SCIENTIFIC ARTICLE

Disturbances in the oral cavity in pediatric long-term survivorsafter different forms of antineoplastic therapyMargareta N~isman, DDS Olle Bj6rk, MD, PhD Stefan S6derh~ll, MD, PhDOlle Ringd6n, MD, PhD G6ran Dahll6f, DDS, PhD

AbstractOral health and disturbances in dental development were studied in long-term survivors after antineoplastic therapy. Fifty-

seven children treated with combination chemotherapy and 19 children treated with total body irradiation (TBI) prior to bonemarrow transplantation (BMT) were examined. The variables studied were dental caries, salivary flow, salivary microbialcounts, enamel disturbances, and disturbances in dental development. The results showed no increased caries experience inchildren treated with BMT or chemotherapy compared with controls. Children treated with BMT had a significantly lowersalivary secretion rate of O.7 ~0.4 ml/min, compared with 1.1 ~_ 0.5 in the chemotherapy group, and 1.3 S0.6 in the control group(P < 0.05). The clinical examination showed equal numbers of teeth affected by disturbances in enamel mineralization in theBMT and chemotherapy groups. A mean 15.9 ~ 8.2 teeth were affected by disturbances in root development in the BMT groupcompared with 1.2 ~ 1.6 in the chemotherapy group (P < 0.001). The results show that children who are long-term survivorsof pediatric malignant diseases exhibit a wide range of disturbances in the oral cavity. In this study the most severe disturbancesare found in children treated with total body irradiation prior to BMT. (Pediatr Dent 16:217-23, 1994)

IntroductionAdvances in treatment of malignancy in childhood

have resulted in an increasing number of long-termsurvivors. The treatments include multiagent chemo-therapy alone or in combination with radiotherapy orsurgery. Bone marrow transplantation (BMT) is nowan established therapy for patients with malignant andnonmalignant disorders.

The immediate effects of chemotherapy and irradia-tion on soft tissues are well documented, but less isknown about the long-term effects on oral health anddeveloping dental tissues2 In a study by Welbury, etal., 2 children treated for leukemia or solid tumors hadsatisfactory dental health with no abnormalities in den-tal caries or periodontal disease. On the other hand, ithas been shown that children receiving antineoplastictherapy had significantly higher mean decayed, miss-ing and filled surface (dmfs) scores compared controls.3

Regarding salivary function, Jones, et ale4 found thatsalivary flow rates and levels of mutans streptococcidecreased after pretransplant cytoreductive therapyand post-transplant prophylactic antibiotic therapy inadult patients treated with BMT. Normal levels re-turned with time after the patients left the protectedenvironment. Lactobacilli counts were not affected.Brown, et al. 5 found increased numbers of mutans strep-tococci and lactobacilli in irradiated patients treatedfor head and neck cancers several years after therapy.

Concerning the effect on dental development,Rosenberg, et al. 6 reported tha t in a group of long-termsurvivors of pediatric acute lymphoblastic leukemia

treated with chemotherapy, 5 of 17 patients exhibitedaltered dental root development with a marked short-ening of premolar roots. Children less than 5 years ofage treated with combination chemotherapy and 24 Gycranial irradiation exhibited disturbances in dental andcraniofacial development/Dahll6f, et al. 8 found thatall patients conditioned with total body irradiation (TBI)before BMT exhibited severe disturbances in dentaldevelopment.

The aim of this investigation was to study oral healthand disturbances in dental development in childrenwho are long-term survivors after treatment with che-motherapy or BMT.

Methods and materialsPatients

BMT group. Nineteen children (8 boys and 11 girls)younger than 12 years old treated with BMT9, 10 atHuddinge Hospital who survived more than 3 yearswere selected for this study. Mean age at the bonemarrow transplantation was 6.5+ 3.5 years. Fifteen chil-dren were treated for acute leukemia, one for a B-celllymphoma, three for Gaucher’s disease, and one for asevere combined immunodeficiency. The preoperativeconditioning before BMT in patients with malignantdiseases, immunodeficiency, and Gaucher’s diseaseincluded both cyclophosphamide and TBI given as asingle dose of 8-10 Gy. In patients with metabolic dis-orders, cyclophosphamide was combined with TBI (7Gy) in two patients and busulfan (16 mg/kg) in patients.11 To prevent or modify graft-versus-host dis-ease (GVHD), methotrexate (MTX) alone or in combi-nation with cyclosporine (CSA) were given for 1 year

Pediatric Dentistry: May/June 1994 -Volume 16, Number 3 217

after BMT.~2 Acute GVHD was treated withprednisolone in combination with azathioprine or CSA.During the aplastic period the children rinsed the oralcavity twice daily with a 0.1% chlorhexidine solution,nystatin 4x100,000 IU/ml, and 2x0.025% sodium fluo-ride solution. Follow-up examinations were performedat the department of pediatric dentistry, 3, 6, and 12months after BMT, and thereafter on a yearly basis. Themean follow-up time after BMT, was 5.4 years (range3.0-8.6). The children and their parents received in-structions in preventive dental care and individualizedfluoride prophylaxis based on assessment of caries riskfactors. The program consisted of brushing with fluo-ride toothpaste twice daily, taking fluoride tablets, andapplying fluoride varnish every third month. Childrenwith low salivary secretion rates were given treatmentwith sodium fluoride gel 0.1% in customized trays.

Chemotherapy group. Fifty-seven children (33 boysand 24 girls) younger than 12 years old treated formalignant diseases at the department of pediatriconcology, Karolinska Hospital who survived more than3 years after therapy were examined. Twenty-one weretreated for acute leukemia, nine for lymphoma, six forWilm’s tumor, six for rhabdomyosarcoma, three forhistiocytosis-X, three for neuroblastoma, three for op-tic glioma, three for other CNS-tumors, and three forother tumors. The mean age at diagnosis of their malig-nant disease was 5.1 + 3.3 years. The mean follow-uptime between the diagnosis and the dental examinationwas 6.6 years (range 3.0-17.5). The children were treatedaccording to protocols including combinations of che-motherapy and, in some cases, radiotherapy or sur-gery. None of the children received radiotherapy withthe teeth or jaws in the radiation field. Nine of 21 chil-dren with acute leukemia received cranial irradiation.During hospitalization, the oral cavity was rinsed dailywith a 0.25% hydrogen peroxide solution. These chil-dren were not examined by adentist during hospitaliza-tion and received no indi-vidual fluoride prophylaxisduring followup.

Control groups. For eachchild treated with BMT, anage- and sex-matched control(N = 19), was selected frompatients receiving their den-tal treatment at the depart-ment of pediatric dentistry.They lived in a low-fluoridearea and received no addi-tional fluoride prophylaxisapart from brushing twicedaily with fluoride tooth-paste.

For the radiographic ex-amination, panoramic radio-

graphs were obtained from the patient files at the de-partment of orthodontics (N = 76), selecting only chil-dren with a moderate degree of malocclusion. The con-trols were matched with respect to age and sex.

Dental caries. All children were examined clinicallyand bite-wing radiographs were exposed. Decayed andfilled surfaces were recorded clinically according toKoch.~3 Proximal caries was recorded on bite-wing ra-diographs when a radiolucency reached into the den-tine. A radiolucency limited to the enamel was definedas initial caries.

Salivary factors. Paraffin-stimulated whole salivawas collected during 5 min between 09.00-11.00 hr andthe salivary secretion rate was determined. The buffercapacity was estimated using the Dentobuff® (OrionDiagnostica, Espoo, Finland) method.14 The number ofmutans streptococci per ml saliva was estimated ac-cording to Gold, et a125 and the number of lactobacilliper ml saliva was determined according to theDentocult ® (Orion Diagnostica, Espoo, Finland)method)6

Enamel disturbances. All teeth were dried andenamel defects on the buccal and palatal surfaces, theincisal edges, and the cuspal and occlusal surfaces wererecorded. Only permanent teeth were examined. Clas-sification of the enamel defects was based on the indexof developmental defects in dental enameU7

Disturbances in dental development. A panoramicradiograph was available from all children subjected toantineoplastic therapy. Disturbances in dental devel-opment were analyzed using the Dahll6f, et al. method28The disturbances were classified into five major groups:1) arrested root development and premature apicalclosure, 2) arrested root development with short "v"-shaped roots, 3) enamel hypoplasia, 4) microdontia,and 5) aplasia. The panoramic radiographs were blindedby group for the examiner.

Table 1. Caries experience in patients

VariablesChemotherapy BMT Control"Group (N = 57) Group (N = 19) Group (N = 19)x SD x SD x SD

Age at examination 11.7 4.7 11.9 3.9 11.9 3.9Age at diagnosis 5.1 3.3 6.5 3.5 -- --

Permanent dentitionDFS* 5.1 9.7 3.5 2.8 2.7 3.5DS 1.3 4.2 0.6 0.3 0.3 0.6CP* 2.3 3.8 3.4 5.2 4.3 5.7

Deciduous dentitiondfs 5.4 6.4 4.1 4.0 4.3 5.0ds 2.7 5.6 0.6 0.7 0.6 1.2ci 1.6 2.7 0.6 1.5 1.2 2.3

¯ No statistically significant differences were found using Student’s t-test; t D-decayed, F-filled,S-surfaces; * CI-caries initial.

218 Pediatric Dentistry: May/June 1994 -Volume 16, Number 3

Table 2. Salivary microbial counts and buffer capacity

Variables

AChemotherapyGroup (N = 57)

N

BBMT

Group (N = 19)N

CControl

Group (N = 19)N

Significance"

A-B B-C A-C

Mutans streptococci(no. children > 106/ml saliva) 22/52

Lactobacilli(no. children > 106/ml saliva) 16/53

Buffer capacity(no. children pH < 4.5) 18/50

5/19 1/23 n.s. n.s. **

6/19 1/23 n.s. n.s.

8/19 1/23 n.s. **

¯ Chi-square test, levels of significance: * P< 0.05, ** P< 0.01.

All clinical examinations and ratings of enamel anddental disturbances were performed by one examiner(MN).

ResultsClinical variables

Dental caries. As shown in Table 1 there were nostatistically significant differences in caries experiencebetween the three groups, for the primary or the per-manent dentition. The mean number of decayed andfilled surfaces (DFS) in the permanent dentition in thechemotherapy group was 5.1 (range 0-51) and DS was1.3 (range 0-4). The children treated with BMT had mean DFS 3.5 (range 0-14) and mean DS 0.6 (range 6). The control group had a mean DFS 2.7 (range 0-13)and a mean DS 0.3 (range 0-2). Twenty-one percent the children in the chemotherapy group were cariesfree, 4% in the BMT group, and 13% in the controlgroup. In the chemotherapy group the mean DFS inchildren with hematological malignancies was 6.5 +12.2 compared with 3.6 + 6.0 in those treated for solidtumors. The difference in caries experience was notstatistically significant.

Salivary factors. Children treated with BMT had asignificantly lower salivary secretion rate 0.7 + 0.4 ml/min, compared with children treated with chemo-therapy, 1.1 + 0.5 ml/min (P < 0.05), and the healthy

controls 1.3 + 0.6.(P < 0.05). Mutans streptococci andlactobacilli could be detected from all patients in thethree groups examined. As shown in Table 2, a signifi-cantly higher proportion of the children treated withBMT (P < 0.01) or chemotherapy (P < 0.05) harboredhigh counts of mutans streptococci compared with con-trols, and a higher proportion of the children in thechemotherapy and BMT groups exhibited a low buffercapacity of the saliva (P < 0.01).

Disturbances in enamel mineralization. A meannumber of 4.1 + 5.0 teeth were affected by disturbancesin enamel mineralization in the chemotherapy groupcompared with 4.6 + 4.6 in the BMT group, which issignificantly higher than healthy controls, 0.7 + 1.4 (P 0.05). As can be seen in Table 3, white/cream coloredopacities were most commonly diagnosed in all threegroups, followed by yellow/brown opacities. Six chil-dren in the BMT group, treated with TBI between 1.0and 11.6 years, did not exhibit any clinical signs ofenamel disturbances.

Roentgenological variablesDisturbances in dental development were diagnosed

on panoramic radiographs (Table 4). In the controlgroup no disturbances were found. Eighteen of 19 pa-tients receiving TBI prior to BMT exhibited arrestedroot development and premature apical closure com-

Table 3. Prevalence of disturbances in enamel mineralization in the permanent dentition

A B CChemotherapy BMT Control"Group (N = 50) Group (N = 17) Group (N = 17)N % N % N %

Enamel defect

White/cream opacity 34 68" 10 59 5 29

Yellow/brown opacity 13 26 7t 41 1 6

Fine white lines 8 16 5 29 1 6

Hypoplasia 4 8 2 12 0 0

¯ Chi-square test, level of significance: white/cream opacity A vs C P < 0.05.

* Yellow/brown opacity B vs C P< 0.05.

pared with eight of 30 pa-tients receiving chemo-therapy (P < 0.001). All typesof disturbances were morefrequent in children treatedwith BMT compared withthose treated with chemo-therapy, except for enamelhypoplasias (Figs 1 a, b).Children treated with BMTexhibited a mean number of15.9 + 8.2 teeth with distur-bances in root developmentcompared with 1.2 + 1.6 teeth

Pediatric Dentistry: May/June 1994- Volume 16, Number 3 219

Table 4. Number of patients exhibiting disturbances in dental development diagnosedon panoramic radiographs

Treatment

Hematologicalmalignancies

Solid tumors

Bone marrowtransplantation

Age atdiagnosis

(years)x+SD

6.2 ±1.4

5.4 ± 2.3

6.513.5

Type of disturbances'

r

r-8/30

I 2/27 -,* *

Us/19^

//

r2/30

I 2/27 -i* *\ *I-11/19-?

Ill

r-6/30

J. 1/27-,

Ls/19^

IV

p3/30

i 4/27 -|

V

r-3/30

1 8/27 -,h * /i

L js'* Classification of disturbances: I) arrested root development with short "v"-shaped roots, II) arrested root

development with premature apical closure, III) enamel hypoplasia, IV) microdontia, and V) aplasia.f Chi-square test: * P < 0.05; ** P < 0.01; *** P < 0.001; n.s. = nonsignificant.

in the chemotherapy group (P < 0.001) and 0.4 ± 0.7teeth in the control group (P < 0.001). Table 5 shows thedistribution of dental disturbances in individual BMTpatients treated with TBI. Children younger than 5.4years of age at TBI show the most extensive and severedisturbances.

DiscussionThe results of this study indicate that children who

are long-term survivors after pediatric malignant dis-eases exhibit a wide range of disturbances in the oralcavity. Children who were treated with TBI prior toBMT exhibited more severe and extensive disturbancesin dental development than children treated with che-motherapy only.

The preventive regime combining the use of fluo-

ride and chlorhexidine wassuccessful in controllingcaries in the BMT-treatedchildren. The mean numberof new DF surfaces washigher in the chemotherapygroup than the BMT group,but the difference did notreach statistical signifi-cance. The children treatedwith chemotherapy did notreceive any additional fluo-ride prevention during in-duction therapy and followup. Conflicting results havebeen reported previouslyconcerning the caries expe-

rience in children treated for malignant diseases. Theresults of this study agree with Nunn, et al.19 andMaguire, et al.,20 who compared treated children to theirsiblings and found no differences in dental caries, gin-givitis, or oral hygiene. On the other hand, Pajari, et al.3

and Purdell-Lewis, et al.21 reported an increased dmfsand DMFS values, although no bite-wing radiographswere assessed in their studies. In contrast to Pajari, etal.3 no increased caries activity could be found in chil-dren with hematological malignancies compared withthose who had solid tumors.

The salivary secretion rate was significantly reducedin children conditioned with TBI before BMT comparedwith the chemotherapy group and controls. This is incontrast to a study in adults4 subjected to 10.2 Gyfractioned TBI before BMT. In a cross-sectional f ollowup

Fig 1A. Panoramic radiograph of an 8-year-old boy diagnosed with a B-cell lymphoma at 4.2 years of age showing short"v"-shaped roots of the first permanent molars.

220 Pediatric Dentistry: May/June 1994 - Volume 16, Number 3

2.2 years after TBI, no statistically significant differ-ences in salivary secretion rate were found comparedwith pre-TBI values. Studies on salivary secretion inchildren treated for malignant diseases are few. Fromm,et al.22 studied late effects in 20 children treated for softtissue sarcomas of the head and neck. Severely reducedparotid secretory activitytended to follow radiationdoses > 45 Gy to >50% of theparotid gland volume. Eightof 11 parotid glands receiv-ing these radiation dosesfailed to secrete. In our study,eight of 19 children had a sali-vary secretion rate < 0.5 ml/min. Contrary to our previ-ous report,23 3.4 years afterBMT a significantly reducedsalivary secretion rate wasfound in children receiving a10 Gy single dose TBI. Theresults of this study indicatesthat 10 Gy TBI is the primarycausative agent to the reduc-tion in salivary flow.

Thirty-two percent of thechildren treated with BMTexhibited high counts ofmutans streptococci. A shiftin the microbial flora hasbeen seen in patients who re-ceive radiation therapy withan increased number ofmutans streptococci and lac-tobacilli in saliva.5-24"26 Apply-ing 1 % chlorhexidine gel re-

duces the absolute bacterial countsof mutans streptococci and lacto-bacilli. One week after terminationof therapy, the microbial countsalready snowed a rapid recoveryin patients treated with irradia-tion.20 In agreement with a previ-ous study,27 the buffer capacity ofstimulated whole saliva was lowerin children in both treated groupsthan in controls.

Disturbances in enamel miner-alization were frequent in thesegroups. No statistically significantdifference was found between chil-dren receiving only chemotherapycompared with those receiving 10Gy TBI during the period of toothformation. The clinical appearanceof the disturbances in enamel min-eralization are minor. In agreement

with Pajari, et al.28 and Nunn, et al.,19 white/creamopacities were the most often diagnosed enamel le-sions.

Cytotoxic drugs have a short half-life in the humanbody and the drugs are metabolized or excreted fromwithin 24 hr up to a few days. Thus, the effect on fully

Table 5. Disturbances in dental development diagnosed on panoramic radiographs in 19children conditioned with total body irradiation before bone marrow transplantation

Fig 1 B. An 11 -year-old boy diagnosed with acute lymphoblastic leukemia at 4.8 yearsof age, treated with BMT at 5.4 years of age exhibiting severe disturbances in dentaldevelopment.

Patient

123456789

10111213141516171819

Age atBMT

(years)

1.01.72.22.62.83.24.35.45.87.28.18.19.29.39.7

10.110.110.711.6

Age atexam,(years)

9.07.87.35.55.8

11.812.311.610.710.314.213.115.012.316.714.116.216.717.6

Type of disturbances*

Diagnosis'

AMLALLCMLALL

GaucherAMLALLALLAML

LymphomaAMLAMLALLALL

GaucherImmunodef.

ALLAMLALL

/

66642413104

12549108443

;/

6424-241018-

23-3--8--

Ill

8682-4---11-1------

IV

7-2561521—

423_-4-1

V

—293-3421

42--86---

* AML = acute myelogenous leukemia, ALL = acute lymphoblastic leukemia, CML = chronicmyelogenous leukemia.

+ Classification of disturbances: I) arrested root development with short "v"-shaped roots, II) arrested rootdevelopment with premature apical closure, III) enamel hypoplasia, IV) microdontia, and V) aplasia.

Pediatric Dentistry: May/June 1994 - Volume 16, Number 3 221

differentiated cells as ameloblasts and odontoblasts willonly be transient, and undifferentiated surviving cellswill continue to differentiate. 29, 30 Radiation therapy aschemotherapy induces qualitative changes in enamelbut also -- to a greater degree -- quantitative changesas seen in the increased prevalence of disturbances inroot formation and microdontia in children treated withTBI, indicating that the cells in the Hertwig’s root sheathare extremely radiosensitive. 31 The severity and extentof disturbances in tooth formation are related to age atTBI. Children treated between 3.2 and 5.4 years of ageexhibited the most severe disturbances. At this ageinterval, root formation is in initial stage for all perma-nent teeth except the second and third molar. The re-sults also indicate that there are individual differencesbetween patients -- the same treatment results in avariable number of teeth affected and severity of thelesions in different individuals. These results supportSonis, et al. 7 who showed that children younger than 5years old who had received cranial irradiation in com-bination with combination chemotherapy exhibiteddisturbances in dental development -- mainly in rootdevelopment. The teeth affected were the posteriormaxillary teeth. It is possible that previous cranial irra-diation to nine patients in the chemotherapy groupmay have affected the results.

ConclusionsIn conclusion, the results of this study showed:1. No increased caries prevalence in children sub-

jected to anti-neoplastic therapy2. Children treated with TBI during BMT exhib-

ited a decreased salivary secretion rate3. Enamel disturbances were equally distributed in

children treated with chemotherapy only or TBI4. Children treated with TBI exhibited severe dis-

turbances in root development.Furthermore our results showed that children who

completed antineoplastic therapy should be subjectedto follow-up examinations with specific attention todisturbances in growth and development, but also tocaries prevention, salivary function, and changes in theoral microflorao

This study was supported by grants from the Swedish Children’sCancer Foundation.

Dr. N/isman is a postgraduate student, Dr. Dahll6f is associate profes-sor, department of orthodontics and pediatric dentistry, Dr. Bj6rk isassociate professor and chairman, Dr. S6derh~ill is associate profes-sor, pediatric cancer unit, Dr. Ringd6n is professor, department ofclinical immunology, all at Karolinska Institute, Stockholm, Sweden.

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3. Pajari U, Larmas M, Lanning M: Caries incidence and preva-lence in children receiving antineoplastic therapy. Caries Res22:318-20, 1988.

4. Jones LR, Toth BB, Keene HJ: Effects of total body irradiationon salivary gland function and caries-associated oral micro-flora in bone marrow transplant patients. Oral Surg Oral MedOral Pathol 73:670-76, 1992.

5. Brown LR, Dreizen S, Handler S, Johnston DA: Effect of radia-tion-induced xerostomia on human oral microflora. J Dent Res54:740-50, 1975.

6. Rosenberg SW, Kolodney II, Wong GY: Altered dental rootdevelopment in long-term survivors of pediatric acute lympho-blastic leukemia: a review of 17 cases. Cancer 59:1640-48,1987.

7. Sonis AL, Tarbell N, Valachovic RW, Gelber R, Schwenn M,Sallan S: Dentofacial development in long-term survivors ofacute lymphoblastic leukemia: a comparison of three treat-ment modalities. Cancer 66:2645-52, 1990.

8. Dahll6f G, Forsberg C-M, Ringd6n O, Bolme P, Borgstr6m B,N/isman M, Heimdahl A, Mod6er T: Facial growth and mor-phology in long-term survivors after bone marrow transplan-tation. Eur J Orthod 11:332-40, 1989.

9. Thomas ED, Storb R, Sclift RA, Johnson FL, Meiman PE, LernerKG, Glucksberg H, Buckner CD: Bone marrow transplantationI and II. N Engl J MEd 292:832-43, 895-902, 1975.

10. Ringd6n O, Aschan J, Bostr6m L, Dahll6f G, Tollemar J, PaulinT, Gahrton G, Groth CG, Klaesson S, Lindqvist R, Ljungman P,L6nnqvist B, Persson U, Shanwell A, Winiarski J: Allogeneicbone marrow transplantations at Huddinge hospital and strat-egies to improve survival. In Clinical Transplants 1990. TerasakiP, ED. Los Angeles: UCLA, 1991, pp. 175-88.

11. Ringd6n O, Groth CG, Aschan J, Bolme P, Ljungman P,L6nnqvist B, Malm G, M~nsson JE, Shanwell A, SvennerholmL, Tollemar J: Bone marrow transplantation for metabolic dis-orders at Huddinge hospital. Transplant Proc 22:198-202,1990.

12. Ringd6n O, Horowitz MM, Sondel P, Gale RP, Biggs JG,Champlin RE, Deeg HJ, Dicke K, Masaoka T, Powles RL, RimmAA, Rozman C, Sobocinski KA, Speck B, Zwaan FE, BortinMM: Methotrexate, cyclosporine or both to prevent graft-ver-sus-host disease after HLA-identical sibling bone marrow trans-plants for early leukemia. Blood 81:1094-1101, 1993.

13. Koch G: Effect of sodium fluoride in dentifrice and mouthwashon incidence of dental caries in schoolchildren. Odontol Revy18: (suppl 12) 1-125, 1967.

14. Frostell G: A colourimetric screening test for evaluation of thebuffer capacity of saliva. Swed Dent J 4:81-86, 1980.

15. Gold OG, Jordan HV, van Houte J: A selective medium forStreptococcus mutans. Archs Oral Biol 18:1357q54, 1973.

16. Larmas M: A new dip-slide method for the counting of salivarylactobacilli. Proc Finn Dent Soc 71:31-35, 1975.

17. Ainamo J, Cutress TW: An epidemiological index of develop-mental defects of dental enamel (DDE Index). Int Dent J 32:159-67, 1982.

18. Dahll6f G, Barr M, Bolme P: Disturbances in dental develop-ment after total body irradiation in bone marrow transplantrecipients. Oral Surg Oral Med Oral Pathol 65:41-44, 1988.

19. Nunn JH, Welbury RR, Gordon PH, Kernahan J, Craft AW:Dental caries and dental anomalies in children treated by che-motherapy for malignant disease: a study in the north of En-gland. Int J Paediatric Dent 1:131-35, 1991.

20. Maguire A, Craft AW, Evans RGB, Amineddine H, Kernahan J,Macleod RI, Murray JJ, Welbury RR: The long-term effects oftreatment on the dental condition of children surviving malig-nant disease. Cancer 60: 2570-75, 1987.

21. Purdell-Lewis DJ, Stalman MS, Lecuw JA, Humphrey GB,Kalsbeek H: Long-term results of chemotherapy on the devel-oping dentition: caries risk and developmental aspects. Com-munity Dent Oral Epidemiol 16:68-71, 1988.

22. Fromm M, Littman P, Raney B, Nelson L, Handler S, DiamondG, Stanley C: Late effects after treatment of twenty childrenwith soft tissue sarcomas of the head and neck. Cancer 57:2070-76, 1986.

23. Dahll6f G, Heimdahl A, Bolme B, L6nnqvist B, Ringd6n O: Oral

222 Pediatric Dentistry: May/June 1994- Volume 16, Number 3

condition in children treated with bone marrow transplanta-tion. Bone Marrow Transplant 3:43-51, 1988.

24.Epstein JB, Loh R, Stevenson-Moore P, McBride BC, Spinelli J:Chlorhexidine rinse in prevention of dental caries in patientsfollowing radiation therapy. Oral Surg Oral Med Oral Pathol68:401-5, 1989.

25.Keene HJ, Fleming TJ: Prevalence of caries-associated microf-lora after radiotherapy in patients with cancer of the head andneck. Oral Surg Oral Med Oral Pathol 64:421-26, 1987.

26.Llory H, Dammron A, Gioanni M, Frank RM: Some populationchanges in oral anaerobic microorganisms, Streptococcusmutans and yeasts following irradiation of the salivary glands.Caries Res 6:298-311, 1972.

27.Schum CA, Izutsu KT, Molbo, DM, Truelove EL, Gallucci B:Changes in salivary buffer capacity in patients undergoing can-cer chemotherapy. J Oral Med 34:76-80, 1979.

28.Pajari U, Lanning M: Prevalence and location of enamel opaci-ties in children after antineoplastic therapy. Community DentOral Epidemiol 16:222-26, 1988.

29.Rubin P: Late effects of chemotherapy and radiation therapy. Anew hypothesis. Int J Radiation Oncology Biol Phys 10:5-34,1984.

30.Goho C: Chemoradiation therapy: effect on dental develop-ment. Pediatr Dent 15:6-12, 1993.

31.N~isman M, Dahll6f G, Mirabdolbaghi M, Hammarstr6m L: Theeffect of cyclophosphamide on dental development in rat mo-lars. Scand J Dent Res (accepted).

The American Board of Pediatric Dentistry is pleased to announcethe following new Diplomates:

Loren D. Alves ~ Harker Heights, TexasA. Scott Anderson ~ Roanoke, VirginiaDwight J. Ashby ~ Harrisburg, PennsylvaniaCarl O. Atkins, Jr. - Richmond, VirginiaSteven R. Aylard - Napa, CaliforniaAnn T. Azama - San Francisco, CaliforniaD. Gregg Baker ~ Idaho Falls, IdahoBrenda Bohaty ~ Kansas City, MissouriRichard L Cohen ~ Ft. Leavenworth, KansasThomas L. Cox ~ Virginia Beach, VirginiaDennis Carreras ~ APO APPeter A. Caso ~ West Point, New YorkChifan Cheng-Belmont ~ Urbana, IllinoisBrian D. Collins ~ Dallas, TexasRobert A. Davis ~ Beaver, PennsylvaniaMurray Dock ~ Cincinnati, OhioEllen Fo Drazner ~ Bethany, ConnecticutJames J. Ford - Eugene, OregonSheryl E. Goltra ~ North Charleston, South CarolinaPatrice E. Greene ~ Savannah, GeorgiaRonald L. Grothe - Lee’s Summit, MissouriWilliam J. Heimann - Phoenix, ArizonaJeanne A. Hibler ~ Park City, UtahSharon D. Hill ~ Dallas, TexasWilliam C. Horton ~ APO AEJose E. Ibanez-Pabon ~ Travis AFB, CaliforniaJohnny Johnson, Jr. ~ Palm Harbor, FloridaJohnna Jorgensen ~ Gallipolis, OhioJames L. Kozik ~ Parma, OhioSteven E. Krauss ~ Woodmere, New YorkJacob K. Lee ~ Loma Linda, California

Penelope J. Leggott ~ Seattle, WashingtonBarry I. MacDonald ~ Yorktown, VirginiaGeorge B. MacMaster ~ Alpharetta, GeorgiaCurtis L. Mathis, Jr. - Waco, TexasKraig C. McKee ~ Pittsburgh, PennsylvaniaTimothy E. McNutt, Sr. ~ Nashville, TennesseeAlton G. McWhorter ~ Dallas, TexasBarbara J. Merlo - Munster, IndianaMark L. Meyer ~ Winston-Salem, North CarolinaAnthony F. Morelli ~ LaGrange, IllinoisMary M. O’Connor N San Diego, CaliforniaKenneth B. Rogers ~ Winter Haven, FloridaMichael S. Rosenbaum ~ Dresher, PennsylvaniaBrian J. Sanders ~ Indianapolis, IndianaDavid E. Shapter ~ Erie, PennsylvaniaDaniel J. Shoemaker ~ Middletown, ConnecticutMaureen T. Short ~ Diamond Bar, CaliforniaJohn M. Smith N Parma Heights, OhioChester K. Smyth ~ Salt Lake City, UtahRoberto Solares ~ Mexico City, MexicoEdward A. Souza ~ Ft. Riley, KansasWayne E. Svoboda ~ Clarksville, TennesseeFredric S. Tatel - Glenwood, IllinoisLuke Y. Teruya ~ Kaneohe, HawaiiRichard J. Thill ~ Anaheim, CaliforniaJohn B. Thornton ~ Birmingham, AlabamaWayne Turk ~ Scarsdale, New YorkBradley J. Vance ~ Tacoma, WashingtonR. Michael Weaver ~ Fayetteville, North CarolinaTheresa M. White ~ Oklahoma City, OklahomaB. Gene Whitehead ~ Clearwater, Florida

Pediatric Dentistry: May/June 1994 - Volume 16, Number 3 223