View of Oral Health Status in Children with Acute Lymphoblastic Leukemia Undergoing Chemotherapy

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Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 6, 2021, Pages. 19197 - 19207 Received 25 April 2021; Accepted 08 May 2021.

Oral Health Status in Children with Acute Lymphoblastic Leukemia Undergoing Chemotherapy

Dr. Nupur Ninawe^1*, Dr. Priyanka Bhaje², Dr. Deoyani Doifode³, Dr. Arti Dolas⁴, Dr. Rakesh Bahadure⁵, Dr. Surendrakumar Bahetwar⁶

1*Associate Professor, Department of Paediatric & Preventive Dentistry, Government Dental College and Hospital, Nagpur, India

2 Resident, Department of Paediatric & Preventive Dentistry, Government Dental College and Hospital, Nagpur, India

3 Professor, Department of Pediatric &Preventive dentistry, Maitree dental college,Durg, Chattisgarh, India

4 Associate Professor, Department of Paediatric & Preventive Dentistry, Government Dental College and Hospital, Nagpur, India

5 Associate Professor, Department of Paediatric & Preventive Dentistry, Government Dental College and Hospital, Nagpur, India

6 Assistant Professor, Department of Paediatric & Preventive Dentistry, Government Dental College and Hospital, Nagpur, India

*[email protected]

ABSTRACT

Aim: The aim of this study was to evaluate the oral health status of children with acute lymphoblastic leukemia undergoing chemotherapy.

Objectives: a) To evaluate the gingival status of leukemic child patient.

b) To evaluate oral mucositis.

c) To evaluate the oral hygiene status due to chemotherapy.

d) To evaluate the caries status present in the children.

Materials and Methods: The present study was carried out in children of both sexes aged 3-11 years who were attending the treatment of acute lymphoblastic leukemia in the Government Medical College and Hospital, in Department of Pediatric Oncology and radiotherapy, Nagpur, Maharashtra, India, after getting approval from the ethical committee.

Unco-operative, unconscious, severely ill patients, mentally retarded, handicapped children with any other systemic disease were excluded from the study.

Result: In children with acute lymphoblastic leukemia undergoing chemotherapy the oral health status of the individual will be checked. In the oral health status Gingival inflammation, oral

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mucositis, oral hygiene status and dental caries checked.

Conclusion :Majority of the hospitalized leukemic children have history of poor oral health.

Therefore, maintenance of good oral hygiene regimen accompanied with simultaneous caries treatment should be considered mandatory to prevent any dental and periodontal infections which may interfere with general systemic conditions.

Keywords: Acute lymphoblastic leukemia, dental caries, gingival status, oral mucositis

Introduction

Leukemia, first identified by Rudolf Virchow and John Huges Bennet in 1845,¹ is a malignant disease that starts in the blood-forming tissues such as the bone marrow and causes a large number of blood cells to be produced and enter the blood stream.²Leukemia is a malignancy of the bone marrow. Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and accounts for nearly 75% of all newly diagnosed leukemia and 25% of all malignancies in childhood.³ Children between the age group of 3-5 yrs are involved and more frequent in boys than in girls, with its peak incidence at 4 years of age.⁴ Acute lymphoblastic leukemia (ALL) accounts for 1/4th of all childhood cancer and 3/4th of all malignant leukemia. Few cases are associated with inherited genetic syndromes (i.e., Down syndrome, Fanconi anemia), the cause remains largely unknown. Few risk factors associated with pathogenesis of leukemia are ionizing radiation, chemicals (e.g., benzene, heavy metals, pesticides, petroleum distillates), drugs (chemotherapeutic drugs agents, alkylating agents, and etoposide, especially when used with radiotherapy), viral infections, and genetics.³Acute lymphoblastic leukemia (ALL) is a malignant disorder resulting from the clonal proliferation of lymphoid precursors with arrested maturation.⁵ The disease can originate in lymphoid cells of different lineages, thus giving rise to B-cell or T-cell leukemias or sometimes to mixed lineage leukemia. Acute lymphoblastic leukemia was one of the first malignancies to respond to chemotherapy.⁶ Among various leukemia categories, it was the first leukemia that could be cured in a majority of children.⁷Since then, much progress has been made, in regards to prevention of oral problems in children who were undergoing cancer treatment. The most common signs and symptoms of acute lymphoblastic leukemia are anorexia, irritability, lethargy, anemia, bleeding, petechiae, fever, lymphadenopathy, hepatosplenomegaly, and bone pain and arthralgias caused either by leukemic infiltration of the perichondral bone or joint or by leukemic expansion of the bone marrow cavity leading to disability in walking in children.⁸ The most common head, neck, and intraoral manifestations of ALL at the time of diagnosis are lymphadenopathy, sore throat, laryngeal pain, gingival bleeding, and oral ulceration.

Advances in the treatment regimens, including multiagent chemotherapy and radiation therapy, have greatly increased the chances of survival.⁹The treatment modalities widely accepted for ALL are chemotherapy and a combination of chemotherapy with radiation. Radiotherapy to or near the oral cavity may cause mucositis, infection, trismus or xerostomia which further interrupts radiotherapy, inducing malnutrition or systemic infection. Combination of chemotherapy and radiotherapy may

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have an additive if not a synergistic effect on the aforementioned complications.¹⁰

The immediate effects of the chemotherapy or irradiations on the soft tissues are well documented but less is known about the effects on the oral health and developing dental tissues.^11,12 Oral cavity is the part of the body where the side effects are frequently observed. Elimination of the oral symptoms of the disease and creation of a healthy oral environment not only improves the quality of life in these patients, but also has a real impact on the ultimate survival of these patients.Total relief may always not be achieved but creation of a healthy oral condition prior to chemotherapy results in minimized undesirable side effects.¹³

The aim of this study was to evaluate the oral health status of children with acute lymphoblastic leukemia undergoing chemotherapy.

Materials and Methods

The present study was carried out in children of both sexes aged 3-11 years who were attending the treatment of acute lymphoblastic leukemia in the Government Medical College and Hospital, in Department of Pediatric Oncology and radiotherapy, Nagpur,Maharashtra, India, after getting approval from the ethical committee.

Unco-operative, unconscious, severely ill patients, mentally retarded, handicapped children with any other systemic disease were excluded from the study.

A total of 60 children of both sexes who were newly diagnosed with acute lymphoblastic leukemia and who were undergoing different phases of chemotherapy were selected for the study.Informed consent was obtained from the parents of the patients regarding dental check-up of the children.The dental status of the patients was examined with the help of mouth mirror, dental probe, torch and sterile gloves were used for the examination. The oral cavity was examined with mouth mirror and dental probe for gingival status (gingival index byLoe and Silness), mucositis (WHO oral toxicity scale), Oral hygiene status (simplified oral hygiene index) and dental caries (DMFT/ dmft index).¹⁴Dental probe was avoided during gingival examination due to chances of bleeding.Statistical analysis was done using Kruskal-Wallis test.

Results

Gingival status

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On gingival examination, it was observed that mean gingival index of ALL children undergoing chemotherapy was 0.5 (Figure 1).

Table 1 shows grading of children using Gingival index (GI)

Mucositis

The signs and severity of oral mucositis were highest in only children (5%) undergoing chemotherapy in all the stages as shown in (Table 2). Ulcers with extensive erythema associated with difficulty in swallowing were observed in 2% of the children. About 3% of the children had mucosal ulcers without difficulty in swallowing solid food. The common areas of mucositis were mainly on buccal mucosa and lips (Figure 2).

0%

10%

20%

30%

40%

50%

60%

70%

No inflammation

Mild inflammation

Moderate inflammation

Severe inflammation 63%

22%

15%

0%

Figure 1: Grading of children using Gingival index.

Gingival status grading using GI Frequency

No inflammation 63%

Mild inflammation 22%

Moderate inflammation 15%

Severe inflammation 0%

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Table 2: Distribution of children according to oral mucositis during chemotherapy

Oral mucositis %

Absent 95%

Present 5%

Oral hygiene status

On evaluation of oral health status, it was observed that only 1.7% children had poor oral hygiene. The mean value of simplified oral hygiene index (OHI-S) was 0.9 (Figure 3).

Table 3. Distribution of children according to simplified oral hygiene index

Score of OHI-S Frequency

Good 45%

Fair 35%

Poor 1.7%

0%

20%

40%

60%

80%

100%

Absent Present

95%

5%

Figure 2 : Distribution of children according to

oral mucositis during chemotherapy

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Dental caries

On dental examination, it was observed the mean DMF-T score was 0.1 and a mean def-t score of 1.2 was found in ALL children undergoing chemotherapy. DMFT index was found to be increased in 50% of the children. However, the deft index was found to be increased in 60% of the children. Since no active treatment was given during therapy only decay component i.e D was increased (Figure 4).

Table 4: Distribution of mean DMFT and deft index in children undergoing chemotherapy

DMFT deft

50% 60%

0%

10%

20%

30%

40%

50%

Good Fair Poor

45%

35%

1.70%

Figure 3: Distribution of children according to simplified oral hygiene index.

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Discussion

Acute lymphoblastic leukemia is the most common leukemia seen in children resulting from malignant transformation of immature leucocytes which start proliferating first in the bone marrow.¹Care of the oral cavity plays an important role during and after antineoplastic therapy so as to prevent the side effects of the therapy. The most common side effects of antineoplastic therapy include discomfort, sensitivity of teeth and pain, ulceration, gingival hemorrhage, dryness, impaired taste sensation and increased caries incidence.²

Gingival health is commonly affected in children with ALL as compared to healthy children. The gingival hyperplasia is one of the most common findings which is usually generalized and varies in severity. The gingiva is boggy, edematous, deep red, and may bleed easily. In the present study 63% ALL children showed no gingival inflammation whereas 22% ALL children showed mild gingival inflammation. Azher et al.² reported mild to moderate gingival inflammation, which was a contrast to the results obtained by Nasim et al.³ where a significant deterioration of the gingival condition was observed in patients undergoing chemoradiation therapy (52%). Another study conducted by Al-Mashhadane⁴ to evaluate the oral health status of children undergoing chemotherapy, it was found that there was a significant increase in gingival indices.Hegde et al.⁵ studied the periodontal health status in 120 children aged between 4 years and 10 years (90 children with ALL and 30 medically healthy controls). They observed that gingival

0%

10%

20%

30%

40%

50%

60%

70%

DMF-T def-t

50% 60%

Figure 4: Distribution of mean DMF-T and mean

def-t score

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inflammation to be more often in children with ALL as compared to healthy controls and it is more directly associated with the duration of chemotherapy.

Oral mucositis may occur as a result of both "direct" and "indirect" effects of chemotherapy on cells.The direct effect occurs due to the nonspecific effect of antineoplastic drugs on cell proliferation, maturation, and replacement.

Consequently, the renewal rate of the basal epithelium is reduced, and results in mucosal atrophy, mucositis, and ulceration.⁶

In the present study mucositis was present only in 5% of ALL children whereas the study conducted on Brazilian children with a mean age of 5 years, oral mucositis was reported in 71.4% of the children.⁷ In a similar study conducted by Pels to assess oral mucosa in children with ALL during antineoplastic therapy, lesions of the mucositis type were observed in ALL children during the period from 48 hours to 6 months, having various intensities and with periods without pathological lesions, which were related to the intensity of chemotherapy.⁸ Borbasi et al.⁹ reported oral mucositis to be the most distressing symptom experienced among patients who receive a high dose of chemotherapy for acute leukemia and bone marrow transplant.

Poor oral hygiene poses significant problems in patients undergoing chemotherapy as oral lesions are painful, cause ulcerations, and eventually result in poor nutrition, under hydration, and may create a life threat eventually.In the present study only 1.7% ALL children reported poor oral hygiene which is similar with the study conducted by Pels and Mielnik-Blaszczak who found that oral hygiene was significantly better in children with ALL than that in healthy children in the control group. The result was attributed to the oral hygiene regimen that the children were following during the cancer treatment protocol. Similarly, in a study by Pels et al., oral hygiene status was notably better and there was a decreased incidence of dental plaque in children with ALL, compared to children from the control group.¹¹ However, Al-Mashhadane conducted a study to evaluate the oral health status among children receiving chemotherapy. It was found that the chemotherapeutic agents modify the oral health and there was a significant increase in plaque and gingival indices.¹²In a study by Azher et al. more than half of the patients examined had a poor oral hygiene and needed oral care regimen for the maintenance of

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infection-free oral cavity to minimize the negative effects of chemotherapy.¹⁰ An increase in dental caries has been observed in patients with leukemia. However, dental caries does not occur due to the effect of either the disease process or radiotherapy or chemotherapy on the tooth structure. It is due to the alterations in the salivary gland, tendency to have a soft diet, change in oral microflora, and the inability to maintain oral hygiene.

In the present study, DMFT index was found to be increased in 50% of the children.

However, the deft index was increased in 60% of the children. Since no active treatment was given during therapy only decay component i.e D was increased.

Similarly, study conducted by Dholam et al showed 33% increase in DMFT/deft in ALL children.¹²Dens et al. conducted a study and found a significantly higher caries prevalence. Hegde et al. also observed higher caries prevalence in ALL children than the healthy control group. Similarly, Nasim et al. observed a high decayed, missing, and filled teeth (DMFT) in leukemic children who were under treatment. In the Current study, it was found that number of decayed teeth in primary dentition was greater than that in permanent dentition which is in accordance with study conducted by Azher et al. This finding could be due to inadequacy in manual dexterity in the early stages and more prolonged time during which the primary teeth were exposed to the insult of bacterial plaque. However, Maciel et al. found no significant differences in DMFT scores between leukemic children and the controls. This may have been due to the oral hygiene instructions that the multidisciplinary team gave these children and to the redoubled care of parents during treatment. Likewise, Cubukc and Günes reported no significant difference in the caries experience before and after the initiation of chemotherapy in children with ALL.

In the present study more than half of the patients examined needed oral care regimen for the maintenance of infection-free oral cavity, to minimize the negative effects of chemotherapy. Establishment of good oral hygiene in these patients becomes difficult due to their small age and debilitating nature of the disease which

prevents performance of good oral hygiene.

The limitations of this study were the small study population and absence of a healthy control group which prevented drawing of a more definitive conclusion and

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comparison of the results with those of other studies.

Conclusion

In literature, majority of the hospitalized leukemic children have history of poor oral health. Therefore, maintenance of good oral hygiene regimen accompanied with simultaneous caries treatment should be considered mandatory to prevent any dental and periodontal infections which may interfere with general systemic conditions.

Disclosures

No financial support was taken from outside or from any research institute for the study.

Acknowledgement

It was great pleasure to take up this project with and my special thank you to the Cancer and Radiotherapy department and specially the children for their co-operation in the study.

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