Weight gain and height velocity during prolonged first remission from acute lymphoblastic. years and 15 for two years. Three patients who

Transcription

1 Archives f Disease in Childhd, 1985, 60, Weight gain and height velcity during prlnged first remissin frm acute lymphblastic leukaemia C P Q SAINSBURY, R G NEWCOMBE, AND I A HUGHES Departments f Child Health and Medical Cmputing and Statistics, University f Wales Cllege f Medicine, Cardiff SUMMARY A retrspective analysis f the medical recrds f 86 children in prlnged remissin frm acute lymphblastic leukaemia was perfrmed t calculate changes in the rate f increase in height and weight gain. The rate f increase in height decreased during initial treatment, and the ptential fr final adult height was nt regained. Weight gain was excessive; this started during treatment and persisted int the remissin years. Values f weight adjusted fr height did nt return t values fund befre treatment until eight years after diagnsis. Several factrs can accunt fr this weight gain, but there is a practical need t prvide dietary advice, particularly when chemtherapy is stpped. Advances in the management f children with acute lymphblastic leukaemia have led t a nticeable imprvement in prgnsis. Remissin is induced in 90-95% f children, f whm half can be expected t survive fr five years; many will have been cured.' Several studies have reprted n the grwth f children treated fr malignant disease.2 7 Rate f grwth is decreased, mst nticeably during the first year f treatment. Althugh the rate f grwth usually returns t nrmal after the cmpletin f chemtherapy, there is a small but significant reductin in the eventual height reached. Nne f the studies have reprted data n weight gain. We describe a retrspective analysis f weight gain in children with acute lymphblastic leukaemia in relatin t rate f increase in height and the duratin f remissin. Patients and methds The children were treated fr acute lymphblastic leukaemia at three reginal centres (Edinburgh, Glasgw, and Cardiff) and were aged less than 10 years at diagnsis. All had entered int first remissin and nne had relapsed. There was n evidence f leukaemic infiltratin f the brain r any ther disease that may have affected grwth adversely. The recrds f 86 children were examined, 49 f whm were girls. The mean age at diagnsis was 5-1 years (range years). Each child diagnsed 832 after 1970 was treated accrding t the current natinal acute lymphblastic leukaemia trial. Sixty eight children received chemtherapy fr three years and 15 fr tw years. Three patients wh started treatment befre 1970 were treated fr fur, five, and seven years, respectively. Cranial irradiatin ( rads) and cranispinal irradiatin N f 50 patients E] Cranial irradiatin * Crcrispinal irrdiat' N irmdiatin Fig. 1 Ttal number fchildren studied in relatin t type f raditherapy and number fyears' bservatin. Arch Dis Child: first published as /adc n 1 September Dwnladed frm n 1 July 2018 by guest. Prtected by cpyright.

2 Weight gain and height velcity in remissin frm acute lymphblastic leukaemia 833 ( rads) were given t 62 and 14 children, respectively. Ten children received n raditherapy (Fig. 1). All patients were fllwed up fr a minimum f fur years and 35% fr eight years (see Fig. 1). Measurements f height and weight perfrmed at the time f diagnsis (befre treatment) and at yearly intervals thereafter were recrded. Measurements f grwth were taken befre each maintenance cycle t reduce the acute effect f a curse f sterids n weight gain. Height adjusted fr age, weight adjusted fr age, and weight adjusted fr height and age were calculated, as described by Cle,8 based n the standards f Tanner and Whitehuse.9 Results were expressed as a percentage with 100% being the mean value fr age. Data were analysed with and withut lgarithmic 104 g * 98. I &,~10k, 21N 9610 I. 96- I, I ;; - Ge tic mean Edinburgh Giasgw a Cardiff *** *** *** *** *** *** *** ** Signifiance frm diagnsis *** ** NS NS NS NS C0 i 2 3 i transfrmatin t prduce cmpatible results fr the three variables. Changes in these variables with time frm diagnsis were assessed n a within subject basis by paired t tests and an analysis f variance mdel, which tk int accunt that different subsets f children were represented in data fr the different years frm diagnsis. Similarly, differences between grups defined by type f raditherapy, sex, age at diagnsis, and treatment centre were assessed simultaneusly by analysis f variance. The analysis was als perfrmed with adjustment fr the crrespnding value at admissin as cvariate t determine if changes in height and weight depended n these factrs. Results NS Significance fram ne year after diagnsis Gemnetric mean Edinburgh Gkbsgw _Cwdiff ** ** ** *** *** ** NS Significance frm diagnsis * 0 0 -Li U \ U 3 NS NS ** ** * t NS Significance frm ne year after diagnsis I~ ~ ~ Figure 2 shws the mean values fr height fr age at Fig. 2 Change in percentage height fr age after diagnsis f acute lymphblastic leukaemia. Significance cmpared with values at diagnsis and ne year after diagnsis are shwn. *P<0O-O1, **P<0-01, ***P<0 05, tp= , NS=P>0-1. Fig. 3 Change in percentage weightfr age after diagnsis f acute lymphblastic leukaemia. Significance cmpared with values at diagnsis and ne year after diagnsis are shwn. *P<0001, **P<0-01, ***P<005, tp=o05-0-1, NS=P> 0.1. Arch Dis Child: first published as /adc n 1 September Dwnladed frm n 1 July 2018 by guest. Prtected by cpyright.

3 834 Sainsbury, Newcmbe, and Hughes Gemetric mean * Edinburgh Gklsgw * Cardiff 114. *** *** **t*** ** *** *** t Significance e frm diagnsisd Fig. 4 Change in percentage i 110i weight adjusted fr height and age 0 i i 0 0 after diagnsis facute lymph- blastic leukaemia. Significance 0/ \ cmpared with values at diagnsis and ne year after diagnsis $102 / are shwn t* * ** ** * NS Significance frm ne year after diagnsis O 1 2 _P<0001, **P<001, ***P<005, tp= i/ 0-1, NS=P> 01. diagnsis and at yearly intervals. The significance f these values cmpared with thse at diagnsis and 104 ne year after diagnsis are als shwn. The g 102 % children were slightly taller than nrmal at diagnsis. During treatment there was a decrease in the D. \ e - A A. t rate f increase in height, but after three years there * was a return twards nrmal. The last height 96 ^> O... -O Ḍ. attained remained significantly belw values fund 94 befre treatment. The mean values fr weight fr age at diagnsis, during treatment, and subsequently during remissin tgether with their significance are shwn in Fig. 3. A small increase in weight ccurred during 116 the first three years fllwed by a nticeable increase that persisted until the seventh year after diagnsis. 112 Figure 4 gives values f weight adjusted fr height and age. The children were relatively thin at diagnsis but gained weight rapidly during the first t;i, 8. year. This weight gain persisted thrughut treat-.f^/ D Oa XD ment and int the seventh year after diagnsis befre returning twards values fund befre treat- / ~~~~~~~~ment. 100 /. The centre f treatment, type f raditherapy, D, and sex f the child made n difference t the 3 96 af changes in grwth that were bserved, as shwn by Age <3years at diagnsis O analysis f cvariance. The age at diagnsis, hw- Age 3-5years at diagnsis A- - I ever, did have sme effect n subsequent grwth..e6yeratigi. Children aged less than 3 years at diagnsis were.. Age >6 years at diagnsis 0.0 I mre likely t regain their ptential height than lder children and had a mre nticeable and 6 i i 8 prlnged perid f weight gain (Fig. 5). Discussin Fig. 5 Change in percentage height fr age and weight adjusted fr height in relatin t age at diagnsis. This retrspective study shwed that children with Arch Dis Child: first published as /adc n 1 September Dwnladed frm n 1 July 2018 by guest. Prtected by cpyright.

4 Weight gain and height velcity in remissin frm acute lymphblastic leukaemia 835 acute lymphblastic leukaemia were slightly taller at diagnsis but were underweight cmpared with children f the same age. Our values fr height agree with a reprt n stature at presentatin in children with acute lymphblastic leukaemia. 10 Althugh the cause f this is nt knwn, the use f grwth standards derived frm a ppulatin f children studied abut 30 years ag may partially explain the differences.9 Certainly, nn-specific symptms, including anrexia, may precede the diagnsis f acute lymphblastic leukaemia and lead t sme lss in weight withut affecting the rate f increase in height. Spinal irradiatin can inhibit grwth f the spine t a variable degree."1 12 Our study shwed n significant difference in the height attained between children wh received cranispinal irradiatin and thse wh did nt. Unfrtunately, sitting height was nt measured rutinely. A significant effect may nt have been seen due t the small numbers in this grup r because the spinal irradiatin dse used had a minimum effect n spinal grwth. 13 The changes in the rate f increase in height were the same whichever type f raditherapy was used, suggesting that raditherapy was nt a causative factr. Several factrs may affect weight gain, including drugs, diet, raditherapy, and physical exercise. Inductin chemtherapy includes the use f high dse sterids given ver a perid f weeks. Children ften gain weight rapidly during this time. Cntinued use f sterids given as recurrent shrt pulses thrughut the maintenance cycle must als be respnsible fr sme f the persistent weight gain. This des nt, f curse, explain why a further increase in weight ccurs after chemtherapy is stpped. Other drugs such as methtrexate, which may cause malabsrptin,14 are unlikely t prmte weight gain. Damage t the hypthalamus r pituitary by radiatin may result in minr abnrmalities in the secretin f grwth hrmnes,2 4 5 prbably due t a deficiency f hypthalamic grwth hrmne releasing factr.15 In mst children with acute lymphblastic leukaemia this des nt appear t affect the rate f grwth. Hypthalamic damage may cause besity, but this has nt been described after cranial irradiatin. 16 Hypthalamic besity has been reprted in children with acute leukaemia, but this has always been after leukaemic infiltratin f the brain. 17 The psychlgical effects n a family when a child has acute leukaemia are cmplex and varied.'820 The threat f death r serius adverse effects due t treatment causes parents t react differently t their children than they wuld nrmally. They try t allw their child t lead a life as free frm unpleasantness as pssible. This may result in pr dietary habits with the excessive cnsumptin f high energy fds, such as sweets and crisps, and lead t excessive weight gain. Lack f exercise may als cntribute t the excess weight gain. Parents prbably restrict physical activity, particularly while the child is receiving treatment. In this study the children had a relatively uncmplicated curse f treatment and prbably led nrmal active lives during the years after treatment. There was a nticeable decrease in adjusted weight fr height between the seventh and eighth years after diagnsis. Althugh the number f patients in this grup was smaller (30), the change prbably reflects the effect f a pubertal grwth spurt. The results f this study shw that children treated successfully fr acute lymphblastic leukaemia gain excessive weight. This starts early in the treatment phase and persists fr many years. Althugh several factrs prbably cntribute t the weight gain, we suggest that parents be given dietary advice. The apprpriate time fr this wuld be at the end f chemtherapy. We thank the paediatric nclgists at Edinburgh, Glasgw, and Cardiff fr access t the medical recrds f children at these centres. References Lanzkwsky P. Paediatric nclgy: a treatise fr the clinician. New Yrk: McGraw-Hill Inc, 1983: Shalet SM. Abnrmalities f grwth and gnadal functin in children treated with malignant disease: a review. J R Sc Med 1981 ;75: Griffin NK, Wadswrth J. Effect f malignant disease n grwth in children. Arch Dis Child 1980;55: Swift PGE, Hearney PJ, Daltn RG, Bullimre JA, Mtt MG, Savage DCL. Grwth and hrmnal status f children treated fr acute lymphblastic leukaemia. Arch Dis Child 1978;53: Shalet SM, Price DA. Effect f treatment f malignant disease n grwth in children. Arch Dis Child 1981;56: Shalet SM, Price DA, Beardwell CG, Mrris Jnes PH, Pearsn D. Nrmal grwth despite abnrmalities f grwth hrmne secretin in children treated fr acute leukaemia. J Pediatr 1979;94: Price DA, Shalet SM, Beardwell CG,Hann IM, Mrris Jnes PH. Serum smatmedin activity in children with acute lymphblastic leukaemia. Pediatr Res 1978;12: Cle TJ. A methd fr assessing age-standardised weight-fr- 'height in children seen crss-sectinally. Ann Hum Bil 1979;6: Tanner JM, Whitehuse RH, Takaishi M. Standards frm birth t maturity fr height, weight, height velcity and weight velcity. British children 1965, Part II. Arch Dis Child 1966; 41: Brmhall J, May R, Lilleyman JS, Milner RDG. Height and lymphblastic leukaemia. Arch Dis Child 1983;58: Prbert JC, Parker BR, Kaplan HS. Grwth retardatin in children after megavltage irradiatin f the spine. Cancer 1973;32: Arch Dis Child: first published as /adc n 1 September Dwnladed frm n 1 July 2018 by guest. Prtected by cpyright.

5 836 Sainsbury, Newcmbe, and Hughes 12 Park TS, Hffman HJ, Hendrick B, et al. Medullblastma: clinical presentatin and management. Experience at the Hspital fr Sick Children, Trnt J Neursurg 1983;58: Blm HJG, Wallace ENK, Henk JM. The treatment and prgnsis f medullblastma in children. A J R 1969;105: Lewis IJ, Mainwaring D, Martin J. Enterpathy cmplicating maintenance therapy in acute lymphblastic leukaemia. Arch Dis Child 1982;57: IS Ahmed SR, Shalet SM. Hypthalamic grwth hrmne releasing factr deficiency fllwing cranial irradiatin. Clin Endcrinl 1984;21: Bray AB, Gallagher JR. Manifestatins f hypthalamic besity in man: a cmprehensive investigatin f eight patients and a review f the literature. Medicine 1975;54: Shredding f manuscripts 17 Barak Y, Liban E. Hypthalamic hyperphagia, besity and disturbed behaviur in acute leukaemia. Acta Paediatr Scand 1968;57: Schuler D, Plcz A, Revesz T, et al. Psychlgical late effects f leukaemia and their preventin. Med Pediatr Oncl 1981;9: Eiser C. Psychlgical develpment f the child with leukaemia: a review. J Behav Med 1979;2: Maguire GP. Psychlgical cnsequences f childhd leukaemia. J R Sc Med 1980;73: Crrespndence t Dr I A Hughes, Department f Child Health, University f Wales Cllege f Medicine, Cardiff CF4 4XN. Received 21 March Frm 1 January 1986 articles submitted fr publicatin will nt be returned if the paper is rejected unless this is requested at the time f submissin. Authrs whse papers are rejected will be advised f the decisin; the manuscripts will be kept under security fr three mnths t deal with any enquiries and then destryed by shredding. Arch Dis Child: first published as /adc n 1 September Dwnladed frm n 1 July 2018 by guest. Prtected by cpyright.