Transition from laparoscopic to robotic liver surgery: clinical outcomes, learning curve effect, and cost-effectiveness.

The reproducibility of the implementation of robotic liver surgery (RLS) is still debated. The aim of the present study is to evaluate short-term outcomes and cost differences during the implementation of RLS, performed by an early adopter in laparoscopic liver surgery (LLS). Patients undergoing RLS between February 2020 and May 2021 were included. Short-term outcomes of the robotic group (RG) were compared to the "Initial Phase" group (IP) of 120 LLS cases and the 120 most recent laparoscopic cases or "Mastery Phase" group (MP). A cost analysis per procedure for the three groups was performed. Seventy-one patients underwent RLS during the study period. Median operative time in the RG was comparable to the IP, but significantly shorter in the MP (140 vs 138 vs 120 min, p < 0.001). Median intraoperative blood loss in the RG was lower than in both laparoscopic groups (40 ml [20-90 ml] vs 150 ml [50-250 ml] vs 80 ml [30-150 ml], p < 0.001). Median hospital stay in the RG was significantly shorter than the IP group (p < 0.001). There were no significant differences in postoperative complication, conversion, or readmission rates. Procedural cost analysis was in favor of robotic surgery (€5008) compared to the IP (€ 6913) and the MP (€6099). Surgeons with sufficient experience in LLS can rapidly overcome the learning curve for RLS. In our experience, the short-term outcomes of the implementation phase of RLS are similar to the mastery phase of LLS. The total average cost per procedure is lower for RLS compared to LLS.

[Acute and chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation]. / Maladie du greffon contre l'hôte aiguë et chronique après allogreffe de cellules souches hématopoïétiques.

Acute and/or chronic graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). It is a multisystemic inflammatory and/or fibrotic disease that occurs when the immune cells derived from the graft (and therefore originating from the donor) recognize recipient's healthy tissues as foreign and react against them. Acute GVHD is one of the main causes of non-relapse mortality after alloHSCT. Chronic GVHD can be very disabling in its severe form and can also be responsible for late mortality, mainly due to long-term immune deficiency and opportunistic infections. In contrast, GVHD can be associated with certain beneficial effects in patients transplanted for hematological malignancies, through simultaneous «graft versus tumour¼ positive effects. Therefore, one of the challenges of alloHSCT is the prevention and treatment of severe forms of GVHD without losing the beneficial anti-tumour effects of the graft.

: La maladie du greffon contre l'hôte («greffe-versus-hôte¼, GVH) aiguë et/ou chronique est une complication sérieuse de l'allogreffe de cellules souches hématopoïétiques (CSH). Elle correspond à des manifestations inflammatoires et/ou fibrotiques multisystémiques qui se produisent lorsque les cellules immunitaires dérivées de la greffe (et donc originaires du donneur) reconnaissent les tissus sains du receveur comme étrangers et réagissent contre eux. La GVH aiguë est l'une des principales causes de mortalité hors rechute post-greffe. La GVH chronique peut être très invalidante dans sa forme sévère et peut également être responsable d'une mortalité tardive, principalement due à un déficit immunitaire à long terme et à des infections opportunistes. À l'opposé, la GVH est associée à certains effets bénéfiques chez les patients transplantés pour des hémopathies malignes, par les effets simultanés favorables du «greffon contre la tumeur¼. Par conséquent, l'un des défis de l'allogreffe de CSH est la prévention et le traitement des formes sévères de GVH, sans perdre les effets bénéfiques anti-tumoraux du greffon.

[Cellular immunotherapy at the University Hospital of Liege : advances, challenges and prospects]. / Immunothérapie cellulaire au CHU de Liège : avancées, défis et perspectives.

Cellular immunotherapy consists in using the cells of the immune system as a therapeutic weapon. In this constantly evolving field, the therapeutic strategies developed at the University Hospital of Liege are hematopoietic stem cell transplantation, mesenchymal stromal cells and targeted therapy with CAR-T cells (Chimeric Antigen Receptor T cells). The first two modalities represent a form of non-targeted cell therapy that has been developed over the past decades. While hematopoietic stem cell transplantation is established as the reference treatment for many hematological diseases, mesenchymal stromal cells are still under investigation in various pathologies (notably Crohn's disease, organ transplantation, COVID-19 and pulmonary fibrosis). By contrast, CAR-T cells represent a recently developed and extremely promising targeted immunotherapy. This therapeutic approach has already revolutionized the treatment of B-cell lymphopathies, and has the potential to do the same for many other diseases in the near future.

L'immunothérapie cellulaire consiste en l'utilisation de cellules du système immunitaire comme arme thérapeutique. Dans ce domaine en évolution constante, les stratégies thérapeutiques développées au CHU de Liège sont la greffe de cellules souches hématopoïétiques, les cellules stromales mésenchymateuses et la thérapie ciblée par cellules CAR-T («Chimeric Antigen Receptor T cells¼). Les deux premières approches représentent une forme de thérapie cellulaire non ciblée, développées depuis de nombreuses années. Si la greffe de cellules souches hématopoïétiques est établie comme le traitement de référence de nombreuses hémopathies, les cellules stromales mésenchymateuses sont, quant à elles, toujours à l'étude dans diverses pathologies (notamment maladie de Crohn, transplantation d'organes, COVID-19 et fibrose pulmonaire). À l'opposé, les cellules CAR-T représentent une immunothérapie ciblée, développée récemment et extrêmement prometteuse. Cette modalité thérapeutique a déjà révolutionné le traitement des lymphopathies B, et elle possède le potentiel d'en faire de même pour de nombreuses autres pathologies dans un avenir proche.

[Allogeneic hematopoietic stem cell transplantation : general principles and recent progress]. / Allogreffes de cellules souches hématopoïétiques Principes généraux et progrès récents.

Hematopoietic stem cell transplantation is a potentially curative therapeutic option for many oncologic and non-oncologic hematological diseases. There is a constant evolution regarding donor choice, conditioning regimen intensity and immunosuppressive treatments, which leads to a reduction in morbidity and mortality during and after transplantation. In this article, we describe the general principles of hematopoietic stem cell transplantation and discuss the progress of global patient management after transplantation.

L'allogreffe de cellules souches hématopoïétiques constitue un traitement potentiellement curatif pour de nombreuses pathologies hématologiques cancéreuses ou non cancéreuses. Une évolution constante dans le choix du donneur, de l'intensité du conditionnement et des stratégies de traitements immunosuppresseurs, permet une réduction de la morbidité et de la mortalité durant et après la greffe. Cet article a pour but de réexpliquer les principes généraux d'une allogreffe et de discuter des nouvelles avancées et adaptations dans la prise en charge globale des patients greffés.

[Diffuse large B-cell lymphoma: a revolutionary treatment based on genetically-modified immune cells called CAR T cells]. / Le lymphome diffus à grandes cellules B : nouveau traitement révolutionnaire par des cellules immunitaires génétiquement modifiées appelées «CART cells¼.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Firstline immunochemotherapy cures approximatively 60 % of patients. The prognosis of patients with refractory disease or with relapsed disease within the first two years after the end of treatment is highly unfavourable. Since June 2019, a new third-line treatment with CAR T cells (chimeric antigen receptor T cells) seems to completely modify the prognosis of these patients. A significant proportion of long-lasting complete responses is obtained with this revolutionary treatment. Quick specialized intervention is required for the unique side effects of this therapy.

Le lymphome B diffus à grandes cellules (LBDGC) est le type histologique de lymphome non Hodgkinien le plus fréquent. Le traitement de première ligne par immunochimiothérapie ne permet de guérir qu'environ 60 % des patients. Les patients présentant une maladie réfractaire à une première ligne de traitement ou en rechute dans les deux premières années suivant le traitement présentent un mauvais pronostic. Disponible depuis juin 2019, un nouveau traitement de 3ème ligne sous forme d'immunothérapie par CAR T cells (acronyme anglais de «chimeric antigen receptor T cells¼) semble modifier complètement le pronostic de ces patients, avec l'obtention d'une proportion importante de réponses complètes de longue durée. Les effets indésirables spécifiques liés à ce traitement demandent une prise en charge rapide et spécialisée.

Adverse effects of bevacizumab in metastatic colorectal cancer : a case report and literature review.

Colorectal cancer is one of the most frequently diagnosed malignancies worldwide. One of the most important developments in the management of metastatic colorectal cancer is targeted therapy. Bevacizumab, a monoclonal antibody inhibiting VEGF induced angiogenesis, has been accepted as safe and efficient in the treatment of metastatic colorectal cancer for more than a decade. Addition of bevacizumab to fluorouracil-based chemotherapy is also associated with severe adverse events. We present a case of bevacizumab-induced bowel ischaemia associated with gastrointestinal haemorrhage.

Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers.

Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.

Plerixafor prescription modalities in autologous haematopoietic stem cell mobilization in Belgium.

OBJECTIVES: The efficacy and safety of plerixafor, an antagonist of the CXCR4 receptor, in combination with G-CSF has been demonstrated in patients suffering from Iymphoma and multiple myeloma (MM) eligible for autologous haematopoietic stem cell collection. However, different reimbursement criteria have been applied in different countries to select patients eligible for treatment with plerixafor. The objective of this observational study was to describe the plerixafor prescription modalities in daily practice in Belgium. METHODS: This open-label, prospective, observational study was conducted in 11 Belgian centres in 114 patients with lymphoma (Hodgkin's and non-Hodgkin's lymphoma) or MM who were treated with plerixafor according to the SmPC between April 2011 and October 2012. Patients included in another clinical trial with plerixafor were excluded from the study. RESULTS: The use of plerixafor in patients with MM or lymphoma was effective, with a success rate (defined as a total yield >2×10(6) CD34+ cells/kg) of 77%, and well tolerated (one SAE reported). Optimal collection (defined as a total yield >4×10(6) CD34+ cells/kg) was obtained for 43% of the study population (31% in lymphoma patients, compared to 61% in patients with MM). The use of plerixafor was in line with the SmPC and the Belgian reimbursement criteria for all patients. CONCLUSION: This study is showing that the use of plerixafor according to Belgian reimbursement criteria results in similar efficacy and safety as in other centres and countries worldwide.

Sputum cytokine levels in patients undergoing hematopoietic SCT and comparison with healthy subjects and COPD: a pilot study.

Patients undergoing hematopoietic SCT (HSCT) display an airway neutrophilic inflammation before transplantation that persists over the years. In this study, we have investigated the cytokine profile over a period of 1 year in the sputum supernatant of patients who underwent HSCT. We have measured sputum supernatant levels of TNF-α, TGF-ß1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17 and IFN-γ in 49 HSCT patients and compared the results with those found in 40 chronic obstructive pulmonary disease (COPD) and 54 healthy subjects matched for age. Compared with healthy subjects, before transplantation, HSCT patients exhibited raised levels of IL-6 (P<0.001) and IL-8 (P<0.05) while the other cytokines were generally poorly detectable. This picture was rather similar to that seen in COPD even if cytokine levels were much greater in the latter, with IL-8 being significantly greater in COPD than in HSCT patients (P<0.0001). In the 1 year following transplantation, sputum IL-6 and IL-8 did not differ from those in healthy subjects. Overall in HSCT patients, sputum IL-8 and IL-6 correlated with sputum neutrophil counts (r=0.4, P<0.0001; r=0.42, P<0.0001, respectively). In conclusion, sputum IL-6 and IL-8 may play a role in neutrophilic airway inflammation seen in patients undergoing HSCT.

Lung function and airway inflammation monitoring after hematopoietic stem cell transplantation.

BACKGROUND: Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). METHODS: We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT. RESULTS: For the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38-79)} compared to healthy subjects matched for age {Median (IQR): 49% (17-67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA. CONCLUSIONS: There was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test]. / Conduite à tenir devant une anomalie biologique découverte lors du bilan pré-don cellules souches hématopoïétiques: sérologie IgM positive pour le cytomégalovirus, le virus d'Epstein-Barr, la toxoplasmose, ou la syphilis.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant positive pregnancy test and monoclonal gammapathy]. / Conduite à tenir devant un problème du donneur de cellules souches hématopoïétiques: test de grossesse positif et gammapathie monoclonale.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of common issues related to the donor: pre-transplant pregnancy and monoclonal gammopathy.

[Allogeneic hematopoietic stem cell transplantation: what is the upper age limit?]. / Allogreffe de cellules souches hématopoïétiques chez le patient agé: jusqu' a quel age?

In the last decades, the upper age limit for allogeneic hematopoietic cell transplantation has increased from 50-60 years to 70-75 years of age, in part due to the development of allogeneic transplantation following reduced-intensity or truly nonmyeloablative conditioning. This review describes challenges and opportunities of allogeneic hematopoietic cell transplantation in the elderly.

[Chronic graft-versus-host disease: a multidisciplinary approach]. / Maladie du greffon contre l'hôt chronique: une prise en charge multidisciplinaire.

Chronic Graft-Versus-Host Disease (GVHD) is a frequent complication of allogeneic hematopoietic cell transplantation. This review article describes recent advances in the classification and treatment of chronic GVHD.

Elevations of tumor necrosis factor receptor 1 at day 7 and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.

Acute GVHD has remained a significant cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning. The role of TNF-alpha in the biology of acute GVHD after nonmyeloablative conditioning has not been studied thus far. Here, we measured TNF receptor 1 (TNFR1) as a surrogate marker for TNF-alpha in 106 patients before the start of the conditioning regimen (baseline) and 7 days after allogeneic HCT with nonmyeloablative conditioning. The nonmyeloablative regimen consisted of 2 Gy TBI alone (n=15), 2 Gy TBI plus fludarabine 90 mg/m2 (n=73), or 4 Gy TBI plus fludarabine 90 mg/m2 (n=18). TNFR1 levels increased significantly from baseline to day 7 after nonmyeloablative HCT (P<0.0001). Patients conditioned with 4 Gy TBI had higher TNFR1 day 7/baseline ratio than those conditioned with 2 Gy TBI (median 1.65 versus 1.25; P=0.01). In a multivariate Cox model, high TNFR1 day7/baseline ratio was associated with grades II-IV (HR=2.2, P=0.01) and grades III-IV (HR=2.9, P=0.007) acute GVHD, but had no impact on overall survival (P=0.8). In summary, our data suggest that nonmyeloablative conditioning induces the generation of TNF-alpha, and that the magnitude of TNF-alpha generation depends on the conditioning intensity (2 Gy versus 4 Gy TBI). Further, assessment of TNFR1 levels before and on day 7 after nonmyeloablative HCT provided useful information on subsequent risk of experiencing acute GVHD.

Comparison of thrombotic microangiopathy after allogeneic hematopoietic cell transplantation with high-dose or nonmyeloablative conditioning.

The role of conditioning intensity on occurrence of thrombotic microangiopathy (TMA) after allogeneic hematopoietic cell transplantation (HCT) has remained unclear thus far. Here, we retrospectively compared the incidence of TMA in patients given allogeneic hematopoietic stem cells after either nonmyeloablative (n=176) or high-dose (n=111) conditioning. The 1-year cumulative incidence of TMA was 13% in nonmyeloablative recipients versus 15% in high-dose conditioning recipients (P=0.5). In multivariate Cox analysis, occurrence of grade 3-4 acute graft-versus-host disease (GVHD) (hazard ratio (HR)=2.3, P<0.001), older age (HR=1.01, P=0.045), and unrelated donors (HR=1.6, P=0.01) were each associated with a higher risk of TMA, whereas nonmyeloablative conditioning was associated with a lower risk of TMA (HR=0.6, P=0.01). We conclude that acute GVHD, age, donor type, and conditioning intensity might have a role in the physiopathology of TMA after allogeneic HCT.

[Cerebral toxoplasmosis complicating an allograft with hematopoietic stem cells from peripheral blood]. / Toxoplasmose cérébrale compliquant une mini-allogreffe de cellules souches hématopoïétiques du sang périphérique.

We report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.