Les proctopathies et les cystites radiques sont des maladies consécutives aux radiothérapies pelviennes qui peuvent être réfractaires à une thérapie standard. Notre groupe a confirmé dans des modèles ...animaux et lors d’un essai clinique de phase 1 que la thérapie cellulaire représente une option sûre qui peut apporter un bénéfice thérapeutique lorsque les autres traitements ont échoué.
Quatre patients souffrant d’effets secondaires pelviens graves en raison d’une dose excessive d’irradiation après une radiothérapie conformationnelle pour un adénocarcinome de la prostate (accident d’Épinal) ont reçu des injections intraveineuses de cellules stromales mésenchymateuses allogéniques.
L’état clinique des patients s’est amélioré après l’injection de cellules stromales mésenchymateuses. Deux patients ont révélé une réponse clinique confirmée pour la douleur et l’hémorragie. La fréquence des diarrhées douloureuses a diminué de 6jours à 3jours après la première injection et 2jours après la seconde injection chez un patient. Un processus de fistulisation a pu être arrêté chez un patient, ce qui a permis une rémission stable pendant plus de 3 ans. Une modulation des sous-populations de lymphocytes vers un schéma de régulation et une diminution des cellules T activées a accompagné la réponse clinique. La thérapie par les cellules stromales mésenchymateuses a été efficace sur la douleur, la diarrhée, l’hémorragie, l’inflammation, la fibrose et la fistulisation. Aucune toxicité n’a été observée.
Un essai clinique de phase 2 est en cours d’inclusion pour des patients souffrant de complications abdominales et pelviennes après radiothérapie qui n’ont pas vu leurs symptômes s’améliorer après les traitements classiques (NCT02814864, essai évaluant l’efficacité des injections systémiques de cellules stromales mésenchymateuses pour le traitement des complications abdominales et pelviennes graves et chroniques réfractaires au traitement standard, induites par la radiothérapie Prisme). Il implique la participation de six services de radiothérapie pour le recrutement de 12 patients. Ils seront tous pris en charge et suivis dans le service d’hématologie de l’hôpital Saint-Antoine. Les cellules seront préparées dans deux centres (EFS Mondor et CTSA Clamart) appartenant au réseau national EcellFrance de médecine régénératrice et de thérapie cellulaire à base de cellules stromales mésenchymateuses. Les critères d’éligibilité sont un grade supérieur à 2 pour la rectorragie ou l’hématurie à l’inclusion et l’absence de cancer actif. Chaque patient recevra trois injections de cellules stromales mésenchymateuses à 7jours d’intervalle. Les patients seront suivis sur une période de 12 mois. L’objectif principal est une diminution d’un grade sur l’échelle Late Effects Normal Tissue ; Subjective, Objective, Management, Analytic (LENT SOMA) pour la rectorragie ou l’hématurie. L’objectif secondaire est de réduire la fréquence des diarrhées, la consommation d’analgésiques, la douleur et l’amélioration de la qualité de vie.
Lay Summary
During the coronavirus disease 2019 (COVID‐19) pandemic, cancer screening decreased precipitously; home screening for colorectal cancer diminished less than that for colonoscopy and ...breast and cervical cancer screening.
The authors have highlighted approaches for home cancer screening in addition to telemedicine.
During the coronavirus disease 2019 (COVID‐19) pandemic, cancer screening has decreased precipitously. Nevertheless, home screening for colorectal cancer appears to have diminished less than colonoscopy and breast cancer and cervical cancer screening in a large, academic midwestern medical center. Based on these findings, the current study highlights the promise for increasing home cancer screening in addition to telemedicine.
Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a ...significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.
The use of autologous stem cell transplantation (ASCT) as consolidation therapy for adult patients with acute leukemia has declined over time. However, multiple randomized studies in the past have ...reported lower relapse rates after autologous transplantation compared with chemotherapy and lower non-relapse mortality rates compared with allogeneic transplantation. In addition, quality of life of long-term survivors is better after autologous transplantation than after allogeneic transplantation. Further, recent developments may improve outcomes of autograft recipients. These include the use of IV busulfan and the busulfan+melphalan combination, better detection of minimal residual disease (MRD) with molecular biology techniques, the introduction of targeted therapies and post-transplant maintenance therapy. Therefore, ASCT may nowadays be reconsidered for consolidation in the following patients if and when they reach a MRD-negative status: good- and at least intermediate-1 risk acute myelocytic leukemia in first CR, acute promyelocytic leukemia in second CR, Ph-positive acute lymphocytic leukemia. Conversely, patients with MRD-positive status or high-risk leukemia should not be considered for consolidation with ASCT.
In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT) from mismatched unrelated donors or haploidentical donors are potential ...alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo) versus matched (MUD 10/10) or mismatched unrelated donor at a single HLA-locus (MMUD 9/10) for patients with acute leukemia in remission.
Two hundred sixty-five adult patients with de novo acute leukemia in first or second remission that received a Haplo-SCT between January 2007 and December 2013 were compared with 2490 patients receiving a MUD 10/10 and 813 receiving a MMUD 9/10. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups.
The weighted 3-year non-relapse mortality and relapse incidence were 29 and 30% for Haplo, 21 and 29% for MUD 10/10, and 29 and 25% for MMUD 9/10, respectively. The weighted 3-year leukemia-free survival (LFS) and overall survival (OS) were 41 and 46% for Haplo, 50 and 56% for MUD 10/10, and 46 and 48% for MMUD 9/10, respectively. Using weighted Cox model, both LFS and OS were significantly higher in transplants from MUD 10/10 compared from those in Haplo but not different between transplants from MMUD 9/10 and Haplo. The type of donor was not significantly associated with neither acute nor chronic graft-versus-host disease.
Patients with acute leukemia in remission have better outcomes if transplanted from a MUD 10/10. We did not find any significant difference in outcome between transplants from MMUD 9/10 and Haplo, suggesting that both can be equally used in the absence of a 10/10 MUD. KEY POINT 1: Better outcomes using fully (10/10) matched unrelated donor for allo-SCT in acute leukemia in remission. KEY POINT 2: Similar outcomes after allo-SCT from unmanipulated haploidentical graft or mismatched (9/10) unrelated donor in acute leukemia in remission.
The article analyses the international experience of solving the housing problems of forcibly displaced persons during the post-war recovery of the economy and socio-humanitarian space. The author ...characterises the role of the state in developing strategies, determining priorities, consolidating efforts, and institutionally ensuring the process of restoring living space, rebuilding housing and social infrastructure, as well as ensuring control over the use of funds, residential premises, and structures, the use of technologies and standards of construction and reconstruction. National priorities have been determined in the organisation of measures to provide housing for victims of hostilities and forced migrants, prioritisation of reconstruction, and new construction tasks. The necessity of accumulation and optimal use of internal resources, as well as the expediency of attracting foreign investments and the use of external financial assistance for the reconstruction of living space, industrial and social infrastructure with observance of systematicity and compliance with the trends of structural, technological and social development, are argued. The paper clarifies the mechanisms of interaction between the government and private investors, stimulation of entrepreneurial activity, encouragement and support of citizens in their actions regarding the independent restoration of housing, and arrangement of adjacent territories. It was found that the excessive bureaucratisation of assessing the damage caused and drawing up an application for assistance significantly slowed down the process of restoring damaged housing, which caused additional budget costs for providing IDPs with temporary housing. Ignoring the historical and cultural differences of the inhabitants of different territories and the accumulation of socially vulnerable and marginal elements led to an increase in social tension at the local level, and people affected by the war formed a permanent dependence on state aid. The need to consider positive and negative foreign experiences in the state management of the post-war reconstruction of the country’s housing stock is substantiated.
Mesenchymal stem cells (MSCs) possess unique immunomodulatory properties. They are able to suppress allogenic T-cell response and modify maturation of antigen-presenting cells. Their role in the ...treatment of severe graft versus host disease has been reported. The underlying molecular mechanisms of immunosuppression are currently being investigated. Histocompatibility locus antigen (HLA)-G is a nonclassical major histocompatibility complex class I antigen with strong immune-inhibitory properties.
We studied the role of HLA-G on MSC-induced immunosuppression. The expression of HLA-G on human MSCs cultured alone and in mixed lymphocytes reaction (MSC/MLR) was analyzed.
We found that HLA-G can be detected on MSCs by real-time reverse-phase polymerase chain reaction, immunofluorescence, flow cytometry (52.4+/-3.6%), and enzyme-linked immunosorbent assay in the supernatant (38.7+/-5.2 ng/mL). HLA-G protein expression is constitutive and the level is not modified upon stimulation by allogenic lymphocytes in MSC/MLR. The functional role of HLA-G protein expressed by MSCs was analyzed using the 87G anti-HLA-G blocking antibody in a MSC/MLR. We found that blocking HLA-G molecule significantly raised lymphocyte proliferation in MSC/MLR (35.5%, P=0.01).
Our findings provide evidences supporting involvement of HLA-G in the immunosuppressive properties of MSCs. These results emphasize the potential application of MSCs as a relevant therapeutic candidate in transplantation.
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