- Email: [email protected]
ISOTRETINOIN IN CUTANEOUS T-CELL LYMPHOMA
629 validated
radioimmunoassay.2
measurement
of plasma
Cryoscopy
was
used
for
osmolality.
was stable and close to 3 pg/ml. Administration of SRIF resulted in a marked increase of plasma ADH (figure). The peak (13’6±4’ 1 pg/ml) was immediate. Then plasma ADH progressively decreased but did not return to basal values within 30 min of the SRIF injection. Plasma osmolalities
Mean basal
plasma ADH
identical to control values (288-t2 -6mosmol/kg) during this Blood pressure and heart rate were unaffected by the injection of SRIF. SRIF is a potent inhibitor of pituitaryand pancreatic4 hormone release. Its stimulatory effect on ADH secretion is thus noteworthy. This effect is not mediated through a change in blood pressure or plasma osmolality. Our results also provide new insight into the mechanism of the renal effects of SRIF. Indeed, the increased plasma ADH observed after SRIF intravenous administration accounts satisfactorily for the fall in urine flow reported by Walker were
period.
biochemical and radiological evidence of rickets; 3 had severe rickets accompanied by alkaline phosphatase activities more than 17 times the upper limit ofour adult normal range (95 IU/1). Vitamin D metabolite concentrations were measured by radioimmunoassay in these three cases, which are summarised below: At 1 month of age plasma 25-OHD3 concentrations in these three infants were within the adult normal range (see table) while plasma 1,25-(OH)2D3 concentrations were undetectable. Subsequently the 1,25-(OH)2D3 concentrations rose to within the adult normal range, accompanied by an increase in the 25-(OH)D3 concentrations. However, since all these infants were on calcium and vitamin D3 supplements the problem of neonatal rickets cannot be explained simply by dietary deficiency of calcium and vitamin D3. Our results therefore provide direct evidence to support the conclusions of Koo et al, 11 who suggested that these infants are unable to hydroxylate vitamin D3 to its active metabolites. E. G. WALTERS
’
et al.’1
Supported by Institut National de la Sante et de la Recherche Medicale and Faculte de Medecine Saint Antoine. Somatostatin was donated by Ferring SA. INSERM Unit 64,
Departments of
Medical Biochemistry and Child Health, Welsh National School of Medicine, Cardiff
J. F. MURPHY R. C. BROWN
J. S. WOODHEAD O. P. GRAY
W. PRUSZCZYNSKI R. ARDAILLOU
Hôpital Tenon, 75970 Paris, France
ISOTRETINOIN IN CUTANEOUS T-CELL LYMPHOMA VITAMIN D METABOLISM IN RACHITIC PRE-TERM INFANTS
StR,—Dr Tsang, in his June 18 contribution to your nutrition series, suggested that dietary deficiency of calcium and phosphate in preterm infants with may be the most likely cause of Another group found that rickets, a view supported by rickets in preterm infants was abolished by dietary calcium and We are still encountering cases of vitamin D3 rickets in preterm infants despite routine dietary supplementation with calcium 100 mg/kg daily and vitamin D3 400-1600 IU/daily for all preterm infants. Over a 15 month period forty-five babies with a gestational age less 34 weeks, confirmed by the Ballard score,9 were studied. Plasma alkaline phosphatase (PAP) activities were measured weekly by a modification of the method of Bessey et also with an MIII multistat centrifugal analyser. Nine preterm infants had
osteorenia others.
supplementation.8
2. Caillens H, Pruszczynski W, Meyrier A, Ang KS, Rousselet F, Ardaillou R. between change in volemia at constant osmolality and plasma antidiuretic hormone. Mm Electr Metab 1980; 4: 161-71. 3. Hall R, Besser GM, Schally AV, et al. Action of growth hormone-release inhibitory hormone in healthy men and in acromegaly. Lancet 1973; ii: 581-84. 4. Alberti KGMM, Christensen NJ, Christensen SE, et al. Inhibition of insulin secretion by somatostatin. Lancet 1983; ii: 1299-301. 5. Rowe JC, Wood DH, Rowe DW, Raisz LG. Nutritional hypophosphatemic rickets in a premature infant fed breast milk. N Engl J Med 1979; 300: 293-96. 6. Steichen JJ, Gratton TL, Tsang RC. Osteopenia of prematurity: The cause and possible treatment. J Pediatr 1980; 96: 528-34. 7. McIntosh N, Livesey A, Brooke OG. Plasma 25 hydroxyvitamin D and rickets in infants of extremely low birth weight. Arch Dis Child 1982; 57: 848-50. 8. McCowen C, Hey E. Plasma 25 hydroxyvitamin D and rickets in low birth weight babies. Arch Dis Child 1983; 58: 476. 9 Ballard J, Kazmaier K, Driver M. A simplified assessment of gestational age. Pediatr Res 1977; 11: 374-76. 10. Bessey OA, Lowry OH, Brock MJ. A method for rapid determination of alkaline phosphatase with five cubic millimeters of serum. J Bio Chem 1946; 164: 321-29.
Relationship
CLINICAL DATA
SIR,-Kessler et all have reported striking effects with the use of isotretinoin (13-cis-retinoic acid, ’Accutane’) in four patients with cutaneous T-cell lymphoma (CTCL). As part of a study of this drug in patients with lymphoproliferative cancers,2,3 we have to date treated seven patients with CTCL and thus can provide additional information to Lancet readers. All seven of our patients had previously received total skin electron beam therapy. Three patients had never received cytotoxic chemotherapy and one had been given intermittent injections of methotrexate several years earlier. Four patients had disease limited to skin (including erythroderma, plaques, and tumours); three other patients had lymphadenopathy plus skin disease. None had visceral dissemination. Isotretinoin was administered as a single daily dose of 100 mg/m2by mouth for at least 4 weeks. Three patients had excellent improvement in skin disease. One patient had total clearing of both erythroderma and an enlarged axillary lymph node which lasted for 9 months. Repeat biopsy of previously diseased skin showed no evidence of CTCL. Two other patients with disease limited to skin had 50% clearing of plaque lesions lasting for 8 and 7 + months. One of these patients had failed to respond to several conventional cytotoxic drugs. The four remaining patients, all of whom had tumour stage disease, did not
improve. Our preliminary results and the report from the University of Arizona strongly suggest that isotretinoin may have important therapeutic benefit in certain patients with CTCL. Whether these responses derive from a direct effect upon transformed lymphocytes or modulation of target organ (ie, skin) response to neoplastic cells is unclear. Further study should define subsets of patients who are most likely to respond to retinoid treatment. Developmental Chemotherapy, Hematology/Lymphoma, and Dermatology Services, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
RAYMOND P. WARRELL, CRAIG J. COONLEY SANFORD J. KEMPIN PATRICIA MYSKOWSKI BIJAN SAFAI
JR
Department of Oncology and Immunology, Hoffman-LaRoche Inc, New Jersey
Nutley,
LORETTA M. ITRI
11. Koo
WWK, Gupta JM, Nayanar VV, Wilkinson M, Posen S. Skeletal changes in preterm infants. Arch Dis Child 1982; 57: 447-52. 1. Kessler JF, Meyskens FL Jr, Levine N, Lynch PJ, Jones SE. Treatment of cutaneous T-cell lymphoma (mycosis fungoides) with 13-cis-retinoic acid. Lancet 1983; i:
1345-47. 2. Warrell RP Jr,
Coonley CJ, Itri LM Clinical effects of 13-cis-retinoic acid in patients lymphoid cancer. Clin Res 1982; 30: 692A. Coonley CJ, Warrel RP Jr, Itri LM, Lacher MJ. Pilot study of 13-cis-retinoic acid in patients with advanced malignant lymphoma. Proc Am Soc Clin Oncol 1983; 2: 221 with
. At 41/2 months.
normal adult range
3 22 - 5-60
pg/mi.
radioimmunoassay.2
measurement
of plasma
Cryoscopy
was
used
for
osmolality.
was stable and close to 3 pg/ml. Administration of SRIF resulted in a marked increase of plasma ADH (figure). The peak (13’6±4’ 1 pg/ml) was immediate. Then plasma ADH progressively decreased but did not return to basal values within 30 min of the SRIF injection. Plasma osmolalities
Mean basal
plasma ADH
identical to control values (288-t2 -6mosmol/kg) during this Blood pressure and heart rate were unaffected by the injection of SRIF. SRIF is a potent inhibitor of pituitaryand pancreatic4 hormone release. Its stimulatory effect on ADH secretion is thus noteworthy. This effect is not mediated through a change in blood pressure or plasma osmolality. Our results also provide new insight into the mechanism of the renal effects of SRIF. Indeed, the increased plasma ADH observed after SRIF intravenous administration accounts satisfactorily for the fall in urine flow reported by Walker were
period.
biochemical and radiological evidence of rickets; 3 had severe rickets accompanied by alkaline phosphatase activities more than 17 times the upper limit ofour adult normal range (95 IU/1). Vitamin D metabolite concentrations were measured by radioimmunoassay in these three cases, which are summarised below: At 1 month of age plasma 25-OHD3 concentrations in these three infants were within the adult normal range (see table) while plasma 1,25-(OH)2D3 concentrations were undetectable. Subsequently the 1,25-(OH)2D3 concentrations rose to within the adult normal range, accompanied by an increase in the 25-(OH)D3 concentrations. However, since all these infants were on calcium and vitamin D3 supplements the problem of neonatal rickets cannot be explained simply by dietary deficiency of calcium and vitamin D3. Our results therefore provide direct evidence to support the conclusions of Koo et al, 11 who suggested that these infants are unable to hydroxylate vitamin D3 to its active metabolites. E. G. WALTERS
’
et al.’1
Supported by Institut National de la Sante et de la Recherche Medicale and Faculte de Medecine Saint Antoine. Somatostatin was donated by Ferring SA. INSERM Unit 64,
Departments of
Medical Biochemistry and Child Health, Welsh National School of Medicine, Cardiff
J. F. MURPHY R. C. BROWN
J. S. WOODHEAD O. P. GRAY
W. PRUSZCZYNSKI R. ARDAILLOU
Hôpital Tenon, 75970 Paris, France
ISOTRETINOIN IN CUTANEOUS T-CELL LYMPHOMA VITAMIN D METABOLISM IN RACHITIC PRE-TERM INFANTS
StR,—Dr Tsang, in his June 18 contribution to your nutrition series, suggested that dietary deficiency of calcium and phosphate in preterm infants with may be the most likely cause of Another group found that rickets, a view supported by rickets in preterm infants was abolished by dietary calcium and We are still encountering cases of vitamin D3 rickets in preterm infants despite routine dietary supplementation with calcium 100 mg/kg daily and vitamin D3 400-1600 IU/daily for all preterm infants. Over a 15 month period forty-five babies with a gestational age less 34 weeks, confirmed by the Ballard score,9 were studied. Plasma alkaline phosphatase (PAP) activities were measured weekly by a modification of the method of Bessey et also with an MIII multistat centrifugal analyser. Nine preterm infants had
osteorenia others.
supplementation.8
2. Caillens H, Pruszczynski W, Meyrier A, Ang KS, Rousselet F, Ardaillou R. between change in volemia at constant osmolality and plasma antidiuretic hormone. Mm Electr Metab 1980; 4: 161-71. 3. Hall R, Besser GM, Schally AV, et al. Action of growth hormone-release inhibitory hormone in healthy men and in acromegaly. Lancet 1973; ii: 581-84. 4. Alberti KGMM, Christensen NJ, Christensen SE, et al. Inhibition of insulin secretion by somatostatin. Lancet 1983; ii: 1299-301. 5. Rowe JC, Wood DH, Rowe DW, Raisz LG. Nutritional hypophosphatemic rickets in a premature infant fed breast milk. N Engl J Med 1979; 300: 293-96. 6. Steichen JJ, Gratton TL, Tsang RC. Osteopenia of prematurity: The cause and possible treatment. J Pediatr 1980; 96: 528-34. 7. McIntosh N, Livesey A, Brooke OG. Plasma 25 hydroxyvitamin D and rickets in infants of extremely low birth weight. Arch Dis Child 1982; 57: 848-50. 8. McCowen C, Hey E. Plasma 25 hydroxyvitamin D and rickets in low birth weight babies. Arch Dis Child 1983; 58: 476. 9 Ballard J, Kazmaier K, Driver M. A simplified assessment of gestational age. Pediatr Res 1977; 11: 374-76. 10. Bessey OA, Lowry OH, Brock MJ. A method for rapid determination of alkaline phosphatase with five cubic millimeters of serum. J Bio Chem 1946; 164: 321-29.
Relationship
CLINICAL DATA
SIR,-Kessler et all have reported striking effects with the use of isotretinoin (13-cis-retinoic acid, ’Accutane’) in four patients with cutaneous T-cell lymphoma (CTCL). As part of a study of this drug in patients with lymphoproliferative cancers,2,3 we have to date treated seven patients with CTCL and thus can provide additional information to Lancet readers. All seven of our patients had previously received total skin electron beam therapy. Three patients had never received cytotoxic chemotherapy and one had been given intermittent injections of methotrexate several years earlier. Four patients had disease limited to skin (including erythroderma, plaques, and tumours); three other patients had lymphadenopathy plus skin disease. None had visceral dissemination. Isotretinoin was administered as a single daily dose of 100 mg/m2by mouth for at least 4 weeks. Three patients had excellent improvement in skin disease. One patient had total clearing of both erythroderma and an enlarged axillary lymph node which lasted for 9 months. Repeat biopsy of previously diseased skin showed no evidence of CTCL. Two other patients with disease limited to skin had 50% clearing of plaque lesions lasting for 8 and 7 + months. One of these patients had failed to respond to several conventional cytotoxic drugs. The four remaining patients, all of whom had tumour stage disease, did not
improve. Our preliminary results and the report from the University of Arizona strongly suggest that isotretinoin may have important therapeutic benefit in certain patients with CTCL. Whether these responses derive from a direct effect upon transformed lymphocytes or modulation of target organ (ie, skin) response to neoplastic cells is unclear. Further study should define subsets of patients who are most likely to respond to retinoid treatment. Developmental Chemotherapy, Hematology/Lymphoma, and Dermatology Services, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
RAYMOND P. WARRELL, CRAIG J. COONLEY SANFORD J. KEMPIN PATRICIA MYSKOWSKI BIJAN SAFAI
JR
Department of Oncology and Immunology, Hoffman-LaRoche Inc, New Jersey
Nutley,
LORETTA M. ITRI
11. Koo
WWK, Gupta JM, Nayanar VV, Wilkinson M, Posen S. Skeletal changes in preterm infants. Arch Dis Child 1982; 57: 447-52. 1. Kessler JF, Meyskens FL Jr, Levine N, Lynch PJ, Jones SE. Treatment of cutaneous T-cell lymphoma (mycosis fungoides) with 13-cis-retinoic acid. Lancet 1983; i:
1345-47. 2. Warrell RP Jr,
Coonley CJ, Itri LM Clinical effects of 13-cis-retinoic acid in patients lymphoid cancer. Clin Res 1982; 30: 692A. Coonley CJ, Warrel RP Jr, Itri LM, Lacher MJ. Pilot study of 13-cis-retinoic acid in patients with advanced malignant lymphoma. Proc Am Soc Clin Oncol 1983; 2: 221 with
. At 41/2 months.
normal adult range
3 22 - 5-60
pg/mi.