Prevalence of HTLV-I-associated T-cell lymphoma.

In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn.

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.

Undiagnosed adult T-cell leukemia/lymphoma in central Brooklyn, NY.

We present a case, identified by surveillance for adult T-cell leukemia/lymphoma (ATL), who had initial symptoms not specifically related to ATL, and who would not have been identified as having ATL otherwise. A 51-year-old Trinidadian black woman was hospitalized for abdominal pain, nausea, and vomiting. Hematology and clinical chemistry revealed leukocytosis (19,600/mm3), an elevated lymphocyte percent (63%), and hypercalcemia (19.4 mg/dl). The patient was serologically confirmed with HTLV-I-associated ATL. Lymphoma was diagnosed at autopsy. This case is representative of ATL, which along with HTLV-I infection, may be emerging public health problems in urban communities of the northeast and southeast United States.

Chronic hepatitis C in patients with sickle cell disease.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) antibody in patients with sickle cell disease and to analyze the nature of chronic liver disease in these patients. METHODS: A total of 99 patients attending a comprehensive sickle cell and thalassemia program at the Interfaith Medical Center, Brooklyn, NY, participated in the study. Eighty-five patients had sickle cell anemia (ss), eight had sickle C disease (sc), and six had sickle B thalassemia. History of blood transfusion, i.v. drug use, homosexuality, and alcohol abuse was obtained with a questionnaire and chart review. All patients were screened for HCV antibody by a first generation enzyme-linked immunosorbent assay. All positive results were confirmed with radioimmunoblot assay II (RIBA II). Patients were also checked for the presence of hepatitis B surface antigen. ALT levels were measured, and percutaneous liver biopsies were performed in patients positive for HCV antibody and greater than 1.5 times the normal ALT levels. RESULTS: Antibody to HCV was detected in 10/99 patients (10.10%). Seven of 30 patients (23.33%) who received more than 10 U of packed red blood cells were positive for HCV antibody. Only 3/38 (7.9%) patients with less than 10 U of packed red blood cells in the past were positive for HCV antibody. None of the patients who never received blood transfusion were positive for HCV antibody (0/31 or 0%). A total of seven liver biopsies were performed in patients positive for HCV antibody. Two out of seven specimens (28.57%) showed significant liver damage. One revealed cirrhosis, and the other showed chronic active hepatitis. The remainder of liver biopsies (5/7; 71.42%) showed only mild portal inflammation. CONCLUSIONS: The prevalence of HCV antibody is directly related to the number of blood transfusions in patients with sickle cell disease. Chronic HCV infection could be a major cause of cirrhosis of the liver in these patients.

An enhanced surveillance program for adult T-cell leukemia in central Brooklyn.

The Brooklyn Adult T-cell Leukemia/Lymphoma (ATL) study was developed to estimate the incidence of the human T-cell lymphotropic virus type I (HTLV-I)-associated ATL in the Crown Heights/Bedford Stuyvesant community. This central Brooklyn black community is an area which has already been shown in earlier reports to be endemic for HTLV-I-associated ATL. Surveillance has been conducted at seven area hospitals that serve this community, with surveillance already completed at five hospitals. Potential study subjects who are 20 years or older are identified by the review of admission records, discharge summaries, pathology and clinical chemistry reports, or physician referrals. Diagnoses of leukemia or lymphoma, or the presence of leukocytosis or hypercalcemia are used as criteria to identify the subjects. Participating subjects give a sample of blood for the determination of HTLV-I infection by serologic tests. At the time of enrollment, subjects provide demographic information including age, sex and birthplace. After one year of surveillance at five hospitals (39.5% of inpatient beds in the catchment), we have identified 12 cases of HTLV-I-associated ATL. The mean age of the ATL patients was 50 years, with patients being predominantly female (83.3%) and often Caribbean immigrants (83.3%). Interestingly, 42% of our cases were identified solely by findings of hypercalcemia from clinical chemistry reports. The remaining ATL cases were identified by physician referral. This enhanced surveillance program that uses both clinical and laboratory criteria for ATL case ascertainment can serve as a prototype for similar surveillance in other areas endemic for HTLV-I-associated ATL--an important effort because of the strong potential for disease prevention.

Seroprevalence of human T-lymphotropic virus in blacks from a selected central Brooklyn population.

Human T-cell leukemia virus type I (HTLV-I) has been causally linked to adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. Few seroprevalence studies have been carried out in the United States. Because of the number of reports of adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy in blacks from central Brooklyn, New York, we decided to initiate a seroprevalence study in this community. Intravenous drug users and male homosexuals were excluded. A total of 480 individuals from medical clinics and health fairs were surveyed via questionnaire, and their sera were assayed for HTLV-I/II antibody by two laboratories. An overall seroprevalence rate was 21/480 (4.4%). This is almost 200 times greater than a study of a national sample of U.S. blood donors. Rates were similar for individuals originating from the United States and the Caribbean. Nine of the 21 seropositive individuals returned for further testing. Polymerase chain reaction assays revealed that 8 were positive for HTLV-I and 1 for HTLV-II. Although this group may not be representative of the "normal" black population of central Brooklyn, the high seroprevalence rate necessitates that the incidence of HTLV-I-associated illnesses be determined in this community.

Photosensitivity, abnormal porphyrin profile, and sideroblastic anemia.

Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients.

Case report: adult T-cell leukemia/lymphoma associated with recurrent strongyloides hyperinfection.

Adult T-cell leukemia/lymphoma (ATLL) was demonstrated postmortem in a 47-year-old woman initially manifesting severe hypercalcemia and a vertebral compression fracture. Hyperinfection with Strongyloides stercoralis preceded the appearance of ATLL by several months and ultimately dominated the terminal course. Although HTLV-I and S. stercoralis commonly infect the same host, only three other cases of concomitant ATLL and hyperinfection have been reported in English. The apparent rarity of this association suggests that immunologic sequelae of ATLL do not predispose to dissemination and multiplication of Strongyloides. Observations pertinent to this conclusion are reviewed.

Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease.

In 1,814 patients with sickle cell disease who had been transfused, the overall rate of alloimmunization to erythrocyte antigens was 18.6%. The rate of alloimmunization in this group appears to be an explicit function of the number of transfusions received because it increases exponentially with increasing numbers of transfusions. Alloimmunization usually occurred with less than 15 transfusions, although the rate of alloimmunization continued to increase when more transfusions were given. The rate of alloimmunization was less in patients with hemoglobin SC disease and sickle-beta+ thalassemia because these patients had received fewer transfusions. Children less than 10 years old had a slightly lower rate of alloimmunization than patients in other age groups even after correction for the number of transfusions given. Women were more frequently alloimmunized than men; this was largely due to the fact that women received more transfusions than men, but in the age group 16 to 20 years the increase may have been due in part to alloimmunization owing to pregnancy. Forty-five percent of those alloimmunized made antibodies of only one specificity; 17% made four or more antibodies reacting with different antigens. Antibodies to the C and E antigens of the Rh group, the Kell antigen, and the Lewis antigens were most commonly made. These findings may be important in formulating a rational transfusion policy in sickle cell disease.

Endoscopic leukemic polyposis.

Gastrointestinal involvement in leukemia and lymphoma is common and may present with varying clinical manifestations (1). We report a case of gastrointestinal bleeding with endoscopic findings of diffuse leukemic polyposis and the response to radiotherapy, with a brief review of the literature.

Immunodetection of human T-cell lymphotropic virus type I core protein in biological samples by using a monoclonal antibody immunoassay.

A monoclonal antibody-based enzyme immunoassay (EIA) has been developed for detection of human T-cell lymphotropic virus type I (HTLV-I) core protein. The monoclonal antibody (clone 6.11) specifically recognizes the p19 gag gene-encoded protein of the virus. The EIA was over 100 times more sensitive than reverse transcriptase measurement and was capable of responding to less than 500 pg of whole-virus lysate. The assay exhibited type specificity in that HTLV-II antigens failed to produce a positive signal. In addition, a panel of other viruses demonstrated no antigenic cross-reactivity. These included herpesviruses, measles virus, human immunodeficiency viruses, and others. Viral p19 was followed during the course of density gradient ultracentrifugation in the presence of detergent, where it was noted to associate with viral membrane proteins. In comparison, reverse transcriptase activity localized in fractions of higher density containing envelope-free cores. Of clinical interest, the EIA was used to detect HTLV-I antigen in the viral cultures of patients with HTLV-I-associated myelopathies and from symptom-free individuals with proviral integration.

Acute pancreatitis in sickle cell crisis.

A case of acute pancreatitis, complicated by pseudocyst formation, is described in a patient with sickle cell crisis. The differential diagnosis is discussed and the literature reviewed.

Thrombotic thrombocytopenic purpura in patients with the acquired immunodeficiency syndrome (AIDS)-related complex. A report of two cases.

Immune thrombocytopenia has been reported with increased incidence in high-risk persons such as intravenous drug addicts and homosexual men who have serologic evidence of infection with human immunodeficiency virus (HIV). Thrombotic thrombocytopenic purpura, generally regarded as a rare disorder, has also been seen in association with exposure to HIV. Two patients had classical symptoms and laboratory findings of thrombotic thrombocytopenic purpura and the acquired immunodeficiency syndrome (AIDS)-related complex. Both patients belong to high-risk groups. They were treated with conventional therapy for thrombotic thrombocytopenic purpura and followed for 3 months. Their response to treatment was no different from that of other groups of patients with this syndrome. This article alerts physicians to the possible association of thrombotic thrombocytopenic purpura, AIDS, and AIDS-related complex.

Adult T-cell leukemia/lymphoma in Brooklyn.

Fifteen patients with adult T-cell leukemia/lymphoma (ATLL) were identified in less than a two-year period in the Crown Heights-Bedford Stuyvesant section of Brooklyn, NY. All patients were black; nine patients originated from the Caribbean islands and six from the southern United States. Two of the patients were father and daughter, the first evidence of familial occurrence in the United States. Their clinical course was similar to that of previously described patients with this disorder. To our knowledge, these 15 patients represent the largest series of ATLL reported in the United States. We recommend that ATLL be seriously considered in the differential diagnosis of patients with non-Hodgkin's lymphoma, mycosis fungoides, lymphatic leukemia, or hypercalcemia.

The first report of familial adult T-cell leukemia lymphoma in the United States.

Two patients, a daughter and her father, developed the acute type of adult T-cell leukemia/lymphoma (ATLL) within a 3-month period. Antibodies against HTLV-I have been found in both wives of the father. The second wife acquired the infection from her husband within 3 years of marriage. The patients described represent the first cases of familial ATLL in the United States. ATLL continues to be frequently misdiagnosed in the United States. A positive family history consistent with this disease in a patient with a lymphoid malignancy may be a helpful clue for earlier diagnosis.

Length polymorphisms of the human Y chromosome in patients with chronic myelogenous leukemia.

The extent of length heteromorphisms of the human Y chromosomes was measured in 50 patients with chronic myelogenous leukemia and was compared with 50 normal controls. No significant difference (p greater than 0.05) in the size of the Y chromosome was noted between these two groups. These findings differ from an earlier investigation, where a longer heterochromatic segment of Y chromosome was noted in malignant tumors and it was stressed that constitutive heterochromatin plays a role in susceptibility of cancer. Present investigation, however, suggests that this is not the case in patients with chronic myelogenous leukemia.

Chromosomal abnormalities in adult T-cell leukemia/lymphoma (ATL). A report of six cases with review of the literature.

Chromosomal studies were performed on six patients with adult T-cell leukemia (ATL). Structural abnormalities of chromosome 3 were the most common. In one case a complete loss of the short arm of chromosome 10 (10 p-) was noted while in another case a balanced translocation involving chromosome 10p and 4q was found. These abnormalities have not been previously reported. After reviewing the literature, it was concluded that chromosomes 3, 6, 10, 13, 14, and X were most frequently involved in abnormalities. Specific and consistent chromosomal abnormalities were noted in each study. Therefore, it is hypothesised that the mutation rate for this virus may be higher than first expected. Furthermore, the relative consistency of heterogeneous findings in different localities may reflect a geographic clustering of specific chromosomal abnormalities which may in turn be related to specific and geographically associated viral mutations. To support these suggestions not only are more cytogenetic data required but a molecular evaluation of these patients must be carried out to establish a relationship, if any, between genetic abnormalities and the epidemiology of ATL.

Role of heterochromatin during preferential 9q;22q translocation in chronic myelogenous leukemia.

The secondary constriction region (h) of human chromosome 9 was evaluated in 55 chronic myelogenous leukemia (CML) patients with respect to its size and position. Each case was examined by C-banding and distamycin A-4,6-diamidino-2-phenylindole techniques for the expression of the h regions. When one h region of chromosome 9 was larger, it was more frequently involved in the reciprocal translocation with chromosome 22. In addition, there was a higher incidence of pericentric inversions in the h regions in the translocated chromosome 9 when compared with normal homologues. The role of the constitutive heterochromatin of chromosome 9 as a possible influencing factor during 9q;22q translocation in CML is suggested.

Long survival in Philadelphia-chromosome-positive acute leukemia.

A case of Philadelphia (Ph)-chromosome-positive acute leukemia (AL) is presented who went into remission with disappearance of the Ph1 chromosome and later on developed the chronic phase of chronic granulocytic leukemia (CGL) with reappearance of the Ph1 chromosome. The patient is alive 6+ years following the diagnosis. The entity of Ph1-positive AL is discussed. It is suggested that the patients with Ph1-positive AL who develop CGL have a better prognosis than previously described.