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UNEVEN GEOGRAPHICAL DISTRIBUTION OF 15;17-TRANSLOCATION IN ACUTE PROMYELOCYTIC LEUKÆMIA
797 "ALLOPURINOL-TYPE" RASH DUE TO BUSULPHAN
SIR,-In the management of chronic myeloproliferative disorders, busulphan and allopurinol are frequently used in combination, the former to induce myelosuppression and the latter control
hyperuricxmia. Allopurinol produces an itchy erythmaculopapular skin eruption due to an acute hypersensitivity reaction in some patients.We describe here two patients with an "allopurinol-type" rash while on busulphan and allopurinol. The rash settled when the drugs were withdrawn but reappeared on reintroduction of busulphan alone. A 65-year-old male had polycythxmia rubra vera which had been diagnosed in 1973 and treated with radioactive phosphorus. 3 years later polycythasmia recurred and was treated by venesections and a short course of busulphan and allopurinol, apparently without any ill-effects. He was managed by
to
ematous
venesections for a further 18 months. He presented in May, 1978, with moderate splenomegaly and rising white cell and platelet counts. Hb 14 g/dl, white-cell count 22.OxlO9/1, and platelet-count 695 x 109/1. The serum-uricacid was 0.53 mmol/1 (normal 0.12-0.38). He was put on busulphan 4 mg daily and allopurinol 300 mg daily. 5 days later he had an erythematous, pruritic maculopapular rash and pustules over the face, limbs, and trunk. The rash resembled that described in allopurinol hypersensitivity reactions. Both drugs were withdrawn and the rash subsided. Several days later busulphan alone was given and the rash reappeared. This patient is now being managed by periodic venesections. The second case was a 79-year-old male who presented in September, 1977, with plethora, splenomegaly, and a history of gout. Hb 19.5g/dl, white cells 3 5-2x10 VI (neutrophils 85%, lymphocytes 10%, monocytes 2%, basophils 2%, eosinophils No Philadelphia chromosome was seen in the peripheral blood or bone-marrow. The red-cell mass was much increased and the plasma volume was slightly raised. The serum-uric-acid was 0.58 mmol/1. He was venesected and put on busulphan 4 mg daily and allopurinol 300 mg daily. 1 week later a macular, raised erythematous pruritic rash appeared over the face, limbs and trunk. When both drugs were stopped the rash subsided, but on resumption of busulphan alone the rash reappeared within a few days and regressed when busulphan was withdrawn. Since then he has been managed by periodic venesections. The rash resembled that attributed to allopurinol, but the reappearance of the rash after busulphan therapy alone suggests busulphan as the aetiological agent. Such a reaction has not previously been associated with this drug. Reported dermatological side-effects of busulphan include hyperpigmentation, erythema nodosum and urticaria,2 porphyria cutanea tarda,3 and bullous eruptions.4 MICHAEL J. LEYDEN St George Hospital, A. MANOHARAN Kogarah, New South Wales 2217, Australia
periodic
UNEVEN GEOGRAPHICAL DISTRIBUTION OF 15;17-TRANSLOCATION IN ACUTE PROMYELOCYTIC LEUKÆMIA
SIR,-Acute promyelocytic leuksemia (A.P.L.) is a rare disease constituting about 5% of all acute leukxmias in adults.s it is often characterised by increased bleeding tendency due to disseminated intravascular coagulopathy. Rowley et a1.6 have found a conspicuous chromosome anomaly-
Clinically
1
between the long arms of chromosomes 15 and 17, t(15q+;17q-) -in 3 cases of A.P.L. In 1977 the First International Workshop on Chromosomes in Leukaemia reviewed data from 279 patients with acute non-lymphocytic leuksemia (A.N.L.L.). An identical 15;17-translocation was found in 9 of 17 cases of A.P.L., but in no other subgroup of A.N.L.L. Van Den Berghe et a1.8 report 16 Belgian patients with A.P.L., 14 of whom had abnormal karyotype (the 15;17-translocation in 11). Thus 15;17-translocation seems to be a common anomaly in patients with A.P.L. in Belgium and perhaps in the United States also. This anomaly also seems
namely, translocation
specific to A.P.L. In Finland and Sweden the frequency of A.P.L. is about the that reported elsewhere. During the past four years we have investigated cytogenetically 12 patients with A.P.L. 9 of the patients are from different parts of Finland and they constitute all the cytogenetically studied patients with A.P.L. in that country. 3 of the patients are from southern Sweden. The patients were classified as having A.P.L. according to the criteria of the F.A.B. system.96 of the patients had bleeding tendency with disseminated intravascular coagulation at the time of diagnosis. There were 3 early deaths in this series; 2 of them
same as
were
caused by uncontrollable bleeding.
Bone-marrow chromosomes
studied at the time of diagearlier induction course but who was still hsematologically in relapse. The banding technique used was Giemsa staining of trypsin-treated slides; 20-100 cells were studied from each patient. The bone-marrow karyotype was normal in all but 1 case. This patient had complex karyotypic changes, including three marker chromosomes identified as 3p-, t(3;12), and t(3;18). Surprisingly no case of 15;17-translocation was seen in this series of 12 patients. The scarcity of other chromosome abnormalities is also significant, because abnormalities occur in about 50% of
nosis, except in 1 patient with
A.N.L.L.
were an
patients.7
We conclude that typical A.P.L. with bleeding tendency and disseminated intravascular coagulation can occur without 15;17-translocation. Also, because this series includes all cytogenetically analysed cases of A.P.L. from Finland and southern Sweden and because the material of Van Den Berghe et al. is representative for Belgium, there seems to be a striking difference in geographical distribution of this chromosome anomaly in patients with A.P.L. There are some indications that geographical differences in chromosome aberrations may exist in other human neoplasms also. 10 Department of Medicine, University of Helsinki
Third
SF-00290 Helsinki 29, Finland
LASSE TEERENHOVI
Folkhälsan Institute of Genetics, Helsinki
GEORG H. BORGSTRÖM
Department of Clinical Genetics, University Hospital, Lund, Sweden
FELIX MITELMAN
Department of Internal Medicine, University Hospital, Lund Third Department of Medicine, University of Helsinki Department of Medicine, Oulu University Hospital Department of Medicine, Vasa Central Hospital Department of Medical Genetics, University of Helsinki
LARS BRANDT PEKKA VUOPIO TIMO TIMONEN ANDERS ALMQVIST ALBERT DE
LA
CHAPELLE
Rundles, R W., Metz, E. N , Silberman, H. R. Ann.
intern. Med 1966, 64, 229. 2 Kyle, R. A., Schwartz, R. S., Oliner, H. L, Dameshek, W. Blood, 1961, 18, 497. 3 Kyle, R. A., Dameshek, W. ibid 1964, 23, 776. 4 Dosik, H., Hurewitz, D. T , Rosner, F., Schwartz, J M ibid. 1970, 35, 543. 5. Galton, D.A G, Dacie, J. V Blood Cells, 1975, 1, 17 6. Rowley, J. D., Golomb, H. M., Dougherty, C Lancet, 1977, i, 549.
7. First International Workshop in Chromosomes in Leukemia, Cancer Res. 1978, 38, 867. 8. Van Den Berghe, H., Louwagie, A., Broeckaert-van Orshoven, A., David, G., Verwilghen, R., Michaux, J. L., Sokal, G. Cancer (in the press). 9. Bennet, J. M., Catovsky, D., Daniel, M.-T, Flandrin, G., Galton, D. A. G., Gralnick, H. R., Sultan, C. Br. J. Hæmat. 1976, 33, 451. 10. Mitelman, F., Levan, G. Hereditas (in the press).
SIR,-In the management of chronic myeloproliferative disorders, busulphan and allopurinol are frequently used in combination, the former to induce myelosuppression and the latter control
hyperuricxmia. Allopurinol produces an itchy erythmaculopapular skin eruption due to an acute hypersensitivity reaction in some patients.We describe here two patients with an "allopurinol-type" rash while on busulphan and allopurinol. The rash settled when the drugs were withdrawn but reappeared on reintroduction of busulphan alone. A 65-year-old male had polycythxmia rubra vera which had been diagnosed in 1973 and treated with radioactive phosphorus. 3 years later polycythasmia recurred and was treated by venesections and a short course of busulphan and allopurinol, apparently without any ill-effects. He was managed by
to
ematous
venesections for a further 18 months. He presented in May, 1978, with moderate splenomegaly and rising white cell and platelet counts. Hb 14 g/dl, white-cell count 22.OxlO9/1, and platelet-count 695 x 109/1. The serum-uricacid was 0.53 mmol/1 (normal 0.12-0.38). He was put on busulphan 4 mg daily and allopurinol 300 mg daily. 5 days later he had an erythematous, pruritic maculopapular rash and pustules over the face, limbs, and trunk. The rash resembled that described in allopurinol hypersensitivity reactions. Both drugs were withdrawn and the rash subsided. Several days later busulphan alone was given and the rash reappeared. This patient is now being managed by periodic venesections. The second case was a 79-year-old male who presented in September, 1977, with plethora, splenomegaly, and a history of gout. Hb 19.5g/dl, white cells 3 5-2x10 VI (neutrophils 85%, lymphocytes 10%, monocytes 2%, basophils 2%, eosinophils No Philadelphia chromosome was seen in the peripheral blood or bone-marrow. The red-cell mass was much increased and the plasma volume was slightly raised. The serum-uric-acid was 0.58 mmol/1. He was venesected and put on busulphan 4 mg daily and allopurinol 300 mg daily. 1 week later a macular, raised erythematous pruritic rash appeared over the face, limbs and trunk. When both drugs were stopped the rash subsided, but on resumption of busulphan alone the rash reappeared within a few days and regressed when busulphan was withdrawn. Since then he has been managed by periodic venesections. The rash resembled that attributed to allopurinol, but the reappearance of the rash after busulphan therapy alone suggests busulphan as the aetiological agent. Such a reaction has not previously been associated with this drug. Reported dermatological side-effects of busulphan include hyperpigmentation, erythema nodosum and urticaria,2 porphyria cutanea tarda,3 and bullous eruptions.4 MICHAEL J. LEYDEN St George Hospital, A. MANOHARAN Kogarah, New South Wales 2217, Australia
periodic
UNEVEN GEOGRAPHICAL DISTRIBUTION OF 15;17-TRANSLOCATION IN ACUTE PROMYELOCYTIC LEUKÆMIA
SIR,-Acute promyelocytic leuksemia (A.P.L.) is a rare disease constituting about 5% of all acute leukxmias in adults.s it is often characterised by increased bleeding tendency due to disseminated intravascular coagulopathy. Rowley et a1.6 have found a conspicuous chromosome anomaly-
Clinically
1
between the long arms of chromosomes 15 and 17, t(15q+;17q-) -in 3 cases of A.P.L. In 1977 the First International Workshop on Chromosomes in Leukaemia reviewed data from 279 patients with acute non-lymphocytic leuksemia (A.N.L.L.). An identical 15;17-translocation was found in 9 of 17 cases of A.P.L., but in no other subgroup of A.N.L.L. Van Den Berghe et a1.8 report 16 Belgian patients with A.P.L., 14 of whom had abnormal karyotype (the 15;17-translocation in 11). Thus 15;17-translocation seems to be a common anomaly in patients with A.P.L. in Belgium and perhaps in the United States also. This anomaly also seems
namely, translocation
specific to A.P.L. In Finland and Sweden the frequency of A.P.L. is about the that reported elsewhere. During the past four years we have investigated cytogenetically 12 patients with A.P.L. 9 of the patients are from different parts of Finland and they constitute all the cytogenetically studied patients with A.P.L. in that country. 3 of the patients are from southern Sweden. The patients were classified as having A.P.L. according to the criteria of the F.A.B. system.96 of the patients had bleeding tendency with disseminated intravascular coagulation at the time of diagnosis. There were 3 early deaths in this series; 2 of them
same as
were
caused by uncontrollable bleeding.
Bone-marrow chromosomes
studied at the time of diagearlier induction course but who was still hsematologically in relapse. The banding technique used was Giemsa staining of trypsin-treated slides; 20-100 cells were studied from each patient. The bone-marrow karyotype was normal in all but 1 case. This patient had complex karyotypic changes, including three marker chromosomes identified as 3p-, t(3;12), and t(3;18). Surprisingly no case of 15;17-translocation was seen in this series of 12 patients. The scarcity of other chromosome abnormalities is also significant, because abnormalities occur in about 50% of
nosis, except in 1 patient with
A.N.L.L.
were an
patients.7
We conclude that typical A.P.L. with bleeding tendency and disseminated intravascular coagulation can occur without 15;17-translocation. Also, because this series includes all cytogenetically analysed cases of A.P.L. from Finland and southern Sweden and because the material of Van Den Berghe et al. is representative for Belgium, there seems to be a striking difference in geographical distribution of this chromosome anomaly in patients with A.P.L. There are some indications that geographical differences in chromosome aberrations may exist in other human neoplasms also. 10 Department of Medicine, University of Helsinki
Third
SF-00290 Helsinki 29, Finland
LASSE TEERENHOVI
Folkhälsan Institute of Genetics, Helsinki
GEORG H. BORGSTRÖM
Department of Clinical Genetics, University Hospital, Lund, Sweden
FELIX MITELMAN
Department of Internal Medicine, University Hospital, Lund Third Department of Medicine, University of Helsinki Department of Medicine, Oulu University Hospital Department of Medicine, Vasa Central Hospital Department of Medical Genetics, University of Helsinki
LARS BRANDT PEKKA VUOPIO TIMO TIMONEN ANDERS ALMQVIST ALBERT DE
LA
CHAPELLE
Rundles, R W., Metz, E. N , Silberman, H. R. Ann.
intern. Med 1966, 64, 229. 2 Kyle, R. A., Schwartz, R. S., Oliner, H. L, Dameshek, W. Blood, 1961, 18, 497. 3 Kyle, R. A., Dameshek, W. ibid 1964, 23, 776. 4 Dosik, H., Hurewitz, D. T , Rosner, F., Schwartz, J M ibid. 1970, 35, 543. 5. Galton, D.A G, Dacie, J. V Blood Cells, 1975, 1, 17 6. Rowley, J. D., Golomb, H. M., Dougherty, C Lancet, 1977, i, 549.
7. First International Workshop in Chromosomes in Leukemia, Cancer Res. 1978, 38, 867. 8. Van Den Berghe, H., Louwagie, A., Broeckaert-van Orshoven, A., David, G., Verwilghen, R., Michaux, J. L., Sokal, G. Cancer (in the press). 9. Bennet, J. M., Catovsky, D., Daniel, M.-T, Flandrin, G., Galton, D. A. G., Gralnick, H. R., Sultan, C. Br. J. Hæmat. 1976, 33, 451. 10. Mitelman, F., Levan, G. Hereditas (in the press).