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Maintenance treatment in acute non-lymphocytic leukaemia
ABSTRACTS OF A N N U A L MEETING CUTANEOUS LYMPHOMA-A
1979 3 I9
SPECTRUM
J. NORMAN. R. E. SAGE,B. M. DALE.I. J. FORBES & A. LEONG H u r m a t o l o ~ ~ ~ - O n cUnit, o / o ~QUWI ~~ Elizabeth Hospiral, Adelaide In recent years evidence has been accumulating that mycosis fungoides and Sezary syndrome come under the 'umbrella' of cutaneous lymphoma. Cutaneous lymphoma cells are 'T' lymphocytes which have a tendency to localize in the skin and T cell regions of lymphoid tissue, and usually spare the bone marrow. Between 29,'12:78 and 13/3/79 4 cases of cutaneous lymphoma presented to the Haematology-Oncology Unit in our hospital. They comprise a broad clinical and morphologic spectrum. Case I A 73-yr-old man with a 10 yr history of phenytoin treated petit ma1 epilepsy presented with a 6 mth history of a worsening maculopapular rash on legs. thighs, lower abdomen and back, and generalized lymphadenopathy and hepatosplenomegaly. Blood picture was H b 12.22,. platelets 147,00O/ml,W.C.C. 236,000:ml (Y6X lymphocytes). Skin biopsy revealed histological features of rnycosis fungoides and marrow biopsy revealed diffuse involvement by the lymphoma. Cytogenetic analysis of the blood was grossly abnormal. This patient is currently responding very well to weekly courses of cyclophosphamidepincristinc]leucapheresis. Case 2 A 70-yr-old woman presented with a severe exroliative dermatitis thought to be due to indomethacin. I t was associated with generalized lymphadenopathy and hepdtomegaly. Blood picture revealed H b 4.5')". platelets 140,00O/ml, and W.C.C. 61,000 (lymphocytes 9":,, abnormal monocytes lo:(,, lymphoid blasts 147;). Skin biopsy revealed histological features of mycosis fungoides. and in bone marrow aspirate lymphoid blasts comprising 50:;, of nucleated cells. Seven per cent of cells were atypical monocytes with cleaved nuclei. Cytogenetic analysis of the marrow was abnormal. The patient has responded well to intermittent chemotherapy with prednisolone. cyclophosphamide and vincristine but therapy has been complicated by intercurrent problems. Case3 A 55-yr-old man with progressive bilateral deafness, difficulty in speaking and dysphdgia over 4 mth. At presentation he had generalized lymphadenopathy with very large tonsils and hepatosplenomegaly. He also complained of severe pruritus and developed a morbilliforrn rash on back. buttocks and anterior chest. Blood picture was H b 15.1%, platelets 302.000/ml, W.C.C. 19,50O/ml (12% rnonocytes-smear was otherwise normal). There was diffuse hyperglobulinaemia. Lymph node and bone marrow biopsy revealed a diffuse poorly differentiated lymphocytic (small cell non-cleaved) T cell lymphoma. Skin biopsy revealed features of mycosis fungoides. The patient has responded dramatically to intermittent COP therapy. Case 4 A 66-yr-old woman presented with progressive long standing skin lesions over L. scapula. upper anterior chest. right back and thighs. There was no lymphadenopathy or hepatosplenomegaly. Blood picture and bone marrow were normal. Biopsy of one of these lesions revealed deep skin infiltration by mononuclear cells which were characterized by regular non-convoluted nuclei. T-cell disease was diagnosed on skin and blood specimens. There was improvement with 150 rads TBI.
IN VlTRO HAEMOPOIETIC PROGENITOR CELL RESPONSES IN MICE WITH THE TRANSPLANTED LYMPHOID TUMOUR ABE-8
J. H. MCCARTHY, T. BURGESS & D. METCALFCancer Rescwrch Utiir, WuIterandEliza HallInsrirutc., Melbourne BALB/c mice bearing the (transplanted) lymphoma induced by the Abelson virus developed increased levels of neutrophil-macrophage and eosinophil progenitor cells in the bone marrow and spleen. This was accompanied by a grdnulocytosis in the peripheral blood. Increase of granulocyte-macrophage progenitor cells appears t o parallel thc magnitude of leukaemic infiltration, as determined by assaying the numbers of leukaemic colony forming cells in the spleen and bone marrow using a selective cloning system. The phenomenon also was observed in athymic mice indicating that it is unlikely to be T-cell mediated. It was also reproduced using irradiated cells or a cell-free extract of the tumour implying that a humoral factor is responsible for these host responses.
MAINTENANCE TREATMENT IN ACUTE NON-LYMPHOCYTIC LELlKAEMlA
M. G. WHITESIDE, C. PATON,B. S. FARRAGHER & R . C. MCLENNANAlfred Hospital. Mrlbourrir In 1976 we reported the complete remission and survival figures for 13 patients with acute non-lymphocytic leukaemia who had achieved complete remission (C.R.) and who were given immunotherapy and intensive chemotherapy as maintenance treatment. Of the 8 patients still alive at the time of that report only 2 have died and 4
320
HSA AND ASBT
Pathology (1980), 12, April
have been in continual remission, one for nearly 5 yr and 3 for more than 6 yr. The median figure for survival for the 13 cases is now 252+ wk i.e. just on 5 yr and for duration of first C.R., 133 wk. During the next 4 yr a further 37 patients were judged suitable for intensive induction therapy, and 21 of these achieved C.R. The majority were entered into the Australian Adult Leukaemia Trial. Of these 21 cases 9 are at present alive and 6 are in continuing remission. Of the 14 cases achieving C.R. in the years 1975 to 1977 only 3 are still alive; one of these had promyelocytic disease and one was given the earlier chemo-immunotherapy maintenance treatment because he was unsuitable for the trial (age >65 yr). The trial data, reported elsewhere, at present show a median survival of 78+ wk for those given chemoimmunotherapy and 81 + wk for those given chemotherapy only in maintenance. It is suggested that the intensive, significantlymyelotoxic programme of maintenance therapy which included intermittent daunorubicin therapy for up to 18 mth, as used in our earlier series of patients, has been the major factor in the relatively high incidence of long-term remissions seen in that group.
LOW COST AUTOMATIC STORAGE AND QUALITY CONTROL OF COULTER COUNTER RESULTS
A. M. STREETER & G. G. CRANE Department of Haematology. Repatriation General Hospital. Concord, N.S. W . Automatic blood cell counters have allowed haematology departments to process a greatly increased number of blood counts rapidly and accurately, without a proportionate increase in laboratory staff. Clinicians have been quick to take advantage of this improvement in service. However, this type of operation creates a need for an effective quality control system and a fast reporting service. Our solution to these needs has involved the interfacing of a Diehl Alphatronic programmable calculator to the Coulter Counter Model S. The sample number generated by the Coulter S is used to identify each set of results, so avoiding the need for manual entry of sample identification data. The Coulter S is operated in the usual way, and result storage is fully automatic. Retrieval of results is fast, so that laboratory staff can quickly and conveniently reply to telephone enquiries. The on-line quality control system checks each set of results for internal consistency by subjecting them to mathematical tests, and applies other criteria to determine which results require confirmation. Other mathematical tests are used to indicate any results suggestive of thalassaemia. In addition automatic statistical analysis of all normal results is performed to monitor calibration and drift of the Coulter counter. Updated quality control printouts are available on demand without interruption to sample processing. The system is being extended to provide long-term storage of key results, to allow automatic comparison of current results with previous ones for each patient. It is felt that in reliability, flexibility and cost-effectivenessthis system compares favourably with computer based systems.
RISK FACTORS IN APLASTIC ANAEMIA
R. J. TRENT,H. KRONENBERG & T. WILKINSONHaematology Department, Royal Prince Alfred Hospital, Sydney In 1967, Vincent and de Gruchy estimated the mortality associated with aplastic anaemia to be 63%. In the last decade therapy with androgens, corticosteroids, intensive support with blood products and sterile environments has not significantly altered this mortality. The only recent major advance in the treatment of aplastic anaemia has been bone marrow transplantation, and results to date from specialized centres showing greater than 50% long-term survivors from allogeneic grafts in aplasia, are encouraging. However, the use of bone marrow transplantation in donor host combinations, other than identical twins, may result in either graft rejection or graft versus host disease despite matching at HLA-A,B and D loci, and for this reason, such a procedure would only be justified for those patients with aplastic anaemia for whom a fatal outcome is likely. To identify patients with severe aplastic anaemia a number of surveys have looked for risk factors in this disorder. We report here on parameters associated with mortality in 48 patients with aplastic anaemia managed over the years 1960-78 in a Sydney teaching hospital. Thirty-one (65%) patients died. Of these, 14 patients died from infection, 10 with bleeding problems and 3 a combination ofboth. In addition, 7 of the 17survivors have a persistently abnormal blood count 7 mth to 16 yr after diagnosis, and the median time required for blood counts to return to normal was 20 mth. Thirty-seven clinical and
1979 3 I9
SPECTRUM
J. NORMAN. R. E. SAGE,B. M. DALE.I. J. FORBES & A. LEONG H u r m a t o l o ~ ~ ~ - O n cUnit, o / o ~QUWI ~~ Elizabeth Hospiral, Adelaide In recent years evidence has been accumulating that mycosis fungoides and Sezary syndrome come under the 'umbrella' of cutaneous lymphoma. Cutaneous lymphoma cells are 'T' lymphocytes which have a tendency to localize in the skin and T cell regions of lymphoid tissue, and usually spare the bone marrow. Between 29,'12:78 and 13/3/79 4 cases of cutaneous lymphoma presented to the Haematology-Oncology Unit in our hospital. They comprise a broad clinical and morphologic spectrum. Case I A 73-yr-old man with a 10 yr history of phenytoin treated petit ma1 epilepsy presented with a 6 mth history of a worsening maculopapular rash on legs. thighs, lower abdomen and back, and generalized lymphadenopathy and hepatosplenomegaly. Blood picture was H b 12.22,. platelets 147,00O/ml,W.C.C. 236,000:ml (Y6X lymphocytes). Skin biopsy revealed histological features of rnycosis fungoides and marrow biopsy revealed diffuse involvement by the lymphoma. Cytogenetic analysis of the blood was grossly abnormal. This patient is currently responding very well to weekly courses of cyclophosphamidepincristinc]leucapheresis. Case 2 A 70-yr-old woman presented with a severe exroliative dermatitis thought to be due to indomethacin. I t was associated with generalized lymphadenopathy and hepdtomegaly. Blood picture revealed H b 4.5')". platelets 140,00O/ml, and W.C.C. 61,000 (lymphocytes 9":,, abnormal monocytes lo:(,, lymphoid blasts 147;). Skin biopsy revealed histological features of mycosis fungoides. and in bone marrow aspirate lymphoid blasts comprising 50:;, of nucleated cells. Seven per cent of cells were atypical monocytes with cleaved nuclei. Cytogenetic analysis of the marrow was abnormal. The patient has responded well to intermittent chemotherapy with prednisolone. cyclophosphamide and vincristine but therapy has been complicated by intercurrent problems. Case3 A 55-yr-old man with progressive bilateral deafness, difficulty in speaking and dysphdgia over 4 mth. At presentation he had generalized lymphadenopathy with very large tonsils and hepatosplenomegaly. He also complained of severe pruritus and developed a morbilliforrn rash on back. buttocks and anterior chest. Blood picture was H b 15.1%, platelets 302.000/ml, W.C.C. 19,50O/ml (12% rnonocytes-smear was otherwise normal). There was diffuse hyperglobulinaemia. Lymph node and bone marrow biopsy revealed a diffuse poorly differentiated lymphocytic (small cell non-cleaved) T cell lymphoma. Skin biopsy revealed features of mycosis fungoides. The patient has responded dramatically to intermittent COP therapy. Case 4 A 66-yr-old woman presented with progressive long standing skin lesions over L. scapula. upper anterior chest. right back and thighs. There was no lymphadenopathy or hepatosplenomegaly. Blood picture and bone marrow were normal. Biopsy of one of these lesions revealed deep skin infiltration by mononuclear cells which were characterized by regular non-convoluted nuclei. T-cell disease was diagnosed on skin and blood specimens. There was improvement with 150 rads TBI.
IN VlTRO HAEMOPOIETIC PROGENITOR CELL RESPONSES IN MICE WITH THE TRANSPLANTED LYMPHOID TUMOUR ABE-8
J. H. MCCARTHY, T. BURGESS & D. METCALFCancer Rescwrch Utiir, WuIterandEliza HallInsrirutc., Melbourne BALB/c mice bearing the (transplanted) lymphoma induced by the Abelson virus developed increased levels of neutrophil-macrophage and eosinophil progenitor cells in the bone marrow and spleen. This was accompanied by a grdnulocytosis in the peripheral blood. Increase of granulocyte-macrophage progenitor cells appears t o parallel thc magnitude of leukaemic infiltration, as determined by assaying the numbers of leukaemic colony forming cells in the spleen and bone marrow using a selective cloning system. The phenomenon also was observed in athymic mice indicating that it is unlikely to be T-cell mediated. It was also reproduced using irradiated cells or a cell-free extract of the tumour implying that a humoral factor is responsible for these host responses.
MAINTENANCE TREATMENT IN ACUTE NON-LYMPHOCYTIC LELlKAEMlA
M. G. WHITESIDE, C. PATON,B. S. FARRAGHER & R . C. MCLENNANAlfred Hospital. Mrlbourrir In 1976 we reported the complete remission and survival figures for 13 patients with acute non-lymphocytic leukaemia who had achieved complete remission (C.R.) and who were given immunotherapy and intensive chemotherapy as maintenance treatment. Of the 8 patients still alive at the time of that report only 2 have died and 4
320
HSA AND ASBT
Pathology (1980), 12, April
have been in continual remission, one for nearly 5 yr and 3 for more than 6 yr. The median figure for survival for the 13 cases is now 252+ wk i.e. just on 5 yr and for duration of first C.R., 133 wk. During the next 4 yr a further 37 patients were judged suitable for intensive induction therapy, and 21 of these achieved C.R. The majority were entered into the Australian Adult Leukaemia Trial. Of these 21 cases 9 are at present alive and 6 are in continuing remission. Of the 14 cases achieving C.R. in the years 1975 to 1977 only 3 are still alive; one of these had promyelocytic disease and one was given the earlier chemo-immunotherapy maintenance treatment because he was unsuitable for the trial (age >65 yr). The trial data, reported elsewhere, at present show a median survival of 78+ wk for those given chemoimmunotherapy and 81 + wk for those given chemotherapy only in maintenance. It is suggested that the intensive, significantlymyelotoxic programme of maintenance therapy which included intermittent daunorubicin therapy for up to 18 mth, as used in our earlier series of patients, has been the major factor in the relatively high incidence of long-term remissions seen in that group.
LOW COST AUTOMATIC STORAGE AND QUALITY CONTROL OF COULTER COUNTER RESULTS
A. M. STREETER & G. G. CRANE Department of Haematology. Repatriation General Hospital. Concord, N.S. W . Automatic blood cell counters have allowed haematology departments to process a greatly increased number of blood counts rapidly and accurately, without a proportionate increase in laboratory staff. Clinicians have been quick to take advantage of this improvement in service. However, this type of operation creates a need for an effective quality control system and a fast reporting service. Our solution to these needs has involved the interfacing of a Diehl Alphatronic programmable calculator to the Coulter Counter Model S. The sample number generated by the Coulter S is used to identify each set of results, so avoiding the need for manual entry of sample identification data. The Coulter S is operated in the usual way, and result storage is fully automatic. Retrieval of results is fast, so that laboratory staff can quickly and conveniently reply to telephone enquiries. The on-line quality control system checks each set of results for internal consistency by subjecting them to mathematical tests, and applies other criteria to determine which results require confirmation. Other mathematical tests are used to indicate any results suggestive of thalassaemia. In addition automatic statistical analysis of all normal results is performed to monitor calibration and drift of the Coulter counter. Updated quality control printouts are available on demand without interruption to sample processing. The system is being extended to provide long-term storage of key results, to allow automatic comparison of current results with previous ones for each patient. It is felt that in reliability, flexibility and cost-effectivenessthis system compares favourably with computer based systems.
RISK FACTORS IN APLASTIC ANAEMIA
R. J. TRENT,H. KRONENBERG & T. WILKINSONHaematology Department, Royal Prince Alfred Hospital, Sydney In 1967, Vincent and de Gruchy estimated the mortality associated with aplastic anaemia to be 63%. In the last decade therapy with androgens, corticosteroids, intensive support with blood products and sterile environments has not significantly altered this mortality. The only recent major advance in the treatment of aplastic anaemia has been bone marrow transplantation, and results to date from specialized centres showing greater than 50% long-term survivors from allogeneic grafts in aplasia, are encouraging. However, the use of bone marrow transplantation in donor host combinations, other than identical twins, may result in either graft rejection or graft versus host disease despite matching at HLA-A,B and D loci, and for this reason, such a procedure would only be justified for those patients with aplastic anaemia for whom a fatal outcome is likely. To identify patients with severe aplastic anaemia a number of surveys have looked for risk factors in this disorder. We report here on parameters associated with mortality in 48 patients with aplastic anaemia managed over the years 1960-78 in a Sydney teaching hospital. Thirty-one (65%) patients died. Of these, 14 patients died from infection, 10 with bleeding problems and 3 a combination ofboth. In addition, 7 of the 17survivors have a persistently abnormal blood count 7 mth to 16 yr after diagnosis, and the median time required for blood counts to return to normal was 20 mth. Thirty-seven clinical and