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ROLE OF BONE-MARROW TRANSPLANTATION AS RETRIEVAL THERAPY FOR ACUTE LYMPHOBLASTIC LEUKAEMIA IN CHILDHOOD
102 ROLE OF BONE-MARROW TRANSPLANTATION AS RETRIEVAL THERAPY FOR ACUTE LYMPHOBLASTIC LEUKAEMIA IN CHILDHOOD
SIR,-Dr Chessells and her colleagues’ paper (May 31, p 1239) indicates that bone marrow transplantation (BMT) is no better than conventional chemotherapy, whether the relapse occurred on or off therapy, so that paediatric haematologists should not consider BMT as the treatment of choice. I do not think the data presented support those conclusions. They do support the conclusion that adequate first-line treatment is the most important goal for treating children with acute lymphoblastic leukaemia (ALL) because second-line therapy still has problems. The aim of the study was to compare BMT and conventional therapy. Because this comparison is so vital to the conclusions that were drawn, it is important to include in the transplant group only those patients who made it to transplantation and not those patients who were merely eligible. 3 of the 13 patients in the transplant group never made it to transplantation. 5 of the 10 patients who were transplanted are off therapy, alive and well 14 months to 5 years after BMT. Analysed in this way the curves might look a bit different though the numbers of children included in the study may well be too small for any difference in second remission duration between the group undergoing transplantation versus the group not transplanted to be significant. Relapses on therapy differ from those off therapy. Of the patients offered BMT 5 had their initial relapse while on chemotherapy,1 of those 5 (20%) survives. However, in the other group of 40 patients, 21 had had their first relapse while on therapy and only 1 of those patients survives, giving a long-term survival rate of less than 5%, corresponding to that which large cooperative groups have been able to achieve with very intensive conventional chemotherapy. No transplanter would want to compare chemotherapy and transplantation when there are only 5 patients in the transplant group. However, since Chessells et al are drawing conclusions from very small numbers of patients, 20% versus less than 5%can be seen as a clear difference. Chessells et al do not discuss the long-term prognosis of patients who have a second relapse while on conventional therapy. Many can be kept alive for a long time but they have chronic leukaemia. They may be kept alive for months or years before another relapse but the leukaemia cells are still there and they will eventually die from leukaemia. The success of our current therapy in reinducing these patients and in maintaining them long term must be kept in mind, but it is also important to remember that these patients will probably not be cured. Do Chessells et al feel that some of the patients can really be cured? The follow-up in some cases seems too short for certainty on that point. Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
loss of consciousness. He denied alcohol abuse. 12 ml metrizamide (190 mg/ml) was injected into the L3-4 interspace and revealed a herniated nucleus pulposus. After the myelogram the patient was not removed from the supine position, and he had a generalised seizure. Computerised tomography revealed metrizamide in the cerebral sulci and the EEG report was arrhythmia grade II, generalised. Subsequent changes included loss of bladder control, decreased sensation in the toes of his left foot, decreased physical stamina, and sleep disturbance. The patient reported patchy memory for the next 5 months. His wife described rapid and at times incoherent speech, irritability, and poor social and occupational judgment. For example, he owned an exclusive restaurant but began to wear tee-shirts to work and abused customers who commented on the food or service; and he bought tickets for he and a friend to fly to the UK for the day to watch a football match. Because of his irritability, temper, and behaviour, he and his wife separated. An organic personality syndrome secondary to metrizamide was suspected. A neuropsychological evaluation 10 months after the myelogram indicated deficits in attention/concentration, lowered psychomotor speed, and impairments in learning/memory, suggesting mild diffuse brain dysfunction. At 28 months these deficits persisted (table), while general intellectual functioning language and communication skills, gross motor strength, fine motor dexterity, and verbal and nonverbal problem-solving remained intact. At 28 months his psychiatric state had improved; for instance his mood was pleasant, as opposed to hypomania seen at 10 months. He is now the owner/manager of another successful restaurant and he and his wife are together again. In contrast to previous studies showing symptom remission over 4 or 5 days our patient’s psychiatric syndrome persisted for 7 months and mild neuropsychological dysfunction was still present 28 months after the myelogram. This unusually severe complication of the procedure had three phases. For the first 7 months he had an organic personality syndrome. Neuropsychological tests at 10 months revealed only residual hypomania and, consistent with this, personality tests suggested a naive and rosy acceptance of things despite the adversities of marital separation, loss of employment, and decline in health. At 28 months his mental status was normal but personality tests indicated feelings of social inadequacy, worry, and depression. The fact that the patient was not propped up after the myelogram increased the risk of side-effects. The prominence of aphasia, dysnomia, and perseveration in metrizamide-induced organic mental disorders has led clinicians’’ to suggest selective involvement of the temporal and parietal cortex. The neuropsychological findings in our patient indicate bilateral or diffuse cerebral dysfunction (a pattern of impairment often seen
MICHAEL E. TRIGG NEUROPSYCHOLOGICAL SCORES
NEUROPSYCHOLOGICAL IMPLICATIONS OF METRIZAMIDE MYELOGRAPHY
SIR,-Metrizamide is a water-soluble, non-ionic contrast medium used for myelography and other neuroradiological procedures. Side-effects include headache, nausea, vomiting, and dizziness. Electroencephalographic (EEG) abnormalities and seizures have been reported.l Psychiatric sequelae include mania, depression, anxiety, and visual, tactile, and auditory hallucinations. These last for only 3 or 4 days2 and neuropsychological deficits (impaired concentration, orientation, short-term verbal memory, and expressive language) are transient.3’ We report on a 48-year-old man who had an organic personality syndrome after metrizamide myelography. The symptoms persisted for 7 months and mild cognitive dysfunction was still present 28 months after
myelography. The patient was admitted to hospital for evaluation of low back pain. At age 19 he had had a blow to the head while boxing, without
*WAI S-R = Wechsler adult intelligence scale (revised); WMS-Wechsler memory scale with Rjussell revised (raw score); TPT = tactual performance test; MMPI = Minnesota multiphasic personality inventory. tnormal, tmild impairment, §moderate impairment- 1f Welsh code notation.’
SIR,-Dr Chessells and her colleagues’ paper (May 31, p 1239) indicates that bone marrow transplantation (BMT) is no better than conventional chemotherapy, whether the relapse occurred on or off therapy, so that paediatric haematologists should not consider BMT as the treatment of choice. I do not think the data presented support those conclusions. They do support the conclusion that adequate first-line treatment is the most important goal for treating children with acute lymphoblastic leukaemia (ALL) because second-line therapy still has problems. The aim of the study was to compare BMT and conventional therapy. Because this comparison is so vital to the conclusions that were drawn, it is important to include in the transplant group only those patients who made it to transplantation and not those patients who were merely eligible. 3 of the 13 patients in the transplant group never made it to transplantation. 5 of the 10 patients who were transplanted are off therapy, alive and well 14 months to 5 years after BMT. Analysed in this way the curves might look a bit different though the numbers of children included in the study may well be too small for any difference in second remission duration between the group undergoing transplantation versus the group not transplanted to be significant. Relapses on therapy differ from those off therapy. Of the patients offered BMT 5 had their initial relapse while on chemotherapy,1 of those 5 (20%) survives. However, in the other group of 40 patients, 21 had had their first relapse while on therapy and only 1 of those patients survives, giving a long-term survival rate of less than 5%, corresponding to that which large cooperative groups have been able to achieve with very intensive conventional chemotherapy. No transplanter would want to compare chemotherapy and transplantation when there are only 5 patients in the transplant group. However, since Chessells et al are drawing conclusions from very small numbers of patients, 20% versus less than 5%can be seen as a clear difference. Chessells et al do not discuss the long-term prognosis of patients who have a second relapse while on conventional therapy. Many can be kept alive for a long time but they have chronic leukaemia. They may be kept alive for months or years before another relapse but the leukaemia cells are still there and they will eventually die from leukaemia. The success of our current therapy in reinducing these patients and in maintaining them long term must be kept in mind, but it is also important to remember that these patients will probably not be cured. Do Chessells et al feel that some of the patients can really be cured? The follow-up in some cases seems too short for certainty on that point. Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
loss of consciousness. He denied alcohol abuse. 12 ml metrizamide (190 mg/ml) was injected into the L3-4 interspace and revealed a herniated nucleus pulposus. After the myelogram the patient was not removed from the supine position, and he had a generalised seizure. Computerised tomography revealed metrizamide in the cerebral sulci and the EEG report was arrhythmia grade II, generalised. Subsequent changes included loss of bladder control, decreased sensation in the toes of his left foot, decreased physical stamina, and sleep disturbance. The patient reported patchy memory for the next 5 months. His wife described rapid and at times incoherent speech, irritability, and poor social and occupational judgment. For example, he owned an exclusive restaurant but began to wear tee-shirts to work and abused customers who commented on the food or service; and he bought tickets for he and a friend to fly to the UK for the day to watch a football match. Because of his irritability, temper, and behaviour, he and his wife separated. An organic personality syndrome secondary to metrizamide was suspected. A neuropsychological evaluation 10 months after the myelogram indicated deficits in attention/concentration, lowered psychomotor speed, and impairments in learning/memory, suggesting mild diffuse brain dysfunction. At 28 months these deficits persisted (table), while general intellectual functioning language and communication skills, gross motor strength, fine motor dexterity, and verbal and nonverbal problem-solving remained intact. At 28 months his psychiatric state had improved; for instance his mood was pleasant, as opposed to hypomania seen at 10 months. He is now the owner/manager of another successful restaurant and he and his wife are together again. In contrast to previous studies showing symptom remission over 4 or 5 days our patient’s psychiatric syndrome persisted for 7 months and mild neuropsychological dysfunction was still present 28 months after the myelogram. This unusually severe complication of the procedure had three phases. For the first 7 months he had an organic personality syndrome. Neuropsychological tests at 10 months revealed only residual hypomania and, consistent with this, personality tests suggested a naive and rosy acceptance of things despite the adversities of marital separation, loss of employment, and decline in health. At 28 months his mental status was normal but personality tests indicated feelings of social inadequacy, worry, and depression. The fact that the patient was not propped up after the myelogram increased the risk of side-effects. The prominence of aphasia, dysnomia, and perseveration in metrizamide-induced organic mental disorders has led clinicians’’ to suggest selective involvement of the temporal and parietal cortex. The neuropsychological findings in our patient indicate bilateral or diffuse cerebral dysfunction (a pattern of impairment often seen
MICHAEL E. TRIGG NEUROPSYCHOLOGICAL SCORES
NEUROPSYCHOLOGICAL IMPLICATIONS OF METRIZAMIDE MYELOGRAPHY
SIR,-Metrizamide is a water-soluble, non-ionic contrast medium used for myelography and other neuroradiological procedures. Side-effects include headache, nausea, vomiting, and dizziness. Electroencephalographic (EEG) abnormalities and seizures have been reported.l Psychiatric sequelae include mania, depression, anxiety, and visual, tactile, and auditory hallucinations. These last for only 3 or 4 days2 and neuropsychological deficits (impaired concentration, orientation, short-term verbal memory, and expressive language) are transient.3’ We report on a 48-year-old man who had an organic personality syndrome after metrizamide myelography. The symptoms persisted for 7 months and mild cognitive dysfunction was still present 28 months after
myelography. The patient was admitted to hospital for evaluation of low back pain. At age 19 he had had a blow to the head while boxing, without
*WAI S-R = Wechsler adult intelligence scale (revised); WMS-Wechsler memory scale with Rjussell revised (raw score); TPT = tactual performance test; MMPI = Minnesota multiphasic personality inventory. tnormal, tmild impairment, §moderate impairment- 1f Welsh code notation.’