- Email: [email protected]
DELETIONS OF CHROMOSOME 7 IN HÆMATOLOGICAL DISORDERS
1385
exposed to ultraviolet radiation at a wavelength of 2357 A have shown a reduction of mitotic activity and an increase of chromosome aberrations. It must be emphasised that the Airshields unit does not emit these wavelengths. However, further studies will be necessary before it can be entirely accepted that phototherapy has no harmful effect. Department of Child Life and Health, University of Edinburgh.
G. SANDOR.
A NEW TRANSLOCATION RELATED TO THE PHILADELPHIA CHROMOSOME
SiR,-We have found a new type of translocation probably related to the formation of the Philadelphia (PhI) This translocation occurred onto chromochromosome. some A2 rather than C9 and may involve that portion of chromosome G22 missing from the (Ph) chromosome, which is characteristic of cells of patients with chronic myelocytic leukxmia (c.M.L.). In our series of patients with C.M.L., in whose marrow cells translocation onto chromosome C9 is associated with a Ph due to deletion of chromosome G22, one patient was found to have a translocation not hitherto described. This 52-year-old man had typical Ph’-positive C.M.L. His chromosomes from peripheral blood-cells cultured without phytohsmmaglutinin (P.H.A.) and from the bone-marrow showed heteromorphic chromosomes in pairs A2 and G22. Investigation of karyotypes with buffered quinacrinemustard (Q) and trypsin-Giemsa (G) banding methods showed that the larger chromosome A2 had an additional pale fluorescent Q-band or a negative-staining G-band at the end of the long arm (figs. 1 and 2). These bandingpatterns and the size of the band were very similar to those of the missing portion of the smaller chromosome G22. C-bands induced with the NaOH-SSC method were found to be normal in all the chromosomes. Metaphase cells from peripheral blood cultured with P.H.A. showed normal karyotypes. Rowley4 first reported the association between the deletion of chromosome G22, resulting in the Ph, and a translocation involving chromosome C9 in a series of 9 patients with C.M.L. The findings reported by us in this 3. 4.
Parrington, J. M. Cytogenetics, 1972, 11, Rowley, J. D. Nature, 1973, 243, 290.
117.
Fig. 2-Giemsa-banding pattern of chromosomes in marrowcell of the patient here reported (a) and another subject with C.M.L. (b). In (a) the translocation is associated with the long arm of a 2 chromosome, whereas in (b), and in most cases of C.M.L., the translocation is on one of the no. 9 chromosomes.
no.
paper indicate that other translocations, though much rarer than those involving chromosome C9, may occur in Ph1-positive C.M.L. and that the translocation of the missing segment of the Ph chromosome is not specific to a particular chromosome. C.M.L. may, thus, appear to be a result of a position effect, mainly in the long arm of chromosome G22 rather than in any other chromosome of the human karyo-
type. Roswell Park Memorial
Institute,
Buffalo,
New York
U.S.A.
14203,
ISAMU HAYATA SURABHI KAKATI AVERY A. SANDBERG.
DELETIONS OF CHROMOSOME 7 IN HÆMATOLOGICAL DISORDERS
SIR,-Aneuploidy involving group C is the most common chromosome abnormality found in patients with a variety of haematological disorders.1 In hyperdiploid cells, involvement of C-group chromosomes appears to be non-random. Additional chromosomes 8 are reported most frequently,2,3 although additional chromosomes 9,4-6 10,7 and X8 have also been observed. Hypodiploidy due to loss of a C-group chromosome is much less common. In the only report to date, marrow cells from two female patients with acute myelogenous leukaemia showed the loss of one X chromosome.99 The present report describes two nonleuksemic male patients whose marrow cells showed deficiencies involving chromosome 7. Case 1.-Marrow cells showed a mosaic karyotype (45,X/46,XY) when the patient was first seen in 1969 for pancytopenia.1" In 1970, after treatment, he appeared normal both clinically and heematologically, and he had a normal marrow karyotype. In June, 1973, he was re-examined because of easy fatigability; he was found to have anxmia (haemoglobin 10 g. per 100 ml.) and neutropenia (19%). The bone-marrow showed megaloblastic erythroid features and a disturbance of myeloid maturation. The marrow karyotype also showed a change, with a 45,XY,-7 karyotype found in 49 of 50 cells examined. Two-thirds of these cells also contained a small chromosome fragment with uniform
Fig. l-Quinacrine-fluorescent pattern of marrow-cell, showing translocation somes
The
no.
replaces
on
to
the long
arm
of
one
of the
no.
2 chromo-
(arrow). 9 chromosomes are normal, and 22 chromosome (arrow).
a no.
a
Ph’ chromosome
1. Sandberg, A. A., Hossfeld, D. K. A. Rev. Med. 1970, 21, 379. 2. de la Chapelle, A., Schroder, J., Vupio, P. Clin. Genet. 1972, 3, 470. 3. Rowley, J. D. Nature, 1973, 243, 290. 4. Davidson, W. M., Knight, L. A. Lancet, 1973, i, 1510. 5. Rowley, J. D. ibid. 1973, ii, 390. 6. Rutten, F. J., Hustinx, T. W. J., Scheres, J. M. J. C., Wagener, D. J. T. ibid. p. 455. 7. Beck, W. S., Chesney, T. McC. New Engl. J. Med. 1973, 288, 957. 8. Rowley, J. D. Unpublished. 9. Rowley, J. D. Annls Génét. 1973, 16, 109. 10. Rowley, J. D. Br. J. Hœmat. 1971, 21, 717.
1386
pale fluorescence and
no distinct centromere after treatment with NaOH. Case 2.-This patient had polycythxmia vera, which was treated with phosphorus-32 (1954-59) and busulphan. Marrow chromosomes, which were first examined in 1967, have shown a mosaic pattern (46,XY,Cq-/46,XY) on each analysis; the abnormal cells increased from 50% in 1967 to 83% in 1969, and to 96% in 1973. Quinacrine fluorescence revealed that one no. 7 had a deletion of the long arm distal to 7q22,11 which resembled the deletion observed in JIYOYE, a lymphoblastoid line established from a Burkitt’s lymphoma.12
(3) The PhI chromosome, irrespective of its percentage in myeloid cells, is the specific marker of the preleukaemic conditions as a whole. The main consequence of its presence is not The various myeloproliferative the cell hyperproduction. disorders are generally accepted as clinical C.M.L. variants,la-2o and even the very " classic " chronic phase of leukaemia can be considered,21 not as a leuksemic state per se, but as the clinical variety with the higher risk to end sooner or later in an acute blastic crisis. Laboratoire de Cytogénétique, Institut Jules Bordet, Centre des Tumeurs de l’Université Libre de Bruxelles,
Whether the loss of part or all of chromosome 7 in the only two males with missing C chromosomes whom I have examined is fortuitous or not can only be determined by examination of additional patients. Dr B. Erkman-Baylis did the first cytogenetic analysis in 2. I thank Dr Stanley Yachnin for referring patient 1 and Dr Suzanne Larsh and Dr Joseph Baron for referring patient 2. I acknowledge the expert technical assistance of Miss Judith Mikuta, Miss Margaret Ikeda, and Mr David Potter.
Rue Héger Bordet, 1000 Bruxelles, Belgium.
patient
Department of Medicine,
JANET D. ROWLEY.
PHILADELPHIA-CHROMOSOME-POSITIVE PRELEUKÆMIC STATE et al.13 present a case supporting the that the Ph’ chromosome is the marker of a hypothesis preleukxmic state and not the leukxmic process itself. The same opinion has already been proposed.14 We should like to present a case relevant to this question and to show that the presence of a PhI-positive cell line does not necessarily mean a further transformation in the acute phase of chronic myeloblastic leukaemia.
SIR,-Baccarini
A
woman now
aged
81
was
INCREASING THE EFFICACY OF ANTILYMPHOCYTE GLOBULIN
SIR,—Your editorial (Oct. 13,
p. 834) reviews the clinical antilymphocyte globulin (A.L.G.) as an immunosuppressive agent in a variety of immunological disorders and especially renal transplantation. Compelling reasons for continuing to study A.L.G. are seen. Presumably, more impressive results with A.L.G. might be achieved in man if only doses similar to those used in laboratory animals could be given. Such doses, however, are impractical and raise the likelihood of complications. Therefore, a means to increase the efficacy of A.L.G. without increasing its dose would be welcome. One possibility is to take advantage of the synergistic immunosuppressive effects exerted by A.L.G. and methylhydrazine derivatives such as procarbazine (’ Natulan ’). Accordingly, A.L.G. combined with a well-tolerated dose of procarbazine is superior to a higher dose of A.L.G. alone. Experimentally, it has been found in mice that the immunosuppressive potency of antilymphocyte serum (A.L.S.) was greatly increased by doses of procarbazine which, alone, were ineffective.22-24 The addition of procarbazine to a dose of A.L.S. prolonged the survival of skin allografts across strong histocompatibility barriers up to tenfold. A variety of other chemotherapeutic agents provided considerably less or no synergistic effects with A.L.S. The synergy was later confirmed in another species. Combined treatment with procarbazine and anti-thymocyte serum (A.T.s.), in conjunction with total-body irradiation, prevented sensitisation by prior transfusions with donortype blood-to-marrow allografts in dogs. Under the same conditions, A.T.s. or procarbazine alone were insufficient use
Franklin McLean Memorial Research Institute, University of Chicago, Chicago, Illinois 60637, U.S.A.
first examined in 1966.
She had
clinical and ha:matological evidence of polycythaemia vera and was treated from 1966 to 1973 by six administrations of 32p: 4 mCi in July and August, 1966, in April, 1969, and in June, 1970, and 3 mCi in October, 1971, and January, 1973. The last blood-count in April, 1973, was: red cells 4-87x10’’ per c.mm.; Hb 14-8 g. per 100 ml.; white cells 4500 per c.mm; platelets 138,000 per c.mm. The patient is still in good health with no sign of leukasmic transformations. A first cytogenetic analysis was performed in June, 1966: a Ph chromosome was found in 10% of the mitoses analysed (see fig. 5 in the full report 15). BoneLeucocyte alkaline-phosphatase was 30 per 100 cells. marrow was reinvestigated in May, 1971, and July, 1972; the myelogram was normal, the chromosome analysis was completed by a direct method on 30 and 150 mitoses respectively. The second sample was stained by a modified ASG-banding technique.16 No Ph’ chromosome nor other anomalies could be found. Alkaline-phosphatase was 186 per 100 cells in July, 1972.
This 7-year survival prompts
us to
remark:
(1) The presence of the PhI chromosome is illustrated by a picture in the first report of the case 15; and considered as convincing by Sandberg and Hossfeld.17 The Ph could be missed in 1971, but this is less likely in 1972 when 150 mitoses were scrutinised. Thus, this case is probably the first report of the spontaneous disappearance of a Phl-positive cell line in a myeloproliferative disorder. (2) The polycythaemia vera remained quiescent from 1966 to 1973 with the help of a mild treatment. This is perhaps related to the fact that no more Ph’-positive population could be demonstrated after 1966. 11. Paris Conference (1971). Birth Defects: Original Article Series, 1972, 8, no. 7. 12. Steel, C. M. Nature, 1971, 233, 555. 13. Baccarini, M., Zaccaria, A., Tura, S. Lancet, Nov. 10, 1973, p. 1094. 14. Canellos, G. P., Whang-Peng, J. ibid. 1972, ii, 1227.
15. Koulischer, L., Fruhling, J., Henry, J. Eur. J. Cancer, 1967, 3, 159. 16. Reeves, B. R., Lobb, D. S., Lawler, S. D. Humangenetik, 1972, 14, 159.
17. Sandberg, A. A., Hossfeld, D. K. A. Rev. Med. 1970, 21, 379.
A. VERHEST F. VAN SCHOUBROECK.
of
interfere with successful immunisation and to permit sustained graft survival after total-body irradiation. 15-17 The combined treatment with procarbazine and A.T.S. has been used clinically in marrow-graft recipients who had been exposed to transfusions from family members.28 2 patients given the procarbazine/A.T.s. regimen, in addito
Baserga, A., Castoldi, G. L. Biomedicine, 1973, 18, 89. Ghosh, M. L. Postgrad. med. J. 1972, 48, 686. Cervenka, J., Koulischer, L., Gorlin, R. J. Chromosomes in Human Cancer. Springfield, Illinois, 1973. 21. Pedersen, B. Proceedings of the Fourth International Congress of Human Genetics, Paris, 1971 (edited by J. de Grouchy, F. J. G. Ebling, and I. W. Henderson). Amsterdam, 1972. 22. Floersheim, G. L. Transplantation, 1969, 8, 392. 23. Floersheim, G. L., Brune, K. Transplant. Proc. 1971, 3, 688. 24. Floersheim, G. L. Transplantation, 1973, 15, 195. 25. Floersheim, G. L., Kolb, H. J., Graham, T. C., Weiden, P. L., Thomas, E. D., Storb, R. Experientia, 1973, 29, 771. 26. Floersheim, G. L., Storb, R., Weiden, P. L., Kolb, H. J., Graham, T. C., Thomas, E. D. Expl Hematol. (in the press). 27. Storb, R. Floersheim, G. L., Weiden, P. L., Graham, T. C., Kolb, H. J., Lerner, K. G., Schroeder, M. L., Thomas, E. D. Unpub18. 19. 20.
lished. 28.
Storb, R., Thomas, E. D., Buckner, C. D., Clift, R. A., Johnson, F. L., Fefer, A., Glucksberg, H., Giblett, E. R., Lerner, K. G., Neiman, P. Blood (in the press).
exposed to ultraviolet radiation at a wavelength of 2357 A have shown a reduction of mitotic activity and an increase of chromosome aberrations. It must be emphasised that the Airshields unit does not emit these wavelengths. However, further studies will be necessary before it can be entirely accepted that phototherapy has no harmful effect. Department of Child Life and Health, University of Edinburgh.
G. SANDOR.
A NEW TRANSLOCATION RELATED TO THE PHILADELPHIA CHROMOSOME
SiR,-We have found a new type of translocation probably related to the formation of the Philadelphia (PhI) This translocation occurred onto chromochromosome. some A2 rather than C9 and may involve that portion of chromosome G22 missing from the (Ph) chromosome, which is characteristic of cells of patients with chronic myelocytic leukxmia (c.M.L.). In our series of patients with C.M.L., in whose marrow cells translocation onto chromosome C9 is associated with a Ph due to deletion of chromosome G22, one patient was found to have a translocation not hitherto described. This 52-year-old man had typical Ph’-positive C.M.L. His chromosomes from peripheral blood-cells cultured without phytohsmmaglutinin (P.H.A.) and from the bone-marrow showed heteromorphic chromosomes in pairs A2 and G22. Investigation of karyotypes with buffered quinacrinemustard (Q) and trypsin-Giemsa (G) banding methods showed that the larger chromosome A2 had an additional pale fluorescent Q-band or a negative-staining G-band at the end of the long arm (figs. 1 and 2). These bandingpatterns and the size of the band were very similar to those of the missing portion of the smaller chromosome G22. C-bands induced with the NaOH-SSC method were found to be normal in all the chromosomes. Metaphase cells from peripheral blood cultured with P.H.A. showed normal karyotypes. Rowley4 first reported the association between the deletion of chromosome G22, resulting in the Ph, and a translocation involving chromosome C9 in a series of 9 patients with C.M.L. The findings reported by us in this 3. 4.
Parrington, J. M. Cytogenetics, 1972, 11, Rowley, J. D. Nature, 1973, 243, 290.
117.
Fig. 2-Giemsa-banding pattern of chromosomes in marrowcell of the patient here reported (a) and another subject with C.M.L. (b). In (a) the translocation is associated with the long arm of a 2 chromosome, whereas in (b), and in most cases of C.M.L., the translocation is on one of the no. 9 chromosomes.
no.
paper indicate that other translocations, though much rarer than those involving chromosome C9, may occur in Ph1-positive C.M.L. and that the translocation of the missing segment of the Ph chromosome is not specific to a particular chromosome. C.M.L. may, thus, appear to be a result of a position effect, mainly in the long arm of chromosome G22 rather than in any other chromosome of the human karyo-
type. Roswell Park Memorial
Institute,
Buffalo,
New York
U.S.A.
14203,
ISAMU HAYATA SURABHI KAKATI AVERY A. SANDBERG.
DELETIONS OF CHROMOSOME 7 IN HÆMATOLOGICAL DISORDERS
SIR,-Aneuploidy involving group C is the most common chromosome abnormality found in patients with a variety of haematological disorders.1 In hyperdiploid cells, involvement of C-group chromosomes appears to be non-random. Additional chromosomes 8 are reported most frequently,2,3 although additional chromosomes 9,4-6 10,7 and X8 have also been observed. Hypodiploidy due to loss of a C-group chromosome is much less common. In the only report to date, marrow cells from two female patients with acute myelogenous leukaemia showed the loss of one X chromosome.99 The present report describes two nonleuksemic male patients whose marrow cells showed deficiencies involving chromosome 7. Case 1.-Marrow cells showed a mosaic karyotype (45,X/46,XY) when the patient was first seen in 1969 for pancytopenia.1" In 1970, after treatment, he appeared normal both clinically and heematologically, and he had a normal marrow karyotype. In June, 1973, he was re-examined because of easy fatigability; he was found to have anxmia (haemoglobin 10 g. per 100 ml.) and neutropenia (19%). The bone-marrow showed megaloblastic erythroid features and a disturbance of myeloid maturation. The marrow karyotype also showed a change, with a 45,XY,-7 karyotype found in 49 of 50 cells examined. Two-thirds of these cells also contained a small chromosome fragment with uniform
Fig. l-Quinacrine-fluorescent pattern of marrow-cell, showing translocation somes
The
no.
replaces
on
to
the long
arm
of
one
of the
no.
2 chromo-
(arrow). 9 chromosomes are normal, and 22 chromosome (arrow).
a no.
a
Ph’ chromosome
1. Sandberg, A. A., Hossfeld, D. K. A. Rev. Med. 1970, 21, 379. 2. de la Chapelle, A., Schroder, J., Vupio, P. Clin. Genet. 1972, 3, 470. 3. Rowley, J. D. Nature, 1973, 243, 290. 4. Davidson, W. M., Knight, L. A. Lancet, 1973, i, 1510. 5. Rowley, J. D. ibid. 1973, ii, 390. 6. Rutten, F. J., Hustinx, T. W. J., Scheres, J. M. J. C., Wagener, D. J. T. ibid. p. 455. 7. Beck, W. S., Chesney, T. McC. New Engl. J. Med. 1973, 288, 957. 8. Rowley, J. D. Unpublished. 9. Rowley, J. D. Annls Génét. 1973, 16, 109. 10. Rowley, J. D. Br. J. Hœmat. 1971, 21, 717.
1386
pale fluorescence and
no distinct centromere after treatment with NaOH. Case 2.-This patient had polycythxmia vera, which was treated with phosphorus-32 (1954-59) and busulphan. Marrow chromosomes, which were first examined in 1967, have shown a mosaic pattern (46,XY,Cq-/46,XY) on each analysis; the abnormal cells increased from 50% in 1967 to 83% in 1969, and to 96% in 1973. Quinacrine fluorescence revealed that one no. 7 had a deletion of the long arm distal to 7q22,11 which resembled the deletion observed in JIYOYE, a lymphoblastoid line established from a Burkitt’s lymphoma.12
(3) The PhI chromosome, irrespective of its percentage in myeloid cells, is the specific marker of the preleukaemic conditions as a whole. The main consequence of its presence is not The various myeloproliferative the cell hyperproduction. disorders are generally accepted as clinical C.M.L. variants,la-2o and even the very " classic " chronic phase of leukaemia can be considered,21 not as a leuksemic state per se, but as the clinical variety with the higher risk to end sooner or later in an acute blastic crisis. Laboratoire de Cytogénétique, Institut Jules Bordet, Centre des Tumeurs de l’Université Libre de Bruxelles,
Whether the loss of part or all of chromosome 7 in the only two males with missing C chromosomes whom I have examined is fortuitous or not can only be determined by examination of additional patients. Dr B. Erkman-Baylis did the first cytogenetic analysis in 2. I thank Dr Stanley Yachnin for referring patient 1 and Dr Suzanne Larsh and Dr Joseph Baron for referring patient 2. I acknowledge the expert technical assistance of Miss Judith Mikuta, Miss Margaret Ikeda, and Mr David Potter.
Rue Héger Bordet, 1000 Bruxelles, Belgium.
patient
Department of Medicine,
JANET D. ROWLEY.
PHILADELPHIA-CHROMOSOME-POSITIVE PRELEUKÆMIC STATE et al.13 present a case supporting the that the Ph’ chromosome is the marker of a hypothesis preleukxmic state and not the leukxmic process itself. The same opinion has already been proposed.14 We should like to present a case relevant to this question and to show that the presence of a PhI-positive cell line does not necessarily mean a further transformation in the acute phase of chronic myeloblastic leukaemia.
SIR,-Baccarini
A
woman now
aged
81
was
INCREASING THE EFFICACY OF ANTILYMPHOCYTE GLOBULIN
SIR,—Your editorial (Oct. 13,
p. 834) reviews the clinical antilymphocyte globulin (A.L.G.) as an immunosuppressive agent in a variety of immunological disorders and especially renal transplantation. Compelling reasons for continuing to study A.L.G. are seen. Presumably, more impressive results with A.L.G. might be achieved in man if only doses similar to those used in laboratory animals could be given. Such doses, however, are impractical and raise the likelihood of complications. Therefore, a means to increase the efficacy of A.L.G. without increasing its dose would be welcome. One possibility is to take advantage of the synergistic immunosuppressive effects exerted by A.L.G. and methylhydrazine derivatives such as procarbazine (’ Natulan ’). Accordingly, A.L.G. combined with a well-tolerated dose of procarbazine is superior to a higher dose of A.L.G. alone. Experimentally, it has been found in mice that the immunosuppressive potency of antilymphocyte serum (A.L.S.) was greatly increased by doses of procarbazine which, alone, were ineffective.22-24 The addition of procarbazine to a dose of A.L.S. prolonged the survival of skin allografts across strong histocompatibility barriers up to tenfold. A variety of other chemotherapeutic agents provided considerably less or no synergistic effects with A.L.S. The synergy was later confirmed in another species. Combined treatment with procarbazine and anti-thymocyte serum (A.T.s.), in conjunction with total-body irradiation, prevented sensitisation by prior transfusions with donortype blood-to-marrow allografts in dogs. Under the same conditions, A.T.s. or procarbazine alone were insufficient use
Franklin McLean Memorial Research Institute, University of Chicago, Chicago, Illinois 60637, U.S.A.
first examined in 1966.
She had
clinical and ha:matological evidence of polycythaemia vera and was treated from 1966 to 1973 by six administrations of 32p: 4 mCi in July and August, 1966, in April, 1969, and in June, 1970, and 3 mCi in October, 1971, and January, 1973. The last blood-count in April, 1973, was: red cells 4-87x10’’ per c.mm.; Hb 14-8 g. per 100 ml.; white cells 4500 per c.mm; platelets 138,000 per c.mm. The patient is still in good health with no sign of leukasmic transformations. A first cytogenetic analysis was performed in June, 1966: a Ph chromosome was found in 10% of the mitoses analysed (see fig. 5 in the full report 15). BoneLeucocyte alkaline-phosphatase was 30 per 100 cells. marrow was reinvestigated in May, 1971, and July, 1972; the myelogram was normal, the chromosome analysis was completed by a direct method on 30 and 150 mitoses respectively. The second sample was stained by a modified ASG-banding technique.16 No Ph’ chromosome nor other anomalies could be found. Alkaline-phosphatase was 186 per 100 cells in July, 1972.
This 7-year survival prompts
us to
remark:
(1) The presence of the PhI chromosome is illustrated by a picture in the first report of the case 15; and considered as convincing by Sandberg and Hossfeld.17 The Ph could be missed in 1971, but this is less likely in 1972 when 150 mitoses were scrutinised. Thus, this case is probably the first report of the spontaneous disappearance of a Phl-positive cell line in a myeloproliferative disorder. (2) The polycythaemia vera remained quiescent from 1966 to 1973 with the help of a mild treatment. This is perhaps related to the fact that no more Ph’-positive population could be demonstrated after 1966. 11. Paris Conference (1971). Birth Defects: Original Article Series, 1972, 8, no. 7. 12. Steel, C. M. Nature, 1971, 233, 555. 13. Baccarini, M., Zaccaria, A., Tura, S. Lancet, Nov. 10, 1973, p. 1094. 14. Canellos, G. P., Whang-Peng, J. ibid. 1972, ii, 1227.
15. Koulischer, L., Fruhling, J., Henry, J. Eur. J. Cancer, 1967, 3, 159. 16. Reeves, B. R., Lobb, D. S., Lawler, S. D. Humangenetik, 1972, 14, 159.
17. Sandberg, A. A., Hossfeld, D. K. A. Rev. Med. 1970, 21, 379.
A. VERHEST F. VAN SCHOUBROECK.
of
interfere with successful immunisation and to permit sustained graft survival after total-body irradiation. 15-17 The combined treatment with procarbazine and A.T.S. has been used clinically in marrow-graft recipients who had been exposed to transfusions from family members.28 2 patients given the procarbazine/A.T.s. regimen, in addito
Baserga, A., Castoldi, G. L. Biomedicine, 1973, 18, 89. Ghosh, M. L. Postgrad. med. J. 1972, 48, 686. Cervenka, J., Koulischer, L., Gorlin, R. J. Chromosomes in Human Cancer. Springfield, Illinois, 1973. 21. Pedersen, B. Proceedings of the Fourth International Congress of Human Genetics, Paris, 1971 (edited by J. de Grouchy, F. J. G. Ebling, and I. W. Henderson). Amsterdam, 1972. 22. Floersheim, G. L. Transplantation, 1969, 8, 392. 23. Floersheim, G. L., Brune, K. Transplant. Proc. 1971, 3, 688. 24. Floersheim, G. L. Transplantation, 1973, 15, 195. 25. Floersheim, G. L., Kolb, H. J., Graham, T. C., Weiden, P. L., Thomas, E. D., Storb, R. Experientia, 1973, 29, 771. 26. Floersheim, G. L., Storb, R., Weiden, P. L., Kolb, H. J., Graham, T. C., Thomas, E. D. Expl Hematol. (in the press). 27. Storb, R. Floersheim, G. L., Weiden, P. L., Graham, T. C., Kolb, H. J., Lerner, K. G., Schroeder, M. L., Thomas, E. D. Unpub18. 19. 20.
lished. 28.
Storb, R., Thomas, E. D., Buckner, C. D., Clift, R. A., Johnson, F. L., Fefer, A., Glucksberg, H., Giblett, E. R., Lerner, K. G., Neiman, P. Blood (in the press).