309 BIOCHEMICAL MARKERS IN BURKITT’S LYMPHOMA
by a decrease in all marker substances in an approximately parallel fashion. Patients 1 and 4 achieved complete, followed
and all biochemical markers returned
remission, lymphoma is composed of undifferentiated normal levels. Patient 2 developed an apparent clinical remisa rate and with a rapid proliferative high growth lymphoblasts sion, but chemical abnormalities persisted as evidenced by 1 - 5 fraction; it is one of the few tumours in which chemotherapy and 6 fold increases in the excretion of N2,N2-dimethylguanomay be curative.’-3 These characteristics make this tumour sine and &bgr;-A.I.B.A., respectively. This patient relapsed one ideal for studying changes in biochemical markers associated month later. Because of significant renal failure in patient 3, with rapid cell turnover. We have found that patients with the observation of normal urinary marker levels in the preadvanced Burkitt’s lymphoma have, before treatment, very sence of clinical disease was not unexpected. of modified concentrations nucleosides, polyhigh urinary These preliminary studies suggest that monitoring a battery amines, and &bgr;-aminoisobutyric acid (&bgr;-A.I.B.A.).4 A similar corof markers in patients with adequate renal function may be a relation was observed by Arseneau et al. between pre-treatsensitive measure of tumour burden and may supplement roument raised serum lactic-acid dehydrogenase (L.D.H.) tine clinical evaluation in patients with Burkitt’s lymphoma. concentrations and advanced disease. In this study we measustained
SIR,-Burkitt’s
serum L.H.D., urinary nucleosides, polyamines, and P-A.I.B.A. serially in four patients with Burkitt’s lymphoma after chemotherapy and correlated these findings with their
sured
clinical course. The four patients had advanced Burkitt’s lymphoma (stage C and D) according to a new staging classification.’ The diagnosis was made at laparotomy. Patients were treated with systemic cyclophosphamide, vincristine, and methotrexate, intrathecal prophylaxis with methotrexate, and "consolidation" with radiotherapy and immunotherapy.’ Patients 1, 2, and 4 had normal renal, cardiac, or hepatic function; patient 3 had a pericardial effusion and impaired renal function. A patient was considered to be in complete clinical remission when no evidence of disease could be detected by physical examination and routine staging procedures. Urine samples collected for 24 h time periods were analysed for urinary polyamines,8 modified nucleosides,9 and &bgr;-A.I.B.A.I0 Total L.D.H. activity" was determined in serial blood samples. Pre-treatment concentrations of the marker substances for the four patients in this study and 13 normal controls are listed in the table. Before treatment patients 1-3 had significantly raised urinary nucleosides, polyamines, &bgr;-A.I.B.A., and serum-L.D.H. Patient 4, studied at the time of first relapse, had abnormal quantities of polyamines only. Serial measurement of these substances after treatment showed an initial increase in 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. 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., 5.
Levine, A. S., Pomeroy, T. C. Cancer (in the press). Gehrke, C. W., Kuo, K. C., Zumwalt, R. W., Waalkes, T. P J. Chromatogr. 1974, 89, 231 9. 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, 8.
449.
Institute, Bethesda, Maryland 20014, U.S.A.
SAMUEL A. JACOBS DUANE B. LAKINGS CHARLES W. GEHRKE THOMAS ANDERSON JOHN L. ZIEGLER T. PHILLIP WAALKES
Department of Biochemistry, University of Missouri, Columbia, Missouri
CHARLES W. GEHRKE
Laboratory
of Chemical
*&phgr;=pseudouridine; MG=-N2, N2-dimethylguanosine, M1I= 1-methylinosine
Pharmacology,
Medicine Branch, and Pediatric Oncology Branch, National Cancer
CARCINOEMBRYONIC ANTIGEN IN DERMATOSES
SIR,-Carcinoembryonic antigen (C.E.A.) was first reported by Gold and Freeman. 1In subsequent studies the antigen has been found in the serum of patients with various malignancies such as pancreatic, colonic, gastric, mammary, bronchial, prostatic, and cervical cancer and also in leukwmias.1 correlates Despite its apparent lack of specificity, its presence well with proven malignancies and their course.4 have also been observed in several inflammatory diseases, cirrhosis,67and in
Raised levels of
non-neoplastic
C.E.A.
chronic cigarette smokers.3 11 We assayed c.E.A. in forty patients with various skin diseases a radioimmunoassay using a zirconyl-phosphate gel.9 Cutaneous malignancies such as basal-cell epitheliomas (B.C.E.), mycosis fungoides, and Kaposi’s sarcoma, were examined. One patient with Bowen’s disease (carcinoma in situ) was studied. Patients with xeroderma pigmentosum, keratoacan-
employing
thoma, actinic keratosis, and psoriasis
were
also studied. All
patients 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. 16, 1. 6. Zamcher, N., Moore, T. L., Dhar, P., Kupchik, H. New Engl. J. Med.
1971,
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
tl’u=putrescme, Spd=spermidme; Sp=spermme formal range=115-340 I.U /l.
to
BURKITT’S
LYMPHOMA
310 RESULTS OF C.E.A. ASSAY IN SERA OF
36
PATIENTS WITH VARIOUS
DERMATOSES
production. However, neutropenia
was seen in some patients who had never been iron deficient who were given iron as a - tonic. It is possible that there is a directly toxic effect on the bone-marrow. If so, this would seem to be a property of a large number of different oral preparations as well as parenteral iron. It is also possible that the neutrophils phagocytose iron and that this affects their margination, producing low blood-counts but not altering whole-body levels.
We
are
investigating some of these possibilities.
Department of Pathology, Royal Victoria Hospital, Bournemouth BH1 4JG The results are shown in the table. A C.E.A. above 2.5 ng/ml is considered positive. A third of patients with B.C.E. had positive levels. Two-thirds of patients with mycosis fungoides and one patient with Bowen’s disease had positive levels. No significant levels of C.E.A. were detected in patients with Kaposi’s sarcoma, xeroderma pigmentosum, keratoacanthoma, actinic
keratosis,
or
psoriasis.
Department of Dermatology, State University of New York at Buffalo, School of Medicine, Buffalo, N.Y. 14203, U S.A.
Diagnostic Immunology Laboratory, Rosewell Park Memorial
Institute, Buffalo
A. RAZZAQUE AHMED T. MING CHU
’Present address: Department of Immunology and Microbiology, U. C. L. A. School of Medicine, Los Angeles, California 90024, U.S.A.
NEUTROPENIA AND IRON THERAPY
TERRY HAMBLIN TONY SIMMONDS
SENSITISATION TO NEUROBLASTOMA
SIR,—We read with interest the report of Dr Graham-Pole and his colleagues (June 26, p.1376) concerning the frequency of reactivity of neuroblastoma patients and patient contacts to neuroblastoma extracts. For the past two years we have been conducting a similar investigation in patients and contacts of patients with neuroblastoma, melanoma, and epidermoid carcinoma of the head and neck. Using a modification1 of the leucocyte adherence inhibition test (L.A .I.)2and 3mol/l potassium chloride extracts4 of tumours, we have, likewise, found a high frequency of reactors among the contacts (cohabitants) of these cancer patients. This reactivity showed a degree of specificity in that the response of family contacts of patients with one tumour type were found in high frequency only when tested with the’homologous tumour extract (see table). RELATIVE RESPONSIVENESS TO TUMOUR EXTRACTS
our patients became neutropenic while responding iron treatment, and this led us to look for a possible association. We studied three groups of women: (A) 100 women who were receiving iron at the time of their blood-count, (B) 100 women diagnosed as having iron-deficiency ansemia on the basis of blood-count and film examination, and whose doctor confirmed that they had not received treatment with iron, and (C) 100 women with normal blood-counts also not receiving iron. White-blood-cell counts were performed using a Coulter S electronic counter, and differential counts were performed by standard methods:1 Mean neutrophil-count Group (x 109/l) (± S.D.)
SIR,—Two of to
A B C
3.198±0.957
5.008±2.258 4.260+1.038
is
by a decrease in all marker substances in an approximately parallel fashion. Patients 1 and 4 achieved complete, followed
and all biochemical markers returned
remission, lymphoma is composed of undifferentiated normal levels. Patient 2 developed an apparent clinical remisa rate and with a rapid proliferative high growth lymphoblasts sion, but chemical abnormalities persisted as evidenced by 1 - 5 fraction; it is one of the few tumours in which chemotherapy and 6 fold increases in the excretion of N2,N2-dimethylguanomay be curative.’-3 These characteristics make this tumour sine and &bgr;-A.I.B.A., respectively. This patient relapsed one ideal for studying changes in biochemical markers associated month later. Because of significant renal failure in patient 3, with rapid cell turnover. We have found that patients with the observation of normal urinary marker levels in the preadvanced Burkitt’s lymphoma have, before treatment, very sence of clinical disease was not unexpected. of modified concentrations nucleosides, polyhigh urinary These preliminary studies suggest that monitoring a battery amines, and &bgr;-aminoisobutyric acid (&bgr;-A.I.B.A.).4 A similar corof markers in patients with adequate renal function may be a relation was observed by Arseneau et al. between pre-treatsensitive measure of tumour burden and may supplement roument raised serum lactic-acid dehydrogenase (L.D.H.) tine clinical evaluation in patients with Burkitt’s lymphoma. concentrations and advanced disease. In this study we measustained
SIR,-Burkitt’s
serum L.H.D., urinary nucleosides, polyamines, and P-A.I.B.A. serially in four patients with Burkitt’s lymphoma after chemotherapy and correlated these findings with their
sured
clinical course. The four patients had advanced Burkitt’s lymphoma (stage C and D) according to a new staging classification.’ The diagnosis was made at laparotomy. Patients were treated with systemic cyclophosphamide, vincristine, and methotrexate, intrathecal prophylaxis with methotrexate, and "consolidation" with radiotherapy and immunotherapy.’ Patients 1, 2, and 4 had normal renal, cardiac, or hepatic function; patient 3 had a pericardial effusion and impaired renal function. A patient was considered to be in complete clinical remission when no evidence of disease could be detected by physical examination and routine staging procedures. Urine samples collected for 24 h time periods were analysed for urinary polyamines,8 modified nucleosides,9 and &bgr;-A.I.B.A.I0 Total L.D.H. activity" was determined in serial blood samples. Pre-treatment concentrations of the marker substances for the four patients in this study and 13 normal controls are listed in the table. Before treatment patients 1-3 had significantly raised urinary nucleosides, polyamines, &bgr;-A.I.B.A., and serum-L.D.H. Patient 4, studied at the time of first relapse, had abnormal quantities of polyamines only. Serial measurement of these substances after treatment showed an initial increase in 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. 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., 5.
Levine, A. S., Pomeroy, T. C. Cancer (in the press). Gehrke, C. W., Kuo, K. C., Zumwalt, R. W., Waalkes, T. P J. Chromatogr. 1974, 89, 231 9. 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, 8.
449.
Institute, Bethesda, Maryland 20014, U.S.A.
SAMUEL A. JACOBS DUANE B. LAKINGS CHARLES W. GEHRKE THOMAS ANDERSON JOHN L. ZIEGLER T. PHILLIP WAALKES
Department of Biochemistry, University of Missouri, Columbia, Missouri
CHARLES W. GEHRKE
Laboratory
of Chemical
*&phgr;=pseudouridine; MG=-N2, N2-dimethylguanosine, M1I= 1-methylinosine
Pharmacology,
Medicine Branch, and Pediatric Oncology Branch, National Cancer
CARCINOEMBRYONIC ANTIGEN IN DERMATOSES
SIR,-Carcinoembryonic antigen (C.E.A.) was first reported by Gold and Freeman. 1In subsequent studies the antigen has been found in the serum of patients with various malignancies such as pancreatic, colonic, gastric, mammary, bronchial, prostatic, and cervical cancer and also in leukwmias.1 correlates Despite its apparent lack of specificity, its presence well with proven malignancies and their course.4 have also been observed in several inflammatory diseases, cirrhosis,67and in
Raised levels of
non-neoplastic
C.E.A.
chronic cigarette smokers.3 11 We assayed c.E.A. in forty patients with various skin diseases a radioimmunoassay using a zirconyl-phosphate gel.9 Cutaneous malignancies such as basal-cell epitheliomas (B.C.E.), mycosis fungoides, and Kaposi’s sarcoma, were examined. One patient with Bowen’s disease (carcinoma in situ) was studied. Patients with xeroderma pigmentosum, keratoacan-
employing
thoma, actinic keratosis, and psoriasis
were
also studied. All
patients 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. 16, 1. 6. Zamcher, N., Moore, T. L., Dhar, P., Kupchik, H. New Engl. J. Med.
1971,
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
tl’u=putrescme, Spd=spermidme; Sp=spermme formal range=115-340 I.U /l.
to
BURKITT’S
LYMPHOMA
310 RESULTS OF C.E.A. ASSAY IN SERA OF
36
PATIENTS WITH VARIOUS
DERMATOSES
production. However, neutropenia
was seen in some patients who had never been iron deficient who were given iron as a - tonic. It is possible that there is a directly toxic effect on the bone-marrow. If so, this would seem to be a property of a large number of different oral preparations as well as parenteral iron. It is also possible that the neutrophils phagocytose iron and that this affects their margination, producing low blood-counts but not altering whole-body levels.
We
are
investigating some of these possibilities.
Department of Pathology, Royal Victoria Hospital, Bournemouth BH1 4JG The results are shown in the table. A C.E.A. above 2.5 ng/ml is considered positive. A third of patients with B.C.E. had positive levels. Two-thirds of patients with mycosis fungoides and one patient with Bowen’s disease had positive levels. No significant levels of C.E.A. were detected in patients with Kaposi’s sarcoma, xeroderma pigmentosum, keratoacanthoma, actinic
keratosis,
or
psoriasis.
Department of Dermatology, State University of New York at Buffalo, School of Medicine, Buffalo, N.Y. 14203, U S.A.
Diagnostic Immunology Laboratory, Rosewell Park Memorial
Institute, Buffalo
A. RAZZAQUE AHMED T. MING CHU
’Present address: Department of Immunology and Microbiology, U. C. L. A. School of Medicine, Los Angeles, California 90024, U.S.A.
NEUTROPENIA AND IRON THERAPY
TERRY HAMBLIN TONY SIMMONDS
SENSITISATION TO NEUROBLASTOMA
SIR,—We read with interest the report of Dr Graham-Pole and his colleagues (June 26, p.1376) concerning the frequency of reactivity of neuroblastoma patients and patient contacts to neuroblastoma extracts. For the past two years we have been conducting a similar investigation in patients and contacts of patients with neuroblastoma, melanoma, and epidermoid carcinoma of the head and neck. Using a modification1 of the leucocyte adherence inhibition test (L.A .I.)2and 3mol/l potassium chloride extracts4 of tumours, we have, likewise, found a high frequency of reactors among the contacts (cohabitants) of these cancer patients. This reactivity showed a degree of specificity in that the response of family contacts of patients with one tumour type were found in high frequency only when tested with the’homologous tumour extract (see table). RELATIVE RESPONSIVENESS TO TUMOUR EXTRACTS
our patients became neutropenic while responding iron treatment, and this led us to look for a possible association. We studied three groups of women: (A) 100 women who were receiving iron at the time of their blood-count, (B) 100 women diagnosed as having iron-deficiency ansemia on the basis of blood-count and film examination, and whose doctor confirmed that they had not received treatment with iron, and (C) 100 women with normal blood-counts also not receiving iron. White-blood-cell counts were performed using a Coulter S electronic counter, and differential counts were performed by standard methods:1 Mean neutrophil-count Group (x 109/l) (± S.D.)
SIR,—Two of to
A B C
3.198±0.957
5.008±2.258 4.260+1.038
is
