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  Table of Contents  
Year : 2017  |  Volume : 54  |  Issue : 4  |  Page : 609-615

Clinicoepidemiological profiles, clinical practices, and the impact of holistic care interventions on outcomes of pediatric hematolymphoid malignancies - A 7-year audit of the pediatric hematolymphoid disease management group at Tata Memorial Hospital

1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 ImPaCCT Foundation of Pediatric Oncology Division, Mumbai, Maharashtra, India
3 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
4 Department of Cytogenetics, Tata Memorial Hospital, Mumbai, Maharashtra, India
5 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
6 Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
7 Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, India
8 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication30-Jul-2018

Correspondence Address:
Gaurav Narula
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_487_17

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 » Abstract 

INTRODUCTION: The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) at a tertiary cancer care hospital developed extensive patient support programs to improve retention and outcomes while focusing on protocols adapted to meet patient needs. An audit of measures and outcomes was done for a 7-year period from January 2010 to December 2016. MATERIALS AND METHODS: DMG protocols and patient support activities over the study period were documented and audited. Data was retrieved from internal databases and records. Measures taken and their impact were assessed by descriptive analytical tools. Survival outcomes were calculated using Kaplan–Meier method on SPSS v. 24™ software. RESULTS: Holistic patient support measures were undertaken through a charitable foundation entirely under pediatric oncology. Activities included infrastructure growth, socioeconomic support, provision of accommodation, nutrition, education, and multiple blood component donation drives. Patient registrations increased from 502 in 2009 to 874 in 2016, with the steepest rise in acute lymphoblastic leukemia (ALL) – 330 (2009) to 547 (2016). Treatment refusal and abandonment rates decreased from 32% to 3.4% over the same period, and male to female ratio decreased from 2.56 to 2.28:1. Early mortality in acute myeloid leukemia (AML) fell within 2 years from 26.7% in 2009 to 7%. Five-year overall survival (OS) was 69.5% for all patients registered in 2010, whereas disease-specific 5-year OS was ALL 67.1%, AML 49.3%, chronic myeloid leukemia 100%, Hodgkin lymphoma 90.4%, and non-Hodgkin lymphoma 74.2%. CONCLUSIONS: Holistic patient support-specific activities and adapted protocols made a measurable impact on patient outcomes. High survival outcomes of patients have been achieved despite relatively few receiving salvage therapies or stem cell transplant.

Keywords: Hematolymphoid malignancies, outcome audits, pediatrics

How to cite this article:
Narula G, Prasad M, Jatia S, Subramanian PG, Patkar N, Tembhare P, Shetty D, Khanna N, Laskar S, Shet T, Epari S, Kembhavi S, Shah S, Qureshi S, Gujral S, Banavali SD. Clinicoepidemiological profiles, clinical practices, and the impact of holistic care interventions on outcomes of pediatric hematolymphoid malignancies - A 7-year audit of the pediatric hematolymphoid disease management group at Tata Memorial Hospital. Indian J Cancer 2017;54:609-15

How to cite this URL:
Narula G, Prasad M, Jatia S, Subramanian PG, Patkar N, Tembhare P, Shetty D, Khanna N, Laskar S, Shet T, Epari S, Kembhavi S, Shah S, Qureshi S, Gujral S, Banavali SD. Clinicoepidemiological profiles, clinical practices, and the impact of holistic care interventions on outcomes of pediatric hematolymphoid malignancies - A 7-year audit of the pediatric hematolymphoid disease management group at Tata Memorial Hospital. Indian J Cancer [serial online] 2017 [cited 2022 Oct 2];54:609-15. Available from:

 » Introduction Top

The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) is a multidisciplinary group that provides comprehensive medical diagnostic, counseling, management, follow-up, and palliative services to children below 15 years of age diagnosed with hematolymphoid malignancies. It evolved in 2010 from the traditional Pediatric Oncology Division, which separated into two major DMGs – PHL and pediatric solid tumor (PST). From the outset, the policy of the DMG has been to develop indigenous, cost-effective protocols taking into consideration existing infrastructure as well as the need to execute treatment on outpatient basis to the maximum extent possible. Due to severe socio-economic constraints of a majority of the families coupled with the highly curative nature of malignancies with potentially more than 80 % cure rates, dealt with by the DMG[1] the group recognized that intervention in these issues could help save lives and improve outcomes quantitatively and qualitatively. Toward this end, the group has helped develop an extensive support system to provide financial aid, accommodation, nutrition, blood and blood product support, continued education of children, sporting and fun activities, outings and cultural programs as part of its service program. The profile of patients, protocols and practices followed, the initiation of this holistic social intervention program, and its impact on outcomes were audited from the time of the formation of the DMG in 2010 till December 2016.

 » Materials and Methods Top

All patients registered with the DMG from January 2010 to December 2016 were eligible for analysis. Numerous changes in practices occurred during this period that impacted data collection, patient enrollments, compliance, and outcomes. These changes took place in terms of management protocols for individual diseases, supportive care strategies, especially interventions in the fields of infection control, nutrition, transfusion support and education, social support for finances and accommodation, and infrastructure changes. The major changes were audited and their impacts on outcomes were assessed. Data was analyzed by descriptive analytic tools, survival outcomes were measured by Kaplan–Meier method, and tests for significance by Chi-square test using IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp (USA).

 » Results Top

During the study period, several changes occurred in terms of infrastructure, capacity building, social interventions, and protocol changes. While some impacted data collection, others affected outcomes.

Infrastructural changes

Case records

The hospital moved to a complete e-filing system in phases during this period, and from 2014 onward, complete electronic medical records (EMR) became available. Due to the complex nature of hematolymphoid medication orders and to avoid errors at point of delivery, a paper system is still used for medication instructions to augment the EMR.

Pediatric ward renovation

In 2013, the entire pediatric ward was renovated with upgraded facilities for patients, nursing staff, and treating physicians. Child-friendly, themed rooms, amenities for attendants, and a playroom, which now also doubles as a “classroom,” were made. However, this involved a shift to another ward for a period of 10 months in 2013 and a temporary disruption in infection control due to construction and shifting activity.

Improving Pediatric Cancer care and Treatment foundation and holistic patient support

Improving Pediatric Cancer Care and Treatment (ImPaCCT) foundation was established in October 2010 to ensure that every child with cancer coming to Tata Memorial Hospital (TMH) receives treatment and other support regardless of the family background and serves with the motto “each child with cancer deserves the best chance at cure.” Under this umbrella, an elaborate support team of volunteers, social workers, dieticians, counselors, pharmacists, and others was established that works in coordination with administration, government and nongovernment agencies, and corporates to oversee several activities related to patient care. These include, though are not limited to, the following:

Socioeconomic support

Three social workers and two volunteers work in tandem with TMH medical social service department, various trusts, and individual donors in the community to provide seed money on arrival and larger funds for complete treatment of children. Funds directed toward patient treatment increased from Rs. 20,000,000 in 2010 to more than Rs. 160,000,000 in 2016.

Accommodation support

Clean and reasonably priced places to live were provided in partnership with several organizations. Our major partner, St Jude Child Care Centre, steadily increased capacity to provide accommodation to more than half of the families of pediatric patients reporting to TMH providing beautiful “Home-away-from-Home” (HAH) facilities with food grains and hygienic community kitchens. Poor patients who need to stay in other places were reimbursed through ImPaCCT foundation for their accommodation, if required.

Nutritional support

Four dieticians in the team do nutritional assessment as well as dietary counseling and guidance, especially focusing on low-cost food supplements. The team runs a nutritional support program every day, in which free specially designed high calorie and protein lunch and snacks are provided to all children and one parent attending the outpatient department (OPD) since March 2013. In addition, all malnourished children get free commercial supplements and micronutrient supplements, along with ready to use therapeutic food, which was started in collaboration with a nutritional research center at Lokmanya Tilak Municipal Medical College at Sion, Mumbai. In addition, weekly rations of rice, flour, pulses, sugar, and oil are distributed to 150 families every Monday.

Educational support

To address the issue of missed education and poor motivation for school reenrollment post-treatment, the DMG teamed with different organizations. One initiative included a nongovernmental organizations (NGO), which tied up with municipal authorities to run a school near the hospital premises. In addition, a professional group of teachers from an organization called “Mindsprings” with expertise in innovative educational solutions conducts classes in waiting area of the OPDs as well as in the ward playroom for inpatients. The program can deliver educational sessions to children of different ages, speaking different languages, and from different backgrounds, by engaging in common and smaller group activities with lessons incorporated in fun and innovative ways.

Transfusion support

Most of our patients come from outside Mumbai and do not have blood or platelet donors. Hence, the team along with the Nargis Dutt Foundation started a drive called “Save a Life” to recruit platelet donors from all colleges and corporate houses in Mumbai and started a volunteer platelet donor registry at TMH. The program has been highly successful with 2280 donors registered to date, of which more than 1000 have already donated, several of them being multiple donors, ensuring an uninterrupted supply of blood products.

Emotional support and treatment counseling

Volunteers and nurses were trained to guide families regarding the treatment and various supports available and help them to face the emotional burden of the diagnosis of cancer and its treatment.

Events, outings, cultural and fun activities

These are arranged frequently to keep children and parents engaged in activities that improve outlook and attitudes toward the challenges faced.

Patient guidance booklets and videos

The PHL-DMG has designed information booklets related to cancer, infection control, nutrition, hygiene, and other treatment-related issues in a simple sentences and with representative illustrations in multiple languages. A video made for the purpose is played regularly in waiting areas as well as in monthly parent support group meetings. This benefited the less literate and reinforced the message for the literate. Every 15 days, a parent support meeting is held in an auditorium where information is given to parents about cancer and its management, and all their queries are answered in an open forum.

Protocols followed and changes in strategies

The protocols followed by the DMG for investigation, risk-stratification, and management are standardized and available in the public domain.[2] The protocols are mostly indigenous and were designed considering the available infrastructure and challenges. These include high patient volumes, limited beds, limited use of central venous access devices and total parenteral nutrition, and the low and middle socioeconomic strata of most of our patients, leading to both economic constraints and higher incidence of malnutrition compromising chemotherapy tolerance. The protocols have been modified from time to time based on internal audits of outcomes and analysis for failures when applicable. When necessary, entire treatment strategies were changed. The protocols at the annexure represent current practice and not necessarily what the patients received through the entire review period. Furthermore, to cater to the twin features of high curability and limited infrastructure of only forty beds, the DMG has a policy of not accepting patients for treatment who have already initiated cancer-specific therapy before presentation. This includes patients referred postrelapse. However, medical treatment opinion and relevant workup for the same are offered to all such patients who can then continue treatment under primary physician or another center of choice based on their preference.


Since the inception of the DMG system in 2010, 5261 patients registered for treatment, increasing nearly 1½ times over this period from 589 in 2010 to 874 in 2016. The proportion of “General Category” patients indicating those availing subsidized treatment and in need of social support remained steady during this period being 83.2% in 2012 and 84.6% in 2016. The steepest rise of registrations occurred for acute lymphoblastic leukemia (ALL) from 330 to 547 from 2010 to 2016 [Figure 1]. All other diseases also showed modest increases [Figure 1], [Figure 2], [Figure 3]. While only 56% of registrations were managed with “intent-to-treat” at TMH in 2010, this increased to 80% by 2016. The remaining had either come for second opinions or referred to other centers for further management. Due to the available social and financial support, every newly diagnosed patient was offered treatment, irrespective of the family's financial status. All outcome analyses were done further on the “intent-to-treat” at our center cohort only.
Figure 1: Registrations of acute leukemias: 2010–2016

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{Figure 1}
Figure 2: Registrations of lymphomas: 2010–2016

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Figure 3: Registrations of other hematolymphoid malignancies: 2010–2016

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The biggest challenge to the DMG for patients in the era before 2010 was treatment refusal and abandonment (TR and A). Nearly one-third of patients out of sheer destitution would either refuse treatment or abandon it soon thereafter, daunted by the enormity of the task at hand, finances involved, and search for a decent place to stay in a metropolitan city like Mumbai. Since initiating the holistic approach, as detailed above, TR and A rates came down from a high of 32% in 2009 to 3.4% in 2016. This occurred even as the total number of cases increased by nearly 150% in the same period [Figure 4]. There appears to be a threshold level just below 5% achieved within a short time by 2012, which has not been breached despite dramatic improvement in social support during this period. There was also a steady improvement in the sex ratio although it remains skewed in favor of boys [Figure 5]. The incidence of TR and A in girls was significantly higher at 8.5% compared to boys at 4.5%. The TR and A incidence in girls decreased from 11% in 2010 to 4.5% in 2015 with targeted social support initiatives for girls.
Figure 4: Decline in treatment refusal and abandonment despite increasing registrations after introducing a holistic care social support program

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Figure 5: Improving sex-ratio of children initiating and not abandoning treatment

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The social interventions had their deepest impact on early mortality, especially for acute myeloid leukemia (AML) where these issues become amplified due to the aggressive nature of the disease and the intensive supportive care needed in induction [Figure 6]. The recent marginal rise in 2016 for induction-related mortality for all acute malignancies after being stable at around and below 5% for preceding 4 years relates more to the rise in multidrug-resistant organisms (MDRO)-related infections. The DMG now screens all patients at registration for colonization of MDRO and extended-spectrum beta-lactamase organisms (ESBLs) by rectal swab. At present, the rate of MDRO and ESBL colonization at presentation stands at 32% and 36%, respectively, (data from January 2015 to July 2016).
Figure 6: Impact on mortality after introducing a holistic care social support program

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For ALL, early mortality continued to decline steadily even after 2012. This coincided with a change in protocol for B-ALL to the standard arms of Indian Childhood Collaborative Leukemia Protocol (ICiCle) Pilot study from 2013, significantly reducing the intensity of therapy in over 60% of ALL cases. To assess the impact of ICiCLe on ALL outcomes, an interim analysis was done for patients recruited since initiation of the protocol till December 2015 with a follow-up period till December 2016. Projected 3-year overall survival (OS) was 90.4% ± 1.4% with a median follow-up of 23 months (range, 1–48), while event-free survival (EFS) was 70.7 ± 2.3% [Figure 7]a and b], with 70% of the mortality occurring in intensive phases of treatment.
Figure 7: (a) A: 3-year overall survival for B-acute lymphoblastic leukemia on ICiCLe Pilot (n = 713). (b) 3-year event-free survival for B-acute lymphoblastic leukemia on ICiCLe (n = 713)

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Five-year OS for all 589 cases registered in the DMG in 2010 stood at 69.5%, while median survival was not reached [Figure 8]. In contrast to above, 5-year OS for ALL (n = 330) patients in this cohort treated on a non risk-stratified protocol was 67%. About half of all AML patients, and the entire cohort of Chronic Myeloid Leukemia (CML) patients diagnosed in 2010 were alive 5 years later. Similarly, for this cohort, more than 90% of Hodgkin lymphoma and three-fourth of all non-Hodgkin lymphomas (NHLs) survived till 2016 [Table 1].
Figure 8: Overall survival patients registered in 2010 (all patients, n = 589)

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Table 1: Five-year overall survival disease wise for patients registered in 2010 (n=589)

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In 2010, the early mortality of AML patients had been particularly high prior to the institution of the comprehensive support program as presented. To gain a closer look at representative outcomes, we also examined the AML cohort of 2011 (n = 65), where 3-year OS, EFS, and disease-free survival (DFS) were 66.2%, 49.3%, and 66.1%, respectively. Considering that relapse patients require more aggressive treatment, including stem cell transplant, and the need to be managed with the same competing infrastructure and resources for newly diagnosed patients, the DMG is presently not concentrating on treatment of high-risk relapsed ALL and AML patients. Less than 10% of all relapses among the acute leukemias and NHLs have undergone second-line treatment, and less than 10% of these have undergone transplant. Patients with HL and Langerhans cell histiocytosis (LCH) frequently received several lines of salvage therapy. Only 10 pediatric hematolymphoid patients from this cohort underwent SCT during this period from all disease groups. In a 9-year period from November 2007 till December 2016, a total of only 128 children underwent an SCT at our center, including HL – 40 (30.8%), ALL – 22 (18.5%), AML – 15 (11.5%), marrow failure syndromes – 13 (10%), CML – 8 (6.2%), and others – 30 (23.1%).

 » Discussion Top

Before 2010, pediatric patients with hematolymphoid malignancies faced huge challenges in the form of expenses for treatment, access to accommodation, adequate nutrition, transfusion support, gender bias exacerbated by limited resources, and motivation for treatment. These are challenges common to most low and middle income countries (LMICs), especially those where access to pediatric oncology care itself may have been particularly low.[3],[4] In a study from North India, it was estimated that 34% of fathers of children with cancer lost their jobs and nonmedical expenses were 2.5 times the average per capita income.[5] Even in developed countries, significant financial impact has been noted, especially for families that had to travel the furthest to access oncology care.[6],[7] It has been well recognized that improvement in social support services may have a significant impact on outcomes in both, developed countries and in India. While excessive reliance on charitable funding was flagged as a concern in the United Kingdom where an extensive public health program is in existence, the way ahead in India may well be through the charities and NGOs' route.[8],[9]

Our hospital has an elaborate Medical Social Work department that has been providing support to weaker socioeconomic strata patients for decades, as this is a well-recognized factor that can have a bearing on outcomes. However, sheer numbers of patients in need overstretched their capacities. Toward this end, the DMG embarked on a social support program in conjunction with the PST DMG by creating the ImPaCCt foundation to enhance support for children with cancer. This program was unique in its scale and ambition, and our results show a quantum jump in improvement of outcomes, both quantitatively and qualitatively, even in the absence of significant medical advances in the period. This has allowed us to undertake major changes in protocols after bringing all patients onto an even keel by reducing disparity, that can further enhance outcomes. It also helps to make outcome analysis of protocols and trials more authentic and reflective by ensuring consecutive enrollment and completion of treatment by minimizing the impact of socioeconomic status in imparting a selection bias.

We attribute the rise in patient registrations and retention directly to the institution of this program. However, there was a sharp rise in ALL registrations, and the impact of the program on this may have been more nuanced. Cancer registries' data from India reflect a rising incidence of childhood malignancies in general, and leukemias more specifically. The standardized incidence rate for India ranged from 38 to 124 per million children per year in data derived from the 2006 National Cancer Registry Program reports for the years 2001–2004.[10] In the subsequent period from 2006 to 2011, a slight increase in actual incidence was noted, especially in boys, which increased by 18.6 to 159.6 per million across all regions, the largest contributor being leukemias. Even so, the increase by nearly two-third in the number of leukemia registrations cannot be attributed to any extrapolation of the registry data. The increase in lymphomas on the other hand was more in line with the secular trends noted from the registry reviews. Therefore, we must conclude that the differences cannot be entirely attributable to our social intervention either, at least for ALL. A more long-term analysis and deeper correlation with national trends would be needed to assess this aspect.

The major areas of impact of the social support program have been in the gender ratios and TR and A rates. Historically, sex ratios have been skewed in favor of males beyond expected rates in cancer registries from all parts of India except the northeast.[10] In a more recent systematic review on childhood ALL from India, sex ratios were found to be approximately 2.5:1. We saw a steady improvement in gender ratios in the study period reducing to 2.28:1 by 2015. The importance of reducing TR and A is well recognized. In a cross-sectional online survey conducted in 2012, with respondents from 101 countries collated with data from public sources, it was estimated that 15% of 155,088 children less than 15 years of age abandon therapy and 99% of these occurred in LMICs.[11] The immediate impact of the introduction of our social support program was to bring the TR and A rates from historic highs of above 30% to below 14% in the first year and to well below 5% by 2016. Here too, there was a measurable impact on gender with marked decline in TR and A for girls in our own analysis over a different overall time period.[12] Other factors have also recently emerged as important for TR and A, such as perceived prognosis, apparent deterioration, or apparent improvement in the child's condition when mixed with preconceived notions of curability and preferences for alternative medicines.[13] Some of these factors, including unavoidable domestic compulsions, are too deep rooted and endemic in society for efforts of a single institution to counter, and we feel the threshold TR and A levels between 3 and 5% for the last 3 years may be difficult to breach in the foreseeable future.

Another area of impact was the drop in mortality in all hemato-lymphoid malignancies. This decrease was most dramatic in AML, a disease that due to its peculiar biology and intensive induction, needs large amounts of funds to be made available early in the treatment. The recent modest increase in mortality seen across all hematolymphoid disease groups is attributable to the rising incidence of colonization by MDRO detected in more than 20% cases at baseline and resultant bloodstream infections reported by our group earlier and internal data under analysis.[14],[15]

OS rates of close to 70% are reflective of the highly curable rates of pediatric hematolymphoid malignancies in general[1] and are in excess of those reported from most single centers in India.[16],[17] While survival rates are typically higher in developed countries, they are also a reflection of the availability of effective salvage options including stem cell transplant for the vast majority of their patients, which is a major limitation in our setting.[16],[18] These rates were achieved despite significant challenges of presentation with advanced disease, malnutrition, and resistant infections seen at our center. With institution of support systems since 2010 and streamlining of patient management guidelines and tracking, along with adoption of risk-stratified approaches and sophisticated disease monitoring including flow cytometry and positron emission tomography-computed tomography-based response assessment, patients starting treatment in 2015 are expected to have further improved OS and DFS. The immediate outcome is already palpable in improved 3-year OS of ALL patients from 2013 to 2015 to above 90%, although this is expected to fall modestly over the next two years as relapse mortalities catch up. This still compares far more favorably than best-reported outcomes of 70%–81.4% in the more recent literature and reviews from India for single center-reported data[17] and our own previous results of 67% OS for childhood ALL.[19]

AML remains a challenging disease within our DMG. However, OS of close to 50% for patients starting treatment in 2010 is remarkable compared to established OS of a dismal 23% to at best 53% reported from India, where the latter occurred in single centers with higher rates of salvage SCT than that accessible to our patients.[16] In fact, the extremely dismal picture painted for pediatric AML was contested by our group quoting better outcomes in centers where social support had been instituted.[20] This has also been contributed to by the innovative use of oral metronomic chemotherapy both as a bridge to standard therapy and as subsequent maintenance therapy.[21] As seen in our own AML cohort of 2011, when availability of social support had a direct impact on early mortality in AML, 3-year OS improved to 66%. The success of the modified approach and innovative use of metronomic therapy can be seen in their DFS of 66%. In favorable group AML patients, this has brought OS close to 70% without SCT. As early mortality has gone down in all disease groups including AML since 2011, we expect further improvement in OS and DFS by this approach in the later years of this period. The OS in all other disease categories such as lymphomas and LCH is comparable to international standards and published literature for primary treatment.[22],[23],[24],[25] Most patients are unable to opt for salvage options on relapse as this often involves SCT for most hemato-lymphoid malignancies.


The Pediatric Hematolymphoid Group acknowledges with deep gratitude the contributions of former member Dr. Brijesh Arora, whose work in the group forms the foundation of so much of what has been achieved.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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