A software tool to support follow-up care in a French childhood cancer cohort: construction and feasibility.

BACKGROUND: Treatment summaries and a personalized survivorship care plans based on internationally approved, organ-specific follow-up care recommendations are essential in preserving the health and quality of life for cancer survivors. Cohorts made up of survivors of childhood cancer have made significant contributions to the understanding of early mortality, somatic late complications, and psychosocial outcomes among former patients. New treatment protocols are needed to enhance survival and reduce the potential risk and severity of late effects, and working with treatment databases is crucial in doing so. CONSTRUCTION AND CONTENT: In the GOCE (Grand Ouest Cancer de l'Enfant [Western Region Childhood Cancer]) network, in a participative approach, we developed the LOG-after medical tool, on which health data are registered and can be extracted for analysis. Its name emphasizes the tool's goal, referring to 'logiciel' (the French word for software) that focuses on the period "after" the acute phase. This tool is hosted on a certified health data server. Several interfaces have been developed that can be used depending on the user's profile. Here we present this innovative co-constructed tool that takes national aspects into account, including the results of the feasibility/satisfaction study and its perspective. UTILITY AND DISCUSSION: The database contains data relating to 2558 patients, with samples from 1702 of these (66.54%) being held in a tumor bank. The average year in which treatment started was 2015 (ranging from December 1967 to November 2022: 118 patients were treated before 2012 and registered retrospectively when seen in long-term follow-up consultations or for another cancer since November 2021). A short questionnaire was distributed to healthcare professionals using the tool (physicians and research associates or technicians, n = 14), of whom 11 answered and were all satisfied. Access to the patient interface is currently open to 124 former patients. This was initially offered to 30 former patients who were over 15 years old, affected by the disease within the last 5 years, and had agreed to test it. Their opinions were collected by their doctor by e-mail, telephone, or during a consultation in an open-ended question and a non-directive interview. All patients were satisfied with the tool, with interest in testing it in the long term. Some former patients found that the tool provided them with some ease of mind; one, for instance, commented: "I feel lighter. I allow myself to forget. I know I will get a notification when the time comes." CONCLUSIONS: Freely available to all users, LOG-after: (1) provides help with determining personalized survivorship care plans for follow-up; (2) builds links with general practitioners; (3) empowers the patient; and (4) enables health data to be exported for analysis. Database URL for presentation: https://youtu.be/2Ga64iausJE.

Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling.

Glucocorticoid (GC) resistance in childhood relapsed B-cell acute lymphoblastic leukemia (B-ALL) represents an important challenge. Despite decades of clinical use, the mechanisms underlying resistance remain poorly understood. Here, we report that in B-ALL, GC paradoxically induce their own resistance by activating a phospholipase C (PLC)-mediated cell survival pathway through the chemokine receptor, CXCR4. We identify PLC as aberrantly activated in GC-resistant B-ALL and its inhibition is able to induce cell death by compromising several transcriptional programs. Mechanistically, dexamethasone (Dex) provokes CXCR4 signaling, resulting in the activation of PLC-dependent Ca2+ and protein kinase C signaling pathways, which curtail anticancer activity. Treatment with a CXCR4 antagonist or a PLC inhibitor improves survival of Dex-treated NSG mice in vivo. CXCR4/PLC axis inhibition significantly reverses Dex resistance in B-ALL cell lines (in vitro and in vivo) and cells from Dex resistant ALL patients. Our study identifies how activation of the PLC signalosome in B-ALL by Dex limits the upfront efficacy of this chemotherapeutic agent.

[Preventive and therapeutic strategies for relapse after hematopoietic stem cell transplant for pediatric AML (SFGM-TC)]. / Stratégies préventives et thérapeutiques de la rechute après allogreffe de cellules souches hématopoïétiques pour les LAM pédiatriques (SFGM-TC).

Treatment of pediatric high-risk acute myeloid leukemia (AML), defined either on molecular or cytogenetic features, relies on bone marrow transplant after cytologic remission. However, relapse remains the first post-transplant cause of mortality. In this 13th session of practice harmonization of the francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), our group worked on recommendations regarding the management of post-transplant relapse in AML pediatric patients based on international literature, national survey and expert opinion. Overall, immunomodulation strategy relying on both measurable residual disease (MRD) and chimerism evaluation should be used for high-risk AML. In very high-risk (VHR) AML with a 5-year overall survival ≤30 %, a post-transplant maintenance should be proposed using either hypomethylating agents, combined with DLI whenever possible, or FLT3 tyrosine kinase inhibitors if this target is present on leukemia cells. In the pre-emptive or early relapse settings (< 6 months post-transplant), treatments combining DLI, Azacytidine and Venetoclax should be considered. Access to phase I/II trails for targeted therapies (menin, IDH or JAK inhibitors) should be discussed in each patient according to the underlying molecular abnormalities of the disease.