637

ABSENCE OF CHROMOSOMAL CHANGES IN FETUSAFTER PATERNAL CHEMOTHERAPY

SIR,-Cytotoxic drugs cause transitory alterations of gon-adal function.1.2 The possibility of chromosomal alterationsafter chemotherapy is of interest because of the increasingnumber of patients who undergo either adjuvant chemo-therapy courses for limited periods or successful treatment formetastatic disease such as testicular carcinoma,3 small cell car-cmoma of lung,4 and acute lymphatic leukaemia.5A 29-year-old man had a left orchiectomy in December,

1977, for testicular teratoma with elements of embryonal car-cinoma. A staging lymphadenectomy revealed no evidence ofmetastatic disease. Additional search for metastases includingchest X-ray, bone survey, liver and bone scan, lymphography,and blood biochemistry were negative. The patient was put on5-day courses of adjuvant chemotherapy consisting of vinblas-une 10 mg on the first day only, bleomycin 15 mg/day, andactinomycin D 0.5 mg/day every day on alternating courses.Six courses were given and all chemotherapy was stopped inAugust, 1978. No evidence of metastatic disease was noted atany time.

Six months after cessation of chemotherapy the patient’swife became pregnant (there is no reason to doubt the patient’sfatherhood). Because of the previous chemotherapy, preg-nancy was terminated at 8 weeks gestation. No macroscopicfetal abnormalities were observed. Fetal cells were cultured for7 days (F 10 nutrient medium, enriched with 20% fetal calfserum) and G-banded from PI passage. Chromosomes wereanalysed in ten cells after trypsin denaturation; the karyotypewas 46,XY without evidence of numerical or structural aber-rations of the chromosomes.

Products of conception after one of the parents has receivedchemotherapy are valuable in the study of possible adverseeffects of chemotherapy on chromosomes. Most reports con-cern the effect of drugs given to pregnant women on the fetus.In previous reports6.7 of infants born after paternal chemo-therapy for acute leuksmia (1, 2, and 5 years before concep-tion) two of the three infants were born with diverse congenitalmalformations.

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Chemotherapy in our patient resulted in no apparent grossabnormalities or chromosomal changes in the fetus. Informa-tion about fetal chromosomes and chemotherapy is limited,and termination of pregnancy may not be indicated in allcases.

Units of Oncology andClinical Genetics,

Kaplan Hospital,Rehovot, Israel

A. SHANIM. TALPAZ

J. CHEMKES. RAPPAPORT

Department of Oncology,Rokah Medical Centerand Tel Aviv UniversityMedical School J. A. STEIN

PRENATAL DIAGNOSIS OF CONGENITAL ADRENALHYPERPLASIA

SIR,-Although we have reported on the prenatal diagnosisof congenital adrenal hyperplasia (CAH) by HLA typing of

1. Kumar R, Biggart JD, McEvoy J, McGeown MG. Cyclophosphamide andreproductive function. Lancet 1972; i: 1212-14.

2. Rostom AY, White WF. Hodgkin’s disease, chemotherapy, and fertility. Lan-cet 1979, i: 555.

3. Weiss JH, Hinman F. Factors affecting the success or failure of "sandwichtherapy" for embryonal and teratocarcinoma of the testis. J Urol 1974;112: 779-82.

4. Einhorn LH, Bond WH, Hornback N, Joe BT. Long term results in com-bined modality treatment of small cell carcinoma of the lung. Semin Oncol1978; 5: 309-13.

5. Isawa T, Yamashiro T, Aoki K, et al. Five year survivors among childrenwith acute leukemia in Japan. Cancer 1977; 40: 349-57.

6. Hinks E, Platkin D. Reversible drug induced sterility in a patient with acuteleukemia. JAMA 1973; 223: 1490-91.

7. Russel JA, Powells RL, Oliver RTD. Conception and congenital abnormali-ties after chemotherapy of acute myelogenous leukaemia in two men. BrMed J 1976; i: 1508.

amniotic cells,’ we share with Dr Steffes and Dr Wong (Aug.11, p. 303) the view that the prenatal diagnosis of CAH is notan indication for therapeutic abortion and we offer, both tofamilies and physicians, the encouragement that, with propertreatment, normal growth and development, sexual function,and fertility can be achieved.2 Nevertheless, there are parentswho want prenatal diagnosis-they do not want anotheraffected child or an affected female with ambiguous genitalia,or they wish to be fully prepared before the birth of the infant-and as physicians it is our responsibility to provide parentswith the information which current medical knowledge per-mits. The determination of amniotic-fluid concentration of17-hydroxyprogesterone may be an accurate method of pre-natal diagnosis of CAH due to 21-hydroxylase deficiency.Determination of A 4-androstenedione concentration may alsobe useful. There is still not enough experience with these hor-monal determinations to know the incidence of false negativeand false positive determinations. HLA typing of amniotic cellsprovides an additional means of prenatal diagnosis and confir-mation of the prediction based on amniotic fluid hormone con-centrations.

Division of Pediatric Endocrinology,Department of Pediatrics,New York Hospital-Cornell Medical Center,New York, N.Y. 10021, U.S.A.

LENORE S. LEVINEMARIA I. NEW

Tissue Typing Laboratory,Sloan Kettering Institute for Cancer Research,New York

MARILYN POLLACKBO DUPONT

PRENATAL DIAGNOSIS OF SEVERE VONWILLEBRAND’S DISEASE

SiR,—Dr Hoyer and his colleagues are to be congratulatedon their letter on the prenatal evaluation of fetal von Wille-brand’s disease (vWd).4 In view of the recent interest in thissubject 5-7 we wish to make some comments.Dilution of the fetal blood-samples with amniotic fluid (by

factors of 49, 47, and 176) is an important constraint on theaccuracy of their assays of both factor VIII coagulant antigen(VIIICAg) and factor-VIII-related antigen (VIIIRAg). Thecoefficient of variation of their VIIICAg assay is about 10% atnormal levels,8 and the arithmetical correction necessary at’high dilution will compound any inaccuracy in the method. Inaddition, such dilution lessens the assay’s sensitivity, which forVIIICAg is between 0.01 and 0.03 u/mP and for VIIIRAgreaches 0-002 u/m1.6

If, in samples diluted 49 and 47 fold, the lower limit ofsensitivity is approached (fetal sample 1) or exceeded (sample3) it is not surprising that the two VIIICAg values obtained atthe same fetoscopy differ by 100% (table ii).1 Hoyer et al. statethat fetoscopy samples may be diluted up to 200 times inamniotic fluid, in which case the potential inaccuracy of thistechnique must be even higher, and diagnostic conclusionsbased on results so derived must be unsafe.

1. Pollack MS, Maurer D, Levine LS, New MI, Pang S, Duchen M, Owens RP,Merkatz IR, Nitowsky HM, Sachs G, Dupont B. Prenatal diagnosis ofcongenital adrenal hyperplasia (21-hydroxylase deficiency) by HLAtyping. Lancet 1979; i: 1107.

2. New MI, Levine LS. Congenital adrenal hyperplasia. In: Harris H, Hirsch-horn K, eds. Advances in human genetics. New York: Plenum Press, 1973:251-326.

3. Pang S. Amniotic fluid concentrations of &Dgr;4 and &Dgr;5 steroids in midgestation.Endocrine Society annual meeting (Anaheim, California, June 1979);program and abstr 22/78.

4. Hoyer LW, Lindsten J, Blomback M, Hagenfeldt L, Cordesius E, StrombergP, Gustavii B. Prenatal evaluation of fetus at risk for severe von Wille-brand’s disease. Lancet 1979; ii: 191-92.

5. Peake IR, Bloom AL. Immunoradiometric assay of procoagulant factor VIIIantigen in plasma and serum and its reduction in hæmophilia: preliminarystudies on adult and fetal blood. Lancet 1978; i: 473-75.

6. Firshein SI, Hoyer LW, Lazarchick J, Forget BG, Hobbins JC, Clyne LP,Pitlick FA, Muir WA, Merkatz IR, Mahoney MJ. Prenatal diagnosis ofclassic hemophilia. N Engl J Med 1979; 300: 937-41.

7. Mibashan RS, Rodeck CH, Thumpston JK, Edwards RJ, Singer JD, WhiteJM, Campbell S. Plasma assay of fetal factors VIIIC and IX for prenataldiagnosis of hæmophilia. Lancet 1979; i: 1309-11.

8. Lazarchick J, Hoyer LW. Immunoradiometric measurement of the factorVIII procoagulant antigen. J Clin Invest 1978; 55: 1048-52.