Dental abnormalities in children after chemotherapy treatment for acute lymphoid leukemia
Introduction
Acute lymphoblastic leukemia (ALL) is a hematological malignancy that predominantly affects children up to the age of 14 years. In this period, odontogenesis occurs beginning in the fourth week of uterine life and finishing around the age of 21 years. Chemotherapy and cranial radiotherapy are the treatment modality that has been widely used for ALL. However, since chemotherapy and radiotherapy are administered during the age of tooth formation, they might affect stages of odontogenesis.
The radiosensitivity of developing teeth has been demonstrated in animal models. Mature ameloblasts are permanently damaged by 10 Gy of radiation halting tooth development from the time the teeth are irradiated. Radiation damage occurs simultaneously in the bone, periodontal ligament and pulp. Radiation effects on teeth are limited to the irradiated area [1]. The nature and severity of the potential side effects of radiation on developing teeth vary with the child’s age at diagnosis, the stage of tooth development, the doses and schedules of treatment and the anatomic region treated. The principal dental abnormalities caused by radiation include destruction of the tooth germ with failure of tooth development, stunted growth of the whole tooth or root, incomplete calcification, tapering roots, etc. [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11].
Chemotherapy attempts to destroy tumor cells with minimal toxicity on normal cells. Chemotherapy is selectively toxic to actively proliferating cells by interfering with DNA synthesis and replication, RNA transcription and cytoplasmic transport mechanisms [4].
Although chemotherapy is a systemic treatment for malignant diseases, it may have effects on the oral cavity regardless of the local and type of neoplasia. The most common effects observed are: mucositis [12], [13], [14], temporary xerostomia [14], infection [14], gingival hemorrhage [13] and dental abnormalities [4].
Chemotherapy interferes with the cell cycle and with intracellular metabolism and in the teeth may thereby cause retarded dental development, microdontia, enlarged pulp chamber and root stunting [4]. These dental abnormalities are more frequent in patients with leukemia, solid tumors and other malignant diseases treated with chemotherapy only or chemotherapy and radiotherapy [4], [13], [15], [16], [17], [18], [19], [20], [21]. The nature and extent of dental sequelae vary with the type of drugs used, their doses and the frequency of treatment cycles [1], as well as the age of the patient at diagnosis [4].The abnormal maxillary (hypo-development of the jaws) and dental development (hypodontia) may be caused either by the direct effect of chemotherapeutic drugs or by an indirect effect induced by the growth hormone deficiency [22], [23].
Cyclophosphamide is a cytostatic agent used in cancer therapy that acts as an alkylating agent that cross-links the guanine bases in double stranded DNA, thus inhibiting cell division or causing mutations. Such an effect on the sensitive odontogenic mesenchymal cells apparently interferes with dentine formation and, if the lesion is sufficiently severe, with enamel formation [4], [24], [25], [26], [27], [28].
The study of the rat incisors using the colchicine technique and tritiated thymidine showed that the cells in the internal enamel epithelium were not always homogeneous regarding epithelium cell proliferative activity. In addition, this study showed that a higher number of mitoses occurred in the apical extremity of the pulp and that the highest concentration of mitoses occurred adjacent to the terminal odontogenic epithelium [29], [30]. Karim and co-worker also observed osteodentin formation in the rat incisors after adriamycin administration [31], [32].
The aim of this study is to determine the frequency of the different types of dental abnormalities in pediatric patients diagnosed with ALL who were treated with chemotherapy and with or without cranial radiotherapy.
Section snippets
Patients
Two hundred and eighty children with were admitted to the Department of Pediatrics of the Cancer Hospital in São Paulo, Brazil, from January 1980 to December 1990. One hundred and twenty-four of them who had been off chemotherapy for at least 6 months were contacted to participate in this study. Of these 76 responded and were available.
Clinical and radiographic evaluations
Clinical evaluation—dental conditions, such as caries, restorations, absent teeth and extracted teeth were evaluated. The dental abnormalities, such as
Results
The 76 children treated (43 male and 33 female), were 1–12 years old (mean age 5.1 years) in the beginning of ALL treatment. The mean age of these patients in the period of study was 10.7 years. Thirteen patients (17.1%) showed no dental abnormalities, of which eight were at the age of dental formation. The remaining 63 children (82.9%) had at least one dental abnormality. The frequency of the abnormalities was highest in GII and less in GIII and GI, respectively (Table 2).
The relationship
Discussion
Dental development may be affected by illness, trauma, chemotherapy [17], [18], [23], [24], [36] or radiation therapy [12], [16], [23], [24], [36] at any time before complete maturation.
Dental abnormalities were detected in survivors of ALL who had received multi-agent chemotherapy with and without cranial radiation.
Kaste et al. evaluated 423 children treated for ALL with and without cranial radiation. These authors observed that 50% of the patients in the “radiation” group had dental
Acknowledgements
We wish to thank Dr. Daisy Maria Fávero Salvadori for critical reading of the manuscript, Dr. Luis Marcelo Sêneda, Miss Yara Pinto Chaves, Mrs. Heloı́sa Maria Pardini Toledo, Miss Ana Emı́lia Costa da Fonseca, and Dr. José Carlos Neiva C. Silva for technical assistance. E.M. Minicucci and L.F. Lopes contributed equally to the concept, design, assembly of data, analysis of data, drafting and revising the manuscript and giving final approval. A.J. Crocci provided the statistical expertise and
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