733
Despite an initial response he had persistent pyrexia with worsening headache on days 2 and 3 of treatment. On day 5 he had neck rigidity, vomited, and became peripherally cyanosed. The antibiotic therapy was changed to chloramphenicol 500 mg 6-hourly. The CSF contained 240 x 106 white cells/1 (50% polymorphs), protein 28 g/1, and glucose of 15 mmol/1. No organisms were seen in the gram-stained film but culture yielded a scanty growth of N meningitidis. Within 24 hours his clinical state had improved and his temperature settled. He was discharged 1 week later. There have been reports of N merzingitidis with reduced sensitivity to penicillin from other countries/,3 and some of these organisms have been penicillinase producers. The organism in this case was N rneningitidis, group C, type 2B. The meningococcus isolated from both CSF specimens had a minimum inhibitory concentration to benzylpenicillin of 0-64 mg/1 (expected value, if fully sensitive less than 008). Both isolates were penicillinase negative. The dose of benzylpenicillin used was low by some recommendations,"but has given satisfactory results in this unit and elsewhere.s This case suggests the advisability of using high-dose benzylpenicillin in the initial treatment of meningococcal infection. Ifa satisfactory response is not obtained, a further antibiotic, such as chloramphenicol, should be started pending sensitivity results. Connrmadon of grouping, typing, and MIC values were kindly done by the meningococcus reference laboratory of Manchester Public Health
Laboratory. Leeds Regional Public Health Leeds LS15 7TR, UK
Laboratory,
P. C. TURNER K. W. SOUTHERN
Department of Infectious Disease,
N. J. B. SPENCER
Seacroft Hospital. Leeds
H. PULLEN
Sutcliffe EM, Jones DM, El-Sheikh S, Percival A. Penicillin-insensitive meningococci in the UK. Lancet 1988; i: 657-58. 2. Saex-Nieto JA, Fontals D, Garcia De Jalon J, et al. Isolation of Neiserria meningitidis strains with increase of penicillin minimal inhibitory concentrations. Epidemiol Infect 1987; 99: 463-69. 3. Botha P. Penicillin-resistant Neisseria meningitidis in South Africa. Lancet 1988; i: 54. 4. Macleod J, Edwards S, Bouchier J, eds. Davidson’s principle and practice of medicine, 15th ed. Edinburgh: Churchill Livingstone, 1987: 639. 5. Sangster G, Murdoch J, Gray JA. Bacterial meningitis 1940-79. J Infect 1982; 5: 1.
245-55.
Treatment of acute lymphoblastic leukaemia after relapse SIR,-Professor Graham-Pole (Dec 23/30, p 1517) describes an unsuccessful study in America attempting to evaluate the role of megatherapy with bone-marrow rescue in children with relapsed acute lymphoblastic leukaemia (ALL). The trial was stopped because of the low number of patients who reached the stage of receiving an allograft. Of 100 patients enrolled only 16 had HLA-matched donors and of these only 7 eventually had
transplants. Although allogeneic transplant procedures have received considerable publicity in recent years these data exemplify the limited role that this procedure has in practice’ and there is clearly an urgent need to seek alternative methods of second-line treatment.
Until better ways of reducing the morbidity from mismatched or matched unrelated donors are found clinicians must rely on retreatment with slightly modified conventional
donor either
chemotherapy
or
megatherapy
with
autologous
bone-marrow
rescue.
Authors of reports of small, often single-centre, studies have claimed encouraging results with the latter approach,2,3 but in view of the considerable cost and potential morbidity of high-dose chemotherapy/radiotherapy it is essential, as Graham-Pole suggests, to evaluate this treatment in a randomised fashion. The Medical Research Council working party on leukaemia in childhood plans to embark on such a study later this year. All children (excluding late isolated testicular relapse) who relapse after the standardised UKALL ALL regimens and who do not have an allogeneic donor will be eligible for study. Because prior therapy will be the same in all patients, the limitation present in many previous studies of patient selection and heterogeneous
chemotherapy regimens should be avoided. The study will probably receive widespread support from paediatric oncologists and haematologists who treat most children with leukaemia in the UK, with referral of patients to paediatric transplant centres as necessary. After first
marrow or extramedullary relapse patients will undergo reinduction therapy with a standard four-drug regimen. They then will receive an "extended consolidation" phase based on the German BFM protocols and following this be randomised to either megatherapy with cyclophosphamide, total body irradiation, and unpurged autologous bone-marrow rescue, or 18 months’
continuing chemotherapy. The latter will be based on the St Jude’s rotating drug regimen, which has the best reported non-transplant results in childhood ALL.4 In the UK about 100 children per
annum have relapses in the bone marrow and would be eligible for the study. This study would be one of the few prospective randomised evaluations of megatherapy and it is hoped should provide an answer within 3-4
years. Department of Haematology, Children’s Hospital,
DARBYSHIRE
Birmingham
P.
Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK
C. R. PINKERTON
Royal Manchester Children’s Hospital, Manchester
R. F. STEVENS
J.
Royal Hospital for Sick Children,
A. OAKHILL
Bristol
1. Chessells J, Rogers DW, Leiper AD, et al. Bone marrow transplantation has a limited
role in prolonging second marrow remission in childhood lymphoblastic leukaemia. Lancet 1986; i: 1239-41. 2. Kersey JH, Weisdorf D, Nerbet ME, et al. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med 1987; 317: 461-67. 3. Sallan SE, Niemeyer CM, Billet AL, et al. Autologous bone marrow transplantation for acute lymphoblastic leukemia. J Clin Oncol 1989; 7: 1594-601. 4. Rivera GK, Buchanan G, Boyett JM, et al. Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse: a pediatric oncology group study. N Engl J Med 1986; 315: 273-78.
Prodromal cutaneous lesions in adult T-cell
leukaemia/lymphoma SIR,-Dr Bunker and colleagues (Feb 17, p 426) report the use of the polymerase chain reaction (PCR) to identify proviral human T-lymphotropic virus type-1 (HTLV-1) integration during both the indolent cutaneous and lymphomatous phase of HTLV-1 infection. We report a similar case, albeit with a shorter prodrome, which
was
identified when adult T-cell
leukaemia/lymphoma
(ATLL) developed 5 years later. A 56-year-old Jamaican woman resident in the UK since 1955 presented in October, 1984, with intermittent crops of pruritic papules on her upper arms, back, and buttocks. She had flesh coloured, hyperpigmented papules 3-5 mm in diameter with overlying lichenification secondary to scratching. Identical papules recurred and in 1988 skin biopsy of the upper arm showed hyperkeratosis, mild acanthosis, and negligible perivascular infiltrate of lymphocytes; prurigo was diagnosed. Her skin problems fluctuated but in January, 1990, the same eruptions appeared on the forehead and cheeks as discrete soft dermal papules 3-5mm in diameter, in addition to those on the arms, back, and buttocks. Malaise, vomiting, and abdominal pain necessitated admission to hospital, when she proved to have supraclavicular, paratracheal, and hilar nodes. Serum calcium was 5-09 mmol/l. Biopsy of a non-excoriated papule and a supraclavicular lymph node showed ATLL. She had mild leucocytosis (13-6 x 109/1); however, large pleomorphic T cells showing multilobed nuclei were present. Bone marrow was not infiltrated. Fluorescence cytometry showed the T cells were of helper (CD4) phenotype with expression of IL2 receptor (CD25) and HLA-DR characteristic of ATLL. Seropositivity to HTLV-1was confirmed by ELISA. She is having intensive chemotherapy. Subclinical ATLL associated with cutaneous lesions, antibody to HTLV-1, mild abnormal lymphocytosis, and long-term survival is
Despite an initial response he had persistent pyrexia with worsening headache on days 2 and 3 of treatment. On day 5 he had neck rigidity, vomited, and became peripherally cyanosed. The antibiotic therapy was changed to chloramphenicol 500 mg 6-hourly. The CSF contained 240 x 106 white cells/1 (50% polymorphs), protein 28 g/1, and glucose of 15 mmol/1. No organisms were seen in the gram-stained film but culture yielded a scanty growth of N meningitidis. Within 24 hours his clinical state had improved and his temperature settled. He was discharged 1 week later. There have been reports of N merzingitidis with reduced sensitivity to penicillin from other countries/,3 and some of these organisms have been penicillinase producers. The organism in this case was N rneningitidis, group C, type 2B. The meningococcus isolated from both CSF specimens had a minimum inhibitory concentration to benzylpenicillin of 0-64 mg/1 (expected value, if fully sensitive less than 008). Both isolates were penicillinase negative. The dose of benzylpenicillin used was low by some recommendations,"but has given satisfactory results in this unit and elsewhere.s This case suggests the advisability of using high-dose benzylpenicillin in the initial treatment of meningococcal infection. Ifa satisfactory response is not obtained, a further antibiotic, such as chloramphenicol, should be started pending sensitivity results. Connrmadon of grouping, typing, and MIC values were kindly done by the meningococcus reference laboratory of Manchester Public Health
Laboratory. Leeds Regional Public Health Leeds LS15 7TR, UK
Laboratory,
P. C. TURNER K. W. SOUTHERN
Department of Infectious Disease,
N. J. B. SPENCER
Seacroft Hospital. Leeds
H. PULLEN
Sutcliffe EM, Jones DM, El-Sheikh S, Percival A. Penicillin-insensitive meningococci in the UK. Lancet 1988; i: 657-58. 2. Saex-Nieto JA, Fontals D, Garcia De Jalon J, et al. Isolation of Neiserria meningitidis strains with increase of penicillin minimal inhibitory concentrations. Epidemiol Infect 1987; 99: 463-69. 3. Botha P. Penicillin-resistant Neisseria meningitidis in South Africa. Lancet 1988; i: 54. 4. Macleod J, Edwards S, Bouchier J, eds. Davidson’s principle and practice of medicine, 15th ed. Edinburgh: Churchill Livingstone, 1987: 639. 5. Sangster G, Murdoch J, Gray JA. Bacterial meningitis 1940-79. J Infect 1982; 5: 1.
245-55.
Treatment of acute lymphoblastic leukaemia after relapse SIR,-Professor Graham-Pole (Dec 23/30, p 1517) describes an unsuccessful study in America attempting to evaluate the role of megatherapy with bone-marrow rescue in children with relapsed acute lymphoblastic leukaemia (ALL). The trial was stopped because of the low number of patients who reached the stage of receiving an allograft. Of 100 patients enrolled only 16 had HLA-matched donors and of these only 7 eventually had
transplants. Although allogeneic transplant procedures have received considerable publicity in recent years these data exemplify the limited role that this procedure has in practice’ and there is clearly an urgent need to seek alternative methods of second-line treatment.
Until better ways of reducing the morbidity from mismatched or matched unrelated donors are found clinicians must rely on retreatment with slightly modified conventional
donor either
chemotherapy
or
megatherapy
with
autologous
bone-marrow
rescue.
Authors of reports of small, often single-centre, studies have claimed encouraging results with the latter approach,2,3 but in view of the considerable cost and potential morbidity of high-dose chemotherapy/radiotherapy it is essential, as Graham-Pole suggests, to evaluate this treatment in a randomised fashion. The Medical Research Council working party on leukaemia in childhood plans to embark on such a study later this year. All children (excluding late isolated testicular relapse) who relapse after the standardised UKALL ALL regimens and who do not have an allogeneic donor will be eligible for study. Because prior therapy will be the same in all patients, the limitation present in many previous studies of patient selection and heterogeneous
chemotherapy regimens should be avoided. The study will probably receive widespread support from paediatric oncologists and haematologists who treat most children with leukaemia in the UK, with referral of patients to paediatric transplant centres as necessary. After first
marrow or extramedullary relapse patients will undergo reinduction therapy with a standard four-drug regimen. They then will receive an "extended consolidation" phase based on the German BFM protocols and following this be randomised to either megatherapy with cyclophosphamide, total body irradiation, and unpurged autologous bone-marrow rescue, or 18 months’
continuing chemotherapy. The latter will be based on the St Jude’s rotating drug regimen, which has the best reported non-transplant results in childhood ALL.4 In the UK about 100 children per
annum have relapses in the bone marrow and would be eligible for the study. This study would be one of the few prospective randomised evaluations of megatherapy and it is hoped should provide an answer within 3-4
years. Department of Haematology, Children’s Hospital,
DARBYSHIRE
Birmingham
P.
Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK
C. R. PINKERTON
Royal Manchester Children’s Hospital, Manchester
R. F. STEVENS
J.
Royal Hospital for Sick Children,
A. OAKHILL
Bristol
1. Chessells J, Rogers DW, Leiper AD, et al. Bone marrow transplantation has a limited
role in prolonging second marrow remission in childhood lymphoblastic leukaemia. Lancet 1986; i: 1239-41. 2. Kersey JH, Weisdorf D, Nerbet ME, et al. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med 1987; 317: 461-67. 3. Sallan SE, Niemeyer CM, Billet AL, et al. Autologous bone marrow transplantation for acute lymphoblastic leukemia. J Clin Oncol 1989; 7: 1594-601. 4. Rivera GK, Buchanan G, Boyett JM, et al. Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse: a pediatric oncology group study. N Engl J Med 1986; 315: 273-78.
Prodromal cutaneous lesions in adult T-cell
leukaemia/lymphoma SIR,-Dr Bunker and colleagues (Feb 17, p 426) report the use of the polymerase chain reaction (PCR) to identify proviral human T-lymphotropic virus type-1 (HTLV-1) integration during both the indolent cutaneous and lymphomatous phase of HTLV-1 infection. We report a similar case, albeit with a shorter prodrome, which
was
identified when adult T-cell
leukaemia/lymphoma
(ATLL) developed 5 years later. A 56-year-old Jamaican woman resident in the UK since 1955 presented in October, 1984, with intermittent crops of pruritic papules on her upper arms, back, and buttocks. She had flesh coloured, hyperpigmented papules 3-5 mm in diameter with overlying lichenification secondary to scratching. Identical papules recurred and in 1988 skin biopsy of the upper arm showed hyperkeratosis, mild acanthosis, and negligible perivascular infiltrate of lymphocytes; prurigo was diagnosed. Her skin problems fluctuated but in January, 1990, the same eruptions appeared on the forehead and cheeks as discrete soft dermal papules 3-5mm in diameter, in addition to those on the arms, back, and buttocks. Malaise, vomiting, and abdominal pain necessitated admission to hospital, when she proved to have supraclavicular, paratracheal, and hilar nodes. Serum calcium was 5-09 mmol/l. Biopsy of a non-excoriated papule and a supraclavicular lymph node showed ATLL. She had mild leucocytosis (13-6 x 109/1); however, large pleomorphic T cells showing multilobed nuclei were present. Bone marrow was not infiltrated. Fluorescence cytometry showed the T cells were of helper (CD4) phenotype with expression of IL2 receptor (CD25) and HLA-DR characteristic of ATLL. Seropositivity to HTLV-1was confirmed by ELISA. She is having intensive chemotherapy. Subclinical ATLL associated with cutaneous lesions, antibody to HTLV-1, mild abnormal lymphocytosis, and long-term survival is
