262 veloped. The patient died a few days later. At necropsy the diagnosis of histiocytic medullary reticulosis was confirmed and was found to inv...

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veloped. The patient died a few days later. At necropsy the diagnosis of histiocytic medullary reticulosis was confirmed and




involve mediastinal and mesenteric


nodes, spleen, liver, and bone-marrow. An immature teratoma in the anterior mediastinum and acute hepatic necrosis were also noted. Possible cases of malignant histiocytosis related to inmunosuppressive therapy are those of Clark and Dawson9 and Shreiner!O Both reports related to acute lymphoblastic leukaemia in which Robb-Smith’s disease was diagnosed after induction treatment. Our case would seem to be the first in which this rare disease has been found in a recipient of an allograft.

Postgraduate "Farreras

School of



Department of Pathology, and Kidney Transplant Unit, Hospital Clinico y Provincial, Barcelona -11, Spain



IMMUNOLOGICAL INERTIA OF VIVIPARITY SIR,-In commenting upon pregnancy, your editorial


where the real action is. The partners in pregnancy, mother and fetus, fail to reject each other, although they are capable of doing so after parturition and of rejecting unrelated tissues during pregnancy. In a number of species when skin grafts can be exchanged between the partners during pregnancy or immediately post partum, they often survive without rejection or after an abortive rejection process. This immunological inertia of viviparity2-l4is partner specific, mutual, and temporary, indicating that bodies of precise information about individual tissue specificities-presumably HLA antigen profiles-have been exchanged between the partners. This clearly leads, in many cases at least, to specific suppression of rejection reactions. Thus the real action takes place within the lymphoreticular systems of mothers and fetuses, and there is little need to postulate active immunological participation of trophoblast, except possibly for a time shortly after implantation and before development of the fetal lymphoreticular system. It is comprehension of the mechanisms of immunological inertia and of their kinetics that is likely to yield information exploitable in cancer. The statement that fetal escape from rejection depends largely upon properties of the trophoblast, which you do not define, is not acceptable. The many findings of generalisedH-17 and of partner-directed 18--21 immunosuppression in fetuses and young offspring and in mothers are ignored. Also you attempt to draw correlations amongst hydatidiform mole, choriocarcinoma, and viviparity, whilst failing to emphasise the very important differences amongst these biological systems. Although mechanisms with similarities may exist therein, and in abortions and pre-eclampsia, 22 -24 it is not possible at present to characterise them precisely. Thus blanket statements about undefined properties of the trophoblast are mis-

malignant trophoblast’ diverts attention from


and an insupportable basis for constructing a stateabout the significance of recent advances in HLA typing and choriocarcinoma.

leading ment

Surgical Division, Royal Infirmary,


Glasgow G4 0SF

CONGENITAL FOLATE-DEPENDENT MEGALOBLASTIC ANÆMIA OF UNKNOWN ÆTIOLOGY a moderately retarded girl congenital familial megaloblastic anaemia for 15 years by giving her large doses of folic acid to maintain a normal clinical status. She was the product of a consanguineous marriage, and a sister died of severe anaemia in 1959. At age 1 month megaloblastic anxmia was noted. It failed to respond to parenteral vitamin B12 associated with small ("physiological") doses of folinic acid. Only with large ("pharmacological") doses of oral folic acid or parenteral folinic acid was recovery complete. Therefore, permanent therapy with oral folic acid (5 mg daily) was prescribed. Vitamin B,2 (1000 jj.g weekly) was added to folic acid to prevent possible neurological disturbances.’ Discontinuation of vitamin B,, had no

SIR,-We have been treating




clinical or haematological effects. When the patient was 13 vears old, a progressive irritability was the first manifestation of a severe megaloblastic ansmia which failed to respond to her usual dosage (5 mg daily) of folic acid. At this time the patient had severe anaemia (Hb 6g/dl), leukopenia (2.3x 109/1), and thrombocytopenia (70x 109/1). Severe purpura, epistaxis, and progressive diminution of vision were noted. Her bone-marrow picture was strikingly megaloblastic. Treatment with parenteral folinic acid (’Leucovorin’) at doses of 20 mg daily was started. After 20 days she had a complete remission of clinical and haematotogical symptoms. When her Hb reached 14 g/dl therapy was continued with oral folic acid (20 mg daily) and vitamin B12 (1000 p.g weekly). In February, 1975, when the patient was 15, treatment was discontinued for 1 month. Her Hb fell to 6.5 g/dl and her bone-marrow showed intense megaloblastic features. Her serum-vitamin-B,2 was 440 pg/ml and her serum-folic-acid was 6 ng/ml. R.B.c. folates were up to 1480 ng/ml. Urine 4-amino-5imidapole carboxamide was absent and there was no abnormal aminoacid pattern in either plasma or urine. Oroticaciduria was not found. Treatment was reinstated with parenteral leucovorin (32 mg daily). A high reticulocyte response was followed by a complete remission of clinical and haematologica! symptoms. When Hb reached normal level, therapy was continued with oral folic acid (30 mg daily) and vitamin B12 (1000 jg weekly). The patient is still receiving folic acid and remains clinically well and haematologically normal. Mental retardation and diminution of vision have not got worse. Our patient does not have a deficiency of either vitamin Bu or folic acid since her serum levels were normal while not on treatment. The increased R.B.c. folate while on folic acid indicated that she does not have an.intracellular deficiency of folic acid. The lack of response to parenteral physiological doses of folinic acid indicates that she is able to reduce folinic acid normally. Some rare megaloblastic ansemias associated with1 either oroticaciduria, 1-5 formiminotransferase deficiency,"

15. Hill, C. A., Finn, R., Denye, V. Br. med. J. 1973, iii, 513. 16. Kasakura, S. J. Immun. 1971, 107, 1296. 17. Stimson, W. H. Clin. exp. Immun. 1976, 25, 199. 18. Ceppellini, R., Bonnard, G. D., Coppo, F., Miggiano, V. C., Pospish, M., Curtoni, E. S., Pellegrino, M. Transplant. Proc. 1971, 3, 58. 19. Hellstrom, K. E. Hellstrom, I. Brawn, J. Nature, 1969, 224, 914. 20. Leventhal, B. G., Buell, D. N., Yankee, R., Rogentine, G. N. Terasaki, P. Proc. 5th Leucocyte Culture Conf. 1970, p. 473. 21. Youtananukorn, V., Matangkasombut, P. Nature new Biol. 1973, 242, 110. 22. Berne, B. H. Fed Proc. 1974, 33, 290. 23. Stimson, W. H. I.R.C.S. med. Sci. 1973, (73-3) 17-1-3. 24. Than, G. N., Csaba, I. F., Karg, N. J., Szabo, D. G., Novak, P. F. ibid. 1975b, 3, 94.

1. Will J. J., Mueller, J. F., Brodine, C., Kiely, C. E., Friedman, B., Hawkins, V. R., Dutra, J., Vilter, R. W. J. Lab. clin. Med. 1959, 53, 22. 2. Heinle, R. W., Welch, A. D. Am. med. Ass. 1947, 133, 739. 3. Huguley, C. M., Bain, J. A., Rivers, S. L., Scoggins, R. B. Blood, 1959,14, 615. 4. Bercroft, D. M., Philips, L. I. Br. med. J. 1965, i, 547. 5. Haggard, M. E., Lockhard, L. H. Am. J. Dis. Child. 1967, 113, 733. 6. Arakawa, T., Ohara, K., Kudo, Z., Tada, K., Hayashi, T., Mizuno, T. Tohoku. J. exp. med. 1963, 80, 370. 7. Arakawa, T., Takahashi, Y., Ogasawara, J., Hayashi, T., Chiba, R., Wada, Y., Tada, K., Mizuno, T., Okamura, T., Yoshida, T. Ann. Paediat. 1965, 205, 1.

9. Clark, B. S., Dawson, P. J. Am. J. Med 1969, 47, 314. 10. Shreiner, D. P. J. Am. med. Ass. 1975, 231, 838. 11. Lancet, 1976, ii, 1232. 12. Anderson, J. M. Nature, 1966, 206, 786. 13. Anderson, J. M. Proc. R. Soc. B. 1970, 176, 115. 14. Anderson, J. M. Nature’s Transplant: the Transplantation


Viviparity; p. 45. London, 1972.