- Email: [email protected]
SURVIVAL FROM MELPHALAN OVERDOSE
1048
Changes in creatinine protein challenge.
clearance
(CLCR; ml/minl1o73m2)
after
B = before; PL = after protein load; C = control.
and 6 days later. In five patients the GFR fell, and in the other three the GFR rose slightly but not significantly (see figure). The mean deviation from baseline GFR for all eight patients was 21 -0% (0’<0’ 05, t test for the comparison of paired investigations). These preliminary data demonstrate that, unlike normal subjects, patients with advanced liver disease cannot increase their GFR after a protein load. Whether the underlying failure to increase the GFR is due to reduced production of glomerulopressin remains to be clarified. However, we can tentatively speculate from our data that normal liver function is necessary to enable the kidney to augment the GFR when challenged with a protein load. Department of Medicine II, St Joseph-Krankenhaus I, Baumerplan 24, 1000 Berlin 42 (Tempelhof), West Germany
R. D. A. K.
HIRSCHBERG VON HERRATH PAULS SCHAEFER
A, Bergström J. Glomerular hyperfiltration after protein ingestion, during glucagon infusion, and in insulin-dependent diabetes is induced by a liver hormone: deficient production of this hormone in hepatic failure causes hepatorenal syndrome. Lancet 1984; i: 195-97. 2. del Castillo E, Fuenzalida R, Uranga J. Increased glomerular filtration rate and glomerulopressin activity in diabetic dogs. Horm Metab Res 1977; 9: 46-53. 3. Bosch JP, Saccagi A, Lauer A, Ronco C, Belledonne M, Glabman S. Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate. Am J Med 1. Alvestrand
1983; 75: 943-50.
SURVIVAL FROM MELPHALAN OVERDOSE
SIR,-A 6-month-old boy presented with
a
5-day history
of-
bilateral proptosis and a large abdominal mass. A bone-marrow aspirate and the very high urinary catecholamines confirmed stage iv neuroblastoma. The child was started on cytotoxic chemotherapy, including melphalan. There was a rapid response and by 22 weeks of chemotherapy very little tumour remained. The child was seen 6 months from diagnosis and a dose of 14 mg melphalan was ordered (1-22 mg/kg). The child received the melphalan dose and had vomited only slightly. 4 h later the pharmacy notified the attending physician that the melphalan had been erroneously diluted and that the child had received 140 mg. The parents were notified and the child was brought back to the hospital 8 h after the infusion of the melphalan. He was admitted to the intensive-care unit. There were no immediate untoward effects. He was put on continuous central hyperalimentation from the day of admission. While pronounced lymphocytopenia was seen within 24 h, there were no significant side-effects from the overdose noted until the 7th hospital day when neutropenia, thrombocytopenia, and diarrhoea developed. At no time were there signs of significant bowel haemorrhage. The child also had moderate oral ulceration.
Clinical course and haematological overdose in 6-month-old boy.
picture after ten-fold melphalan
On temperature chart positive (t) and negative ( ) blood cultures are shown. Blood and platelet transfusion, are indicated on haemoglobin and platelet-count charts, respectively. Cell counts are lymphocytes (—) and
.
’
..
granulocytes (--).
The child’s clinical course, haemoglobin level, granulocyte count, and lymphocyte count are summarised in the figure. The ’ child is well 9 months after the overdose. There has been no reduction in marrow tolerance for cytotoxic therapy nor have there,1, been any abnormalities in hepatic or renal function. At the time of.; delayed primary resection, a small residual ganglioneuroblastoma was removed. High-dose melphalan has been used for treatment of several neoplasms in conjunction with autologous marrow transplant. The highest dose of melaphalan administered in conjunction with :. marrow transplantation was 140 mg/m2.1-3 The highest dose administered without autologous transplant was 125 mg/m2.2,3 At this dose, marrow recovered within 22 days. Our patient received 12-44 mg/kg (254 mg/m 2) as a single dose. Because of cross-checking procedures in our pharmacy, we were able to confirm that an error was made and that the patient was given 140 mg intravenous melphalan. Despite the prolonged hospital course, the bone marrow recovered within 40 days without autologous transplant. With vigorous hyperalimentation and close surveillance during the period of suppression, the patient has had no long-term complications. We hope that this unfortunate incident will be of use in the design of protocols utilising high-dose melphalan. ’
,
Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University Medical Center, Indianapolis, Indiana 46223, USA 1.
THOMAS D. COATES
SB Intensive chemotherapy for solid tumours: Current clinical applications Cancer Chemother Pharmacol 1982; 9: 127-33. 2 McElwain TJ, Hedley DW, Burton C, et al Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-
Kaye
dose
melphalan Br J Cancer 1979, 40: 72-80. J, McElwain TJ, Graham-Pole J High-dose melphalan with autologous marrow for treatment of advanced neuroblastoma Br JCancer 1982, 45: 86-93
3 Pritchard
Changes in creatinine protein challenge.
clearance
(CLCR; ml/minl1o73m2)
after
B = before; PL = after protein load; C = control.
and 6 days later. In five patients the GFR fell, and in the other three the GFR rose slightly but not significantly (see figure). The mean deviation from baseline GFR for all eight patients was 21 -0% (0’<0’ 05, t test for the comparison of paired investigations). These preliminary data demonstrate that, unlike normal subjects, patients with advanced liver disease cannot increase their GFR after a protein load. Whether the underlying failure to increase the GFR is due to reduced production of glomerulopressin remains to be clarified. However, we can tentatively speculate from our data that normal liver function is necessary to enable the kidney to augment the GFR when challenged with a protein load. Department of Medicine II, St Joseph-Krankenhaus I, Baumerplan 24, 1000 Berlin 42 (Tempelhof), West Germany
R. D. A. K.
HIRSCHBERG VON HERRATH PAULS SCHAEFER
A, Bergström J. Glomerular hyperfiltration after protein ingestion, during glucagon infusion, and in insulin-dependent diabetes is induced by a liver hormone: deficient production of this hormone in hepatic failure causes hepatorenal syndrome. Lancet 1984; i: 195-97. 2. del Castillo E, Fuenzalida R, Uranga J. Increased glomerular filtration rate and glomerulopressin activity in diabetic dogs. Horm Metab Res 1977; 9: 46-53. 3. Bosch JP, Saccagi A, Lauer A, Ronco C, Belledonne M, Glabman S. Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate. Am J Med 1. Alvestrand
1983; 75: 943-50.
SURVIVAL FROM MELPHALAN OVERDOSE
SIR,-A 6-month-old boy presented with
a
5-day history
of-
bilateral proptosis and a large abdominal mass. A bone-marrow aspirate and the very high urinary catecholamines confirmed stage iv neuroblastoma. The child was started on cytotoxic chemotherapy, including melphalan. There was a rapid response and by 22 weeks of chemotherapy very little tumour remained. The child was seen 6 months from diagnosis and a dose of 14 mg melphalan was ordered (1-22 mg/kg). The child received the melphalan dose and had vomited only slightly. 4 h later the pharmacy notified the attending physician that the melphalan had been erroneously diluted and that the child had received 140 mg. The parents were notified and the child was brought back to the hospital 8 h after the infusion of the melphalan. He was admitted to the intensive-care unit. There were no immediate untoward effects. He was put on continuous central hyperalimentation from the day of admission. While pronounced lymphocytopenia was seen within 24 h, there were no significant side-effects from the overdose noted until the 7th hospital day when neutropenia, thrombocytopenia, and diarrhoea developed. At no time were there signs of significant bowel haemorrhage. The child also had moderate oral ulceration.
Clinical course and haematological overdose in 6-month-old boy.
picture after ten-fold melphalan
On temperature chart positive (t) and negative ( ) blood cultures are shown. Blood and platelet transfusion, are indicated on haemoglobin and platelet-count charts, respectively. Cell counts are lymphocytes (—) and
.
’
..
granulocytes (--).
The child’s clinical course, haemoglobin level, granulocyte count, and lymphocyte count are summarised in the figure. The ’ child is well 9 months after the overdose. There has been no reduction in marrow tolerance for cytotoxic therapy nor have there,1, been any abnormalities in hepatic or renal function. At the time of.; delayed primary resection, a small residual ganglioneuroblastoma was removed. High-dose melphalan has been used for treatment of several neoplasms in conjunction with autologous marrow transplant. The highest dose of melaphalan administered in conjunction with :. marrow transplantation was 140 mg/m2.1-3 The highest dose administered without autologous transplant was 125 mg/m2.2,3 At this dose, marrow recovered within 22 days. Our patient received 12-44 mg/kg (254 mg/m 2) as a single dose. Because of cross-checking procedures in our pharmacy, we were able to confirm that an error was made and that the patient was given 140 mg intravenous melphalan. Despite the prolonged hospital course, the bone marrow recovered within 40 days without autologous transplant. With vigorous hyperalimentation and close surveillance during the period of suppression, the patient has had no long-term complications. We hope that this unfortunate incident will be of use in the design of protocols utilising high-dose melphalan. ’
,
Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University Medical Center, Indianapolis, Indiana 46223, USA 1.
THOMAS D. COATES
SB Intensive chemotherapy for solid tumours: Current clinical applications Cancer Chemother Pharmacol 1982; 9: 127-33. 2 McElwain TJ, Hedley DW, Burton C, et al Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-
Kaye
dose
melphalan Br J Cancer 1979, 40: 72-80. J, McElwain TJ, Graham-Pole J High-dose melphalan with autologous marrow for treatment of advanced neuroblastoma Br JCancer 1982, 45: 86-93
3 Pritchard