CAR-T cellsare a new type of therapy that offers high hopes for cancer fighting. With this video, the SiRIC CURAMUS, the film director Cyprien Bisot and Dr Françoise Norol guide you through the functioning of this immunotherapy and its method of production with a passage in the Service ofClinical Hematology of Pitié-Salpêtrière and in the Novartis Cell For Cure production center.
👉 Find the video below:
📌 In addition, find the long version of this video which includes a description of the prospects for improving the effectiveness of these treatments:
In 2019, a SiRIC CURAMUS interdisciplinary team led by Marie-Pierre Dann, specialised clinical nurse (Hematology Department of the Pitié-Salpêtrière Hospital) won the Force Hemato award with « Trials of Damocles ». This research project aims better to understand the needs, expectations and experiences of patients diagnosed with chronic lymphocytic leukemia (CLL), stage A. About half of these patients, under active surveillance and often asymptomatic, may not ever need treatment. This short paper aims to present the context and the interrogations of this research project as well as to explain how the humanities and social sciences, and more particularly philosophy, may bring a pertinent and precious outlook on such a topic.
From 27th to 30th October 2022 will be held in Madrid the 11th International Workshop on Walendström’s Macroglobulinemia (WM), one of the diseases studied in CURAMUS in the program 2 “Rare immuno-haematological cancers”.
Pr Véronique Leblond will co-chair the session “Chemoimmunotherapy” in which she will make a présentation “FILO Bendamustine Rituximab Study”, and will have a talk on “Obinutuzumab and Idelalisib in WM” in the session “Novel Treatment Approaches to WM-Clinical I”. Moreover, Dr Damien Roos-Weil will present “Integration of cytogenetic and molecular screening for first line patients” in the session“WM Genomics I” and “DNA Methylation Profiling in WM” in the session “WM Genomics II”.
Patients with cancer and contaminated by the COVID-19 show an important mortality rate, from 29% to 39%.
Among these patients, those with haematological cancers -that affect white cells of the immune system- are particulary sensitive to infections like the COVID-19. Due to the immunodepression caused by the cancer itself or its associated treatments (e.g immunosuppressors for patients engrafted with bone marrow, etc),it is likely that these patients represent one of the population the most at risk and with fatal evolution.
Moreover, these patients have often numerous preventive treatments against infections from all origins (bacteria, fungi, viruses and parasites). They are vaccinated when it is possible, or receive regular infusions with antibodies withdrawn from healthy donors. Therefore, infections are one of the most frequent complications.
Nowadays, there are few specific studies on patients with haematological diseases and infected by the COVID-19, but the data on a low number of patients confirm the severity of this infection in this particulary fragile population.
So, it is urgent to create a register describing the characteristics and the evolution of these patients, the impact of the COVID-19 infection on their haematological disease care, as well as their capacity to get immunized against this virus. Their immunization status will be examined through a serological study, allowing the detection of COVID-19-targeted antibodies through a blood test. Patients concerned are those with haematological disease and monitored in hospitals haematological centers from the three most impacted french regions that are Ile-de-France, Grand-Est and Bourgogne Franche Comté. Nowadays, 33 haematological centers have given their agreement to take part to this register and to the serological study.
Ultimately, our goal is to propose a better care of these patients the most exposed to COVID-19 mortality.
Pitié-Salpêtrière hospital is one of the reference center for cancers arising in immunosupressed patients, and benefit of an excellence research label (SiRIC) attributed by the National Cancer Institute, the Ministry of Health and Solidarities and Inserm.
The CLIP² Galilée (INCa Labeled Early Stage Centre), first labeled by the National Cancer Institute in 2015, was renewed in 2019 for a period of 5 years. Coordinated at the Pitié-Salpêtrière by Prof. Jean-Philippe Spano, CLIP² Galilée has just launched its new website www.clip2galilee.com.
Thanks to the support of SiRIC CURAMUS and the Institut Universitaire du Cancer, this new website provides real-time information on CLIP² Galilée’s early phase clinical trials currently open to cancer inclusions (oncology and hematology).
Thus, information from nearly 80 early phase trials opened in the Pitié-Salpêtrière, Henri-Mondor, Tenon, Saint-Antoine hospitals and the Créteil Intercommunal Hospital Center are already available on the site. A search by organ allows you to quickly find the list of trials by major type of cancer.
All CLIP² Galilee teams are counting on you to promote therapeutic innovation within AP-HP. Sorbonne-University and keep this website up to date.
Within the framework of the ParPedia19 call for projects “Accelerating research in pediatric oncology: aid for pooling, structuring and sharing research data” financed by the INCa in 2019, one of the winning projects is the one led by Prof. Arnaud PETIT for the DOREMy project.
The DOREMy project focuses on the “Harmonized clinical and biological data base for integrated research in the management of paediatric acute myeloid leukaemia”.
Acute myeloid leukaemia in children and adolescents (AML) is a group of rare diseases whose relapse rate remains high (45%) and whose prognosis remains poor (<70%) despite therapeutic advances. The therapeutic protocols LAME89/91, ELAM02, the post-ELAM02 registry and the current Myechild01 protocol have enabled the collection of clinical-biological data since 1989 and the constitution of a tumour library for AML since 2005. In order to better understand the pathophysiology of these diseases, the CONECT AMLnetwork of 12 research teams in France was created in 2017 as part of the Programme d’Actions Intégrées de Recherche (PAIR) in pediatric oncology. The various projects include genomic analyses, new experimental models (PDX, cells of the medullary microenvironment, drug testing). The protocol and research data thus generated, the tumour library, the samples dispersed in the research teams are recorded on independent databases, which does not allow an optimal exploitation of these resources.
Goals: to integrate all clinical data into a single database; to integrate the research data from CONECT AML; to adapt these data to the OSIRIS set as well as to the international paediatric AML database, PedAL; to list all leukaemia samples or derived products from the ELAM02 biobank and to create a virtual tumour library of samples stored by the CONECT AML research teams.
Data structuring work must allow interaction with national and international databases. The pooling of data will make it possible to better characterise high-risk subgroups of rare patients; identify new therapeutic targets; reduce the rate of relapse and
improve the survival of pediatric AML; promote data and sample sharing for collaborative work.
Chapiro E, Pramil E, Diop M, Roos-Weil D, Dillard C, Gabillaud C, Maloum K, Settegrana C, Baseggio L, Lesesve JF, Yon M, Jondreville L, Lesty C, Davi F, Le Garff-Tavernier M, Droin N, Dessen P, Algrin C, Leblond V, Gabarre J, Bouzy S, Eclache V, Gaillard B, Callet-Bauchu E, Muller M, Lefebvre C, Nadal N, Ittel A, Struski S, Collonge-Rame MA, Quilichini B, Fert-Ferrer S, Auger N, Radford-Weiss I, Wagner L, Scheinost S, Zenz T, Susin SA, Bernard OA, Nguyen-Khac F. Blood. 2019 Nov 21;134(21):1821-1831
This work has just been published in Blood (n°1 journal in Hematology). The article has been selected for an editorial commentary and for an international CME (continuing medical education) training course. This work had been selected for oral communication at the last annual American International Congress (ASH). This is the world’s largest series of an aggressive form of chronic lymphocytic leukemia: B prolymphocytic leukemia.
Prolymphocytic B leukemia (PBL) has been a long debated entity within mature B-hematopathies, often being classified as either aggressive chronic lymphocytic leukemia or mantle cell lymphoma. It is a rare, poorly studied haemopathy, affecting the elderly, with a rapid progression and no known prognostic factor. Diagnosis is difficult because cytology is based on the presence of prolymphocytes representing more than 55% of blood lymphoid cells.
We report here a cytogenetic and molecular study of a national series of 34 LPLB, the largest described to date. The cytological diagnosis was reviewed by 3 experts independently. We showed that LPLB was often associated with a complex (> 3 chromosomal abnormalities) and very complex (> 5 abnormalities) karyotype (73% and 45% respectively). The most frequent chromosomal abnormalities were translocations involving the MYC [t(MYC)] gene (62%), deletion (del) 17p (involving the TP53 gene) (38%), trisomy (sorting) 18 (30%), del13q (29%), tri3 (24%), tri12 (24%) and del8p (23%). A large majority of patients (76%) had MYC aberration, either by translocation or gain (14%), these two abnormalities being mutually exclusive. Sequencing of the exomes revealed recurrent mutations in the TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4 and BCLAF1 genes. The majority of the LPLBs (89%) used the IGHV3 or IGHV4 genes preferentially, and expressed mutated IGHVs (79%).
We propose a hierarchical model with 3 cytogenetic groups: low risk (no MYC anomaly), intermediate (MYC anomaly without del17p), and high risk with double hit (MYC anomaly and del17p) with the shortest survival (p=0.0006).
Finally, we tested the combination bcl2 inhibitor + OTX015 (bromodomain inhibitor and extraterminal motif targeting MYC) on primary samples in in vitro experiments, and concluded that these drugs can induce the death of LPLB cells with t(MYC) translocation.
In total, we show that LPLB has a particular genomic profile, different from other mature B-haemopathies, and confirm the need to distinguish it in the World Health Organization (WHO) classification. We recommend that cytogenetic analysis (karyotype and fluorescent in situ hybridization) be performed in any patient with a difficult-to-classify B hemopathy. On the one hand it is an important diagnostic aid and on the other hand it is an important prognostic factor.
Prolymphocytic B leukemia (PBLL) has been a long debated entity within mature B haemopathies, often being classified as either aggressive chronic lymphocytic leukemia or mantle cell lymphoma. It is a rare, poorly studied, elderly hemopathy, with a rapid progression, no known prognostic factor, and difficult to diagnose.
With cytogenetic analyses and high-throughput sequencing, we have shown that LPLB has a particular profile of genomic abnormalities, distinct from other B haemopathies, with frequent abnormalities of the MYC (activation) and TP53 (inactivation) genes, two genes frequently involved in blood (leukaemia) and lymph node (lymphoma) cancers. In addition, we showed that when these two genes were abnormal concomitantly, the prognosis was unfavourable. Finally, the combination of molecules including drugs targeting the MYC gene could be a lead to treat certain LPLB. We propose to perform a cytogenetic analysis on all difficult-to-classify B-haemopathies, as it is a simple to perform analysis that is important for diagnosis and prognosis.
The French CANCERVIH network, coordinated by Prof. Jean-Philippe Spano of the Medical Oncology Department of the Pitié-Salpêtrière Hospital AP-HP and Sorbonne University, studied the efficacy and safety of immunotherapy on the world’s largest series of HIV-infected people with cancer treated in routine care (excluding clinical trials).
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