Program 15 : Young Adults Cancer - Cancer Institute AP-HP. Nord

PROGRAM LEADERS

Pr Nicolas BOISSEL, is Head of the Adolescent and Young Adults Unit, Department of Haematology, Saint-Louis Hospital, and Professor of Medicine at Université de Paris, France. After beginning his career as a research fellow at the Pasteur Institute and as an intern at Paris Municipal Hospitals, he did a PhD at the Department of Immunology at Saint-Louis Hospital in 2002 while completing his MD at the University of Paris VI. In 2005, he went on to become Assistant Professor at Saint-Louis hospital in the Acute Leukemia unit headed by Professor Hervé Dombret, before taking up his current position in 2010. He is engaged in therapeutics for patients with bone marrow disorders including acute leukaemia, lymphoma, and aplastic anaemia, with a specific focus of adolescent and young adult comprehensive care. He is the chairman of the Group of Research on Adult Acute Lymphoblastic Leukemia (GRAALL) and former president of the French Oncohematology Group for Adolescents and Young Adults (GO-AJA). He is involved in many trials designed to improve the outcome of acute leukaemia patients. His clinical research interests include the role of new oncogenic events and minimal-residual disease to stratify therapeutic approaches in acute leukaemia, and the development of immunotherapy in the field.

Dr. Nathalie DHEDIN, is in charge of hematopoietic stem cell transplant activity in the the Adolescent and Young Adults Unit, Department of Haematology, Saint-Louis Hospital. After working in Salpêtrière Hospital as Hematologist, she joined in 2011 the new unit of Haematology dedicated to Adolescent and Young Adults. She is engaged in transplant for haematological malignancies and the management of long term complications focusing on fertility preservation. She is member of the Societé Française de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) and of the Groupe de Recherche et d’Etude de la Conservation de l’Ovaire et du Testicule (GRECOT). She has developed the activity of hematopoietic stem cell transplant in the population of adolescents and adults with sickle cell disease and she is the principal investigator of several multicentric studies evaluating transplant in this pathology.

HEALTHCARE EXECUTIVE

Nadia AHAMADA

STRENGTHS IN THE FOLLOWING AREAS

Cancer Care

The hematology adolescent and young adult (AYA) unit was created in 2010 to take care of patients aged 15-25 years old diagnosed with blood diseases. In this age range, the vast majority of blood cancers are acute leukemias and high-grade lymphomas.

The AYA program meets the requirements of the National Cancer Institute (INCa) and Ministry of Health (DGOS) directive on the organization of care for AYAs with cancer (DGOS/R3/INCA/2016/177, 2016). This directive recommends implementing 1) multidisciplinary tumor boards (MTB) with double pediatric and adult competences and 2) a specific supportive care offer (fertility preservation, psychosocial support, survivorship program, access to education, professional and social reintegration programs, etc.).

The program produces each year an annual activity report for the Regional Health Agency (ARS). This report summarizes the local organization (healthcare practitioners, post-acute facilities, association/charities, etc.) along with different indicators (patient recruitment, number of patients discussed in mixed MTBs, etc.).

The AYA transplant (allogeneic/autologous hematopoietic stem cell transplantation) and CAR-T cell program has been accredited by the Joint Accreditation Committee ISCT-Europe & EBMT (JACIE).

ONCORIF network, the AYA structures in Ile-de-France: https://www.oncorif.fr/prises-en-charge-specifiques/adolescents-et-jeunes-adultes-aja/

Multidisciplinarity

The AYA program relies on a multidisciplinary team, which includes all healthcare professionals dedicated to AYA cancer care (coordinating nurses, physicians, nurses, psychologists, social workers, nutritionists, physiologists, etc.) as well as association/charity volunteers or employees (education, professional and social reintegration, adapted physical and recreational activities, etc.).

Therapeutic decision-making occurs in multiple local, regional, and national MTBs (see hematology and allogeneic stem cell transplant programs) of the regional CANPEDIF network (see below).
The national directive on AYAs with cancer requires the participation of both pediatricians and adult oncologists to the tumor boards involved in the discussion of AYA patients.
Four local boards (acute leukemia, lymphoma, allogeneic stem cell transplant, and CAR-T cells) are involving different units from the hematology department. Underage patients and complex cases (relapse, children relapsing in adulthood) are discussed at the regional level within a network of pediatric tumor boards (CANPEDIF network = Pediatric Cancerology Network of Ile-de-France). Local and regional tumor board organizations fulfil the National Cancer Institute recommendations.

Pursuing our actions in patient involvement and empowerment

AYAs with cancer face distinct psychosocial challenges because of the multiple developmental processes usually occurring in such population. The AYA program and its multidisciplinary team are committed to maintaining some of these processes despite disease and treatment and to promoting empowerment.

Institutional and local tools are developed to evaluate patient satisfaction, collect their feedback, and involve them more deeply in the therapeutic strategy.
Collectively designed brochures aim at providing information on the organization of the unit, on the care pathways, and especially on the post-allograft period.
The AYA unit is currently implementing a national patient education program (PEP) called DYNAMO, which has been developed within the network of French AYA programs so as to improve patient empowerment and treatment adherence. This PEP addresses specific questions arising along the AYA patient’s journey, including knowledge on disease and treatment, nutrition, body image and sexual health, and fertility preservation.

Improving prevention and early detection

The issue of prevention is poorly applicable to hematological cancer. Both lymphoma and AYA units have participated to a national information campaign to promote early detection of lymphoma, the first cancer in the adolescent population. The charity organization France Lymphome Espoir is leading this program.

Research

Research

PHRC, PRTK, PLBIO, PRIME, ANR, CLIIP, AAP ARC, Ligue contre le cancer, FRM, GEFLUC, PAIR:
- PHRC 2015: Health and quality of life evaluation in patients treated with intensive chemotherapy for acute lymphoblastic leukemia
- PHRC 2018: Gemtuzumab ozogamicin for Core Binding Factor Acute Myeloid Leukemia
- PHRC 2018: Dual CD19/CD22 CAR-T for adults with Acute Lymphoblastic Leukemia
- PHRC 2020 : Adaptative CD33 CAR-T for adults with Acute Myeloid Leukemia

FHU, SIRIC, RHU:
- IHU THEMA, National Center for Precision Medicine in Leukemia

Basic science:
- UMR-7212/ U944, Génomes, biologie cellulaire et thérapeutique (Pr. Jean Soulier)
- UMR-1131, Hémopathies myéloïdes: cellules souches, modèles précliniques, recherche translationnelle (Pr. S. Giraudier)
- UMR-S 1172, Facteurs de persistance des cellules leucémiques (Pr. C. Preudhomme)
- U1151, Différentiation lymphoïde normale et pathologique (Pr. E. Macintyre et Pr. V. Asnafi, Imagine, Necker)

The AYA program in hematology has developed different research axes from clinical to more basic research within the URP-3518 (Clinical research in hematology, immunology and transplantation, Pr. H. Dombret), and specifically two research groups within Team 1: Acute Leukemia Cohort Group, and Humanities and Social Sciences (HSS) Group (Pr. N. Boissel). The four research axes are as follows:

1) Improvement of AYA cancer therapy,

2) Characterization and prognostication of AYA hematological malignancies,

3) Evaluation and improvement of fertility preservation,

4) Evaluation of psychosocial outcome and needs in survivors, and study of the representations of AYA care in healthcare providers.

Improvement of AYA cancer therapy. Frontline and early-phase trials aiming at improving patient outcome and reduce long-term effects, with a focus on immunotherapy in acute leukemia, including immune cell engagers (bispecific antibodies, etc.) and CAR-T cells. The AYA department is accredited by the Regional Health Agency (ARS) to conduct first-in-human trials in AYAs (LRIPH).

Characterization and prognostication of AYA malignancies. This research program relies on the clinical and biological annotation of local and national cohorts within cooperative groups (SFCE, GRAALL). Locally, the AYA unit participates in the THEMA program from the National Center for Precision Medicine in Leukemia with the support of basic science laboratories.

Evaluation and improvement of fertility preservation. The fertility research program is based on a large experience of ovarian tissue cryopreservation and transplantation (analysis of local and regional cohorts managed by Pr. C. Poirot). We aim at improving the rate of patients transplanted, especially those with acute leukemia, for whom the risk of disease re-implantation is high. Translational research to develop ex-vivo oocyte maturation or sperm production is supported by collaborative networks, with the URP-3518 involved in data analyses.

Evaluation of psychosocial outcome and needs in survivors and study of the representations of AYA care in healthcare providers. This research is co-coordinated by psychologists from Université Paris Cité, Université Paris 13, and physicians. PhD students are recruited to address specific questions related to either survivorship and/or healthcare providers’ representations of taking care of AYAs. Partners of this research are part of the HSS group of URP-3518 and of the interdisciplinary institute La Personne en Médecine (ILPEM, iDEX) within Université de Paris Cité.

Education

At the national level, AYA programs are federated within a multidisciplinary cooperative Group for OncoHematology in AYAs (Go-AJA, former president N. Boissel). Go-AJA cooperates with “organ”-specific cancer cooperative groups in children and adults to promote the specificities of AYAs with cancer.

National Go-AJA congress, 1x/year (N. Boissel)
Go-AJA session at the French Society of Hematology, 1x/year (N. Boissel)
Regional pluriprofessional training “AJA & Cancer” (AYA programs from Institut Curie, Gustave Roussy, and Saint-Louis), 1x/year (N. Boissel)
ESMO/SIOPE training course, 2018 (N. Boissel)
National “Inter-University Diploma” (DIU) on “AYA and cancer” (Co-coordination by University of Paris, N. Boissel)

Recent review/recommendations/guidelines:

COVID-19 and ALL in children and adolescents, Bull Cancer 2020
How I treat AYA with ALL, Blood 2018
Bull Cancer, special issue on AYA and cancer, 2016