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BONE-MARROW PATTERNS AND CLINICAL STAGING IN CHRONIC LYMPHOCYTIC LEUKÆMIA
606 cases could be the effect of a single cause introduced into the Faeroes at a single time before 1944. A high percentage of inhabitants of the Orkney and Shetland Islands have been exposed to dogs (personal communication, Dr David Poskanzer) and veterinarians inform us that canine distemper is endemic on these islands and may not be controlled; only 5% of dogs receive a primary vaccination and less than 1% receive a booster. In contrast, the chief veterinary officer of the Faeroe Islands, Dr D. J. Baerentsen, tells us that there has been no canine distemper on the Faeroes since 1956, presumably as a result of a strict control on the import of dogs, and consequently dogs are not vaccinated against the disease. Bxrentsen has examined the records of his predecessor, Mr C. J. Bech, and found that canine distemper had not been recorded in the islands before 1939 (restrictions apparently operated on dog influx even at that time). However, after the arrival of British troops in the early 1940s there was an epidemic of canine distemper in the Faeroes, apparently introduced by dogs brought in by British officers. Three-quarters of all dogs in the Faeroes may have died and Bech remarked in his records that "nervous complications were marked in the affected dogs with both convulsive seizures and encephalitic
BONE-MARROW INFILTRATION AND CLINICAL STAGING IN C.L.L.
nodular and diffuse bone-marrow lymphocytic infiltration6) and the clinical,stage assessed as proposed by the Committee of the Chronic Leukemia-Myeloma Task Force’ (see table). Our findings confirm the prognostic value of the marrow infiltration pattern, even if biopsy is done some time after diagnosis or the start of chemotherapy. ANTONINO CARBONE ARMANDO SANTORO Istituto Nazionale per lo Studio SILVANA PILOTTI e la Cura dei Tumori, 20133 Milan, Italy FRANCO RILKE -
signs". Thus two diseases, apparently non-existent before the war and since 1960 (except for 1 case of M.S. in 1961 and 1 in 1970), occurred in epidemics in the Faeroe Islands between 1940 and 1960, canine distemper infection of dogs preceding M.S. in man. Commenting on this epidemic of M.S. in the Faeroes Kurtzke and Hyllested postulated that "M.S. was transmitted to the Faeroese by the British forces (and /or their impedimenta)"." Dogs with distemper seem to have been among these impedimenta and, coupled with the epidemiological data obtained from individual M.S. patients, these findings strengthen the possibility that c.D.v. may be at least one of the factors involved in the aetiology of M.S. It should be stressed, however, that the association between c.D.v. and M.S. described here is only a temporal one, and much more work is required before any more direct link can be established. Veterans Administration Hospital, East Orange, and Department of Neurosciences, New Jersey Medical School, Newark, New Jersey, U.S.A.
S. D. COOK P. C. DOWLING
Division of Virology, National Institute for Medical Research, London NW7
W. C. RUSSELL
BONE-MARROW PATTERNS AND CLINICAL STAGING IN CHRONIC LYMPHOCYTIC LEUKÆMIA
SIR,-Hernandez-Nieto et al.’ showed in chronic lymphocytic leukaemia (C.L.L.) a significant correlation between the histological picture of bone-marrow lymphocytic infiltration evaluated by Rywlin,2and the clinical stage classified according to Rai et al.,3 and stressed the prognostic usefulness of bone biopsies. Charron et a1.4 also found a relationship between the type of marrow infiltration and the clinical stage evaluated by Rai’s modified classification.5 We have studied 30 patients with c.L.L. (median interval between diagnosis and bone biopsy 13 months, range 0.5 to 213 months) of whom 13 were under treatment at the time of biopsy. We found a statistically significant correlation (P<0.02) between the histological findings (classified by the 1. Hernandez-Nieto, L.,
Montserrat-Costa, E., Muncunill, J., Rozman, C. Lancet, 1977, i, 1269. 2. Rywlin, A. M. Histopathology of the Bone Marrow; p. 110. Boston, 1976. 3. Rai, K. R., Sawitsky, A., Cronkite, E. P., Chanana, A., Levy, R. N., Pasternak, B. S. Blood, 1975,46,219. 4. Charron, D., Dighiero, G., Raphael, M., Binet, J. L. Lancet, 1977, ii, 819. 5. Binet, J. L., and others. Cancer, 1977, 40, 855.
PENICILLAMINE IN PREGNANCY SIR,-Scheinberg and Sternliebl and Walshe2 agree that penicillamine improves the prospects for successful pregnancy in women with Wilson’s disease, that itis not teratogenic, and that it has no discernible adverse effect on their children’s connective tissue. M)0lner0d et al.3 reported the death at 7 weeks of an infant born to a woman who had taken 2 g of penicillamine daily for cystinuria during her pregnancy. There was evidence of a connective-tissue defect, attributed to penicillamine. Solomon et al .,4 reporting a similar history in which the mother had taken penicillamine for rheumatoid arthritis (R.A.), suggests that the drug is a teratogen except when used in Wilson’s disease. They argue that excess maternal copper mops up the penicillamine and thus, in this condition only, protects the fetus, and that penicillamine should not be prescribed for women with the other disorders who may be pregnant. Penicillamine should not normally be started for the treatment of R.A. during pregnancy, but what should be done if a woman conceives while already taking the drug? Solomon et al. stopped penicillamine in their patient’s 16th week of pregnancy. Her arthritis relapsed, the drug was reintroduced, and abortion was advised, but was refused. In my former capacity as medical director of Dista Products Ltd I wrote to forty-five clinicians who sometimes prescribed penicillamine for cystinuria or R.A., asking for the numbers of their patients who had taken penicillamine in early, or throughout, pregnancy and for the numbers of offspring who were normal or abnormal at birth and in early infancy. I received replies from forty-one. Twenty-seven had not knowingly prescribed penicillamine for any pregnant patient. Two had advised termination because the patient was taking penicillamine. The remaining twelve gave details of 27 pregnancies. 8’ women had taken penicillamine to term (4 for R.A., 4 for cystinuria) and all 8 children were normal. 19 had stopped taking the drug in the early weeks or months of pregnancy (15 for R.A., 4 for cystinuria):’1 child had a small ventricular septal defect and the other 18 were normal. This small series does not suggest that penicillamine is more 6.
Duhamel, H. Histopathologie climque de la moelle
osseuse;
p. 71, Paris,
1974. 7. Committee of the Chronic Leukemia-Myeloma Task Force. Cancer Chemother. Rep. 1973, 4, 159. 1. Scheinberg, I. H., Sternlieb, I. New Engl. J. Med. 1975, 293, 1300. 2. Walshe, J. M. Q. Jl Med. 1977, 46, 73. 3. Mjølnerød, O. K., Rasmussen, K., Dommerud, S. A., Gjeruldsen, S. T. Lancet,
1971, i, 673. Abrams, G., Dinner, M., Berman, L. New Engl J. Med. 1977,
4. Solomon, L., 296, 54.
BONE-MARROW INFILTRATION AND CLINICAL STAGING IN C.L.L.
nodular and diffuse bone-marrow lymphocytic infiltration6) and the clinical,stage assessed as proposed by the Committee of the Chronic Leukemia-Myeloma Task Force’ (see table). Our findings confirm the prognostic value of the marrow infiltration pattern, even if biopsy is done some time after diagnosis or the start of chemotherapy. ANTONINO CARBONE ARMANDO SANTORO Istituto Nazionale per lo Studio SILVANA PILOTTI e la Cura dei Tumori, 20133 Milan, Italy FRANCO RILKE -
signs". Thus two diseases, apparently non-existent before the war and since 1960 (except for 1 case of M.S. in 1961 and 1 in 1970), occurred in epidemics in the Faeroe Islands between 1940 and 1960, canine distemper infection of dogs preceding M.S. in man. Commenting on this epidemic of M.S. in the Faeroes Kurtzke and Hyllested postulated that "M.S. was transmitted to the Faeroese by the British forces (and /or their impedimenta)"." Dogs with distemper seem to have been among these impedimenta and, coupled with the epidemiological data obtained from individual M.S. patients, these findings strengthen the possibility that c.D.v. may be at least one of the factors involved in the aetiology of M.S. It should be stressed, however, that the association between c.D.v. and M.S. described here is only a temporal one, and much more work is required before any more direct link can be established. Veterans Administration Hospital, East Orange, and Department of Neurosciences, New Jersey Medical School, Newark, New Jersey, U.S.A.
S. D. COOK P. C. DOWLING
Division of Virology, National Institute for Medical Research, London NW7
W. C. RUSSELL
BONE-MARROW PATTERNS AND CLINICAL STAGING IN CHRONIC LYMPHOCYTIC LEUKÆMIA
SIR,-Hernandez-Nieto et al.’ showed in chronic lymphocytic leukaemia (C.L.L.) a significant correlation between the histological picture of bone-marrow lymphocytic infiltration evaluated by Rywlin,2and the clinical stage classified according to Rai et al.,3 and stressed the prognostic usefulness of bone biopsies. Charron et a1.4 also found a relationship between the type of marrow infiltration and the clinical stage evaluated by Rai’s modified classification.5 We have studied 30 patients with c.L.L. (median interval between diagnosis and bone biopsy 13 months, range 0.5 to 213 months) of whom 13 were under treatment at the time of biopsy. We found a statistically significant correlation (P<0.02) between the histological findings (classified by the 1. Hernandez-Nieto, L.,
Montserrat-Costa, E., Muncunill, J., Rozman, C. Lancet, 1977, i, 1269. 2. Rywlin, A. M. Histopathology of the Bone Marrow; p. 110. Boston, 1976. 3. Rai, K. R., Sawitsky, A., Cronkite, E. P., Chanana, A., Levy, R. N., Pasternak, B. S. Blood, 1975,46,219. 4. Charron, D., Dighiero, G., Raphael, M., Binet, J. L. Lancet, 1977, ii, 819. 5. Binet, J. L., and others. Cancer, 1977, 40, 855.
PENICILLAMINE IN PREGNANCY SIR,-Scheinberg and Sternliebl and Walshe2 agree that penicillamine improves the prospects for successful pregnancy in women with Wilson’s disease, that itis not teratogenic, and that it has no discernible adverse effect on their children’s connective tissue. M)0lner0d et al.3 reported the death at 7 weeks of an infant born to a woman who had taken 2 g of penicillamine daily for cystinuria during her pregnancy. There was evidence of a connective-tissue defect, attributed to penicillamine. Solomon et al .,4 reporting a similar history in which the mother had taken penicillamine for rheumatoid arthritis (R.A.), suggests that the drug is a teratogen except when used in Wilson’s disease. They argue that excess maternal copper mops up the penicillamine and thus, in this condition only, protects the fetus, and that penicillamine should not be prescribed for women with the other disorders who may be pregnant. Penicillamine should not normally be started for the treatment of R.A. during pregnancy, but what should be done if a woman conceives while already taking the drug? Solomon et al. stopped penicillamine in their patient’s 16th week of pregnancy. Her arthritis relapsed, the drug was reintroduced, and abortion was advised, but was refused. In my former capacity as medical director of Dista Products Ltd I wrote to forty-five clinicians who sometimes prescribed penicillamine for cystinuria or R.A., asking for the numbers of their patients who had taken penicillamine in early, or throughout, pregnancy and for the numbers of offspring who were normal or abnormal at birth and in early infancy. I received replies from forty-one. Twenty-seven had not knowingly prescribed penicillamine for any pregnant patient. Two had advised termination because the patient was taking penicillamine. The remaining twelve gave details of 27 pregnancies. 8’ women had taken penicillamine to term (4 for R.A., 4 for cystinuria) and all 8 children were normal. 19 had stopped taking the drug in the early weeks or months of pregnancy (15 for R.A., 4 for cystinuria):’1 child had a small ventricular septal defect and the other 18 were normal. This small series does not suggest that penicillamine is more 6.
Duhamel, H. Histopathologie climque de la moelle
osseuse;
p. 71, Paris,
1974. 7. Committee of the Chronic Leukemia-Myeloma Task Force. Cancer Chemother. Rep. 1973, 4, 159. 1. Scheinberg, I. H., Sternlieb, I. New Engl. J. Med. 1975, 293, 1300. 2. Walshe, J. M. Q. Jl Med. 1977, 46, 73. 3. Mjølnerød, O. K., Rasmussen, K., Dommerud, S. A., Gjeruldsen, S. T. Lancet,
1971, i, 673. Abrams, G., Dinner, M., Berman, L. New Engl J. Med. 1977,
4. Solomon, L., 296, 54.