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BIOCHEMICAL MARKERS IN BURKITT’SLYMPHOMA

SIR,-Burkitt’s lymphoma is composed of undifferentiatedlymphoblasts with a rapid proliferative rate and a high growthfraction; it is one of the few tumours in which chemotherapymay be curative.’-3 These characteristics make this tumourideal for studying changes in biochemical markers associatedwith rapid cell turnover. We have found that patients withadvanced Burkitt’s lymphoma have, before treatment, veryhigh urinary concentrations of modified nucleosides, poly-amines, and &bgr;-aminoisobutyric acid (&bgr;-A.I.B.A.).4 A similar cor-relation was observed by Arseneau et al. between pre-treat-ment raised serum lactic-acid dehydrogenase (L.D.H.)concentrations and advanced disease. In this study we mea-sured serum L.H.D., urinary nucleosides, polyamines, and

P-A.I.B.A. serially in four patients with Burkitt’s lymphomaafter chemotherapy and correlated these findings with theirclinical course.

The four patients had advanced Burkitt’s lymphoma (stageC and D) according to a new staging classification.’ The diag-nosis was made at laparotomy. Patients were treated with sys-temic cyclophosphamide, vincristine, and methotrexate, in-trathecal prophylaxis with methotrexate, and "consolidation"with radiotherapy and immunotherapy.’ Patients 1, 2, and 4had normal renal, cardiac, or hepatic function; patient 3 hada pericardial effusion and impaired renal function. A patientwas considered to be in complete clinical remission when noevidence of disease could be detected by physical examinationand routine staging procedures.

Urine samples collected for 24 h time periods were analysedfor urinary polyamines,8 modified nucleosides,9 and &bgr;-A.I.B.A.I0Total L.D.H. activity" was determined in serial blood samples.

Pre-treatment concentrations of the marker substances forthe four patients in this study and 13 normal controls are listedin the table. Before treatment patients 1-3 had significantlyraised urinary nucleosides, polyamines, &bgr;-A.I.B.A., andserum-L.D.H. Patient 4, studied at the time of first relapse, hadabnormal quantities of polyamines only. Serial measurementof these substances after treatment showed an initial increasein the excretion of the urinary markers and in serum-L.D.H.,

1. O’Conor, G. T., Rappaport, H., Smith, E. B. Cancer, 1965, 18, 411.2. Ziegler, J L. ibid. 1972, 30, 1534.3. Ziegler, J. L., Bluming, A. Z., Fass, L., Morrow, R. H., Iverson, O. H. Bibl

Hæmat. 1973, 39, 1046.4. Waalkes, T. P., Gehrke, C. W., Bleyer, W. A., Zumwalt, R. W., Olweny,

C. L. M., Kuo, K. L., Lakings, D. B., Jacobs, S. A. Cancer Chemother.Rep. 1975, 59, 721.

5. Arseneau, J C., Canellos, G. P., Banks, P. M., Berard, C. W., Gralnick,H. R., DeVita, V. T. Am. J. Med. 1975, 58, 314.

6. Ziegler, J. L., Magrath, I. T. Pathobiol. Ann. 1974, p. 129.7. Ziegler, J. L., DeVita, V. T., Graw, R. G., Herzig G., Leventhal, B. G.,

Levine, A. S., Pomeroy, T. C. Cancer (in the press).8. Gehrke, C. W., Kuo, K. C., Zumwalt, R. W., Waalkes, T. P J. Chromatogr.

1974, 89, 2319. Chang, S. Y., Lakings, D. R., Zumwalt, R W., Gehrke, C W., Waalkes,

T. P. J. Lab. clin. Med. 1974, 94, 113.10. Kaiser, F. E., Gehrke, C. W., Zumwalt, R. W, Kuo, K C. J Chromatogr.

1974, 94, 113.11. Wacker, W. E. C., Ulmer, D. D., Vallee, B. L. New Engl. J. Med. 1956, 255,

449.

followed by a decrease in all marker substances in an approxi-mately parallel fashion. Patients 1 and 4 achieved complete,sustained remission, and all biochemical markers returned tonormal levels. Patient 2 developed an apparent clinical remis-sion, but chemical abnormalities persisted as evidenced by 1 - 5and 6 fold increases in the excretion of N2,N2-dimethylguano-sine and &bgr;-A.I.B.A., respectively. This patient relapsed onemonth later. Because of significant renal failure in patient 3,the observation of normal urinary marker levels in the pre-sence of clinical disease was not unexpected.

These preliminary studies suggest that monitoring a batteryof markers in patients with adequate renal function may be asensitive measure of tumour burden and may supplement rou-tine clinical evaluation in patients with Burkitt’s lymphoma.

Laboratory of Chemical Pharmacology,Medicine Branch, and Pediatric Oncology Branch,National Cancer Institute,Bethesda, Maryland 20014, U.S.A.

SAMUEL A. JACOBS DUANE B. LAKINGSCHARLES W. GEHRKETHOMAS ANDERSON

JOHN L. ZIEGLERT. PHILLIP WAALKES

Department of Biochemistry,University of Missouri,Columbia, Missouri CHARLES W. GEHRKE

CARCINOEMBRYONIC ANTIGEN IN DERMATOSES

SIR,-Carcinoembryonic antigen (C.E.A.) was first reportedby Gold and Freeman. 1 In subsequent studies the antigenhas been found in the serum of patients with various malig-nancies such as pancreatic, colonic, gastric, mammary, bron-chial, prostatic, and cervical cancer and also in leukwmias.1Despite its apparent lack of specificity, its presence correlateswell with proven malignancies and their course. 4

Raised levels of C.E.A. have also been observed in several

non-neoplastic inflammatory diseases, cirrhosis,67 and inchronic cigarette smokers.3 11

We assayed c.E.A. in forty patients with various skin diseasesemploying a radioimmunoassay using a zirconyl-phosphategel.9 Cutaneous malignancies such as basal-cell epitheliomas(B.C.E.), mycosis fungoides, and Kaposi’s sarcoma, were exam-ined. One patient with Bowen’s disease (carcinoma in situ) wasstudied. Patients with xeroderma pigmentosum, keratoacan-thoma, actinic keratosis, and psoriasis were also studied. Allpatients had a histologically proven diagnosis.

1. Gold, P., Freedman, S. O. J. exp. Med. 1965, 121, 439.2. Gold, P., Freedman, S. O. ibid. 1965, 122, 467.3. Hansen, M. J., and others Hum. Path. 1974, 5, 139.4. Chu, T. M. Sem. nucl. Med. 1975, 5, 255.5. Moore, T. L., Ruphir, H., Marcon, W., Zamcher, N. Am. J. dig. Dis. 1971,

16, 1. 6. Zamcher, N., Moore, T. L., Dhar, P., Kupchik, H. New Engl. J. Med. 1972,

286, 83.7. Rule, A. H., Straus, E., Vandevoorde, J., Janowitz, H. D. ibid. 1972, 287,

24.8. MacSween, J. M., Warner, N. L., Bankhurst, A. D., MacKay, I. R. J.

Cancer, 1972, 26, 356.9. Chu, T. M., Reynoso, G. Clin. Chem. 1972, 118, 918.

PRETREATMENT MARKER LEVELS IN PATIENTS WITH STAGE C AND D BURKITT’S LYMPHOMA

*&phgr;=pseudouridine; MG=-N2, N2-dimethylguanosine, M1I= 1-methylinosinetl’u=putrescme, Spd=spermidme; Sp=spermmeformal range=115-340 I.U /l.