Adult T-cell Leukemia Cases Research Articles

TWO CASES OF ADULT T-CELL LEUKEMIA ASSOCIATED WITH OTHER MALIGNANCIES

We encountered two cases of adult T cell leukemia (ATL) associated with a cancer of other organs. In both cases, atypical lymphocytes were found in the peripheral blood, with the anti HTLV-1 antibody test being positive. Careful examination revealed that these cases were smoldering ATL.One case had bloody stool. Barium enema and fiberoptic colonoscopy resulted in a diagnosis of carcinoma of the anal canal, and abdominoperineal excision of rectum was performed.In the other case, a mass was palpated in the right side of the neck, and with a diagnosis of submandibular carcinoma based on cervical CT scan and echography, the mass was resected.In cases of ATL, compromised immunocompetence seems to be included in the mechanisms of development of multiple cancer, where a probable high risk of gastrointestinal carcinoma is considered. Since ATL associating with multiple cancer poses many therapeutic problems and the authors also have had troubles in the treatment, these cases are reported for reference.

A Case of Adult T-Cell Leukemia with a Defective HTLV-I Proviral DNA, in which the Single T-Cell Clone Appeared to Have Progressed from Chronic Phase to Crisis

A Case of Adult T-Cell Leukemia with a Defective HTLV-I Proviral DNA, in which the Single T-Cell Clone Appeared to Have Progressed from Chronic Phase to Crisis

急性肝不全の経過の前後で肝組織像を観察し得た成人Ｔ細胞白血病の１剖検例

急性肝不全で死亡した成人T細胞白血病(ATL)の発症早期および死亡時に肝組織像を観察し得た1例を報告する.症例は53歳男性.慢性ATLの診断で経過観察されていたが肝機能異常は認められていない.入院約10日前より全身倦怠感,皮疹,皮膚の黄染が出現.入院時肝は腫大し,血清総ビリルビン(TB)値10.6mg/dl, GOT 4,167IU/lと高度の肝機能障害を認めた.末梢白血球数は18,900/mm3で,うち75%がATL細胞であった.肝生検で,門脈域を中心にATL細胞を含む単核球の著明な浸潤が認められた.G-I療法,インターフェロン,mPSL大量療法,血漿交換等の治療に抵抗してTB値は50.3mg/dlと著増,PT活性値は32%まで低下し入院20日目に死亡した.剖検肝は黄色調で910gと萎縮し,組織上は広範な肝細胞壊死と出血が認められ,臓器Schwartzman反応の関与が考えられた.報告されている急性肝不全を呈したATL症例6例をまとめ,肝障害の機序について考察した.

Adult T-cell leukemia/lymphoma of the tongue

A case of posterior tongue lymphoma associated with adult T-cell leukemia (ATL) that occurred as a lesion in the lingual dorsal portion is reported in a 64-year-old woman. Initially, a diagnosis of Hodgkin's lymphoma was considered as no findings associated with ATL except lymphadenopathy and serum anti-ATLA antibodies were present. Combined radiotherapy and chemotherapy were administered with favorable results; however, 4 months later, Pneumocystis carinii pneumonia developed, and 2 months later, generalized lymphadenopathy and hypercalcemia evolved. At this time, a diagnosis of ATL was made. The patient died of renal dysfunction 6 months after the initial presentation. In suspected cases of ATL and malignant diseases of T-cell lineage, namely, malignant lymphoma and mycosis fungoides, the presence of HTLV-I infection should be confirmed by testing for anti-ATLA antibodies.

Reclassification of Leukemia among A-Bomb Survivers in Nagasaki Using French-American-British (FAB) Classification for Acute Leukemia

The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85% agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2%. The present study suggests that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure.

An Autopsy Case of Adult T-cell Leukemia with Marked Melena due to Small Intestine Involvement

An Autopsy Case of Adult T-cell Leukemia with Marked Melena due to Small Intestine Involvement

Hypercalcemia and osteoclast proliferation in adult T-cell leukemia.

Eighteen autopsy cases of adult T-cell leukemia (ATL) were investigated clinicopathologically. Thirteen of the patients had hypercalcemia during their clinical course. Nine of the thirteen had a high level of serum calcium at the terminal stage, even after extensive chemotherapy. Microscopic examination of the bone revealed proliferation of osteoclasts and bone resorption in eight patients. No osteoclast proliferation or bone resorption was found in the other nine normocalcemic patients. The infiltration of ATL cells was observed in only two patients--one was hypercalcemic and the other, normocalcemic. The factors affecting the serum calcium level were examined in two hypercalcemic patients. Hypercalcemia could not be accounted for by parathyroid hormone or prostaglandins E levels, which were in the normal range, or by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, which were low. Our findings are consistent with the mechanism proposed by several investigators, that the malignant T-lymphocytes produced an osteoclast-activating-factor-like substance that caused osteoclast proliferation and hypercalcemia.

A CLINICOPATHOLOGICAL REVIEW OF 12 AUTOPSIED CASES OF ADULT T‐CELL LEUKEMIA

Twelve autopsied cases with adult T-cell leukemia (ATL) were reviewed clinicopathologically. The prognosis of three cases who had suffered from severe cutaneous lesions was much better than that of the other nine cases with no or negligible cutaneous lesions. The surface marker of leukemic cells from six cases was ordinary inducer/helper phenotype (OKT4+ and 8-), but in one case leukemic cells showed OKT4+ and 8+. In another case, a significant amount of leukemic cell infiltration was found in the thymic cortex. Calcium content in the bone of ATL cases was lower than that of the patients without ATL (control group), and six cases with ATL (50%) were complicated by severe hypercalcemia. Neither adenoma nor hyperplasia of the parathyroid glands was found in any case. In most severely hypercalcemic patients, bone trabeculae were actively absorbed by numerous osteoclasts and partly replaced by fibrous tissues. In two normocalcemic patients, skeletal calcium content was also markedly reduced by osteoporosis, but the activation of osteoclasts was inconspicuous. It was speculated that the manner of bone resorption in ATL cases was diverse and there were some clinicopathological subtypes in ATL from the viewpoints of cutaneous lesions, hypercalcemia, and bone lesions.

Familial disposition of adult T-cell leukemia and lymphoma.

Sixteen families, each with two or more cases of adult T-cell leukemia or lymphoma were found in the Nagasaki district. Eight of the families had a parent with lymphoma. In the other eight families siblings were involved. Four families with sibling cases are presented in detail. Antibody titres to adult T-cell leukemia associated antigen (ATLA) in cases of ATL, CTL, T-CLL, and pre-ATL cases in Nagasaki were all positive. Of the non-leukemic T-cell malignant lymphoma 62.5 per cent were positive for antibody. The positive rate in healthy spouses and siblings of ATLL patients for ATLA antibody was high (67.5 per cent and 40 per cent respectively). The possibility of ATLV infection through spouses or from mother to child and the meaning of the high familial incidence of ATLL is discussed.

An Autopsy Case of Adult T-cell Leukemia with Chromosome Abnormality and OKT4 and OKT8 Subsets, Complicated with Intestinal Involvements

An Autopsy Case of Adult T-cell Leukemia with Chromosome Abnormality and OKT4 and OKT8 Subsets, Complicated with Intestinal Involvements

A Case of Adult T-cell Leukemia (Chronic Type) with Helper Activity of Peripheral T-cells on Immunoglobulin Production of B-cells

A Case of Adult T-cell Leukemia (Chronic Type) with Helper Activity of Peripheral T-cells on Immunoglobulin Production of B-cells

Human T-cell leukemia virus: causative roles in development of adult T-cell leukemia and provirus integration into leukemic cell DNA.

AbstractHuman T‐cell leukemia virus (HTLV) was isolated from a cutaneous T‐cell lymphoma patient by Gallo and his colleagues (Poiesz et al., 1980) and adult T‐cell leukemia virus (ATLV) was isolated from patients with adult T‐cell leukemia (ATL) in Japan (Yoshida et al., 1982). Originally, these two viral isolates were thought to be different since they were isolated from apparently different tumors. However, we have shown that HTLV in the Caribbean and ATLV in Japan are the same virus (Watanabe et al., 1983, 1984) and the patient from which HTLV was isolated was identified as an atypical case of ATL (Bunn et al., 1983).

ADULT T‐CELL LEUKEMIA COMPLICATED BY HYPERCALCEMIA

Three autopsy cases of adult T-cell leukemia (ATL) complicated by a severe hypercalcemia are presented. In two of them, the hypercalcemia itself was the direct cause of death. There was no evidence of an increase of serum PTH in all three cases. Prostaglandins were within normal range in two of them. By a bioassay, a bone-resorbing factor, osteoclast activating factor (OAF)-like substance, was demonstrated in the culture medium of leukemic cells from one patient. Also, various degrees of osteoclastic activation were found in the bones of all three patients by the postmortem examination. It may be that the hypercalcemia occurring in cases of ATL is partly caused by the humoral factor, which is released from leukemic cells and activates a bone resorption by osteoclasts. Similar cases in which a significant activation of osteoclasts was practically demonstrated by histopathologic examination in addition to the detection of a bone-resorbing factor have been rarely reported.

Variation in the clinical courses of adult T-cell leukemia

Twenty-nine cases of adult T-cell leukemia were classified into four types according to the clinical features and course: smoldering, chronic, crisis, and acute. Only 2 of 14 patients with the acute type responded to therapy. The four types showed apparent differences in clinical features, complications, and prognosis, suggesting the need for different therapeutic regimens. For smoldering and chronic cases, no chemotherapy is recommended. However, in crisis and acute cases, aggressive chemotherapy is necessary, although the acute type cases showed extremely poor prognosis despite the most aggressive chemotherapy.

A retrovirus associated with a human leukemia, adult T-cell leukemia.

Most human lymphoid malignancies are of B-lymphocyte origin. Lymphoma and leukemia of peripheral T-lymphocyte origin are more frequent in Japan than in the United States and Europe (T- and B-cell Malignancy Study Group 1981). Adult T-cell leukemia (ATL) was proposed by Takatsuki’et al. to be a new disease distinct from other known T-cell malignancies (Takatsuki’et al. 1977; Uchiyama’etal. 1977). Subsequently, much attention has been paid to this disease in Japan because of its characteristic neoplastic cell morphology, clinical and pathological features, and the endemic distribution of birthplaces of patients in southwestern Japan. Hanaoka’et al. (1979) characterized the cyto- logical and histological features of ATL. With accumulation of pathological and clinical findings on cases of ATL and nonleukemic pleomorphic T-cell lymphoma (one type of malignant T-cell lymphoma), these two diseases were included in one category called adult T-cell leukemia/lymphoma (ATLL) (Hanaoka’etal. 1982). However, the abbreviation “ATL”, not 7“ATLL”, will be used in this review for the sake of simplicity, unless otherwise stated. In 1980, over 100 cases of ATL were evaluated in a nationwide survey on T- and B-cell malignancies carried out with the Cooperation of 27 medical institutions in Japan (T- and B-cell Malignancy Study Group 1981). This survey clearly demon- strated the unusually high incidence of T-cell malignancies in Kyushu, in the southwest of Japan, compared with the total incidence of lymphoid malignancies: The incidence in all Japan was 49% of the total malignancies, whereas it was 70% in southwestern Japan, mainly due to the high incidence of ATL in this region. These results suggested the possible involvement of a microorganism or, more likely, a virus in this disease.

A Case of Adult T-Cell Leukemia who Developed Systemic Swelling of Lymphnodes After 4 Years of Remission Disappeared Dermal Symptoms

A Case of Adult T-Cell Leukemia who Developed Systemic Swelling of Lymphnodes After 4 Years of Remission Disappeared Dermal Symptoms

A Case of Adult T-Cell Leukemia with Disseminated Strongyloidosis

A Case of Adult T-Cell Leukemia with Disseminated Strongyloidosis

Immunoglobulin G antibodies binding to a synthetic peptide deduced from the nucleotide sequence of the ENV gene of HTLV I in patients with leukemia and rheumatoid arthritis, HLA sensitized persons and blood donors

A synthetic pentadecapeptide preparation, env 406–420, with an amino acid sequence deduced from the envelope glycoprotein gene of human T cell leukemia virus type 1 (HTLV I), was used as the antigen in an enzyme immunoassay for inununoglobulin G antibodies, exploring its usefulness for seroepidemiological purposes. The frequency of reactivity in the test groups, presented in decreasing order was: (i) patients with rheumatoid arthritis; (ii) multitransfused nonleukemic patients; (iii) Japanese cases of adult T cell leukemia (ATL); (iv) HLA sensitized persons; (v) Swedish cases of adult acute leukemia; and (vi) Swedish blood donors. Three American cases of ATL and 12 HTLV I seropositive monkeys did not react. In RF positive sera from patients with rheumatoid arthritis, no quantitative correlation between RF activity and anti- env 406–420 activity was seen. Anti- env 406–420 positive sera did not react or reacted only weakly with four control peptide preparations with different amino acid sequences. The experience with oligopeptide serology still is limited. Our results illustrate that unexpected cross-reactions which are hard to interpret can occur. Although absorption experiments indicated an HTLV I specific component of the reactivity, antibodies against epitopes of allo- and auto-immune specificity may also have participated.

A Case of Adult T-Cell Leukemia Initiated with Central Nervous System Symptoms

We treated a 52-year-old Japanese woman with adult T-cell leukemia (ATL) initiated with central nervous system (CNS) symptoms. Her chief complaints were paraplegia and left facial palsy. CNS-ATL was diagnosed because of the following three features. 1) Various sized lymphoid cells with marked nuclear convolution were numerous in her cerebrospinal fluid. 2) These cells were a monoclonal proliferation of T lymphocytes with OKT 4 marker. 3) The patient's serum was positive for anti-ATL associated antigen (ATLA). Although the neurological signs and symptoms improved markedly after intrathecal administration of combined chemotherapy (methotrexate, cytarabine and corticosteroid), these ATL cells were highly resistant to radiation therapy. The abdominal mass which developed in the course of the disease was diagnosed as a tumor formed of ATL cells, and VEPA (vincristine, endoxan, prednisolone and adriamycin) was administered with marked success.

Changes of adult T cell leukemia cell surface antigens at relapse or at exacerbation phase after chemotherapy defined by use of monoclonal antibodies

Surface phenotypes of leukemic cells from six patients with adult T cell leukemia (ATL) were analyzed by the use of monoclonal antibodies, both at the time of initial diagnosis and at either relapse or exacerbation phase after chemotherapy. Changes of cell surface antigens were observed in four of the six cases. The majority of the leukemic cells of these patients were reactive with anti-Leu-1 and anti-Leu-3a, but unreactive with anti-Leu-2a and MAS 036c monoclonal antibodies at the time of initial diagnosis, indicating that ATL cells are of peripheral inducer/helper T cell origin. In three cases, the Leu-1 antigen disappeared at relapse or at exacerbation phase, and in one of these cases, a small percentage of ATL cells became reactive with MAS 036c, which identifies cortical thymocyte antigen. ATL cells of one other case did not have Leu-1 antigen from the start, but gained Leu-2a antigen at exacerbation phase and became double-labeled cells (Leu-2a+, 3a+), which is known to be a feature of thymocytes. Thus, it appeared that ATL cells sometimes change their surface phenotype to that of an earlier stage of T cell differentiation at relapse or at exacerbation phase. Chronic myelocytic leukemia (CML) cells also usually change to immature cells at blastic crisis involving morphological change. However, this morphological change was not so prominent in the ATL cases studied, except one, in which typical ATL cells with nuclear indentation changed to large immature cells with basophilic cytoplasm at relapse.