363

TREATMENT OF OVERT MENINGEAL

LEUKÆMIA

SiR,—The conclusion of Duttera et al.l that " Irradiationwith 2400 r to the cranial vault added nothing to thetherapeutic efficacy of intrathecal methotrexate

"

promptsus to report the preliminary results of the current M.R.C.trial on the treatment of meningeal leukaemia in children.Our findings are consistent with the above statement, butsuggest that the addition of spinal irradiation, 1000 r, tothe combination of intrathecal methotrexate plus cranialirradiation markedly delays recurrence of leukaemic cellsin the cerebrospinal fluid (see accompanying figure).The M.R.C. trial differed from that of Duttera et al. in

that no intrathecal (LT.) methotrexate was given after theradiotherapy. The subsequent duration of C.N.s. remissionwas therefore " unmaintained " with respect to Lot. therapy,whereas the Bethesda trial included continuing monthly4c maintenance " l.T. methotrexate (or cytosine arabinoside).Prolqnged C.N.s. remission in the M.R.C. trial cannot,therefore, be attributed to possible masking of residualleukaemic foci by subsequent LT. chemotherapy.An initial course of a minimum of six LT. injections of

methotrexate (10 mg. per sq. m.) was given at weeklyintervals. After clearance of the c.s.F. blast cells on atleast two successive lumbar punctures, patients were

randomised to receive either cranial irradiation alone

(2500 rad supervoltage in 12 fractions given over 2tweeks), or this plus spinal irradiation (1000 rad super-voltage or a biologically equivalent orthovoltage dose in4-5 fractions over 4-6 days). Patients in their first menin-

geal relapse were randomised separately from those withtheir second or subsequent relapse. None had received

previous radiotherapy to the c.N.s. After completion of theradiotherapy the duration of meningeal remission was

ascertained by examination of the c.s.F. at 8-week intervals,or sooner if clinically indicated.Among those being treated for their first meningeal

relapse, 7 out of 8 in the " cranial only " group have had arecurrence of blast cells in the C.S.F., compared with 0out of 8 in the " craniospinal " group (1 dying of systemicdisease at 69 weeks). Among those treated for second orsubsequent meningeal relapse, 7 out of 7 in the cranialonly " group have relapsed and 4 out of 5 in the cranio-spinal " (1 of these showing weight gain but no blast cellsin the C.S.F.). The apparently beneficial effect of additional

Duration of C.N.S. remission after meningeal leukaemia:cranial v. craniospinal radiotherapy following intrathecalmethotrexate.

spinal irradiation seen in patients with early disease is notmirrored in those with the more advanced infiltration that

presumably is present at subsequent relapses.Intake to the trial is now closed, since a difference between

the two groups is apparent. Continued follow-up will benecessary to determine the ultimate duration of C.N.S.

remission obtained in the craniospinal group.Royal Hospital for Sick

Children,Yorkhill, Glasgow C3.

M. L. N. WILLOUGHBY,On behalf of the M.R.C. WorkingParty for Childhood Leukaemia.

1. Duttera, M. J., Bleyer, W. A., Pomeroy, T. C., Leventhal, C. M.,Leventhal, B. Lancet, 1973, ii, 703.

HÆMORRHAGE FROM VARICOSE VEINS

SraR,-Mr Evans and his colleagues 1 describe threenew fatal cases of haemorrhage from varicose veins withulceration, a further non-fatal case, and twenty-threedeaths in 1971 from figures supplied by the Office of

Population, Census, and Surveys. Unfortunately no

details of local treatment are given in this paper.Dermatologists regularly see patients who have been

applying powerful steroid ointments and creams to theirvenous ulcers. The applications have generally beenadvised for use on adjacent eczema, and the patient hasmisunderstood the instructions, but it is not uncommon tofind that the prescription has been given deliberately forapplication to the ulcer itself. Clinical experience clearlysuggests that potent steroids, applied in this way, delayhealing, cause even deeper perforation of ulcers, andinvite secondary infection.

Is the surprisingly high incidence of fatal haemorrhagereported due, in part, to this mistaken use of steroids ?Details of treatment in these fatalities are needed badly.Department of Dermatology,

Royal Infirmary,Bristol BS2 8HW. R. R. M. HARMAN.

1. Evans, G. A., Evans, D. M. D., Seal, R. M. E., Craven, J. L.Lancet, 1973, ii, 1359.

WOUND INFECTION IN

ACUTE APPENDICITIS

SiR,—I disagree with Mr Benson and his colleagues 1that this subject has been " flogged to death "-a statementwhich implies that either the best possible result has beenachieved or no further improvement is possible. In myview neither of these implications is true and I agree withDr Martin 2 and Mr Gilmore 3 that more controlledstudies are needed. It is perhaps significant that few

bacteriological results are available in any of the six studiescited by Mr Benson.The improvements in laboratory techniques and more

emphasis on the isolation of strict anaerobic bacteria makeit possible to rediscover the bacteriology of acute appen-dicitis first reported by Veillon and Zuber 4 and to approachthe problem of postoperative wound infection on a selectivebasis. In the High Wycombe area over 80% of post-appendicectomy wound infections are caused by anaerobicbacteria, commonly Bacteroides. It can be shown that thepresence of certain bacteria, usually anaerobic, in the

appendix fossa at the time of surgery but before openingthe appendix is associated with an increased incidence ofinfection and that early treatment with appropriate chemo-therapy-namely, lincomycin-can prevent the develop-ment of infection (unpublished data).There are many questions concerning postoperative

infections after intestinal surgery that remain to be answered,and it is essential that a selective approach is made so thattreatment can be given to those patients who require it