Introduction Despite numerous therapeutic advances, first line standard care for eligible multiple myeloma (MM) patients still include high-dose melphalan and autologous stem cell transplantation (ASCT). Methods Our study concerned MM patients who received ASCT followed or not by consolidation and maintenance, treated in two reference centers in France (Lyon n=342) and in Algeria (Oran n=452) before the daratumumab era. Results Despite differences in resources, we showed similar long-term Overall Survival (OS) for the two groups and similar survival for patients who did not receive any chemotherapy after ASCT for relapse. After using the instant ratio, we found a longer Time to Next Treatment for Algerian patients compared to French patients. Regarding patients who relapsed after ASCT we found a significantly better OS for French patients who received up to 3 lines of treatment after ASCT compared to Algerian patients Conclusion The study of long-term overall survival of MM patients after ASCT remains very useful particularly for countries for which innovative therapies including immunotherapy are not accessible, and the differences observed during ASCT management and after relapse could point to paths for improving certain clinical situations regarding the offer of MM care in these countries.

Les unités de thérapie cellulaire sont confrontées à une saturation persistante de leurs capacités de stockage en azote des préparations de thérapie cellulaire (PTC). Cette situation compromet la sécurité des PTC en raison du vieillissement et de l’augmentation du nombre de containers, avec un risque accru de défaillance des équipements. Elle engendre également une hausse importante des coûts, liée principalement à la consommation d’azote liquide. Il apparaît donc essentiel de mieux maîtriser le stockage, pour des raisons à la fois économiques et environnementales. Cet atelier constitue une actualisation des précédentes recommandations de 2014, en introduisant notamment une durée maximale de conservation de cinq ans, dans un contexte où les PTC conservées depuis plus de cinq ans représentent 64 % du stock, alors que leur probabilité d’utilisation clinique reste très faible. Par ailleurs, des recommandations relatives aux critères de destruction des unités de sang placentaire intrafamiliales et à la cellulothèque ont été ajoutées.

Cet article a pour but d’aborder les alternatives à la COBE2991® (Terumo BCT©) pour la préparation de produits de thérapie cellulaire, en raison de son arrêt de commercialisation prévu en 2025. Les unités de thérapie cellulaire (UTC) doivent trouver des méthodes alternatives face à des restrictions réglementaires et à l’obsolescence des équipements. Actuellement, la COBE2991® (Terumo BCT©) est largement utilisée en France, mais son remplacement nécessitera des validations multiples et un ajustement des pratiques, car il n’existe pas d’équipement unique équivalent. Les recommandations pour harmoniser ces pratiques ont été discutées lors d’un atelier spécifique en septembre 2024 après une enquête menée auprès de 25 centres de thérapie cellulaire francophones.

The aim of this article is to discuss alternatives to COBE2991® (Terumo BCT©) for the preparation of cell therapy products, in view of its planned cessation of commercialization in 2025. Cell therapy units need to find alternative methods in the face of regulatory restrictions and equipment obsolescence. Currently, COBE2991® (Terumo BCT©) is widely used in France, but its replacement will require multiple validations and adjustment of practices, as there is no single equivalent equipment. Recommendations for harmonizing these practices were discussed at a specific workshop in September 2024, following a survey of 25 French-speaking cell therapy centers.

La pandémie COVID-19 a bouleversé les activités de greffe et a nécessité le recours à la cryopréservation des greffons de cellules souches hématopoïétiques allogéniques pour sécuriser la procédure, tant au niveau du patient que du donneur. La cryopréservation en situation allogénique, habituellement anecdotique, a été utilisée par tous les centres francophones. Les données collectées auprès de 24 centres ont été analysées afin d’évaluer l’impact de la cryopréservation sur la qualité du greffon. Cette analyse démontre le rôle délétère du transit prolongé (plus de 48heures) sur la récupération des progéniteurs CD34+, l’importance de l’augmentation de la dose de progéniteurs CD34+ demandée, justifiant la nécessité d’un contrôle de qualité après décongélation.

Introduction Despite all the therapeutic progress made in multiple myeloma (MM), the standard of care for eligible patients remains an intensive induction therapy followed by high dose melphalan and autologous stem cell transplantation (ASCT). Material and methods This present retrospective study included MM patients treated in Lyon between 1997 and 2020. All patients received induction chemotherapy followed by intensive chemotherapy and ASCT, with or without consolidation and maintenance therapy. Number and type of therapeutic lines administered for relapse after ASCT were analyzed. All data were reported in the European blood and marrow transplantation (EBMT) PROMISE registry. Statistical analysis Descriptive analyses were used for demographic variables, biological parameters, and treatment characteristics. Overall survival (OS) and progression-free survival (PFS) were presented using the Kaplan-Meier method and log-rank tests were performed to compare survival curves. Univariate and multivariate analyses were computed using Cox regressions and the multivariate analyses considered the variables for which the univariate ANOVA p-value was≤ 10%. Statistical analyses and graphics were computed with R v4.1.2, with the help of ‘survival’ and ‘ggplot2‘ packages. Results Before ASCT A total of 342 patients were included in the study (median 60 years (range: 28-73), 58% were male, 89.4% were diagnosed with a type III myeloma according to the Salmon and Durie classification. No genetic analysis was performed at that time. Most patients (92.5%) had a performance status (PS) of 0 or 1. The type of myeloma was heavy chain and light chain myeloma for 75.7% patients (68.9% of IgG kappa) and light chain myeloma in 23.1%. The median delay between diagnosis and ASCT was 4.8 months. Before ASCT, patients received an induction therapy with VTD in 54.1% of cases, VD in 30.1%, and more recently VRD in 16.1%. Disease status before ASCT was complete remission (CR) for 17.5% of the patients, partial remission (PR) and very good partial remission (VGPR) for 79.2% of patients and progressive disease or relapse for 3.0% of them. After ASCT The median duration of aplasia was 11 days. At day 100, the response was CR in 166 patients (50.5%), 182 patients (54.7%) received a consolidation treatment and 71 patients (20.8%) a maintenance therapy (Revlimid® for 90% of them). Overall, 227 (66.4%) patients relapsed. The median delay between ASCT and relapse was 22.5 months (0.89-229.13) and the median follow-up duration was 46.7 months (0.33-287.97). Among the 227 patients who relapsed, 6 patients were not treated, 79 patients (23.1%) received one chemotherapy line, 32 patients (9.4%) received two lines, 38 (11.1%) received 3 and 72 (21.1%) received at least 4 lines and up to 8. Overall survival and progression free survival The median OS was 132 [95% CI 110.6; NR] months from diagnosis and 122.8 [100.9; NR] months from ASCT. The median PFS was 39.35 [36.25; 43.37] months from diagnosis and 31.07 [28.42; 35.91] months from ASCT (Figure 1 A, B). In multivariate analysis on OS, the shorter aplasia duration (p<0.001) and consolidation and maintenance (p<0.001) were significantly associated with a significant better OS. The median OS was not reached from ASCT for patients who have received both consolidation and maintenance treatments and no death was reported. (Figure 1 C). For patients receiving chemotherapy lines for relapses after ASCT (Figure 1D) regardless of the number of lines the median OS was102.4 months and the 10-year OS probability was 45.6%. The OS of patients who received 3 lines of treatment was identical to that of patients who received one or 2 lines after ASCT. The median OS after 1 to 2 lines of chemotherapy after ASCT was not reached and was 127.15 months [70.6-NR] for those receiving 3 lines (Figure 4B). The OS of patients who received more than 4 chemotherapy lines after ASCT was significantly lower compared to the OS (p=0.0096) with a median [95%CI] OS of 85.5 months [65.61-106.15]. In conclusion this study showed the significant positive impact on OS of the association consolidation and maintenance. We have also studied the impact of number of chemotherapy lines and the impact on OS and PFS of kind of treatment will be discussed.

The COVID-19 pandemic disorganized the allogeneic stem cell transplantation activities all over the world, with the necessity to cryopreserve allografts to secure the procedure for both the recipient and the donor. Cryopreservation, usually anecdotal, has been used by all the French speaking centers; data collected from 24 centers were assessed in order to determine the impact of cryopreservation on the quality of allografts. Our analysis clearly demonstrates that increasing transit time (more than 48hours) is deleterious for CD34+ recovery, legitimates the slight increase of the requested CD34+ cell dose with respect to the average recovery rate as well as the importance of the quality control on the infused product.

Purpose of the Report We aimed to evaluate the role of F-18-FDG PET/CT in predicting patient outcome following chimeric antigen receptor T (CAR T) cells infusion in aggressive B-cell lymphoma. Methods F-18-FDG PET/CT data before leukapheresis, before CAR T-cell infusion and 1 month (M1) after CAR T-cell infusion, from 72 patients were retrospectively analyzed. SUVmax, total lesion glycolysis (TLG), metabolic tumor volume (MTV), and parameters describing tumor kinetics were calculated for each F-18-FDG PET/CT performed. The aim was to evaluate the prognostic value of F-18-FDG PET/CT metabolic parameters for predicting progression-free survival (PFS) and overall survival (OS) following CAR T-cell therapy. Results Regarding PFS, increment MTVpre-CAR and increment TLG(pre-CAR) were found to be more discriminating compared with metabolic parameters at preinfusion. Median PFS in patients with a increment MTVpre-CAR of less than 300% was 6.8 months (95% confidence interval [CI], 2.8 months to not reached) compared with 2.8 months (95% CI, 0.9-3.0 months) for those with a value of 300% or greater (P = 0.004). Likewise, median PFS in patients with increment TLG(pre-CAR) of less than 420% was 6.8 months (95% CI, 2.8 months to not reached) compared with 2.7 months (95% CI, 1.3-3.0 months) for those with a value of 420% or greater (P = 0.0148). Regarding OS, metabolic parameters at M1 were strongly associated with subsequent outcome. SUVmax at M1 with a cutoff value of 14 was the most predictive parameter in multivariate analysis, outweighing other clinicobiological variables (P < 0.0001). Conclusions Disease metabolic volume kinetics before infusion of CAR T cells seems to be superior to initial tumor bulk itself for predicting PFS. For OS, SUVmax at M1 might adequately segregate patients with different prognosis.

Chimeric antigen receptor (CAR) T-cells are a new class of cancer treatments manufactured through autologous or allogeneic T cells genetic engineering to induce CAR expression directed against a membrane antigen present at the surface of malignant cells. In Europe, tisagenlecleucel (Kymriah™) has a marketing authorization for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia in children and young adults and for the relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (Yescarta™) is the treatment of relapsed/refractory DLBCL and mediastinal B-cell lymphoma. Both products are "living drugs" and genetically modified autologous T cells directed against CD19 which is an antigen expressed throughout B lymphoid differentiation and on many B malignancies. This collaborative work - part of a series of expert works on the topic - aims to provide practical advice to assist collection facilities that procure the starting material i.e. blood mononuclear cells for autologous CAR T-cell manufacturing.

The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 10 7 TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7–90.7) and 79.3% (72.6–86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5–35.1) and 34.3% (27.0–43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts.

Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P < .001). Likewise, the only factor associated with a shorter OS was CRP >30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2016 in Lille, France. The objective of our workshop is to provide a discussion on the conservation and congelation of hematopoietic stem cells in a pediatric setting as well as our recommendations for this technique.

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a procedure with a high infection risk. Strict isolation of patients is the rule to prevent such condition. Objective: We compared the occurrence of severe infections (bacteremia and invasive fungal infection, IFI) in children undergoing alloHSCT before and after the move to a new protected unit with decreases in isolation methods. Methods: The study was conducted over a 10-year period. Unit 1 (2002-2007) consisted of laminar airflow rooms where caregivers were required to wear a sterile outfit (gown, gloves, hat, and mask). Unit 2 (2008-2012) included spacious positive air pressure rooms with HEPA filters where only a clean gown and mask were required to be worn. Results: Two hundred eighty-six alloHSCTs were performed (144 in Unit 1 and 142 in Unit 2). We reported a total incidence of 4.78 infections/1000 hospital-days including 4.4 episodes of bacteremia and 0.38 episodes of IFI. There was no statistical difference in the incidence of infections: n = 4.98/1000 hospital-days in Unit 1 vs. n = 4.6/1000 in Unit 2 (P = 0.63). Conclusion: The lack of difference in the occurrence of severe infection supports our decision to decrease unnecessary high protection in alloHSCT units to improve children's daily life.

Allogeneic hematopoietic stem cell transplantation can efficiently treat patients with severe hematological diseases. A human leukocyte antigen-compatible donor is required for performing transplantation. The occurrence of unexpected acute severe diseases in a donor can compromise the feasibility of allogeneic hematopoietic stem cell transplantation. However, when a severe health problem occurs in a donor while the recipient has already received a conditioning regimen, hematologists have to find the best solutions for the recipient, while the team in charge of the donor has to find the best medical solutions for the donor. We describe here the occurrence of psychiatric acute complications in an unrelated donor while the myeloablative conditioning regimen had already been given to the recipient. We report the successive decisions that were made in an emergency based upon the expertise of physicians specialized in hematology, apheresis, cell therapy, and psychiatry to preserve the donor’s health and recipient’s life.

In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the "book" at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called "EasyMatch®" that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels. The goal of our study is to report a single monocentric user-experience with EasyMatch®, demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors. The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children=before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children=after score). For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p<0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31days (p<0.0001). EasyMatch® estimates the number of potentially identical donors, but doesn't foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification.

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative strategy for high-risk acute myeloid leukemia (AML) patients. However, the risk for disease recurrence following allo-HSCT remains significant and associated with poor outcomes. The ability to predict relapse before detectable morphologic recurrence may allow for preemptive interventions, such as immune modulation, donor lymphocyte infusion (DLI), or initiation of hypomethylating agents, to potentially augment graft-versus-leukemia effect. Post-transplantation peripheral blood chimerism analysis, represents a potential tool to predict disease recurrence, although a validated consensus on the use of this technique in the post-allo-HSCT follow-up has not been established yet and its precise role in this setting remains unclear. The aim of our study is to evaluate the impact of chimerism evaluation 3 months after allo-HSCT in AML patients who were in first complete remission (CR1) before transplantation and remained in clinical and morphological CR at day 90 post-transplantation, on overall survival (OS) and relapse incidence. Patients and methods: We evaluated 194 AML patients who received allo-HSCT at our center between January 2006 and December 2014 and for whom chimerism follow-up has been performed at 3 months. There were 103 (53%) males and 91 (47%) females with a median age of 43 years (range: 18-67). Patients were classified according to the European LeukemiaNet classification for cytogenetic and molecular biology markers (Dohner et al. Blood 2010), accordingly, 64% patients were unfavorable and 36% were in intermediate II risk group. At allo-HSCT, all patients were in CR1; 136 (70%) received a full intensity conditioning (MAC) and 58 (30%) received a reduced intensity conditioning (RIC). HSC donors were 72 (37%) HLA identical siblings (44 BM and 36 PBSC), 54 (28%) 10/10 HLA matched unrelated donors (35 BM and 19 PBSC), 33 (17%) 9/10 HLA mismatched unrelated donors (16 BM and 17 PBSC) and 35 (18%) double cord blood units (only 7 were 6/6 HLA matched). Chimerism analysis was performed on marrow and/or blood samples every month following allo-HSCT using polymerase chain reaction (PCR) based on informative polymorphic short tandem repeat, a mixed chimerism was defined by having 5% or more of recipient cells. Results: At day 90 after transplantation, all patients remained in clinical and cytological CR at time of chimerism evaluation, 155 (80%) had a full donor chimersim (FDC) and 39 (20%) had a mixed chimerism (MC) ranging from 65% to 95% of donor cells. Among patients with MC, 9 (23%) received increasing doses of DLI (5 of them reached FDC at 6 months), while 20 (51%) could not receive DLI (7 because transplanted from cord blood, and 13 because of the presence of GVHD), the rest of patients were left with a transient MC and regained FDC during follow-up. After a median follow-up of 34 months (range: 4-96) for the surviving patients, the median OS in patients with FDC was not reached with a 3 years probability of 62% (95% CI: 58-66), and for patients with MC, it was 18 months (12-24) with a 3 years probability of 32% (95% CI: 23-41), (p=0.01). Twenty-two patients in the MC group have progressed during the follow-up and 17 among them died from disease progression. The cumulative incidence of relapse at 3 years was 25% (95% CI: 21-29) for FDC patients and it was 70% (95% CI: 62-80) for MC patients, (p<0.001). The impact of mixed chimerism was still valid in multivariate analysis after including patient age, type of donor, HSC source and risk group, and was independent from the intensity of the conditioning regimen with a Hazard Ratio of 4.7, and a 95% CI: 2.6-8.4, p<0.001. Conclusion: We demonstrated that chimerism evaluation at day 90 after allo-HSCT is an independent predictor of disease relapse in patients who remain in CR at that time and significantly impacts on long term survival. The standardization of this evaluation may lead to the identification of patients with high-risk of relapse risk suggesting the need of early preemptive intervention. Figure 1. Figure 1. Disclosures Nicolini: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.