1388
disease-related symptoms develop or the disease progresses. Experimental data also justify the distinction between those with a symptomatic stable disease and those with symptomatic and/or progressive disease.1 It is generally recommended that interferon-ex be stopped after a year, even though recurrence-free survival is shorter if the proportion of residual hairy cells exceeds 30% at that time.2 This treatment policy might need to be changed when new drugs with the potential to cure HCL become generally available. 3,4 Haematology and Oncology, Department of Medicine III, University of Ulm, D-7900 Ulm, Germany
F. PORZSOLT
J. DEMETER
1. Demeter J, Pálóczi K, Lehoczky D, Benczur M. Hairy cell leukaemia: observations on natural killer activity in different clinical stages of the disease. Br J Haematol 1989; 71: 239-44. 2. Ratain MJ, Golomb HM, Vardiman JW, et al. Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables. J Clin Oncol 1988; 6: 1714-21. 3. Blick M, Lepe-Zuniga L, Doig R, Quesada R. Durable complete remissions after 2’-deoxycoformycin treatment in patients with hairy cell leukemia resistant to
interferon alpha.
Am J Hematol 1990; 33: 205-09.
4. Piro LD, Carrera CJ, Carson DA, Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med 1990; 322: 1117-21. I
0
Neuron-specific enolase as a marker for medulloblastoma SIR,-Medulloblastoma is a tumour sensitive to platinum-based chemotherapy,1.2 At St Bartholomew’s Hospital and the Hospital for Sick Children, London, the incidence of systemic metastases in this disease is 8% (4% as isolated systemic metastases and 4% in conjunction with central-nervous-system recurrence). This incidence is unrelated to ventriculoperitoneal shunt insertion. the most common first manifestation Sclerotic bone metastases of systemic spread seen radiologically. No useful cerebrospinal fluid or serum marker of medulloblastoma has been described. Enolase (2-phospho-D-glycerate hydrolase) is a glycolytic enzyme distributed widely in human tissues, and existing as isoenzyme dimers (approximately 80 kD). The dimers are combinations of the immunologically distinct subunits a, &bgr;, and y. The y subunit occurs in high concentrations in neurons and neuroendocrine/amine precursor uptake and decarboxylation cells. This neuron-specific enolase (NSE) is now recognised as a serum marker for tumours of neuronal/neuroendocrine lineage, including childhood neuroblastoma.3,4 The median concentrations of serum NSE in neuroblastoma patients with stages I, II, III, and IV disease are 13,23,40, and 214 µg/1, respectively.’ I have described NSE as a serum marker for Merkel cell tumour (primary neuroendocrine tumour of skin);’ I now report a 38-year-old man with relapsed medulloblastoma in whom serum NSE concentrations mirrored relapse and response to chemotherapy. The patient first presented at age 30 with headache and diplopia. Computed tomography showed an enhancing left sided cerebellar mass. During posterior craniectomy, a 2 cm tumour was found deep in the left cerebellar hemisphere. A complete macroscopic resection of the tumour was done. The patient received whole nauraxis radiotherapy to 35 Gy in 20 fractions before the posterior fossa was boosted in two phases such that the total tumour dose was 55 Gy in 32 fractions. The patient remained well for 7 years before presenting with bone pains. Bone scan showed multiple hot spots, and X-ray showed sclerotic bone metastases. Histological examination of a bone biopsy specimen of an abnormal lesion revealed medulloblastoma (positive histochemical staining for NSE). Serum NSE was 154 ltg/1 (normal range up to 12 µg/1), and cerebrospinal fluid NSE was 4 µg/1. Cerebrospinal fluid cytology was normal, as was computed tomography of the brain. The patient received OPEC chemotherapy.6 After one course bone pain was relieved and serum NSE fell to 11 µg/1. The patient had a repeat bone scan after three courses, which showed clearing of disease, and serum NSE had subsequently remained within the normal range (figure). He remains in remission at 5 months. This case shows that relapse and response to therapy in metastatic medulloblastoma can be monitored by measurement of serial serum are
2
4
6 TIME
8
10
12
(WEEKS)
Serum NSE concentrations during chemotherapy for metastatic medulloblastoma.
NSE concentrations. Raised concentrations in metastatic disease were, in this case, of the same order as has been reported in metastatic neuroblastoma.3 Radiotherapy Department, St Bartholomew’s Hospital, London EC1A 7BE, UK
P. N. PLOWMAN
1. Allen JC, Walker R, Luks E, Jennings H, Barfoot S, Tan C. Carboplatin and recurrent
childhood brain tumours. J Clin Oncol 1987; 5: 459-63. 2. Douek E, Plowman PN, Kingston JE. Platinum based chemotherapy for recurrent non-gliomatous brain tumours in young patients. J Neurol Neurosurg Psychiatry (m
press). 3. Zeltzer PM, Marangos PJ, Evans AE, Schneider SL. Serum neuron-specific enolase m children with neuroblastoma: relationship to stage and disease course. Cancer
1986; 57: 1230-34. Pritchard J, Bailey CC, Ninane J. Serum neuron-specific enolase in children’s cancer. Br J Cancer 1987; 56: 65-67. 5. Plowman PN. Serum marker for Merkel cell tumour. Clin Radiol 1990; 40: 542. 6. Shafford EA, Rodgers DW, Pritchard J. Advanced neuroblastoma: improved response rate using multiagent regimen (OPEC) including sequential cisplatinum and VM26. J Clin Oncol 1984; 2: 742-47. 4.
Cooper EH,
responses to interferon SIR,-Dr Grander and colleagues (Aug 11, p 337) report
Predicting
a
correlation between in-vitro induction of 2’,5’-oligoadenylate (2’,5’-A) synthetase by interferon-ex (IFN-&agr;) and responses of patients with carcinoid tumours to IFN-a treatment. They suggest that this assay could be used to predict responses to IFN-ot. Dr Galvani (Sept 29, p 824) argued that the in-vitro assay cannot be extrapolated to predict sensitivity of patients with chronic granulocytic leukaemia (CGL), as suggested by De Mel et al,l and that in-vitro effects may parallel clinical responsiveness without being involved in the anti-tumour action of IFN-cx. Galvani’s letter calls for comment. Clinicians do need biological tests allowing prediction of a patient’s sensitivity to IFN, even if they correspond to in-vitro effects unrelated to mechanisms of IFN action. With CGL the data are contradictory: Rosenblum et al2 found high levels of 2’,5’-A synthetase in patients responding to IFN-a compared with non-responders, a result that does not seem to be due to differential induction of mRNA for the enzyme;.3 whereas De Mel et all found an increase in induction of 2’,5’-A synthetase mRNA but not of enzyme concentrations in responders compared with non-responders. In a study4 on low-grade nonHodgkin lymphoma, a B-cell malignancy in which IFN-ot induces a response rate of about 50%, we found exactly the same correlation as Grander et al when using the in-vitro assay with lymph-node tumour cells, but not when using the in-vivo assay with peripheral
disease-related symptoms develop or the disease progresses. Experimental data also justify the distinction between those with a symptomatic stable disease and those with symptomatic and/or progressive disease.1 It is generally recommended that interferon-ex be stopped after a year, even though recurrence-free survival is shorter if the proportion of residual hairy cells exceeds 30% at that time.2 This treatment policy might need to be changed when new drugs with the potential to cure HCL become generally available. 3,4 Haematology and Oncology, Department of Medicine III, University of Ulm, D-7900 Ulm, Germany
F. PORZSOLT
J. DEMETER
1. Demeter J, Pálóczi K, Lehoczky D, Benczur M. Hairy cell leukaemia: observations on natural killer activity in different clinical stages of the disease. Br J Haematol 1989; 71: 239-44. 2. Ratain MJ, Golomb HM, Vardiman JW, et al. Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables. J Clin Oncol 1988; 6: 1714-21. 3. Blick M, Lepe-Zuniga L, Doig R, Quesada R. Durable complete remissions after 2’-deoxycoformycin treatment in patients with hairy cell leukemia resistant to
interferon alpha.
Am J Hematol 1990; 33: 205-09.
4. Piro LD, Carrera CJ, Carson DA, Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med 1990; 322: 1117-21. I
0
Neuron-specific enolase as a marker for medulloblastoma SIR,-Medulloblastoma is a tumour sensitive to platinum-based chemotherapy,1.2 At St Bartholomew’s Hospital and the Hospital for Sick Children, London, the incidence of systemic metastases in this disease is 8% (4% as isolated systemic metastases and 4% in conjunction with central-nervous-system recurrence). This incidence is unrelated to ventriculoperitoneal shunt insertion. the most common first manifestation Sclerotic bone metastases of systemic spread seen radiologically. No useful cerebrospinal fluid or serum marker of medulloblastoma has been described. Enolase (2-phospho-D-glycerate hydrolase) is a glycolytic enzyme distributed widely in human tissues, and existing as isoenzyme dimers (approximately 80 kD). The dimers are combinations of the immunologically distinct subunits a, &bgr;, and y. The y subunit occurs in high concentrations in neurons and neuroendocrine/amine precursor uptake and decarboxylation cells. This neuron-specific enolase (NSE) is now recognised as a serum marker for tumours of neuronal/neuroendocrine lineage, including childhood neuroblastoma.3,4 The median concentrations of serum NSE in neuroblastoma patients with stages I, II, III, and IV disease are 13,23,40, and 214 µg/1, respectively.’ I have described NSE as a serum marker for Merkel cell tumour (primary neuroendocrine tumour of skin);’ I now report a 38-year-old man with relapsed medulloblastoma in whom serum NSE concentrations mirrored relapse and response to chemotherapy. The patient first presented at age 30 with headache and diplopia. Computed tomography showed an enhancing left sided cerebellar mass. During posterior craniectomy, a 2 cm tumour was found deep in the left cerebellar hemisphere. A complete macroscopic resection of the tumour was done. The patient received whole nauraxis radiotherapy to 35 Gy in 20 fractions before the posterior fossa was boosted in two phases such that the total tumour dose was 55 Gy in 32 fractions. The patient remained well for 7 years before presenting with bone pains. Bone scan showed multiple hot spots, and X-ray showed sclerotic bone metastases. Histological examination of a bone biopsy specimen of an abnormal lesion revealed medulloblastoma (positive histochemical staining for NSE). Serum NSE was 154 ltg/1 (normal range up to 12 µg/1), and cerebrospinal fluid NSE was 4 µg/1. Cerebrospinal fluid cytology was normal, as was computed tomography of the brain. The patient received OPEC chemotherapy.6 After one course bone pain was relieved and serum NSE fell to 11 µg/1. The patient had a repeat bone scan after three courses, which showed clearing of disease, and serum NSE had subsequently remained within the normal range (figure). He remains in remission at 5 months. This case shows that relapse and response to therapy in metastatic medulloblastoma can be monitored by measurement of serial serum are
2
4
6 TIME
8
10
12
(WEEKS)
Serum NSE concentrations during chemotherapy for metastatic medulloblastoma.
NSE concentrations. Raised concentrations in metastatic disease were, in this case, of the same order as has been reported in metastatic neuroblastoma.3 Radiotherapy Department, St Bartholomew’s Hospital, London EC1A 7BE, UK
P. N. PLOWMAN
1. Allen JC, Walker R, Luks E, Jennings H, Barfoot S, Tan C. Carboplatin and recurrent
childhood brain tumours. J Clin Oncol 1987; 5: 459-63. 2. Douek E, Plowman PN, Kingston JE. Platinum based chemotherapy for recurrent non-gliomatous brain tumours in young patients. J Neurol Neurosurg Psychiatry (m
press). 3. Zeltzer PM, Marangos PJ, Evans AE, Schneider SL. Serum neuron-specific enolase m children with neuroblastoma: relationship to stage and disease course. Cancer
1986; 57: 1230-34. Pritchard J, Bailey CC, Ninane J. Serum neuron-specific enolase in children’s cancer. Br J Cancer 1987; 56: 65-67. 5. Plowman PN. Serum marker for Merkel cell tumour. Clin Radiol 1990; 40: 542. 6. Shafford EA, Rodgers DW, Pritchard J. Advanced neuroblastoma: improved response rate using multiagent regimen (OPEC) including sequential cisplatinum and VM26. J Clin Oncol 1984; 2: 742-47. 4.
Cooper EH,
responses to interferon SIR,-Dr Grander and colleagues (Aug 11, p 337) report
Predicting
a
correlation between in-vitro induction of 2’,5’-oligoadenylate (2’,5’-A) synthetase by interferon-ex (IFN-&agr;) and responses of patients with carcinoid tumours to IFN-a treatment. They suggest that this assay could be used to predict responses to IFN-ot. Dr Galvani (Sept 29, p 824) argued that the in-vitro assay cannot be extrapolated to predict sensitivity of patients with chronic granulocytic leukaemia (CGL), as suggested by De Mel et al,l and that in-vitro effects may parallel clinical responsiveness without being involved in the anti-tumour action of IFN-cx. Galvani’s letter calls for comment. Clinicians do need biological tests allowing prediction of a patient’s sensitivity to IFN, even if they correspond to in-vitro effects unrelated to mechanisms of IFN action. With CGL the data are contradictory: Rosenblum et al2 found high levels of 2’,5’-A synthetase in patients responding to IFN-a compared with non-responders, a result that does not seem to be due to differential induction of mRNA for the enzyme;.3 whereas De Mel et all found an increase in induction of 2’,5’-A synthetase mRNA but not of enzyme concentrations in responders compared with non-responders. In a study4 on low-grade nonHodgkin lymphoma, a B-cell malignancy in which IFN-ot induces a response rate of about 50%, we found exactly the same correlation as Grander et al when using the in-vitro assay with lymph-node tumour cells, but not when using the in-vivo assay with peripheral
