Paediatric oncology in the Eastern Mediterranean region (EMR): the current state and challenges.

The WHO Eastern Mediterranean region (EMR) is characterised by highly economically diverse countries, with healthcare systems in various phases of development. Childhood cancer care provision also ranges from that provided in centres able to deliver sophisticated therapy resulting in outcomes comparable to those seen in highly developed nations, to countries with no provision for care of children with cancer. At 10·1 per 100,000 children at risk, the age standardised incidence-rate for cancer in children below 14 years of age is relatively low but may be consequent to poor registration. Shortages in trained care providers were identified in many regional countries, particularly in low and lower-middle income countries, however, implementation of training programs are beginning to counter this deficit. Significant diversity in patient care capacity exists in the region, leading to inequitable access to quality paediatric oncology care. There is strong potential for regional collaboration towards infrastructure and capacity improvement, with facilities available within the EMR for twinning and educational support to those centres and countries that need them. While cancer care coverage is available to citizens of high-income countries, in the lower-income countries out-of-pocket health expenditure can reach 75%. Some relief is achieved through the contribution of multiple charitable foundations working to support childhood cancer care in the region, as well as the provision of care in, often overburdened, public sector hospitals. War and other geo-political turmoil, as well as natural disasters, have negatively impacted healthcare capacity, including childhood cancer care, in several regional countries. Despite all this, the trajectory for change is upward and initiatives such as the WHO Global Initiative for Childhood Cancer are igniting positive change.

Global Immunization Crisis Amid the COVID-19 Pandemic: Implications for Pediatric Oncology.

Declining herd immunity and severe manifestation of vaccine preventable infections underscores the need for vaccinations campaigns to urgently vaccinate children who missed their routine immunizations.

A regional virtual case discussion forum in pediatric oncology: Experience of the Pediatric Oncology East and Mediterranean Group.

BACKGROUND: The Pediatric Oncology East and Mediterranean (POEM) group that aims to share expertise among pediatric oncology providers across the Middle East, North Africa, and East Asia region initiated a virtual Case Discussion Forum (CDF) in 2013. METHODS: Meeting records from September 2013 till June 2021 were reviewed. Detailed minutes were available starting August 2016; case data were analyzed including diagnoses, purpose of presentation and recommendations. A 38-item survey assessing perception of benefits, challenges, and opportunities of the forum was distributed to members of the POEM group and results analyzed. RESULTS: A total of 140 cases were presented from 14 countries. After August 2016, 67 cases were presented, and those were analyzed regarding reasons for discussion, barriers, and recommendations. Details are presented in this report, and the most common challenges identified were related to histopathologic/molecular diagnosis (24%), imaging interpretation (18%), resource limitations (12%), and surgical difficulties (9%). A survey was distributed to all POEM members in 28 countries, and 76 responded. The main benefit reported was the provision of recommendations regarding treatment and evaluation, while the main challenges reported were time zone difference and workload. Recognized opportunities included conducting regionally relevant research studies based on clinical problems identified during discussions, and setting guidelines for resource-adapted treatment regimens. CONCLUSIONS: The POEM CDF identified areas for multi-institutional regional studies and led to a twinning project between two centers in the region for improving diagnostic infrastructure. Such forums can identify specific resource limitations in pediatric cancer and direct efforts for targeted capacity building.

Exploring the 'January effect' at a university hospital in Pakistan: a retrospective cohort study investigating the impact of trainee turnover on patient care quality outcomes.

OBJECTIVE: There are reports of a potential rise in a teaching hospital's morbidity and mortality rates during the trainee turnover period, i.e., with the induction of new residents and house staffs, and the changeover of clinical teams. The published literature displays mixed reports on this topic with lack of reproducible observations. The current study was conducted to explore existence of any such phenomenon (January effect) in Pakistan. METHODS: This retrospective cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan. Five-year (2013-2018) record of all the patients in all age groups related to these outcomes was retrieved and recorded in specifically designed questionnaire. Different outcome measures were used as indicators of patient care and change in these outcomes at the time of new induction was related to possible January effect. RESULTS: During the five-year study period, more than 1100 new trainees were inducted into the post graduate medical education program (average of 237 per year) with more than 22,000 inpatient admissions (average of 45,469 per year). Some patterns were observed in frequencies of surgical site infections, medication errors, sentinel events, patient complaints, and adverse drug reactions. However, these were not consistently reproducible and could not be directly attributed to the trainee turnover. All other indicators did not show any pattern and were considered inconclusive. No effect of overlap was observed. CONCLUSIONS: Inconsistency in the patient care quality indicators do not favor existence of January effect in our study. Further research is recommended to establish our results.

Effectiveness of levofloxacin in the induction of chemotherapy in high-risk acute lymphoblastic leukaemia in children in a developing country.

Background: Infections significantly predominate during induction chemotherapy for acute lymphoblastic leukaemia (ALL) in children. Antibacterial prophylaxis is one strategy that lowers the risk of these infections. This study evaluates the role of levofloxacin prophylaxis on the frequency of infections, febrile neutropenia (FN) and outcomes associated with it along with the development of drug-resistance. Subject and methods: This was a single-centre cohort study in which the data were collected from electronic health records between two cohorts of high-risk ALL patients in the induction phase: the first one before the initiation of levofloxacin prophylaxis and the second was after the implementation of levofloxacin prophylaxis. The variables were compared between both the groups and odds ratios were calculated for clinical outcomes. Results: Out of 227 patients, 115 were given levofloxacin prophylaxis and 112 were in the no prophylaxis group. Both cohorts were similar in demographic factors, treatment regimen and supportive care services. There was a significant difference in total in-patient admissions along with FN admissions (p = 0.026). Microbiologically documented infections and infection-related critical interventions were significantly higher in the no prophylaxis group (p < 0.05). Odds ratios with a 95% confidence interval were applied to both groups for clinical outcomes in patients with and without FN which also illustrated similar results. Overall mortality and drug resistance patterns were similar among both groups. Conclusion: This study emphasised that levofloxacin is effective in reducing inpatient admissions with FN and its complications but did not affect the drug-resistance pattern. Long-term monitoring for antibiotic resistance is mandatory.

Measuring the patient safety culture at a tertiary care hospital in Pakistan using the Hospital Survey on Patient Safety Culture (HSOPSC).

BACKGROUND: Patient safety is a top priority for many healthcare organisations worldwide. However, most of the initiatives aimed at the measurement and improvement of patient safety culture have been undertaken in developed countries. The purpose of this study was to measure the patient safety culture at a tertiary care hospital in Pakistan using the Hospital Survey on Patient Safety Culture (HSOPSC). METHODS: The HSOPSC was used to measure the patient safety culture across 12 dimensions at Aga Khan University Hospital, Karachi. 2,959 individuals, who had been working at the hospital, were administered the HSOPSC in paper form between June and September 2019. RESULTS: The response rate of the survey was 50%. In the past 12 months, 979 respondents (33.1%) had submitted at least one event report. Results showed that the personnel viewed the patient safety culture at their hospital favourably. Overall, respondents scored highest in the following dimensions: 'feedback and communication on error' (91%), 'organisational learning and continuous improvement' (85%), 'teamwork within units' (83%), 'teamwork across units' (76%). The dimensions with the lowest positive per cent scores included 'staffing' (40%) and 'non-punitive response to error' (41%). Only the reliability of the 'handoffs and transitions', 'frequency of events reported', 'organisational learning' and 'teamwork within units' was higher than Cronbach's alpha of 0.7. Upon regression analysis of positive responses, physicians and nurses were found to have responded less favourably than the remaining professional groups for most dimensions. CONCLUSION: The measurement of safety culture is both feasible and informative in developing countries and could be broadly implemented to inform patient safety efforts. Current data suggest that it compares favourably with benchmarks from hospitals in the USA. Like the USA, high staff workload is a significant safety concern among staff. This study lays the foundation for further context-specific research on patient safety culture in developing countries.

Addressing the Gap in Research Methodologies Education in Pediatric Oncology in the Eastern Mediterranean Region.

PURPOSE: Formal training in clinical research methodologies is limited in limited-resource countries. Through collaboration among high- and middle-resource settings and in response to an identified need verbalized by regional pediatric oncology practitioners, Pediatric Oncology East & Mediterranean Group and St Jude Global developed a workshop focused on capacity building in research skills. Here, we describe its structure, implementation, and early results. METHODS: Leveraging virtual capabilities, the format included lectures and small group breakout exercise sessions, for 3 hours per day on 2 consecutive days per week for 2 consecutive weeks. Topics included basics of study design, introduction to health care statistics, research ethics, data registries, and scientific writing. Applicants were required to submit an abstract for a potential research project. Each breakout group selected one abstract for further development and presented the final version in a groupwide session. The participants' experience was evaluated through an online survey. RESULTS: Attendance included 29 registrants from 12 countries and six disciplines. Each breakout group was assigned a themed category: cohort studies, clinical trials, or registries. Critical feedback from the breakout sessions helped strengthen the selected projects, which included a retrospective study, a prospective observational study, a prospective interventional study, and a registry proposal. After the workshop, participants were invited to further develop their original abstracts, and three proposals received additional mentoring, one of which was a multi-institutional prospective study that was subsequently submitted through the Pediatric Oncology East & Mediterranean Group network for implementation. The postworkshop survey revealed an overall highly positive experience, and feedback provided potential themes for future workshops. CONCLUSION: This workshop demonstrated the potential for collaborative network partnerships in targeting research training gaps in pediatric oncology. Lessons learned will be applied to future workshops to strengthen research in limited-resource settings.

Pediatric oncology infrastructure and workforce training needs: a report from the Pediatric Oncology East and Mediterranean (POEM) Group.

BACKGROUND: Inadequate numbers of trained healthcare providers (HCPs), contribute to poor pediatric oncology (PO) outcomes, particularly in low- and lower middle-income countries (L/LMICs). An understanding of the characteristics of the workforce challenges are vital for addressing these problems. METHODS: The Pediatric Oncology East and Mediterranean (POEM) Group surveyed PO centers in countries of the North Africa, Middle East, Central Asia and Indian subcontinent on infrastructure and workforce capacity, service availability, and training opportunities for HCPs. Participating centers were categorized by the World Bank income levels for their countries and correlated with services, workload and staffing characteristics, and training needs. RESULTS: Fifty of 82 member-centers (61%) from 21 countries responded to the survey. 299 pediatric oncologists and 1,176 nurses treated 12,496 new PO patients/year, with a 1,451 beds utilization. The majority (71%) of new cases occurred in L/LMICs. The availability of HCPs correlated with country income level, as did pediatric subspecialty access, while availability of support services was unrelated. Twenty-five centers in 11 countries offered PO fellowship training for physicians, whereas 13 PO nurse training centers in 9 countries had the capacity to train 273 nurses annually. The survey respondents indicated that, among their existing workforce, an average of 3·5 physicians and 14 nurses per institution would benefit from additional PO training opportunities. CONCLUSIONS: The participating centers exhibited intra-regional heterogeneity in financial resources, infrastructure, workload, workforce, and medical services. Our findings provide insight into the disparities and regional resources available to POEM, which can be mobilized to rectify specific deficiencies. This article is protected by copyright. All rights reserved.

Estimated incidence, prevalence, mortality, and registration of childhood cancer (ages 0-14 years) in the WHO Eastern Mediterranean region: an analysis of GLOBOCAN 2020 data.

BACKGROUND: There is little evidence about childhood cancer burden in the WHO Eastern Mediterranean region (EMR). We aimed to provide an estimate of childhood cancer burden in the EMR, examine the connection between age-standardised mortality rate and level of income (gross domestic product [GDP] per capita), and reflect on the current status of childhood cancer registration in the EMR. METHODS: Using the GLOBOCAN 2020 data from the Cancer Surveillance Unit of the International Agency for Research on Cancer, we extracted data for childhood cancer (at ages 0-14 years) incidence, prevalence, and mortality for 22 countries in the EMR, the EMR as a whole, and other WHO regions, and categorised by main cancer types. Childhood cancers were classified according to the 10th revision of the International Classification of Diseases. We also searched MEDLINE, Google Scholar, and the grey literature between May 17 and Aug 2, 2021, for English-language articles and reports about the status of childhood cancer registration in the EMR. We further examined the connection between age-standardised mortality rate and GDP per capita for the 22 countries in the EMR. FINDINGS: The total estimated number of incident childhood cancer cases in the EMR was 23 847 in 2020, with an age-standardised incidence rate of 10·1 per 100 000 children at risk, ranging from 7·3 per 100 000 children at risk in Pakistan to 13·8 per 100 000 children at risk in Iran. The estimated number of incident cases was 7451 (age-standardised incidence rate 3·10 per 100 000 children at risk) for leukaemia, 3006 (1·30 per 100 000 children at risk) for brain and CNS tumours, 2222 (0·92 per 100 000 children at risk) for non-Hodgkin lymphoma, 1569 (0·67 per 100 000 children at risk) for kidney cancers, and 1420 (0·58 per 100 000 children at risk) for Hodgkin lymphoma. In 2020, the number of total estimated childhood cancer deaths in the EMR was 10 535, with an age-standardised mortality rate of 4·4 (per 100 000 children at risk, ranging from 0·8 per 100 000 children at risk in Qatar to 7·2 per 100 000 children at risk in Somalia. A negative correlation was found between countries' GDP per capita (income level) and mortality rates (r=-0·77, p<0·0001). The scarcity of data and quality of cancer registries in EMR countries prevented further analysis. INTERPRETATION: Given the variable quality and coverage of cancer registries in EMR countries, these findings are likely to be underestimates. Nevertheless, these data, especially the high mortality rates, reflect a need for effective national childhood cancer plans in line with the WHO Global Initiative for Childhood Cancer to improve survival. FUNDING: Friends of Cancer Patients.

Pediatric oncology infrastructure and workforce training needs: A report from the Pediatric Oncology East and Mediterranean (POEM) Group.

BACKGROUND: Inadequate numbers of trained health care providers (HCPs) contribute to poor pediatric oncology (PO) outcomes, particularly in low- and lower middle-income countries (L/LMICs). An understanding of the characteristics of the workforce challenges is vital for addressing these problems. METHODS: The Pediatric Oncology East and Mediterranean (POEM) Group surveyed PO centers in countries of North Africa, Middle East, Central Asia, and Indian subcontinent on infrastructure and workforce capacity, service availability, and training opportunities for HCPs. Participating centers were categorized by the World Bank income levels for their countries and correlated with services, workload and staffing characteristics, and training needs. RESULTS: Fifty of 82 member centers (61%) from 21 countries responded to the survey. Two hundred ninety-nine pediatric oncologists and 1176 nurses treated 12 496 new PO patients/year, with a 1451-bed utilization. The majority (71%) of new cases occurred in L/LMICs. The availability of HCPs correlated with country income level, as did pediatric subspecialty access, while availability of support services was unrelated. Twenty-five centers in 11 countries offered PO fellowship training for physicians, whereas 13 PO nurse training centers in nine countries had the capacity to train 273 nurses annually. The survey respondents indicated that, among their existing workforce, an average of 3.5 physicians and 14 nurses per institution would benefit from additional PO training opportunities. CONCLUSIONS: The participating centers exhibited intraregional heterogeneity in financial resources, infrastructure, workload, workforce, and medical services. Our findings provide insight into the disparities and regional resources available to POEM, which can be mobilized to rectify specific deficiencies.

Childhood cancer care in the Middle East, North Africa, and West/Central Asia: A snapshot across five countries from the POEM network.

BACKGROUND: The Pediatric Oncology East and Mediterranean (POEM) network, through this report, provides a snapshot view of an expected child's treatment journey in five countries in the region. METHODS: Pediatric oncologists from cancer centers in Egypt, Lebanon, Iraq, Jordan, and Pakistan provided input on referral pathways, barriers to care, and patient outcomes, based on personal experience and published data. Outcome data were extracted from institutional registries. A literature review of articles and meeting abstracts was conducted, and results summarized. RESULTS: Countries across the Middle Eastern, North African, and West Asian region face common difficulties relating to the provision of pediatric oncology care. National registries are largely lacking, with unavailability of outcome data. Economic barriers are a common theme, leading to delays in patient diagnosis, and interruptions and abandonment of therapy. Insufficient infrastructure and human resources, high rates of toxic deaths, and lack of common national protocols are common. The establishment of successful fundraising organizations linked to specific cancer hospitals showcase several success stories, enhancing services, improving patient access, and leading to outcomes comparable to those in developed countries. All identified published literature is institution-based and from only one or a few hospitals. Therefore, outcomes at a national level likely differ due to disparate cancer care capabilities. CONCLUSION: Well-designed national registries are essential for identifying gaps, and clear referral networks are needed to address delays to diagnosis and therapy. National and transversal programs to improve infrastructure, facilitate knowledge transfer, and promote advocacy, are needed to accelerate progress in the region.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.

Evaluation of Baseline Cardiac Function by Echocardiography and its Association With Nutritional Status in Pediatric Cancer Patients at The Indus Hospital in Karachi, Pakistan.

INTRODUCTION: Evidence on conducting baseline echocardiogram before starting chemotherapy in pediatric cancer patients is limited from developing countries where malnutrition and infections are common and which may result in cardiac dysfunction. MATERIALS AND METHODS: A prospective, observational study was conducted from October 2016 to May 2017 at The Indus Hospital, Karachi, Pakistan, among children 1 to 16 years of age suffering from cancer. Echocardiography was performed before starting chemotherapy. Associations between body mass index and cardiac abnormalities were studied. RESULTS: A total of 384 children met the inclusion criteria. The median (interquartile range) age was 8.0 (5.0 to 12.0) years and 62.0% (n=238) were male individuals. Twenty-two of 384 (5.7%) children had systolic dysfunction. Four of 22 had moderate-systolic and one of 22 had mild systolic dysfunction, for whom the therapy was altered, and they were treated without anthracyclines. Four of these 5 patients died, and only 1 of 5 survived through high-risk protocol. Seventeen of 22 children had low-normal systolic dysfunction. We found no evidence of an association between body mass index for age and abnormal left ventricular ejection fraction and abnormal fractional shortening (P-trend=0.587; 0.487, respectively). No associations were found of weight-for-age and height-for-age with these outcomes. CONCLUSIONS: In developing countries, echocardiograms should be expeditiously performed and technology made more accessible to rule out cardiac dysfunction and avoid delay in chemotherapy. Malnutrition was not associated with cardiac dysfunction.

Incidence, clinical distribution, and patient characteristics of childhood cancer in Saudi Arabia: A population-based analysis.

PURPOSE: Information regarding the incidence and patterns of childhood malignancies is disproportionately overrepresented by high-income countries, representing mainly the Caucasian population. There is a need to evaluate and disseminate information for other ethnicities, particularly from the Middle East. METHODS: Data from the National Cancer Registry, Saudi Arabia (SA-NCR), for pediatric patients (age 0-14 years) diagnosed between 2005 and 2009 and for similar patients at our institution during the same period were analyzed. Population numbers reported in the 2007 national census were used to calculate the annual incidence of childhood cancer. RESULTS: Data from SA-NCR on 3885 patients were included in this analysis. The median age was 5.58 years, and 57.3% were males. The annual age-specific cancer incidence rate (ASR) for children in SA is 99.83 per million population; ASR per million for lymphoid leukemia is 25.75, 12.05 for brain tumors, and 9.82 for Hodgkin lymphoma. Of all childhood cancers in SA, 35% were treated at our institution. The five-year overall survival for these 1350 patients is 74.6% (median follow-up 7.52 years [95% confidence interval: 7.36-7.68]). Significant differences in the distribution of childhood malignancy subtypes were evident compared with other countries. CONCLUSION: We have reported differences in the cancer ASR and cancer subtype distribution for children in SA as compared with the worldwide incidence and with other populations. This paper provides a comprehensive epidemiological overview of childhood cancer in SA, which could be extrapolated to other regional Arab populations.

Predictors of treatment abandonment for patients with pediatric cancer at Indus Children Cancer Hospital, Karachi, Pakistan.

BACKGROUND: Abandonment of treatment is one of the toughest challenges to deal with in pediatric oncology. It leads to unnecessary mortality and morbidity in patients from low- and middle-income countries. PROCEDURE: The objective of our retrospective study was to determine the prevalence and predictors for abandonment among children with cancer at our hospital in Karachi, Pakistan. We analyzed data on patients younger than 18 years, diagnosed with any malignancy between November 2014 and May 2016. RESULTS: From a total of 821 patients, one hundred and eighty-two (22.2%) patients abandoned treatment at various stages, 92 (11.2%) patients did not initiate treatment at all, and the remaining 90 (11.0%) left during treatment. The gender ratio at registration was skewed toward males but not statistically significant for abandonment. Of 295 registered females, 74 (25.1%) abandoned treatment compared to 108 (20.5%) abandonments among 526 males. In multivariable regression analysis, the type of malignancy, guardian's profession, and travelling from outside the city of Karachi (odds ratio [OR]: 1.48; 95% confidence interval [CI] 1.02-2.15; P = 0.039) correlated with increased abandonment. Treatment abandonment was higher among patients with brain tumors (45.7%) and solid tumors (30.8%) and among those whose guardians were associated with a rural profession (24.7%). Monthly income, age, and number of siblings had no impact on the decision to abandon treatment. CONCLUSION: Despite the provision of free treatment, the prevalence of abandonment was high. More qualitative data need to be collected to identify and target groups of individuals who may be likely to abandon treatment, thus improving outcome of patients.

Risk-adapted stratification for optimally intensive treatment assignment of pediatric patients with non-Hodgkin lymphoma is an effective strategy in developing countries.

BACKGROUND: Pediatric patients with non-Hodgkin lymphoma (NHL) in developing countries (DCs) present with greater tumor load even at lower stages and with comorbidities that impact therapy delivery. This causes toxic mortality with "standard" intensive protocols or recurrences with "gentler" treatment. OBJECTIVES: We developed and evaluated a risk stratification schema that guides intensity of therapy. DESIGN/METHODS: Sixty-nine patients were prospectively assigned to five risk groups (A-E; n = 6, 15, 16, 15, and 17) following staging and treated with protocols of risk-stratified intensity. Risk stratification utilized St. Jude stage, disease bulk, and sites involved. RESULTS: Between 2006 and 2011, 69 patients with B-cell NHL were enrolled. Among these, 72.5% were boys with mean age of 6.9 years (±3.33 [SD]; range 2.4-14.2 years). Eighty-seven percent had Burkitt lymphoma, 82.6% had advanced stage (25 [36.2%] stage III; 32 [46.4%] stage IV), and 24.6% were central nervous system positive. Mean lactate dehydrogenase increased progressively across the risk strata. Among these, 0/6, 1/15, 3/16, 2/15, and 7/17 patients relapsed/progressed within each risk stratum. Fifteen patients died; three from treatment-related toxicity. At a median follow-up of 6.2 years, the overall and event-free survival (EFS) for all patients was 78.1 and 75.4%, respectively; EFS was related to risk assignment. The frequency of documented infectious and noninfectious toxicities increased with higher risk group assignment causing prolongation of admissions and potential treatment delays. CONCLUSIONS: Reduction in treatment intensity for an identified subset of patients with NHL is feasible, while high-intensity therapy is required for high-risk groups. This risk stratification system may be a first step toward improving the outcomes in some DCs.

The Impact of Socioeconomic Factors on the Outcome of Childhood Acute Lymphoblastic Leukemia (ALL) Treatment in a Low/Middle Income Country (LMIC).

Survival for childhood acute lymphoblastic leukemia (ALL) has improved significantly, but these benefits may not be available to many children from low and middle income countries, where reasons for treatment failure may be unique to their environment. We retrospectively reviewed data on pediatric (1 to 18 y or younger) patients with newly diagnosed ALL treated over 5 years at a children's cancer hospital in Pakistan. Patients were treated with modified Berlin-Frankfurt-Muenster -based therapy without risk stratification. There were 255 children with a median age of 7 years (mean, 7.65 y) and a male preponderance (M:F=1.6:1). 20% had T-ALL, one-third had white blood cells >50×10/L and 13.7% central nervous system disease. A majority (56.5%) was malnourished. In total, 49 (19.2%) died before the end of induction and 21 died in complete remission. Most deaths were infection-related. A total of 50 patients relapsed and 19 abandoned therapy after complete remission. Five-year overall survival is 52.9% with abandonment censored and 45.8% with abandonment as an event. Overall survival was related to socioeconomic status but not to known risk factors. The outcome of ALL at our center is suboptimal and associated with factors not commonly seen in developed countries. Special attention to early diagnosis, infection control, and parental educational are needed to improve the survival.

Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies.

Background. We studied DNA chimerism in cell-free DNA (cfDNA) in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN) cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126) showed that, of 84 patients with 100% donor DNA in PMN, 16 (19%) had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19%) showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41%) showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse.