1302 This case differs from all others in which the Ph’ chromohas been found. Previously the Ph’ chromosome has been directly associated with a recognisably malignant cell and has been notable for its absence from P.H.A.-stimulated lymphocytes. The repeated finding in the present case of the Ph’-positive clone in P.H.A.-stimulated blood-cultures during remission, when no blast-cells were detectable, seems to indicate (1) that the Ph’ chromosome is not directly related to the blast-cells of the acute leukaemia and (2) that it is present in lymphocytes capable of responding to P.H.A. and morphologically indistinguishable from normal. The case will be reported fully elsewhere. some
We thank Dr Sylvia D. Lawler and Prof. R. M Hardisty for their help with this case and Mrs Barbara Perry, Mr Derek Denman, and Miss Lynn Hughes for technical assistance. The work was supported by grants from the Leukaemia Research Fund.
Department of Cytogenetics and
Immunology, Royal Marsden Hospital, Fulham Road, London SW3.
LORNA M. SECKER WALKER
Hospital for Sick Children, Great Ormond Street, London WC1.
J.
D. HARDY
SURVIVAL IN ACUTE MYELOID LEUKÆMIA
SIR,-Complete remission was obtained in 14 out of 15 successive children (93%) presenting with acute myeloblastic, myelomonocytic, pure monocytic leukaemia or erythroleukaemia being treated at the Royal Hospital for Sick Children in Glasgow and the Dumfries and Galloway Royal Infirmary since December, 1970. Combination chemotherapy with daunorubicin or adriamycin plus cytarabine with or without thioguanine was given together with the use of maximum available supportive and isolation facilities (laminar flow and
gut sterilisation in the Glasgow cases). Refractory patients treated with TRAMPCO’ or the schedule described by Smith and McElwain.2 The single death during remission induction was due to cardiac tamponade from leukacmic pericarditis. 11 of these 15 children are still alive at periods up to 5 years (see figure). The first of these patients was diagnosed on Dec. 12, 1970, and has now been off all chemotherapy for 1 year. Another, diagnosed 3yyears ago, has been off chemotherapy for 6 months. Maintenance chemotherapy was generally with "split dose" daily oral thioguanine plus 6-mercaptopurine with weekly or fortnightly subcutaneous cytarabine. Full details of this series will be published elsewhere. We present these facts to counteract the therapeutic pessimism expressed by Dr Burge and Professor Prankerd and by
were
1. 2.
Spiers, A. S. D. Br. J. Hæmat. 1972, 23, 262. Smith, I. E., McElwain, T. J. Lancet, 1974, i, 161.
Dr Rose
(Nov. 29,
children with
acute
1091). Their statements myeloid leukaemia.
p.
do
not
apply to
Departments of Hæmatology and Child Health, Royal Hospital for Sick Children, Glasgow G3 8SJ, and Department of Pædiatrics, M. L. N. WILLOUGHBY Dumfries and Galloway Royal (New District Hospital), Dumfries DG1 4AP.
Infirmary,
SHEENAH J. M. RUSSELL J. R. GRAHAM-POLE
BLAST-CELL TRANSFORMATION IN CHRONIC GRANULOCYTIC LEUKÆMIA
SIR,-We should like which has
to
draw attention
to an
unusual
case
responded well to treatment.
43-year-old housewife was admitted to this hospital in December, a brief history of back pain and bruising. Examination revealed moderate splenomegaly but no lymphadenopathy. A peripheral-blood count showed thrombocytopenia and white-cell count 80 x 10/1, with promyelocytes, myelocytes, and occasional blast-cells. Leucocyte alkaline phosphatase (L.A.P.) score was low and serum-vitamin-BIl was greater than 750 pg/ml. A bone-marrow aspirate was hypercellular, with abundant early myeloid precursors and 60% blastcells. These exhibited a high nuclear/cytoplasmic ratio, with occasional nuclear clefts and folds, one or two nucleoli, no Auer rods, and few granules. They were sudan-black negative. However, 20% of these cells were periodic-acid/Schiff (P.A.S.) positive, many containing large blocks of such material. The Philadelphia chromosome was present in A
1974, with
80% of all nucleated cells. We considerd this to be blastic crisis in chronic granulocytic leukaemia (C.G.L.) but because of the morphology and cytochemistry, which suggested lymphoblastic rather than myeloblastic transformation, and because of the poor prognosis in this group, we decided to begin therapy with vincristine 1 - 5 mg/mz and prednisolone 40 mg/m2. Owing to a prescribing error, 12.5mg vincristine was administered over 5 days, but the only side-effects were a temporary peripheral neuropathy, alopecia, and constipation. After 17 days the marrow was in remission, and maintenance therapy was begun with adriamycin and cytarabine alternating fortnightly with vincristine and prednisolone. Initially busuphan, 2 mg/day, was given continuously in addition but had to be stopped because of leucopenia. After 8 months of therapy cyclophosphamide and thioguanine were introduced in place of adriamycin and cytarabine to reduce the risk of cardiotoxicity. Throughout the 12 months since initial diagnosis the marrow has remained in remission. No problems have occurred, apart from occasional infections, and the patient was able to return to her previous employment 7 months ago. Canellos and his colleagues’ have described 30 cases of blastic transformation in c.G.L., although they gave no indication of morphology or cytochemistry. Complete or partial remission was obtained in 30% of patients on a dosage schedule of vincristine 2.0 mg/m2 weekly together with prednisolone 60 mg/m2 daily. The mean total dose of vincristine required to achieve remission was 8-2 mg/m2. Thus it seems that our patient inadvertently received a remission-inducing dose at the beginning of therapy. Marmont and Damasio’ have published similarly encouraging findings with vincristine and prednisolone therapy, although only in patients with "agranular blasts". Our patient fell into this category. P.A.S. positivity of the blast-cells is unusual, although this finding has been reported previously. Two explanations are possible: (i) the stain is an unreliable means of distinguishing between myeloblasts and lymphoblasts (an opinion being increasingly suggested), or (ii) the cells are lymphoblasts representing a new clone. We therefore suggest that the P.A.s. reaction may be a useful additional guide to deciding the initial treatment of this condition. Department of Hæmatology, Gibson Laboratories, Radcliffe Infirmary, Oxford. 1. Canellos, G. P.,
DAVID HOWES PAULINE M. EMERSON
De Vita, V. T., Whang-Peng, J., Carbone, P. P. Blood, 1971, 38, 671. 2. Marmont, A. M., Damasio, E. E. Acta hæmat. 1973, 50, 1. 3. Litwin, J., Stacher, A. Blut, 1974, 28, 161.
We thank Dr Sylvia D. Lawler and Prof. R. M Hardisty for their help with this case and Mrs Barbara Perry, Mr Derek Denman, and Miss Lynn Hughes for technical assistance. The work was supported by grants from the Leukaemia Research Fund.
Department of Cytogenetics and
Immunology, Royal Marsden Hospital, Fulham Road, London SW3.
LORNA M. SECKER WALKER
Hospital for Sick Children, Great Ormond Street, London WC1.
J.
D. HARDY
SURVIVAL IN ACUTE MYELOID LEUKÆMIA
SIR,-Complete remission was obtained in 14 out of 15 successive children (93%) presenting with acute myeloblastic, myelomonocytic, pure monocytic leukaemia or erythroleukaemia being treated at the Royal Hospital for Sick Children in Glasgow and the Dumfries and Galloway Royal Infirmary since December, 1970. Combination chemotherapy with daunorubicin or adriamycin plus cytarabine with or without thioguanine was given together with the use of maximum available supportive and isolation facilities (laminar flow and
gut sterilisation in the Glasgow cases). Refractory patients treated with TRAMPCO’ or the schedule described by Smith and McElwain.2 The single death during remission induction was due to cardiac tamponade from leukacmic pericarditis. 11 of these 15 children are still alive at periods up to 5 years (see figure). The first of these patients was diagnosed on Dec. 12, 1970, and has now been off all chemotherapy for 1 year. Another, diagnosed 3yyears ago, has been off chemotherapy for 6 months. Maintenance chemotherapy was generally with "split dose" daily oral thioguanine plus 6-mercaptopurine with weekly or fortnightly subcutaneous cytarabine. Full details of this series will be published elsewhere. We present these facts to counteract the therapeutic pessimism expressed by Dr Burge and Professor Prankerd and by
were
1. 2.
Spiers, A. S. D. Br. J. Hæmat. 1972, 23, 262. Smith, I. E., McElwain, T. J. Lancet, 1974, i, 161.
Dr Rose
(Nov. 29,
children with
acute
1091). Their statements myeloid leukaemia.
p.
do
not
apply to
Departments of Hæmatology and Child Health, Royal Hospital for Sick Children, Glasgow G3 8SJ, and Department of Pædiatrics, M. L. N. WILLOUGHBY Dumfries and Galloway Royal (New District Hospital), Dumfries DG1 4AP.
Infirmary,
SHEENAH J. M. RUSSELL J. R. GRAHAM-POLE
BLAST-CELL TRANSFORMATION IN CHRONIC GRANULOCYTIC LEUKÆMIA
SIR,-We should like which has
to
draw attention
to an
unusual
case
responded well to treatment.
43-year-old housewife was admitted to this hospital in December, a brief history of back pain and bruising. Examination revealed moderate splenomegaly but no lymphadenopathy. A peripheral-blood count showed thrombocytopenia and white-cell count 80 x 10/1, with promyelocytes, myelocytes, and occasional blast-cells. Leucocyte alkaline phosphatase (L.A.P.) score was low and serum-vitamin-BIl was greater than 750 pg/ml. A bone-marrow aspirate was hypercellular, with abundant early myeloid precursors and 60% blastcells. These exhibited a high nuclear/cytoplasmic ratio, with occasional nuclear clefts and folds, one or two nucleoli, no Auer rods, and few granules. They were sudan-black negative. However, 20% of these cells were periodic-acid/Schiff (P.A.S.) positive, many containing large blocks of such material. The Philadelphia chromosome was present in A
1974, with
80% of all nucleated cells. We considerd this to be blastic crisis in chronic granulocytic leukaemia (C.G.L.) but because of the morphology and cytochemistry, which suggested lymphoblastic rather than myeloblastic transformation, and because of the poor prognosis in this group, we decided to begin therapy with vincristine 1 - 5 mg/mz and prednisolone 40 mg/m2. Owing to a prescribing error, 12.5mg vincristine was administered over 5 days, but the only side-effects were a temporary peripheral neuropathy, alopecia, and constipation. After 17 days the marrow was in remission, and maintenance therapy was begun with adriamycin and cytarabine alternating fortnightly with vincristine and prednisolone. Initially busuphan, 2 mg/day, was given continuously in addition but had to be stopped because of leucopenia. After 8 months of therapy cyclophosphamide and thioguanine were introduced in place of adriamycin and cytarabine to reduce the risk of cardiotoxicity. Throughout the 12 months since initial diagnosis the marrow has remained in remission. No problems have occurred, apart from occasional infections, and the patient was able to return to her previous employment 7 months ago. Canellos and his colleagues’ have described 30 cases of blastic transformation in c.G.L., although they gave no indication of morphology or cytochemistry. Complete or partial remission was obtained in 30% of patients on a dosage schedule of vincristine 2.0 mg/m2 weekly together with prednisolone 60 mg/m2 daily. The mean total dose of vincristine required to achieve remission was 8-2 mg/m2. Thus it seems that our patient inadvertently received a remission-inducing dose at the beginning of therapy. Marmont and Damasio’ have published similarly encouraging findings with vincristine and prednisolone therapy, although only in patients with "agranular blasts". Our patient fell into this category. P.A.S. positivity of the blast-cells is unusual, although this finding has been reported previously. Two explanations are possible: (i) the stain is an unreliable means of distinguishing between myeloblasts and lymphoblasts (an opinion being increasingly suggested), or (ii) the cells are lymphoblasts representing a new clone. We therefore suggest that the P.A.s. reaction may be a useful additional guide to deciding the initial treatment of this condition. Department of Hæmatology, Gibson Laboratories, Radcliffe Infirmary, Oxford. 1. Canellos, G. P.,
DAVID HOWES PAULINE M. EMERSON
De Vita, V. T., Whang-Peng, J., Carbone, P. P. Blood, 1971, 38, 671. 2. Marmont, A. M., Damasio, E. E. Acta hæmat. 1973, 50, 1. 3. Litwin, J., Stacher, A. Blut, 1974, 28, 161.
