Health, unpublished data).

The presence in this investigation of family members and sexual contacts who are seropositive for HTLV-I is consistent with current knowledge concerning transmission of HTLV-I infection. Transmission occurs from mother to child; by sexual contact; and through exposure to contaminated blood, either through blood transfusion or sharing of contaminated needles. The source of the patient's sister's infection is obscure. She and her brother may have acquired infection from their mother, who is deceased.

Because of the rarity of ATL in the United States and the potential for learning more about the transmission of HTLV-I in the United States, physicians who see adults with diffuse non-Hodgkin's lymphoma with at least two features consistent with ATL (abnormal lymphocytes on peripheral blood smear, T-cell phenotype of malignant cells, visceral involvement, hypercalcemia, lytic bone lesions, and skin lesions) are encouraged to report these cases through their local and state health departments to the Retrovirus Diseases Branch, Division of Viral Diseases, Center for Infectious Diseases, CDC, telephone number (404) 639-3091.

References

1. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci USA 1980;77:7415-9.

2. Hinuma Y, Nagata K, Hanaoka M, et al. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci USA 1981;78:6476-80.

3. Maeda Y, Furukawa M, Takehara Y, et al. Prevalence of possible adult T-cell leukemia virus-carriers among volunteer blood donors in Japan: a nation-wide study. Int J Cancer 1984;33:717-20.

4. Blattner WA, Kalyanaraman VS, Robert-Guroff M, et al. The human type-C retrovirus, HTLV, in blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma. Int J Cancer 1982;30:257-64.

5. Hunsmann G, Bayer H, Schneider J, et al. Antibodies to ATLV/HTLV-1 in Africa. Med Microbiol Immunol 1984;173:167-70.

6. Hunsmann G, Schneider J, Schmitt J, Yamamoto N. Detection of serum antibodies to adult T-cell leukemia virus in non-human primates and in people from Africa. Int J Cancer 1983;32:329-32.

7. Blayney DW, Blattner WA, Robert-Guroff M, et al. The human T-cell leukemia-lymphoma virus in the southeastern United States. JAMA 1983;250:1048-52.

8. Weiss SH, Ginzburg HM, Saxinger WC, et al. Emerging high rates of human T-cell lymphotropic virus type I (HTLV-I) and HIV infection among U.S. drug abusers. Presented at the third international conference on acquired immunodeficiency syndrome (AIDS), Washington, DC, June 1-5, 1987.

9. Hinuma Y. Natural history of the retrovirus associated with a human leukemia. Bioessays 1985;3:205-9.

10. Kuefler PR, Bunn PA Jr. Adult T cell leukaemia/lymphoma. Clin Haematol 1986;15:695-726.

11. Tajima K, Kuroishi T. Estimation of rate of incidence of ATL among ATLV (HTLV-I) carriers in Kyushu, Japan. Jpn J Clin Oncol 1985;15:423-30.

12. Kondo T, Nonaka H, Miyamoto N, et al. Incidence of adult T-cell leukemia-lymphoma and its familial clustering. Int J Cancer 1985;35:749-51.

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