269 were found in several non-proliferative granulocytes after 13 and 28 days in diffusion chamber culture (fig. 1). Thus, in this case of acute promyelocytic leukaemia, continuation of cell maturation was made possible by a change in the microenvironment, which released the leukaEmic cells from a blockage of differentiation within 7 days of culture.
which
This work was
supported by grants from
Landesamt fur
Forschung,
Nordrhein-Westfalen.
Innere Universitätsklinik (Tumorforschung), Westdeutsches Tumorzentrum, D-4300 Essen 1, West Germany
W. R. BOECKER S. ÖHL D. K. HOSSFELD C. G. SCHMIDT.
HODGKIN’S DISEASE DURING ACUTE LEUKÆMIA IN REMISSION
SIR,-We were interested in the paper by Dr Woodruff and his
colleagues’ because we had just diagnosed Hodgkin’s disduring remission of acute lymphoblastic leukaemia (A.L.L.). We could find only one previously published case of this.2 In two reviews3,4 108 children with second malignant neoplasms were found, but none was A.L.L. the first and Hodgease
kin’s disease the second. A boy born in August, 1971, was admitted to hospital in December, 1975, with a 2 week history of fever, abdominal pain, and malaise. Laboratory tests showed leukopenia, anaemia, and mild thrombocytopenia. A.L.L. was diagnosed. The boy was treated with vincristine and prednisolone. Complete remission was achieved after 4 weeks. Prophylactic central-nervous-system therapy consisted of cranial irradiation (2400 rad) and five intrathecal methotrexate injections. Thereafter the patient received a maintenance chemotherapy with daily 6-mercaptopurine and weekly methotrexate and cyclo-
phosphamide. In
September, 1977, a symptomatic upper left cervical lym-
phadenopathy
was
noticed. Penicillin had
no
effect. Fine-
aspiration biopsy showed no signs of leukaemia. Serological tests for infectious mononucleosis, toxoplasmosis, cytomegalovirus disease, and ornithosis were all negative. Thelymphnode grew to approximately 2-5x3-5cm and it was removed. The nodal structure was severely deranged with marked infiltration of eosinophils, plasma cells, and numerous Hodgkin cells including typical Reed-Sternberg cells. Thus all the criteria for Hodgkin’s disease, mixed cellular type, were met. A bone-marrow aspiration showed continuous remission of the leukaemia (22 months after diagnosis). Further investigations included surgical biopsy of bone-marrow and Waldeyer’s ring, percutaneous fine-needle aspiration biopsies of liver and spleen, and a staging laparotomy with splenectomy. In all these specimens there was no evidence of Hodgkin’s disease or A.L.L. Abdominal lymph-nodes were lymphocyte depleted for a patient of this age. The patient thus had stage IA Hodgkin’s disease during complete remission of leukaemia. Both diseases have been treated conventionally and independently-the upper mantle technique for Hodgkin’s disease and maintenance chemotherapy for A.L.L. Leukaemia complicating Hodgkin’s disease is well known and has usually been of the acute myelocytic type (A.M.L.). In all such cases studied cytogenetically, chromosome changes have been seen; these are much less common in "spontaneous" A.M.L.6 This may well be an expression for different mechanisms behind the two forms of A.M.L. The one complicating needle
1. Woodruff, R. K., and others Lancet, 1977, ii, 900. 2. Grant, M. D., Coleman, M. J. J. Am. med. Ass. 1975, 231, 623. 3. Li, F. P. Cancer, 1977, 40, 1899. 4. Meadows, A. T., D’Angio, G. J., Miké, V., Banfi, A., Harris, C., Jenkin, R. D. T., Schwartz, A. ibid. p. 1903. 5. Coleman, C. N., Williams, C. J., Flint, A., Glatstein, E. J., Rosenberg, S. A., Kaplan, H. S. New Engl. J. Med. 1977, 297, 1249. 6. Cavallin-Ståhl, E., Landberg, T., Ottow, Z., Mitelman, F. Scand. J. Hœmat.
1977, 19, 273.
Hodgkin’s disease develops in patients treated with both largetarget-volume, high-absorbed-dose radiotherapy and intensive chemotherapy, both modalities being potential carcinogens. However, in studies on second malignant neoplasms in children3.4 most second cancers were in the field of prior radiotherapy and were attributable to the oncogenic effect of radiation. Direct oncogenic effect of chemotherapy or its enhancing effect on radiation oncogenesis was not noted. All patients who have had Hodgkin’s disease during remission of
A.L.L.
have received cranial irradiation and combined
chemotherapy. The xtiological relation, if any, between the two diseases or the treatment remains purely speculative. It is, nevertheless, striking that the histology of Hodgkin’s disease occurring in patients with leukaemia does not reflect the usual incidence of different histological types in this disease. The three young adult patients showed lymphocyte depletion and the two children showed mixed cellularity type. In our case undiseased lymph-nodes were relatively depleted of lymphocytes. We believe that this histological appearance is caused by chemotherapy for leukxmia. Therefore, the histological appearance may not have the same prognostic significance as in "naturally" occurring Hodgkin’s disease. Until further knowledge about Hodgkin’s disease complicating leukaemia has been collected, it may be warranted to evaluate and treat the two diseases independently. STANISLAW GARWICZ STEFAN ARONSON BENGT ANDRÉASSON TORSTEN LANDBERG Departments of Pædiatrics, Oncology, and Pathology, EVA CAVALLIN-STÅHL University Hospital, HANS HENRIKSON S-221 85 Lund, Sweden
INTRAVENOUS VERSUS INHALED SALBUTAMOL
SIR,-Your editorial (Jan. 14,
p. 80) appeared on the same trial was published.’ Using a double-blind randomised allocation of treatment, we concluded that wet nebulised salbutamol given with spontaneous respiration was as effective in severe asthma as intravenous salbutamol and was free from the side-effects of the latter. The paper2 on which your editorial was based concluded that in severe asthma the intravenous route was the method of choice. Patients in this trial were all first given nebulised salbutamol by intermittent positive-pressure ventilation (I.P.P. v.) followed by intravenous salbutamol. Peak flow rates showed greater improvement after intravenous salbutamol. However, the results could equally well indicate that the second dose of salbutamol, by whatever route, was more effective than the first since no crossover or alternative order of dosage was attempted. Also, since no attempt was made to make the trial blind, the beneficial psychological effect of an intravenous in’ jection compared with the possible unpleasant effect of the LP.P.V. mask or mouthpiece could easily account for the
day
as our
results. There is evidence that I.P.P.V., especially in obstructive airways disease, increases the maldistribution of the inspired air. Nebulised drugs given by i.P.P.v. may thus be less effective than when given with spontaneous ventilation.3 This may partly explain the results obtained by Williams and Seaton with nebulised salbutamol. We suggest that nebulised salbutamol has a place in the management of acute severe asthma and is best given using a simple nebuliser with spontaneous breath-
ing. Northwick Park Hospital, Middlesex HA1 3UJ
1. 2. 3.
P. LAWFORD
J. S. MILLEDGE
Lawford, P., Jones, B. J. M., Milledg&ebreve;, J. S. Br. med. J. 1978, i, 84. Williams, S., Seaton, A. Thorax, 1977, 32, 555. Dolovich, M. B., and others. Am. Rev. resp. Dis. 1977, 115, 397.
which
This work was
supported by grants from
Landesamt fur
Forschung,
Nordrhein-Westfalen.
Innere Universitätsklinik (Tumorforschung), Westdeutsches Tumorzentrum, D-4300 Essen 1, West Germany
W. R. BOECKER S. ÖHL D. K. HOSSFELD C. G. SCHMIDT.
HODGKIN’S DISEASE DURING ACUTE LEUKÆMIA IN REMISSION
SIR,-We were interested in the paper by Dr Woodruff and his
colleagues’ because we had just diagnosed Hodgkin’s disduring remission of acute lymphoblastic leukaemia (A.L.L.). We could find only one previously published case of this.2 In two reviews3,4 108 children with second malignant neoplasms were found, but none was A.L.L. the first and Hodgease
kin’s disease the second. A boy born in August, 1971, was admitted to hospital in December, 1975, with a 2 week history of fever, abdominal pain, and malaise. Laboratory tests showed leukopenia, anaemia, and mild thrombocytopenia. A.L.L. was diagnosed. The boy was treated with vincristine and prednisolone. Complete remission was achieved after 4 weeks. Prophylactic central-nervous-system therapy consisted of cranial irradiation (2400 rad) and five intrathecal methotrexate injections. Thereafter the patient received a maintenance chemotherapy with daily 6-mercaptopurine and weekly methotrexate and cyclo-
phosphamide. In
September, 1977, a symptomatic upper left cervical lym-
phadenopathy
was
noticed. Penicillin had
no
effect. Fine-
aspiration biopsy showed no signs of leukaemia. Serological tests for infectious mononucleosis, toxoplasmosis, cytomegalovirus disease, and ornithosis were all negative. Thelymphnode grew to approximately 2-5x3-5cm and it was removed. The nodal structure was severely deranged with marked infiltration of eosinophils, plasma cells, and numerous Hodgkin cells including typical Reed-Sternberg cells. Thus all the criteria for Hodgkin’s disease, mixed cellular type, were met. A bone-marrow aspiration showed continuous remission of the leukaemia (22 months after diagnosis). Further investigations included surgical biopsy of bone-marrow and Waldeyer’s ring, percutaneous fine-needle aspiration biopsies of liver and spleen, and a staging laparotomy with splenectomy. In all these specimens there was no evidence of Hodgkin’s disease or A.L.L. Abdominal lymph-nodes were lymphocyte depleted for a patient of this age. The patient thus had stage IA Hodgkin’s disease during complete remission of leukaemia. Both diseases have been treated conventionally and independently-the upper mantle technique for Hodgkin’s disease and maintenance chemotherapy for A.L.L. Leukaemia complicating Hodgkin’s disease is well known and has usually been of the acute myelocytic type (A.M.L.). In all such cases studied cytogenetically, chromosome changes have been seen; these are much less common in "spontaneous" A.M.L.6 This may well be an expression for different mechanisms behind the two forms of A.M.L. The one complicating needle
1. Woodruff, R. K., and others Lancet, 1977, ii, 900. 2. Grant, M. D., Coleman, M. J. J. Am. med. Ass. 1975, 231, 623. 3. Li, F. P. Cancer, 1977, 40, 1899. 4. Meadows, A. T., D’Angio, G. J., Miké, V., Banfi, A., Harris, C., Jenkin, R. D. T., Schwartz, A. ibid. p. 1903. 5. Coleman, C. N., Williams, C. J., Flint, A., Glatstein, E. J., Rosenberg, S. A., Kaplan, H. S. New Engl. J. Med. 1977, 297, 1249. 6. Cavallin-Ståhl, E., Landberg, T., Ottow, Z., Mitelman, F. Scand. J. Hœmat.
1977, 19, 273.
Hodgkin’s disease develops in patients treated with both largetarget-volume, high-absorbed-dose radiotherapy and intensive chemotherapy, both modalities being potential carcinogens. However, in studies on second malignant neoplasms in children3.4 most second cancers were in the field of prior radiotherapy and were attributable to the oncogenic effect of radiation. Direct oncogenic effect of chemotherapy or its enhancing effect on radiation oncogenesis was not noted. All patients who have had Hodgkin’s disease during remission of
A.L.L.
have received cranial irradiation and combined
chemotherapy. The xtiological relation, if any, between the two diseases or the treatment remains purely speculative. It is, nevertheless, striking that the histology of Hodgkin’s disease occurring in patients with leukaemia does not reflect the usual incidence of different histological types in this disease. The three young adult patients showed lymphocyte depletion and the two children showed mixed cellularity type. In our case undiseased lymph-nodes were relatively depleted of lymphocytes. We believe that this histological appearance is caused by chemotherapy for leukxmia. Therefore, the histological appearance may not have the same prognostic significance as in "naturally" occurring Hodgkin’s disease. Until further knowledge about Hodgkin’s disease complicating leukaemia has been collected, it may be warranted to evaluate and treat the two diseases independently. STANISLAW GARWICZ STEFAN ARONSON BENGT ANDRÉASSON TORSTEN LANDBERG Departments of Pædiatrics, Oncology, and Pathology, EVA CAVALLIN-STÅHL University Hospital, HANS HENRIKSON S-221 85 Lund, Sweden
INTRAVENOUS VERSUS INHALED SALBUTAMOL
SIR,-Your editorial (Jan. 14,
p. 80) appeared on the same trial was published.’ Using a double-blind randomised allocation of treatment, we concluded that wet nebulised salbutamol given with spontaneous respiration was as effective in severe asthma as intravenous salbutamol and was free from the side-effects of the latter. The paper2 on which your editorial was based concluded that in severe asthma the intravenous route was the method of choice. Patients in this trial were all first given nebulised salbutamol by intermittent positive-pressure ventilation (I.P.P. v.) followed by intravenous salbutamol. Peak flow rates showed greater improvement after intravenous salbutamol. However, the results could equally well indicate that the second dose of salbutamol, by whatever route, was more effective than the first since no crossover or alternative order of dosage was attempted. Also, since no attempt was made to make the trial blind, the beneficial psychological effect of an intravenous in’ jection compared with the possible unpleasant effect of the LP.P.V. mask or mouthpiece could easily account for the
day
as our
results. There is evidence that I.P.P.V., especially in obstructive airways disease, increases the maldistribution of the inspired air. Nebulised drugs given by i.P.P.v. may thus be less effective than when given with spontaneous ventilation.3 This may partly explain the results obtained by Williams and Seaton with nebulised salbutamol. We suggest that nebulised salbutamol has a place in the management of acute severe asthma and is best given using a simple nebuliser with spontaneous breath-
ing. Northwick Park Hospital, Middlesex HA1 3UJ
1. 2. 3.
P. LAWFORD
J. S. MILLEDGE
Lawford, P., Jones, B. J. M., Milledg&ebreve;, J. S. Br. med. J. 1978, i, 84. Williams, S., Seaton, A. Thorax, 1977, 32, 555. Dolovich, M. B., and others. Am. Rev. resp. Dis. 1977, 115, 397.
