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Leukemia Research Vol. 22, No. 2. pp. 197- 199, 1998. 0 1998 Elsevief Science Ltd. All rights reserved

Printed in Great Britain 01455212W98 S19.00 + 0.00

CASE OF THE MONTH

UNUSUAL RELAPSE OF ADULT T-CELL LEUKEMIAKYMPHOMA AFTER SPONTANEOUS REMISSION

Abstract--A 42-year-old man was diagnosed with acute adult T-cell leukemia/lymphoma (ATU L). Abnormal peripheral blood cells (45% of white blood cells) (Fig. la), hypercalcemia, and systemic lymphadenopathy were observed. Flow cytometric analysis (FCM) using peripheral mononuclear cells (PMNC) revealed that the immunophenotype of tumor cells was CD4+CD8CD25+CD45RACD45RO+. Nevertheless, he developed a spontaneous remission 6 months later. At remission, the number of CD4-, CD25-, and CD45RO-positive cells decreased, while CD8- and CD45RA-positive cells increased to normal levels as previously reported by Suzuki et al. [Il. He was then referred to the outpatient clinic where he was periodically evaluated and received no therapy. Because of a serious sense of fullness he wasre-admitted 30 months after diagnosis. Physical examination revealed ascites and small lymphadenopathy in the right axilla. Atypical lymphoid cells were not observed on microscopic examination of the blood smear. FCM using PMNC revealed that CD4+CD25+ cells (3%) were within the normal range. Serum calcium was also within the normal range. Abdominal ultrasound examination showed massive ascites. Paracentesis demonstrated that the .ascitic fluid had a high white blood cell count (3.15 x 10g/l) with a marked increase in abnormal large cells (Fig. lb). FCM using mononuclear cells in the fluid revealed that 87.3% of the cells were double- positive for CD4 and CD25. Southern blot analysis of the cells confirmed monoclonal integration of human T-lymphotropic virus type 1 (HTLV-I) proviral DNA. The integrated genome was considered to be identical with that detected at initial presentation (Fig. 2). A diagnosis of relapsed ATUL, with the same clone as was detected at initial diagnosis, was made. Although he was treated with cytotoxic drugs, he did not respond and he died of renal failure 1 month after relapse. Autopsy revealed nodular invasive lesions at the rectovesical pouch, omentum, diaphragm, and pericardium with peritoneal dissemination. @ Elsevier Science Ltd. All rights reserved.

Key words: Adult T-cell leukemia-/lymphoma, spontaneous remission.

While acute ATL/L generally shows resistance to various therapies and a poor prognosis [2], spontaneous remission of this disease has rarely been observed. To our knowledge, only 10 patients with acute ATL/L have entered spontaneous remission [3-111. Most cases relapsed with a similar clinical presentation to that observed at the time of initial diagnosis. In contrast, our patient developed acute ATL/L with the usual clinical characteristics, spontaneously remitted, but then re- lapsed in an unusual manner. During the spontaneous remission, tumor cells were not recognized in the peripheral blood by routine examination, although Southern blot analysis or polymerase chain reaction analysis for HTLV-1 proviral DNA confirmed residual

Correspondence to: Hiroshi Kawada, M.D., Ph.D., The Fourth Department of Internal Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-11, Japan.

ATL/L clones [ 11. Furthermore, the level of IL-6, which is occasionally produced by HTLV- l-infected cells [ 121, was increased in the ascitic fluid (11300 pg/ml) compared with the serum level (52.4 pg/ml) at relapse. Thus, we suggest that the residual abnormal clone became sequestered and increased in the peritoneal cavity, then invaded the diaphragm and pericardium. Peripheral blood tumor cells, systemic lymphadenopa- thy or hypercalcemia were not observed during relapse. Tumor cell morphology in the ascitic fluid was also quite different from the peripheral blood cells initially observed. Peritoneal invasion is recognized in less than 10% of ATL/L patients, and transformation of ATL/L cells into large cells is also rarely observed [ 131. Although the mechanism remains unclear, ATL/L patients in spontaneous remission should be followed carefully, since an unusual and occult recurrence may develop without the usual signs of disease.

197

198 Case of the Month

Fig. 1. ATL/L cells observed in the present case. (a) Atypical lymphoid cells with lobulated nuclei were detected in the peripheral blood at the time of diagnosis (magnification x 800). (b) Large cells with irregular shaped nuclei were detected in the ascitic fluid at

the time of relapse (magnification x 800).

Unused relapse of adult T-cell leukemiailymphoma 199

A B C D

Mb) M E6 E:, E6 EI:

23.1

4.4

2.3 - 2.0 -

--t

Fig. 2. Southern blot analysis for HTLV-1 proviral DNA. Extracted DNA from patient tumor cells was digested with EcoRI or PsrI, then electrophoresed. The 32P-labeled HTLV- 1 probe was hybridized. Since there is no EcoRI restriction site in the HTLV-1 provirus, DNA digestion by EcoRI shows only one band when monoclonal proliferation of tumor cells occurs. Conversely, the HTLV- 1 proviral genome has many restriction sites for PstI. Therefore, when DNA with monoclonal integration is digested by PstI, a number of internal fragments are produced, and the sizes of these fragments are identical in monoclonal cells. The hybridization using extracted DNA from patient tumor cells at initial diagnosis (C) and relapse (D) demonstrates identical monoclonal integration of HTLV-1 proviral DNA. M, size marker; A, positive control of HTLV-1 monoclonal DNA; B, negative control of human placental

DNA; E, EcoRI; P, PsA.

References

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HiroshiKawada,* RyukiFukuda,* MuneouSuzuki,t Kiyoshi Yamashita,? Hitoshi Matsuokat and

Tomomitsu Hotta* *Fourth Department of Internal Medicine,

Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-l 1, Japan and TSecond Department of Internal Medicine, Miyazaki Medical School, 5200 Kihara, Kiyotake,

Miyazaki 889-16, Japan