[Autoimmune lymphoproliferative syndrome: a case report]. / Syndrome lymphoprolifératif avec autoimmunité: à propos d'un cas.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. It is characterized by non-infectious and non-malignant chronic lymphoproliferation and an increased risk of lymphoid malignancy. The diagnosis of this condition usually combines chronic lymphadenopathy and/or splenomegaly exceeding 6 months, autoimmune cytopenias, with an elevated level of CD3+CD4-CD8- Tαß lymphocytes, known as "double-negative" T cells. Differential diagnosis includes infections, autoimmune diseases or malignancies. Although clinical examination and laboratory tests are highly suggestive, this disease goes widely unrecognized. We here report, for the first time, the case of ALPS, a Moroccan patient, and aged 8 years, with recurrent fever, splenomegaly and adenopathies. Paraclinical examinations revealed chronic pancytopenia, higher than normal TαÎ2 double negative lymphocytes, hypergammaglobulinemia, and elevated serum levels of soluble FAS ligand. The diagnosis of ALPS was made. First-line treatment included corticosteroids and immunoglobulins. Then the patient received mycophenolate followed by Sirolimus. This treatment resulted in better clinical and laboratory tests results. Our aim is to raise awareness of this rare condition, which may be under-diagnosed, among physicians.

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.

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.

HAEMOcare: The First International Epidemiological Study Measuring Burden of Hemophilia in Developing Countries.

Introduction Optimizing hemophilia care remains challenging in developing countries. Burden-of-disease studies are important to develop strategies for improving hemophilia care. Aim The HAEMOcare study evaluated the factors contributing to hemophilia-related orthopedic disease burden in developing countries. Methods HAEMOcare was a noninterventional, cross-sectional, epidemiological study conducted in Algeria, India, Morocco, Oman, and South Africa. Male patients with severe hemophilia ( N = 282) aged ≥6 years, without or with inhibitors, being treated on-demand for bleeding were included. Hemophilia-related orthopedic clinical and functional status was assessed using the Hemophilia Joint Health Score (HJHS), radiological status with the Pettersson Score, and quality of life with the EuroQol five-dimension questionnaire (EQ-5D-3L). Direct and indirect economic costs of hemophilia care were also calculated. Results Patients (mean [standard deviation, SD] age: 20.8 [10.6] years) experienced a mean annualized bleeding rate of 25.8. Overall mean (SD) HJHS and Pettersson score were 17.9 (12.8) and 15.0 (13.5), respectively; scores were similar between patients without or with inhibitors ( p = 0.21 and 0.76, respectively). Approximately 70% of adults reported problems relating to pain/discomfort and mobility parameters in the EQ-5D-3L. Mean distance to a hemophilia treatment center (HTC) was 79.4 km. As expected, total costs of hemophilia were statistically significantly higher in patients with inhibitors versus without inhibitors ( p = 0.002). Conclusion Inadequate access to HTCs and expert care, along with high bleeding rates, led to equivalent hemophilia-related orthopedic morbidity between hemophilia patients without and with inhibitors. HAEMOcare documented the economic and disease burdens associated with suboptimal hemophilia care in developing countries.

High incidence of MYCN amplification in a Moroccan series of neuroblastic tumors: comparison to current biological data.

MYCN protooncogene status was assessed for the first time in Morocco in peripheral neuroblastic tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Correlations with age at diagnosis, stage, mitosis-karyorrhexis index, differentiation, and Shimada histology were evaluated. Thirty-six formalin-fixed, paraffin-embedded peripheral neuroblastic tumor tissue specimens collected between 2007 and 2010 from the Pathology Department were assessed for MYCN amplification using fluorescence in situ hybridization. MYCN amplification was found in 27.8% of cases. An association of MYCN amplification with unfavorable Shimada grading, higher mitosis-karyorrhexis index, and undifferentiated morphologic phenotype was found. We found no correlation with older age, advanced stage, or the presence of metastasis. Our results suggested that the presence of MYCN amplification is a strong biological indicator of a poor outcome and aggressive disease in neuroblastoma and nodular ganglioneuroblastoma.