Implementing the WHO Global Initiative for Childhood Cancer in Morocco: Survival study for the six indexed childhood cancers.

BACKGROUND: In 2018, the World Health Organization (WHO) launched the Global Initiative for Childhood Cancer (GICC). The goal is to achieve a global survival rate of at least 60% for all children with cancer by 2030. Morocco was designated as a pilot country for this initiative. PROCEDURE: This retrospective study included a cohort of children aged 0-15 years, with one of the six indexed cancers (acute lymphoblastic leukemia [ALL], Burkitt lymphoma [BL], Hodgkin lymphoma, retinoblastoma [RB], Wilms tumor or nephroblastoma, low-grade glioma), diagnosed between January 1, 2017 and December 31, 2019 at the six Moroccan Pediatric Hematology and Oncology units. Patients were followed-up until August 31, 2020. The Kaplan-Meier method was used to estimate survival rates, the log-rank test for comparing survival curves, and the Cox model for identifying prognostic factors. RESULTS: Data on 878 patients were included in the study. The most frequently reported cancer type was ALL (n = 383, 43.6%), followed by Wilms tumor (n = 139, 15.8%) and BL (n = 133, 15%). Most patients were less than 5 years of age (n = 446, 50.9%) and the male/female ratio was 1.46. The 1, 2, and 3-year overall survival rates were 80.1%, 73.6%, and 68.2%, respectively. In a multivariable Cox regression model, care center, cancer type, age group, and distance to the care center were statistically significantly associated to survival. Patients aged 10 years and older and patients living more than 100 km from the care center were more likely to die (respectively, HR = 1.39, p = .045 and HR = 1.44, p = .010). CONCLUSION: The reported results represent the baseline for measuring the impact of GICC implementation in Morocco.

[Establishment of Hematopoietic cell transplantation program in developing countries : Guidelines from the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC)]. / Mise en place d'un programme de greffe de cellules souches hématopoïétiques dans les pays en voie de développement. Recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Hematopoietic cell transplantation (HCT) is the curative treatment for many malignant and non-malignant blood disorders and some solid cancers. However, transplant procedures are considered tertiary level care requiring a high degree of technicality and expertise and generating very high costs for hospital structures in developing countries as well as for patients without health insurance. During the 11th annual harmonization workshops of the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC), a designated working group reviewed the literature in order to elaborate unified guidelines, for developing the transplant activity in emerging countries. Access to infrastructure must comply with international standards and therefore requires a hospital system already in place, capable of accommodating and supporting the HCT activity. In addition, the commitment of the state and the establishment for the financing of the project seems essential.

Metro-SMHOP 01: Metronomics combination with cyclophosphamide-etoposide and valproic acid for refractory and relapsing pediatric malignancies.

BACKGROUND: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. AIM OF THE STUDY: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. PATIENTS AND METHODS: From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28-day cycles with daily oral administration of cyclophosphamide (30 mg/m2 ) from days 1 to 21, together with oral etoposide (25 mg/m2 ) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28. RESULTS: Ninety-eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1-18 cycles). One-year progression-free survival of our patients was 19%, and one-year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%). CONCLUSION: This three-drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.

[Indications and management of hematologic microtransplantation: Recommendations of the French Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC)]. / Atelier d'harmonisations 2019 : indications et organisation d'une microtransplantation de cellules souches hématopoïétiques.

Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete remission rates and longer disease free survival and overall survival have been reported. Safety seems acceptable. The most frequent adverse event is non-severe cytokine release syndrome. Risk of GVHD remains very low. Here, we summarize the published data and detail the practical aspects of the procedure. Current data are not strong enough to provide recommendations on indications. Nevertheless, it seems reasonable to propose MT to patients with AML or HR-MDS, regardless of age, presenting an indication for allogeneic stem cell transplantation but ineligible for it. MT is still under investigation and rather be proposed within clinical trials.

Special report: Summary of the first meeting of African Blood and Marrow Transplantation (AfBMT) group, Casablanca, Morocco, April 19-21, 2018 held under the auspices of the Worldwide Network for Blood and Marrow Transplantation (WBMT).

The first meeting of the African Blood and Marrow Transplantation (AfBMT) was held in Casablanca from April 19, 2018 to April 21, 2018, with the aim of fostering hematopoietic stem cell transplantation (HSCT) activity in Africa. Out of the 54 African countries, HSCT is available only in six (Algeria, Egypt, Morocco, Nigeria, South Africa, and Tunisia). During this meeting, African teams and international experts from the Worldwide Network for Blood and Marrow Transplantation (WBMT) gathered to share their experience and discussed ways to help fill the gap. Nurses and patients held their meeting in parallel. International support and collaboration can help by providing expertise adapted to local resources and regional population needs. Local engagement including government and private participants are necessary to initiate and develop local HSCT capability.

[Haploidentical hematopoietic stem cell transplant: How to choose the best donor? Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Greffe de cellules souches hématopoïétiques haplo-identiques avec cyclophosphamide en post-greffe : comment choisir le meilleur donneur en 2019 ? Recommandations de la Société francophone de greffe de mœlle et de thérapie cellulaire (SFGM-TC).

Haploidentical hematopoietic stem cell transplantation has been growing steadily since 2012. The SFGM-TC has twice published guidelines concerning T-cell repleted haploidentical grafts with high dose cyclophosphamide post-transplantation. The 2013 workshop recommended using the non-myeloablative Baltimore protocol with bone marrow and developed prospective protocols to evaluate these transplantations. The 2015 workshop reported improved results of reduced conditioning regimens in Hodgkin's lymphoma and intensive conditioning in myeloid hemopathies, and a similar outcome with 10/10 HLA matched donor with the same disease-risk score thus raising the question of the qualifier "alternative" for haploidentical transplants. The current work concerns the criteria for selecting the donor. The main criterion remains the absence of anti-HLA antibodies directed against the donor present in the recipient sera (DSA - Donor Specific Antibodies). In case of DSA and in the absence of an alternative donor, desensitization protocols exist. The other criteria are impossible to prioritize: age, sex, CMV, and blood type. The degree of relatedness and the number of HLA incompatibilities do not seem to be a criterion of choice. The 'ideal' donor would be a young man, CMV-matched, without major ABO incompatibility with a marrow transplant. There is insufficient data for the KIR-ligand and NIMA/NIPA mismatch. Peripheral stem cell grafts appear to yield more acute GVHD than bone marrow grafts after intensive conditioning, but with comparable survival rates. Based on the literature review, the comparison of haploidentical with unrelated donors encourages inclusion in existing national protocols randomizing these different donors.

Advanced Burkitt Lymphoma in Sub-Saharan Africa Pediatric Units: Results of the Third Prospective Multicenter Study of the Groupe Franco-Africain d'Oncologie Pédiatrique.

PURPOSE: To evaluate the results of an intensive polychemotherapy regimen for Burkitt lymphoma (BL) in sub-Saharan African pediatric centers. PATIENTS AND METHODS: Children with advanced-stage BL (stages II bulky, III, and IV) treated with the GFAOP-Lymphomes Malins B (GFALMB) 2009 protocol in 7 centers between April 2009 and September 2015 were prospectively registered. Treatment regimen contained a prephase with cyclophosphamide followed by 2 induction courses (cyclophosphamide, vincristine, prednisone, high-dose methotrexate [HDMTX]), 2 consolidation courses (cytarabine, HDMTX), and a maintenance phase only for stage IV. HDMTX was given at the dose of 3 g/m2. RESULTS: Four hundred patients were analyzed: 7% had stage II bulky, 76% stage III, and 17% stage IV disease. Median age was 7.3 years, and sex ratio was 1.9:1 (male:female). A total of 221 patients received the whole protocol treatment and 195 achieved complete remission (CR), 11 of them after a second-line treatment. Treatment abandonment rate was 22%. One hundred twenty-five patients died, of whom 49 deaths were related to treatment toxicity. A total of 275 patients are alive, including 25 despite treatment abandonment, but only 110 are known to be in CR with a follow-up > 1 year, indicating a high rate of loss to follow-up. Twelve-month overall survival (OS) was 60% (95% CI, 54% to 66%) and 63%, 60%, and 31%, respectively, for stage II bulky, III, and IV. Patients with stage III disease who started second induction course within 34 days had OS of 76%, versus 57% (P = .0062) beyond 34 days. CONCLUSION: The GFA-LMB2009 protocol improved patients' survival. Early dose intensity of treatment is a strong prognostic factor. Improving supportive care and decreasing loss to follow-up are crucial.

African School of Pediatric Oncology Initiative: Implementation of a Pediatric Oncology Diploma Program to Address Critical Workforce Shortages in French-Speaking Africa.

PURPOSE: In 2012, the French African Pediatric Oncology Group established the African School of Pediatric Oncology (EAOP), a training program supported by the Sanofi Espoir Foundation's My Child Matters program. As part of the EAOP, the pediatric oncology training diploma is a 1-year intensive training program. We present this training and certification program as a model for subspecialty training for low- and middle-income countries. METHODS: A 14-member committee of multidisciplinary experts finalized a curriculum patterned on the French model Diplôme Inter-Universitaire d'Oncologie Pédiatrique. The program trained per year 15 to 25 physician participants committed to returning to their home country to work at their parent institutions. Training included didactic lectures, both in person and online; an onsite practicum; and a research project. Evaluation included participant evaluation and feedback on the effectiveness and quality of training. RESULTS: The first cohort began in October 2014, and by January 2019, 72 participants from three cohorts had been trained. Of the first 72 trainees from 19 French-speaking African countries, 55 (76%) graduated and returned to their countries of origin. Four new pediatric oncology units have been established in Niger, Benin, Central African Republic, and Gabon by the graduates. Sixty-six participants registered on the e-learning platform and continue their education through the EAOP Web site. CONCLUSION: This training model rapidly increased the pool of qualified pediatric oncology professionals in French-speaking countries of Africa. It is feasible and scalable but requires sustained funding and ongoing mentoring of graduates to maximize its impact.

The My Child Matters programme: effect of public-private partnerships on paediatric cancer care in low-income and middle-income countries.

In low-income and middle-income countries, an excess in treatment failure for children with cancer usually results from misdiagnosis, inadequate access to treatment, death from toxicity, treatment abandonment, and relapse. The My Child Matters programme of the Sanofi Espoir Foundation has funded 55 paediatric cancer projects in low-income and middle-income countries over 10 years. We assessed the impact of the projects in these regions by using baseline assessments that were done in 2006. Based on these data, estimated 5-year survival in 2016 increased by a median of 5·1%, ranging from -1·5% in Venezuela to 17·5% in Ukraine. Of the 26 861 children per year who develop cancer in the ten index countries with My Child Matters projects that were evaluated in 2006, an estimated additional 1343 children can now expect an increase in survival outcome. For example, in Paraguay, a network of paediatric oncology satellite clinics was established and scaled up to a national level and has managed 884 patients since initiation in 2006. Additionally, the African Retinoblastoma Network was scaled up from a demonstration project in Mali to a network of retinoblastoma referral centres in five sub-Saharan African countries, and the African School of Paediatric Oncology has trained 42 physicians and 100 nurses from 16 countries. The My Child Matters programme has catalysed improvements in cancer care and has complemented the efforts of government, civil society, and the private sector to sustain and scale improvements in health care to a national level. Key elements of successful interventions include strong and sustained local leadership, community engagement, international engagement, and capacity building and support from government.

Treatment of retinoblastoma in Sub-Saharan Africa: Experience of the paediatric oncology unit at Gabriel Toure Teaching Hospital and the Institute of African Tropical Ophthalmology, Bamako, Mali.

BACKGROUND: Retinoblastoma (Rb) is the most common intraocular primary malignancy in children. In industrialised countries, the cure rate is about 95%. We present the results of a prospective study on the management of Rb in the paediatric oncology unit of Gabriel Touré Teaching Hospital and African Institute of Tropical Ophthalmology, from November 1, 2011 to December 31, 2015. PROCEDURE: The aims of this prospective study were to evaluate the treatment of localised Rb, ocular prosthesis after enucleation, conservative management for bilateral Rb as well as survival rates in all patients. Patients with early stage Rb at diagnosis were included. The treatment was performed according to the retinoblastoma treatment guidelines of the French-African Paediatric Oncology Group. RESULTS: Eighty-eight patients were included in the study. Sex ratio was 1:1 (M = 44, F = 44). Median age at diagnosis was 3 years (range: 2 months-5 years). Unilateral intraocular Rb was predominant (n = 50; 56.8%). Conservative treatments were performed on nine eyes in nine patients. Overall survival and event-free survival of the entire cohort at the end of 4 years were 73% (95% CI 60.8-81.2%) and 59% (95% CI 47.9-69.5%), respectively, with a median follow-up of 3.7 years (0.1-5.6 years). In conclusion, early enucleation in early stage of Rb can improve outcomes in resource-limited countries. Delayed enucleation and refusal of adherence to treatment are still major concerns and remain a barrier to improving overall patient survival.

Assessing National Cancer Control Plan Knowledge, Prioritization, and Engagement Through a Pediatric Oncology Cancer Control Workshop.

This study represents findings from a questionnaire completed before a cancer control workshop by 47 pediatric cancer control stakeholder participants from 27 countries. Respondents reported their knowledge of their country's cancer control plan, their understanding of childhood cancer control priorities in their local setting, and barriers to high-quality pediatric cancer care. Findings reveal a knowledge gap in pediatric oncology professionals' awareness of national cancer control plan existence, with under-recognition of existing plans, and uncertainty regarding whether pediatric cancer was included in the plans. This study supports the potential of a preworkshop needs assessment to inform cancer control planning objectives and a cancer control training agenda.

Well-directed inclusion of hematology in African national cancer control plans.

In the context of a convergent call for noncommunicable disease integration in the global agenda, recognizing cross-cutting needs and opportunities in national strategies across disease fields with shared priorities in low- and middle-income settings can enhance sustainable development approaches. We reviewed publicly available cancer control plans in Africa to evaluate for inclusion of hematology needs and shared service priorities. Pediatric data remain sparse in cancer control plans. While continental Africa represents incredible diversity, recognizing shared priorities and opportunity for collaboration between oncology and hematology services and across age groups may guide prioritized cancer control efforts and reduce programmatic redundancies in resource-limited settings.

A framework to develop adapted treatment regimens to manage pediatric cancer in low- and middle-income countries: The Pediatric Oncology in Developing Countries (PODC) Committee of the International Pediatric Oncology Society (SIOP).

Many children with cancer in low- and middle-income countries are treated in hospitals lacking key infrastructure, including diagnostic capabilities, imaging modalities, treatment components, supportive care, and personnel. Childhood cancer treatment regimens adapted to local conditions provide an opportunity to cure as many children as possible with the available resources, while working to improve services and supportive care. This paper from the Adapted Treatment Regimens Working Group of the Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology outlines the design, development, implementation, and evaluation of adapted regimens and specifies levels of services needed to deliver them.

Improving the prognosis of pediatric Hodgkin lymphoma in developing countries: a Moroccan Society of Pediatric Hematology and Oncology study.

BACKGROUND: The event-free survival (EFS) of children with Hodgkin lymphoma (HL) exceeds 80% in high income countries (HIC), but little is known about this rate in developing countries. PROCEDURE: A prospective national protocol for children with classical HL was implemented in Morocco to increase EFS by careful risk stratification, providing each cycle of therapy on time, decreasing treatment abandonment, improving communication among healthcare providers, and improving data collection. Patients were stratified into a favorable risk group (Ann Arbor stages I and II, no B symptoms, no bulky disease, and no contiguous (E) lesions) and received four cycles of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) or an unfavorable risk group (all others) who received two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) and four cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP). All patients received involved-field radiotherapy 25.5 Gy after completion of chemotherapy. EFS was calculated counting death, relapse/resistant disease, and abandonment as events. RESULTS: From February 2004 to December 2007, 160 patients enrolled; 138 (86%) had unfavorable risk features. Twenty patients (12.5%) abandoned treatment, 16 relapsed or had resistant disease, and 6 died (3 unexplained, 2 varicella, and 1 suicide). The estimated 5-year EFS was 70 ± 4% and overall survival 88 ± 3%. CONCLUSIONS: Good outcomes for pediatric HL patients can be achieved in LMIC using a multidisciplinary team approach, uniform protocol-based therapy, twinning partnership among oncology units in-country and abroad, and a data collection system to monitor compliance and identify gaps in care.

[Retinoblastoma: inventory in Mali and program to develop early diagnosis, treatments and rehabilitation]. / Le rétinoblastome: état des lieux au Mali et programme d'aide au diagnostic précoce, aux traitements et à la réhabilitation.

Retinoblastoma (RB) is a rare embryonic tumour that represents 1/16,000 births in France. In Mali, a study showed the characteristics of a hospital series of cases seen in Bamako in the Pediatric Oncology Unit of Gabriel Touré Teaching Hospital and in the Tropical Ophthalmology Institute of Africa (IOTA) between January 2005 and June 2007. Median age was 4 years versus 2 years in France for unilateral disease. Near two third of children with RB had extra-ocular extension at diagnosis, which is now exceptional in France. Only 11% were bilateral versus 35% in France. Cure rate was around 50%, but it is estimated only on the cases arriving in Bamako and with at least 20% lost of follow-up. Cure rate is over 95% in France within an exhaustive register. RB appears as an exemplary tumor and rapid improvements could be obtained in low-income countries with relatively limited means. This is why, the Alliance mondiale contre le cancer (AMCC), the Institut Curie in Paris, which is the reference center in France for RB, and teams in Bamako were proposing a program to help the development of early diagnosis, treatments, including eye preservation, and rehabilitation of children with RB in sub-Saharan Africa in collaboration with the Groupe franco-africain d'oncologie pédiatrique (GFAOP). The official launching of this program was held in Bamako November 4, 2011 for Mali and the surrounding regions. After this first experience, this program is now implemented in other countries.