Since its inception in 1987, the Pediatric Hematology Oncology (PHO) chapter of the Indian Academy of Pediatrics (IAP) has emerged as one of its most active and impactful chapters. The chapter has played a pivotal role in improving the care of children with cancer and various hematological disorders in India over the past four decades. It has contributed significantly to the development of the subspecialty in India through capacity-building initiatives, national training programs, guideline development, academic teaching, and conferences. The chapter has also fostered global collaborations and multicentric research, resulting in evidence-based, context-specific improvements in clinical practice. Alongside its sister organization-the research foundation-Indian Pediatric Hematology Oncology Group (INPHOG)—the PHO chapter has elevated pediatric hematology oncology care in India to standards comparable with leading international centers.

In this second paper of a Series on childhood cancer in Asia, we provide an overview on the Paediatric Oncology Clinical Trials in Asia. Asia with a population of 4.7 billion constitutes about 60% of the world's population. The continent accounts for about half of the global paediatric cancer burden. Many Asian countries have consequently formed national professional societies in childhood cancer. Multicentre clinical trials are pivotal in advancing survival outcomes in paediatric oncology. The continent's diverse socioeconomic conditions may account for significant disparities in the development of such trials. However some countries with good financial resources are relatively deficient in developing clinical trials. In general, the countries show three distinct levels of clinical trials development: established, emerging and nascent. This article reports the landscape of multicentre clinical trials in Asia and the hurdles that clinicians face to actively engage in quality research and clinical trials. Although a ‘one-size-fits-all’ approach is not feasible, the successful development of clinical trials systems in some countries can offer valuable lessons and insights for others.This is the second in a Series of three papers on childhood cancer in Asia (Paper 3 appears in The Lancet Child and Adolescence Health).

The survival rates for pediatric patients with primary refractory or high-risk relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL), treated with chemotherapy-based protocols and followed by allogeneic hematopoietic cell transplantation (HCT), range from 15% to 30%.1 These outcomes are even more unfavorable in countries with evolving healthcare insurance systems due to treatment-related mortality and financial toxicity.2 The long-term event-free survival for such high-risk relapse of B-ALL is dependent on achieving minimal residual disease (MRD) negativity prior to HCT.3 In the past decade, there have been significant advancements in targeted antibody-based immunotherapies for managing r/r B-ALL.4-11 Blinatumomab (Blina) is a T-cell engager that provides an antileukemic effect by targeting cytotoxic T cells to CD19-expressing cancer cells. Several studies have revealed the excellent efficacy of Blina in low-burden disease.4-8 However, recipients of Blina with high tumor burden have low response rates and are at risk of severe cytokine release syndrome (CRS).9 Whereas, Inotuzumab ozogamicin (InO) targets CD22, which is conjugated to calicheamicin, a potent cytotoxic agent and works well even for high-burden disease with response rates as high as 80%.10, 11 To optimize the use of these novel immunotherapies in r/r B-cell ALL, we designed a disease-burden-adapted protocol of InO followed by Blina for high-burden (minimal residual disease (MRD) > 5%) CD22+ CD19+ disease and Blina only for low-burden (MRD ≤ 5%) CD19+ disease. This is a retrospective analysis of 39 patients with r/r B-cell ALL patients aged 1–18 years treated in three centers from January 2018 to August 2023. Patients were treated with a chemotherapy-based protocol from January 2018 to April 2021 and on a disease-burden-adapted immunotherapy protocol from May 2021 to August 2023. End-of-induction (EOI) MRD of >5% with high-risk cytogenetics or age >16 years and all patients with end-of-consolidation (EOC) MRD > 0.1% irrespective of age or cytogenetics were considered primary refractory. Very early relapse (<18 months from diagnosis; marrow or isolated extramedullary), early relapse (18–36 months from diagnosis or until 6 months off therapy; marrow or isolated extramedullary), and late relapse (≥36 months from diagnosis or >6 months off therapy; marrow or isolated extramedullary) with postrelapse induction MRD of ≥0.1% and second relapse with any level of disease were considered as high-risk. A fractionated dose of InO as 1.8 mg/m2 per course was administered intravenously over 1 h on Days 1, 8, and 15 of 28-day cycle as previously described.10, 11 Blina was given as a 28-day continuous intravenous infusion. The first 7 days of the first cycle were administered at 5 mcg/m2/day, and subsequently, the dose was increased to the maximum tolerated dose, up to a maximum of 15 mcg/m2/day. Flow cytometric immunophenotypic analysis of the bone marrow was done on CD45/side scatter plots for diagnosis and follow-up MRD. In view of Blina and InO therapy, previously described alternate gating strategies were used.12 Bone marrow MRD assessments were conducted after each course of immunotherapy and after HCT at 1-, 2-, 3-, 6-, and 12-month intervals. Treatment responses were classified as complete response if MRD was negative, good response if MRD was detectable to less than 0.01%, partial response if the disease burden reduced but was more than 0.01%, and no response or progressive disease depending on whether the disease burden was stable or progressive. Patients were followed up in the clinic until November 2023. Adverse events including neurotoxicity, cytokine release syndrome, veno-occlusive disease (VOD), and tumor lysis syndrome were graded using the CTCAE, version 5. Overall survival was measured as time from immunotherapy to death, and event-free survival was measured as time from immunotherapy to relapse or death. We also compared the overall survival of high-risk relapsed leukemia patients in the cohort who received immunotherapy with that of high-risk relapsed leukemia patients from January 2018 to April 2021, predating the immunotherapy protocol. The Kaplan–Meier method was used to generate survival curves. This analysis was performed in line with the principles of the Declaration of Helsinki. Bai Jerbai Wadia Hospital Ethics Committee approved retrospective analysis (Ethics No. IEC/BJWHC/AP/2024/025). Nineteen consecutive patients with r/r B-cell ALL were treated with the disease-burden-adapted immunotherapy protocol from May 2021 to August 2023. All patients were consented for immunotherapy. The median age of the cohort was 12 years (range: 2–17 years), and two-thirds of patients were ≥10 years of age. Five were females and 14 were males. Seven patients had high-risk cytogenetics (three low hypodiploidy and one each of ABL1, iAMP21, IKZF1 deletion, and MLL-rearrangement). The demographic, leukemia characteristics, and treatment details of patients are shown in Table 1. Eight patients were primary refractory (4 = induction failure, 4 = consolidation failure). All primary refractory patients were referred from different hospitals across the country. Eleven patients had high-risk relapsed leukemia (2 = very early, 4 = early relapse, 2 = late relapse with post-relapse induction MRD of ≥0.1%, 3 = second relapse). Patients with relapsed leukemia received either three previous chemotherapy protocols (n = 5), two previous chemotherapy protocols (n = 5), or one previous chemotherapy protocol (n = 1). Ten patients received chemotherapy-based relapse induction for the latest relapse, and all had postinduction residual disease. Five of 19 patients (26%) had an extramedullary disease, three were central nervous system positive, and two had testicular involvement. Twelve patients (5 = primary refractory; 7 = relapsed) with MRD ranging from 0.008% to 4.21% received Blina alone (Figure 1A). The median number of Blina cycles was 2 (range: 1–3). All 12 patients achieved MRD-negative remission after the first cycle. Seven patients (3 = primary refractory; 4 = relapsed) with high-burden disease ranging from 5.34% to 78% received one cycle of InO (Figure 1A). Six patients responded to InO; three patients became MRD-negative, and three patients achieved a good response. All six patients received consolidation with Blina and achieved MRD-negative status. One patient progressed on InO and, as a result, received palliative care. Eighteen patients (95%) achieved MRD-negative status with the disease-burden-adapted protocol. Sixteen patients (84%) have undergone allogeneic HCT. Seven patients received grafts from haploidentical donors, six underwent matched unrelated donor HCT, and three received HCT from matched sibling donors. One patient, lacking an HLA-matched donor, underwent an autologous transplant due to high-risk pretransplant factors, such as chronic parvoviremia, intestinal adenovirus shedding, and obesity. Another patient, also without an HLA-matched donor, chose maintenance chemotherapy because of chronic parvoviremia and intestinal adenovirus shedding. Fifteen patients (77%; 95% CI: 49.5–90.6) were alive and in continuous MRD-negative CR with a median postimmunotherapy follow-up of 424 days (range: 117–914; Figure 1B,C). Nine (82%) of 11 patients who received disease-burden-adapted protocol for relapsed leukemia were disease-free at a median follow-up of 317 days (range: 117–853). In contrast, one of 20 patients (5%) were disease-free in the preimmunotherapy high-risk relapsed leukemia cohort with a median survival of 93 days (Figure 1D; p < 0.0001). The comparison of the preimmunotherapy cohort versus the cohort treated with disease-burden-adapted protocol is shown in Supporting Information S1: Figure 1. Nine (50%) patients developed mild CRS with Blina (7 = grade 1, 2 = grade 2). Two (12%) patients experienced grade 1 neurotoxicity that recovered after transient discontinuation of Blina. One patient treated with InO had grade 1 CRS. Six patients who received InO have undergone HCT to date and only one experienced mild VOD during HCT, which responded to fluid restriction and diuretics. No patients experienced immunotherapy-related grade 3 or grade 4 toxicity. There were four deaths in the immunotherapy cohort. The causes of death included disease progression on InO in one patient, post-HCT CD19-negative relapse in another patient, and the other two patients succumbed to transplant-related mortality; one died of acute respiratory distress syndrome and another patient succumbed to early disseminated adenoviremia. Patients diagnosed with refractory ALL inherently exhibit resistance to chemotherapy and those with relapsed ALL acquire resistance during chemotherapy exposure.13 The alternative mechanism of targeting B-cell antigens with antibody-based immunotherapies provides greater opportunities for precision medicine. Clinical trials have shown that using Blina as a bridging regimen before HCT for relapsed B-cell ALL can improve disease-free survival rates.4-8 At a median follow-up of 2 years, the disease-free survival rates for patients who received Blina ranged from 55% to 65%.4, 8 The observations that Blina works better in the MRD setting than in hematological remission, and up to 80% of patients with high tumor burden respond to InO, formed the basis of the protocol.4-11 Notably, no serious side effects were observed in this protocol. Our protocol of consolidating InO response with Blina may also reduce the risk of VOD by allowing more time between InO administration and transplant. Furthermore, exclusive use of Blina in low-burden disease could have abrogated the risk of severe CRS or neurotoxicity. In parallel to the development of antibody-based immunotherapies, advances in cell-based immunotherapies have occurred.14, 15 Cell-based immunotherapies require significant laboratory expertise and are expensive. In addition, at least 50% of patients relapse after CAR T-cell therapies and not all CAR T-cell therapies yield similar results.14, 16, 17 Allogeneic HCT as a consolidative therapy after CAR T cells offsets the potential benefits of autologous CAR T cells. In contrast, antibody-based therapies are off-the-shelf, manufacture-controlled, and do not require infrastructure, making them a more viable option in regions with emerging healthcare insurance systems. To conclude, the disease-burden-adapted protocol is a promising strategy for treating r/r pediatric B-ALL as a bridging regimen before HCT. The report underscores the importance of making these immunotherapies accessible on a global scale through collaborative efforts involving governments, nongovernmental organizations, and pharmaceutical initiatives. While the analysis is retrospective, its findings highlight the efficacy and safety of this strategy allowing a greater number of patients to reach potentially curative HCT. We acknowledge Amgen's Blincyto Humanitarian compassionate access program that helped to treat patients with relapsed-refractory B-cell acute lymphoblastic leukemia. Prashant Hiwarkar conceived the study and analyzed the data. Sanaa Khan, Krishnan VP, Lashkari Harshaprasad, and Purva Kanvinde acquired the data. Sanaa Khan, Krishnan VP, and Prashant Hiwarkar wrote the manuscript. Kunal Sehgal did flow cytometry analysis. Sanaa Khan, Krishnan VP, Yamini Krishnan, Gazel Sainulabdin, Somdipa Pal, Rincy Mathews, Darshan Kataria, Minnie Bodhanwala, Bharat Agarwal, Ambreen Pandrowala, and Prashant Hiwarkar were actively involved in patient care; all authors revised and approved the final manuscript. The authors declare no conflict of interest. This research received no funding. The data sets generated and/or analyzed during the current study are not publicly available because patients and/or legal guardians have not consented to data sharing but are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243–1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes.

In Asia, a few countries have a long and established history of collaborative clinical trials successfully formed national children's cancer study groups, but many still do not have such groups. The process of forming national children's cancer groups is fraught with many hurdles, which varies among the countries. One of the basic requirements for running clinical trials is an affordable health care system in which most of the children with cancer can receive the proposed treatment. The health insurance coverage for children with cancer varies from <20% to as high as 100% among Asian countries, and the operation of clinical trials must also be adjusted accordingly. Shortage of research personnel is common, including medical, nursing, research coordinators, and data managers. The establishment of the Asian Pediatric Hematology and Oncology Group aims to provide a good platform for promotion of international clinical trials in the Asian countries.

Background Transplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome linked to the overactivation of complement pathways. It manifests with microangiopathic hemolytic anemia, consumptive thrombocytopenia, and microvascular thrombosis leading to ischemic tissue injury. Mannose residues on fungi and viruses activate the mannose-binding lectin complement pathway, and hence activation of the lectin pathway could be one of the reasons for triggering TA-TMA. Narsoplimab, a human monoclonal antibody targeting MASP-2 is a potent inhibitor of the lectin pathway. We describe the transplant course of a pediatric patient who developed TA-TMA following Candida-triggered macrophage activation syndrome and was treated with Narsoplimab. The data collection was performed prospectively. Case presentation The six-year-old girl underwent a human leucocyte antigen (HLA) haploidentical hematopoietic stem cell transplant using post-transplant Cyclophosphamide for severe aplastic anemia. In the second week of the transplant, the patient developed macrophage activation syndrome necessitating treatment with steroids and intravenous immunoglobulin. Subsequently, USG abdomen and blood fungal PCR revealed the diagnosis of hepatosplenic candidiasis. Candida-triggered macrophage activation syndrome responded to antifungals, steroids, intravenous immunoglobulin, and alemtuzumab. However, the subsequent clinical course was complicated by thrombotic microangiopathy. The patient developed hypertension in the 2nd week, followed by high lactate dehydrogenase (1010 U/L), schistocytes (5 per hpf), low haptoglobin (< 5 mg/dl), thrombocytopenia, and anemia in the 3rd week. Ciclosporin was stopped, and the patient was treated with 10 days of defibrotide without response. The course was further complicated by the involvement of the gastrointestinal tract and kidneys. She had per rectal bleeding with frequent but low-volume stools, severe abdominal pain, and hypoalbuminemia with a rising urine protein:creatinine ratio. Narsoplimab was started in the 5th week of the transplant. A fall in lactate dehydrogenase was observed after starting Narsoplimab. This was followed by the resolution of gastrointestinal symptoms, proteinuria, and recovery of cytopenia. The second episode of TA-TMA occurred with parvoviraemia and was also successfully treated with Narsoplimab. Conclusion Lectin pathway inhibition could be useful in treating the fatal complication of transplant-associated thrombotic microangiopathy.

Background:Hematopoietic stem cell transplantation in primary immunodeficiency disorders has come a long way since the first transplant in 1968. In India, pediatric stem cell transplantation long-term survival outcomes range from 62.5% to 75%, compared to 90% in high-income countries.Objective:We present single-center data of primary immunodeficiency transplants with immune-reconstitution evaluation after transplantation from a charitable trust hospital.Methods:Retrospective data of children transplanted for primary immunodeficiency disorders from March 2019 to March 2022 in a newly established transplant unit were collected. Data of pretransplant infections and comorbidities, surveillance for carbapenem-resistant Enterobacteriaceae, transplant characteristics, donor source, graft-versus-host disease, posttransplant infections, immune reconstitution, overall survival at 1 year, and immunodeficiency-free survival were collated.Results:Twenty-one patients underwent transplantation for primary immunodeficiency disorders. The median age at transplantation was 3 years and 5 months (range, 7 months to 17 years). Seventy-five percent of the cohort had organ involvement, with lung being the most common organ involved, followed by central nervous system. Fifty-two percent of children had peritransplant infections, with most of them recognized at the pretransplant assessment. Among 20 of 21 children with engraftment, 94% had complete chimerism initially, with 33% developing mixed chimerism over time. The median duration of immunosuppression was 3 months after transplantation, and only 1 child required systemic graft-versus-host disease treatment for more than a year. Immune-reconstitution showed good T-cell recovery at 3 months and naive T-cell production at 6 months. There was no regimen-related or sepsis-related mortality. Overall survival of the cohort was 95% at 1-year follow-up. Immunodeficiency-free survival was 86% after a median follow-up of 20 months.Conclusions:Immunodeficiency-free and graft-versus-host disease-free survival can be achieved in the majority of children with primary immunodeficiencies using enhanced supportive care and the latest transplantation algorithms.

adepartment of Blood and marrow transplantation, Bai Jerbai Wadia Hospital for children, mumbai, india; bdepartment of Pediatric Haematology-oncology, Bai Jerbai Wadia Hospital for children, mumbai, india; cdepartment of Pediatric radiology, Bai Jerbai Wadia Hospital for children, mumbai, india; ddepartment of Pediatric Surgery, Bai Jerbai Wadia Hospital for children, mumbai, india; edepartment of Pediatrics, Bai Jerbai Wadia Hospital for children, mumbai, india

Iron Deficiency(ID) implies depletion of body iron stores which if not treated can progress to Iron Deficiency Anemia(IDA). Other than anemia, ID has been linked with poor cognitive development, behaviour problems, impairment of the immune system any many others. Reticulocyte Hemoglobin Content (CHr) a newer reticulocyte parameter available in CBC coulter counter is a promising parameter for picking up iron deficiency before it progresses to IDA. However its normal ranges in various age groups are not established. Early detection of ID in pediatric population will help us in prevention of its progression to IDA. Objectives Estimate the burden of Iron deficiency and IDA in children visiting pediatric tertiary care hospital. Determine the reference range of CHr in normal children & clinical utility of CHr as an alternative of iron studies for picking up iron deficiency. Methods Prospective, Cross- section study, performed on Children between 1 month to 18 years of age, over 5 months period. All children undergoing a CBC test were included in the study after taking informed consent. Children who received blood transfusion in past 3 months, on hematinic therapy, an established hematological disorder, malignancy or Chronic liver and renal disorders were excluded. Reticulocyte parameters and iron studies were done for included children. Based on CBC & iron profile patients were divided into 4 groups. 1) Normal- Normal Hemoglobin (Hb) and No Iron deficiency (ID). 2) Iron deficiency- Normal Hb with ID. 3) Iron deficiency Anemia- Low Hb with ID 4) Non-iron deficiency anemia- Low Hb and no ID. WHO definition was used to identify children with anemia. To identify iron deficiency Transferrin saturation(TS)% levels were used. (TS<12% for 6 months to 5 years, 14% for 5-10 years & <16% for >10 years). For Children < 6 months, age wise nomograms were used. Results Of the 520 patients included in the study 37.6% (196) were Normal, 18.8% (98) had ID, 34.4% (179) had IDA and 9.2% (47) had non-IDA. Prevalence of anemia in our study population was 43.46% (226/520) with maximum prevalence of IDA i.e 79.2% (179/226) amongst all anemic children. Burden of ID was 34.4% in our population. Maximum burden of ID and IDA was in the age group of 6 month - 59 months i.e 38.8% and 65.9% respectively. Mean (SD) values of CHr in normal children of different age groups were: 1to 3 months 26.98(2.65), 3 to 6 months 24.85(0.68), 6 months to 59 months 26.01(1.72), 5 to12 years 26.73(1.84), 12 -14 years 27.27(1.56) and 15 to 18 years 28.14(3.28) (Table 1). We noted that mean values of CHr were significantly higher in normal children when compared with children having ID and IDA (Table 1). However, in the children of 15-18 years age group statistical significance was not reached as the number of children in this age group were less. Comparison of mean CHr values of normal children with non-IDA children did not show any difference (Table 2) and in children between 12-14 years it was significantly higher in non-IDA 32.85 vs 27.27 in normal children (p value-0.002). We also noted a significantly higher TS% in non-IDA children of this age group, which signifies a good correlation of CHr with TS%. There was only one child of non-IDA with CHr of 22.4 vs 7 normal children with mean CHr of 24.85 in age group of 3-6 months. Normal range of CHr for children between 6 months to 59 months was 25.58 to 26.44 and 5 to 12 years was 26.63 to 27.13 (Table 1). Data in other age group was in similar range, but is not conclusive due to lesser number of patients. Area under the curve (AUC) of CHr for normal children between 6-59 months was 0.89 with 95% CI of 0.85 to 0.93 and for children between 5-12 years was 0.80 with 95% CI of 0.72 to 0.88. Correlation(spearmen) between TS% & CHr among children of 6-59 months and 5-12 years was, 0.70 (p value - 0.0001) and 0.48 (p value- 0.0001) respectively. Iron studies cost 2 times more than the cost of getting CBC and CHr test. As CHr is done in the same CBC machine there is no need of an extra sample/prick as required for iron studies. Conclusion Prevalence of ID and IDA is high in our cohort. In our study we established that CHr in normal and non-IDA conditions is higher than in ID and IDA. Our study concludes good correlation of CHr with TS% and therefore we suggest it to be a cost-effective alternative of iron studies. With the help of Normal ranges of CHr established in this study we will be able to identify ID and intervene early hence reduce associated morbidities in our population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

•Use of Vemurafenib in relapsed/refractory BRAFV600E LCH in India•Monotherapy of Vemurafenib in multisystem LCH•VMF with slow taper to maintain disease in remission and reduce financial burden

To study the clinical course of patients with sickle cell anemia and coinherited hematological disorders. Retrospective analysis of clinical data of patients enrolled at our hospital over last 7 years was performed. Eighty four patients of symptomatic sickling disorders were registered during this period, comprising of HbSS (n = 49), HbS-β thalassemia (n = 28), HbS-HbD disease (n = 5), HbS-β thalassemia with G6PD deficiency (n = 1) and HbS-hemophilia A (n = 1). Among HbS-β thalassemia, 18% suffered from occasional pain crises and 27% required occasional blood transfusion. 40% patients with HbS-HbD disease required occasional blood transfusions, one patient was transfusion dependent, while none suffered from crisis episodes. Patient with HbS-β thalassemia with G6PD deficiency had increased transfusion requirement during first 3 years of life, which decreased after that. Patient with HbS and severe hemophilia A had only one episode of severe bleeding, suffered from 1 crisis episode. In conclusion, HbA reduces severity of HbS in HbS-β + thalassemia. HbS-HbD disease can manifest as a transfusion dependent illness. HbSS reduces severity of G6PD deficiency after first few years of life. HbSS and hemophilia coinheritance ameliorates symptoms of hemophilia.

Childhood cancer is a major global health issue. Every year, almost 100 000 children die from cancer before the age of 15 years, more than 90% of them in resource-limited countries. Here, we review the key policy issues for the delivery of better care, research, and education of professionals and patients. We present a key list of time-limited proposals focusing on change to health systems and research and development. These include sector and system reforms to make care affordable to all, policies to promote growth of civil society around both cancer and Millennium Development Goals, major improvements to public health services (particularly the introduction of national cancer plans), improved career development, and increased remuneration of specialist health-care workers and government support for childhood cancer registries. Research and development proposals focus on sustainable funding, the establishment of more research networks, and clinical research specifically targeted at the needs of low-income and middle-income countries. Finally, we present proposals to address the need for clinical trial innovation, the complex dichotomy of regulations, and the threats to the availability of data for childhood cancers.