Study of Factors Affecting the Time to Diagnosis and Treatment in Pediatric Acute Leukemia Patients- A study from India

Gaurav Singh¹, Neha Goel¹, Amitabh Singh¹, Rani Gera^1*

¹Department of Pediatrics, VMMC & Safdarjung Hospital, New Delhi, India.

Abstract

Timely diagnosis and early initiation of treatment of acute leukemia in children improve survival. Our study aimed to identify the factors associated with delayed diagnosis of acute leukemia in children. A prospective observational study was done at a tertiary care Superspeciality hospital in Northern India. The study included 100 children aged 0–12 years over 18 months with the diagnosis of acute leukemia. A mixed-methods technique was used, combining important variables with qualitative interviews. The primary caregivers of each patient were asked to fill out a standardized questionnaire for this study in addition to the information recorded in the case record form, Demographic, clinical, and Healthcare system data were documented. Patient, physician, and health care system factors that cause delayed diagnosis were studied. Female sex (p-value – 0.003), the primary response to illness (p-value <0.001), lower socio-economic strata, and traveling Time to the nearest health care facility of more than   20-40 minutes were significant factors identified as the reason for the delay in acute leukemia diagnosis by more than eight weeks. There is a significant time lag between the onset of the first symptom and diagnosis of acute leukemia which may adversely affect the outcome. A concerted effort to improve the health care system and raise awareness of signs and symptoms of acute leukemia among caregivers and primary care physicians is required.

Keywords: Leukemia, Diagnosis, Delay, Treatment

Gender, primary reaction to illness, and Time to diagnosis since the onset of symptoms are significantly associated with the delay (p<0.05).

The study found a significantly higher proportion of females (21 out of 32 females) being diagnosed after eight weeks of the onset of symptoms compared to male patients (p-value <0.001). A significantly higher proportion of Patients in the Lower economic class were diagnosed after more than 12 weeks compared to patients in the Lower middle class & Upper Lower Class (p-value 0.016), as per the modified Kuppuswamy scale.

There was a significant correlation between chief complaints and the Time taken for diagnosis since the onset of symptoms. Patients with bleeding had early diagnosis compared with patients with body aches, fever, and pallor (p-value 0.038). There was a significant correlation between the patient's take to reach the healthcare facility and the Time taken for diagnosis since the onset of symptoms (p-value 0.043).

Financial problems (money for outpatient department visits, inpatient expenses on treatment, investigations, treatment, and travel expenses) were significant for patients with delayed diagnoses (p-value 0.019).

Our study aims to find the factors responsible for the delay in diagnosis of pediatric ALL. Numerous pieces of literature regarding the same have been published from developed countries, but there is a lack of data concerning this problem from the developing nations, e.g., India. A thorough understanding of the factors responsible for this delay is necessary so that measures can be taken to reduce and avoid them and improve survival. Our study found that the taken to diagnose leukemia is affected by socioeconomic status, gender, Time taken to reach the health care facility, patient compliance, referral system (delayed referral from primary and secondary HCS to tertiary HCS), and ignorance of mild symptoms. Out of these, gender bias (female child), low socioeconomic status, patient compliance, nature of presenting complaint, primary reaction to sickness (acceptance vs denial, first treatment sought), and Time taken to reach health care facility. Financial problems (money for OPD visits, inpatient expenses on treatment, investigations, treatment, and travel expenses) were significant, with a p-value of < 0.05. The average delay in the diagnosis of acute leukemia was around eight weeks, which caused late initiation of treatment of the patients. Similar results were derived by Venkatasai JP et al.^[17] To minimize this delay, adequate parenteral education and support are needed. Creating a mass awareness regarding the symptomatology and nature of the disease via campaigns, television and radio broadcast, and the internet is necessary. Our study noticed late health-seeking behavior for the mild symptoms in the female child compared to the male child, which led to a delay in diagnosis. There was a male preponderance of cases possibly due to selective health-seeking behavior.^[18] Gender bias in seeking healthcare facilities accounts for an important social problem that exists in LIC-MIC, e.g. in India.^{[19, 20]}

In our study, financial problems were significant in causing this delay. 75.4% showed a delay in diagnosis of more than 12 weeks. Providing financial aid for medical and non-medical expenses might prevent the delay.

A systemic review of observational studies (worldwide) conducted by Richards et al. showed that delays of 3–6 months were associated with lower survival.^[21] In LMIC, these delays can be much longer because of lack of awareness, illiteracy, longer waiting time, disproportionate doctor-patient ratio, and lack of good healthcare facilities in peripheries and tribal areas. Many times some patients are never diagnosed at all; as seen in our study, patients had to face a delay of more than 12 weeks due to various demographic factors.^[22]

A study conducted in Egypt by ER Abdelkhalek et al.^[23] observed that a child's sex, age at diagnosis, type and site of malignancy, family residence, socioeconomic status, and parental educational level played a significant role in causing this delay, and the median total diagnosis delay period was 47 days. Mamtaz Begum et al.^[24] found that 70% of the cases had to wait for more than 90 days for treatment in Bangladesh. In our study, 76% of the children had to face a delay of more than eight weeks in getting a proper diagnosis and treatment.

Patients' delay in our study occurred due to the age at which the disease was presented, the family's financial background, and the parents' education status. Raising awareness among the stakeholders can minimize this problem. 

Indian population has its varied reasons for the increased time interval from symptom onset to diagnosis and treatment. Social beliefs, poverty, lack of easy access to health care, girl child, illiteracy, and beliefs in traditional alternative medicines are a few of the factors responsible for the late presentation of Indian children with cancer.^[25]

Leukemia remains a leading cause of death in children despite the tremendous advancement in pediatric oncology during the past two decades.^[26] Early diagnosis is the fundamental key to leukemia management because it can allow early treatment of the disease, resulting in a better prognosis and positively affecting their quality of life.^{[27, 28]}

Research on diagnosis delays in childhood leukemia is still in its early stages. More studies are needed to investigate the potential impact of delays on prognosis outcomes. The Time taken to diagnose acute leukemia in India is around three months. Female children, lower economic strata, financial problems, and delay in reaching healthcare facilities were some of the significant factors which resulted in a delayed diagnosis of more than three months.

Conclusion

Early diagnosis is recommended to improve the survival rate of children with leukemia. Raising public awareness of the disease will play a vital role in reducing the delay in diagnosis and is a must to identify danger signs, which otherwise are easily ignored by most parents. Counseling the parents and the caregivers regarding the nature of the disease, its symptomatology, nature of the treatment, and durability, and providing adequate and appropriate social support through public support groups can help in the early identification of the symptoms and early seeking of treatment.^[29] There is a need for more quantitative studies with a larger sample size to consolidate our understanding of various factors affecting the outcome of pediatric cancer patients.

Limitations

Our single-centered study with a smaller sample size may not represent the entire population's characteristics. Our study did not take into account delays associated with non-hematological malignancy. Additionally, recall bias due to the chronicity of the disease can be a major confounder in our findings.

Disclaimer

The views expressed in the submitted article are their own and not an official position of the institution or funder.

Acknowledgments

None.

Conflict of interest

None.

Financial support

None.

Ethics statement

IEC/VMMC/SJH/Thesis/October/2018/10 (ethical approval obtained from ethical committee of Vardhman Mahavir Medical College and Safdarjung Hospital, Guru Gobind Singh Indraprastha University, New Delhi, India).

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