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 Table of Contents  
ORIGINAL RESEARCH REPORT
Year : 2021  |  Volume : 18  |  Issue : 2  |  Page : 103-108

Pattern of postchemotherapy-associated complicatioins in a paediatric oncology service in Lagos: An observational study


1 Department of Pediatrics, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
2 Department of Pediatrics, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria

Date of Submission23-Jun-2020
Date of Acceptance14-Sep-2020
Date of Web Publication24-Apr-2021

Correspondence Address:
Dr. Adeseye Michael Akinsete
Department of Pediatrics, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Idi-Araba, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcls.jcls_54_20

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  Abstract 


Background: Globally, there is an increase in the number of pediatric oncology cases with significant morbidity and mortality in the low to middle income countries (LMIC) despite improved survival in the resource endowed nations. The increase in survival is largely due to the revolutionary use of multi strategy therapeutic interventions like chemotherapy, immunotherapy, surgery and radiotherapy. These modalities are however fraught with several complications. AIM The aim of this study was to prospectively observe and document the common complications following treatment of childhood cancers in a tertiary pediatric oncology unit in a resource constrained setting. Methods: This was a longitudinal observational study over a three-year period involving children with various cancers. Ethical approval was obtained from the hospital's human, research and ethics committee. A questionnaire was used to obtain socio-demographic data as well as details of adverse events encountered. Results: A total of 100 children enrolled in the study with acute lymphoblastic leukaemia been the commonest cancer. Gastrointestinal adverse events were the most common in the study cohort with alopecia rarely reported. Conclusion: Increased awareness of the common complications in this environment and prophylactic medications may improve the care of children post chemotherapy thereby reducing overall morbidity and cost of care.

Keywords: Chemotherapy, complications, pediatric oncology


How to cite this article:
Akinsete AM, Fakile UO, Nwobi EI, Awofeso OM. Pattern of postchemotherapy-associated complicatioins in a paediatric oncology service in Lagos: An observational study. J Clin Sci 2021;18:103-8

How to cite this URL:
Akinsete AM, Fakile UO, Nwobi EI, Awofeso OM. Pattern of postchemotherapy-associated complicatioins in a paediatric oncology service in Lagos: An observational study. J Clin Sci [serial online] 2021 [cited 2021 May 17];18:103-8. Available from: https://www.jcsjournal.org/text.asp?2021/18/2/103/314449




  Introduction Top


Globally, there is an increase in the number of pediatric oncology cases with more significance in the low to middle-income countries (LMICs).[1] Despite the improved outcomes recorded in the more advanced countries, morbidity and mortality associated with pediatric oncology is still high in the LMIC.[2] The increase in survival is largely due to the revolutionary use of multistrategy therapeutic interventions such as chemotherapy, immunotherapy, surgery, and radiotherapy. However, these treatment modalities are associated with complications which may be severe and life threatening. In the more advanced societies, these complications are easily managed by the highly developed oncology units with support infrastructure. Furthermore, the aim of newer therapy is targeted interventions that reduce collateral damage and adverse effects.

Unfortunately, most of these newer treatment strategies are not available in resource-constrained settings and LMICs survive on the use of most of the older cytotoxic medications with numerous adverse effects. Multiagent treatment strategies for cancers usually attack rapidly dividing cells in the oral mucosa, bone marrow, and hair follicle causing collateral damage to healthy tissue.[3]

The adverse effects seen in children posttreatment with chemotherapy range from oral mucositis to severe central nervous system manifestations.[4],[5] Although these findings have been largely documented in developed countries, it is unclear if the same effects are seen in pediatric oncology settings in Nigeria because of the paucity of data.

This study was, therefore, designed to document the common adverse effects following chemotherapy, the stage of therapy with the most adverse effects, and the mortality following these events at a university teaching hospital in an LMIC.


  Methods Top


This was a longitudinal observational study conducted at the Lagos University Teaching Hospital from January 2015 to December 2017 at the Pediatric Oncology Unit of the hospital. Ethical approval was obtained from the Hospital's Health, Research, and Ethics committee. All patients who gave consent as well as assent for children older than 7 years were recruited into the study. A total of 100 patients consented to the study and were recruited. Demographic data, histologic diagnosis, treatment administered, blood investigation results, and pattern of complications developed were documented for each participant at each encounter.

Mucositis was graded using the World Health Organization system; Grade 0: no change, Grade 1: soreness and erythema, Grade 2: erythema and ulcers with some tolerance of solids, Grade 3: ulcers and patient can only tolerate liquid diet only, and Grade 4: inability to feed orally.[6],[7]

The participants who were recorded as having vomiting were those who despite adequate antiemetics defined as the presence of at least two different antiemetic agents from two classes still had more than three vomitus per day. The unit algorithm is the use of serotonin antagonist as prophylaxis before chemotherapy and the addition of either a dopamine antagonist, an antihistamine, or steroid if vomiting becomes protracted.

Fever was considered as temperature ≥38.3°C or 38°C on two occasions 1 h apart, while neutropenia was defined as neutrophil count <500/µl. Thrombocytopenia was defined as platelet count <50,000/µl and anemia as hemoglobin <6 g/dl following commencement of treatment. All patients had daily mucosal and skin examination to determine the presence and extent of bleeding as well as mucosal changes. Neurotoxicity was defined as new-onset seizure or neurologic dysfunction following the commencement of chemotherapy. Nephrotoxicity was a reduction in urine output to <1 ml/kg/h or two-fold increase in serum creatinine value despite adequate rehydration following the commencement of chemotherapy. Cardiotoxicity was an alteration in cardiac volumes and pressures demonstrated by echocardiography following the commencement of chemotherapy.


  Results Top


A total of 100 children consented and were recruited for the study; the mean age of patients as at the time of review was 6.44 ± 4.52 years with age ranging from 7 months to 19 years of age. There was a slight male preponderance (59.0% vs. 41.0%).

Acute lymphoblastic leukemia (ALL), nephroblastoma, and retinoblastoma were the most common malignancies seen in these children. Uncommon tumor types were hepatoblastoma, germ cell tumor, pineal gland tumor, sacrococcygeal teratoma, mesenchymal chondrosarcoma, Ewing sarcoma, and spindle cell tumor.

In children <24 months of age, the most common malignancies seen were nephroblastoma and ALL; in children aged 2–5 years, the most common malignancies seen were retinoblastoma and ALL; in children aged between 5 and 10 years, the most common malignancy was ALL, while nephroblastoma and retinoblastoma were not seen in this age group. In children >10 years, ALL and Hodgkin's lymphoma (HL) were the most common malignancy; CML was found only in this age group. There was a statistically significant association between age group and diagnosis (P = 0.010) [Table 1].
Table 1: Diagnoses across the age distribution

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The most common malignancies in both males and females were ALL and nephroblastoma; all cases of osteosarcoma seen occurred in males. However, there was no overall gender predilection (P = 0.405) [Table 2].
Table 2: Diagnosis by gender

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Mucositis was seen in 36% of patients, with Grade 1 being the most common grade. Although febrile neutropenia was seen in 12% of patients, only one of the patients had a positive blood culture result.

Cardiotoxicity was noted in only one of the participants using doxorubicin. A statistically significant association was noted between the use of carboplatin and gastrointestinal (GI) toxicity (P = 0.04), cyclophosphamide use and nephrotoxicity (P = 0.013), cytarabine, daunorubicin, L-asparaginase, and methotrexate use and prevalence of bone marrow suppression (P = 0.014, 0.005, 0.000, and 0.032), imatinib use and nephrotoxicity (P = 0.000), and thiotepa use and neurotoxicity (P = 0.04) [Table 3].
Table 3: Association between chemodrug and adverse events

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When dacarbazine or L-asparaginase was used in the group of patients studied, there was a statistically significant likelihood of an adverse event (P = 0.044 and 0.024) [Table 3].


  Discussion Top


The advent of chemotherapy marked a significant turning point in the management of cancers.[2] In addition, a continual and better understanding of tumor biology and molecular characteristics of cancer cells is impacting the development of available treatment options for cancer management including chemotherapeutic agents.[8],[9] However, despite the enormous impact of the use of chemotherapy in the improvement of survival rates of children and adults living with cancer, it is not without its side effects.[10] With an increase in survival rates of children with pediatric cancers, the target of treatment is shifting beyond just eradication and cure of disease to the reduction of morbidity, especially those that arise as a result of the treatment given.[11]

In this study like previous studies conducted at different centers in Nigeria, there were more males than female children with cancer [Figure 1].[12],[13] However, unlike previous studies, leukemia was the most predominant (31.0%) cancer type in the patients seen [Figure 2]. In a study by Stephen et al. that reviewed the childhood cancer registries in Africa, lymphoma was the most common cancer type seen in Kenya, Tanzania, Sudan, and Malawi. In Uganda, Kaposi sarcoma was the most common cancer type seen, whereas leukemia was the most common in South Africa and Namibia at 27.45% and 22.75%, respectively.[14]
Figure 1: Gender distribution

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Figure 2: Prevalence of cancers. * Others include: Hepatoblastoma, germ cell tumor, pineal gland tumor, sacrococcygeal teratoma, mesenchymal chondrosarcoma, and spindle cell tumor. HL = Hodgkin's lymphoma, NHL = Non-Hodgkin's lymphoma, CML = Chronic myeloid leukemia, AML = Acute myeloid leukemia, ALL = Acute lymphoblastic leukemia

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Overall, the prevalence of complications was high occurring in 80% of patients seen irrespective of diagnosis [Figure 3]. GI-associated complications were the most common types seen [Figure 4]. Oral mucositis was seen in 36% of patients in this study; this finding was seen also in children in India where 58% of children on chemotherapy developed mucositis, however unlike the present study, grade II mucositis was the most common grade seen [Figure 5].[7] The prevalence of mucositis seen was also much lower than those seen in other studies in developing countries like 69%, 55%, and 52% which were reported by Wahlin and Matsson[15] Janković et al.,[16] and Guggenheimer et al.,[17] respectively. This may be attributable to the aggressive mouth hygiene practice of the oncology unit where parents are encouraged to perform thrice daily mouth decontamination with antimicrobials. Following the recommendation of the International Society of Oral Oncology, all of the children with mucositis were managed conservatively and did well, with oral intake resuming after a few days.[18] The percentage of those with grades 3 and 4 mucositis was quite low in this study [Figure 5]. A significant proportion of the participants had chemotherapy-induced nausea and vomiting (CINV). In this review, about two-third of the patients had CINV [Table 4]. This was expected because coupled to the assertion that CINV is one of the most rampant side effects of chemotherapy;[19] it has also been postulated to occur more in children.[20] The proportion of patients with CINV was higher than the 46% reported in a systematic review in Iran,[21] however similar to reports from Malaysian general hospitals where two-third of the patient population had CINV.[16] The use of prophylactic serotonin receptor blockers was instrumental in alleviating the course of the condition in most of the participants in this study.
Figure 3: Prevalence of chemotherapy-induced complications. The prevalence of chemotherapy-induced complications in the study participants was 80.0%. The most common complications seen were gastrointestinal toxicity and bone marrow suppression. Cardiotoxicity was seen in one patient. There was no participant with hepatotoxicity [Figure 2]

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Figure 4: Pattern of chemotherapy-induced toxicity

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Figure 5: Pattern of mucositis in study participants. Mucositis was seen in 36% of patients, with Grade 1 being the most common grade. Although febrile neutropenia was seen in 12% of patients, only one of the patients had a positive blood culture result

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Table 4: Pattern of chemotherapy-induced adverse events

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Febrile neutropenia is an important clinical problem in pediatric cancer patients who are treated with chemotherapy.[22] It is a significant cause of morbidity and mortality. More importantly, it is a major cause of social and economic dysfunction for the affected families and communities.[23] The rates recorded in this study were lower than the rates from Ethiopia and Italy, respectively.[24],[25]

It was interesting to note that although 12% of the patients seen had febrile neutropenia [Table 4], only one of them had a positive blood culture result; this was similar to the Ethiopian study as well as a study carried out in Iran whereof 375 patients recruited, 2.6% had positive blood cultures.[24],[26] The low yield of pathogens may not be unconnected with the prior use of antibiotics among oncology patients who may have had several previous hospital visits. Another reason for the low accrual in this study may be as a result of the low uptake of blood cultures before antibiotic commencement by parents of affected children who have to pay out of pocket for health-care costs. Despite the Cochrane review on the use of oral antibiotics as an acceptable treatment route in the management of febrile neutropenia, all patients in this study received intravenous antibiotic for the management of febrile neutropenia.[27]

Notably, the proportion of patients that experienced nephrotoxicity and cardiotoxicity was <5% [Table 4]. These untoward effects were significantly associated with doxorubicin use for cardiotoxicity, imatinib and cyclophosphamide for nephrotoxicity. These agents while being effective antitumor agents have been known to cause these side effects.[28],[29] Although the use of drugs such as MESNA and Dexrazoxane can mitigate the side effects of cyclophosphamide and doxorubicin, respectively, the financial implication of these drugs often proves to be a huge saddle for resource-limited settings.[1],[30]

It was shocking to note that in spite of the fact that chemotherapy-induced alopecia is a frequent complication in patients with cancer, it was found in 1% of patients in this study. The reason for this is unclear, and it may not be unconnected with the cultural practice of shaving the hair of sick children among several communities in the country. We may need to track alopecia in a more aggressive manner in the future.


  Conclusion Top


GI complications and mucositis are common adverse events postchemotherapy administration. Increased awareness of the common complications in this environment and prophylactic medications may improve the care of children postchemotherapy, thereby reducing overall morbidity and cost of care.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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