Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry.

peer reviewedThe use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II-IV and III-IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III-IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II-IV; 16% for aGVHD III-IV) than with BM (28% for aGVHD II-IV; 8% for aGVHD III-IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III-IV remained higher with PB than with BM graft (HR = 2.0; range [1.17-3.43], p = 0.012)

Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS.

peer reviewedAllogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2-4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32-1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28-1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome

Focal adhesion kinase (FAK), une protéine aux fonctions multiples

FAK (focal adhesion kinase) est une protéine cytoplasmique ubiquitaire retrouvée au sein du complexe d’adhérence. Son activation par les intégrines mais aussi par différents facteurs de croissance, cytokines ou hormones se traduit par l’autophosphorylation d’un résidu tyrosine (397) libérant un site de liaison pour la protéine Src. Cette liaison va permettre l’activation des protéines du complexe d’adhérence, aboutissant à la transmission de signaux régulateurs pour la migration, la survie et la prolifération cellulaires. Un dérèglement de ce système peut limiter ainsi plusieurs fonctions cellulaires, voire entraîner l’apoptose, et pourrait participer aux processus de cancérogenèse. Cet article présente les mécanismes par lesquels FAK contribue à la régulation cellulaire.Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase localized to regions called focal adhesions. Many stimuli can induce tyrosine phosphorylation and activation of FAK, including integrins and growth factors. The major site of autophosphorylation, tyrosine 397, is a docking site for the SH2 domains of Src family proteins. The other sites of phosphorylation are phosphorylated by Src kinases. Phosphorylated FAK binds proteins of focal adhesion and can activate them directly or indirectly by phosphorylation. These activated proteins forming the FAK complex facilitate the generation of downstream signals necessary to regulate cell functions, like motility, survival and proliferation. Dysregulation of FAK could participate in the development of cancer. This review will focus upon the mechanisms by which FAK transmits biochemical signals and elicits biological effects

Impact d'une prophylaxie par Fluconazole versus Posaconazole sur l'incidence des infections fongiques invasives chez des patients recevant une chimiothérapie d'induction pour une leucémie aiguë myéloïde

Les infections fongiques invasives (IFI) restent des complications préoccupantes chez les patients atteints d'hémopathie maligne et notamment de leucémie aiguë myéloïde (LAM), de part leur incidence et leur taux de mortalité attribuable élevés. Compte tenu de ces risques, la prophylaxie antifungique a toujours été discutée. Méthode : Nous avons réalisé une étude rétrospective monocentrique de deux prophylaxies antifongiques (Fluconazole/Posconazole) chez 91 patients consécutifs suivis entre 2005 et 2009 ayant reçu une chimiothérapie d'induction pour une LAM, afin d'évaluer leur impact sur l'incidence des IFI et l'écologie mycologique des patients. Le coût global des antifongiques a par ailleurs été estimé. Résultats : 39 patients ont reçu une prophylaxie par Fluconazole contre 52 pour Posaconazole. Les caractéristiques cliniques des patients sont comparables. 17 patients ont présenté une IFI, sans différence entre les 2 groupes. L'utilisation d'un traitement empirique ou préemptif est similaire quelque soit la prophylaxie occasionnant in fine des coûts identiques entre les groupes. Enfin, l'étude mycologique des selles montre une augmentation de la colonisation par Candida non-albicans dans le groupe Fluconazole au cours du séjour et l'apparition d'une colonisation par Saccharomyces cerevisiae pour les patients sous Posaconazole. Conclusion : II nous semble préférable de privilégier le Posaconazole compte tenu de son AMM, de son large spectre et de sa relative innocuité. Cependant, il nous parait indispensable d'intégrer des dosages systématiques afin d'assurer un contrôle optimal. Le traitement empirique doit être rediscuté compte tenu de son absence d'influence sur l'incidence des IFI et de son coût au profit d'un traitement par Voriconazole dès le diagnostic d'IFI possible. L'amphotéricine B liposomale ou la caspofungine devraient être réservées quand l'administration de posaconazole n'est plus possible ou en cas suspicion d'une IFI non aspergillaire.ST ETIENNE-BU Médecine (422182102) / SudocSudocFranceF

Fulminant hepatitis due to very severe sinusoidal obstruction syndrome (SOS/VOD) after autologous peripheral stem cell transplantation: a case report

Abstract Background Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (SOS/VOD), is a potentially fatal complication of allogeneic or autologous hematopoietic stem cell transplantation. A plethora of transplant and patient-related risk factors predispose to SOS/VOD and should be taken into account for prognosis assessment as well as for adequate therapeutic intervention. Case presentation We describe the case of a mantle cell lymphoma patient who developed a fulminant hepatitis following oxaliplatin-containing intensive chemotherapy and autologous transplantation. This clinical manifestation was secondary to a very severe SOS/VOD. The patient did not exhibit the usual risk factors and presented a non-classical form with major cytolysis, thus puzzling SOS/VOD diagnosis in this context. Conclusion SOS has been previously reported after oxaliplatin-based chemotherapy regimens for colorectal cancers, in particular in patients with colorectal liver metastases. We therefore suspected a potential relationship with oxaliplatin-based regimen as a driver of SOS/VOD in a non-susceptible lymphoma patient. With regards to this case, clinicians and especially intensivists should be aware of this atypical presentation

Impact of fluconazole versus posaconazole prophylaxis on the incidence of fungal infections in patients receiving induction chemotherapy for acute myeloid leukemia

Background: Invasive fungal infections (IFIs) remain one of the worrying complications in patients with acute myeloid leukemia (AML) due to their incidence and high level of attributable mortality. In light of these risks, antifungal prophylaxis has always been debated. We conducted a single-center retrospective study of two prophylactic antifungal agents (fluconazole/posaconazole) in 91 consecutive patients receiving induction chemotherapy for AML between 2005 and 2009, in order to evaluate the impact on the incidence of IFI and on the mycological flora of the patients. Methods: In total, 39 patients received prophylactic fluconazole versus 52 who received posaconazole. The baseline characteristics of the two groups were comparable. Results: Overall, 17 patients developed an IFI, with no difference in frequency between the two groups. Utilization of empirical or pre-emptive therapy was similar irrespective of the type of prophylaxis used. Mycological examination of stools revealed an increase in non-albicans Candida colonization in the fluconazole group during hospitalization and the appearance of Saccharomyces cerevisiae colonization in patients receiving posaconazole. Conclusion: The present study does not distinguish between fluconazole and posaconazole as a primary effective prevention against fungal infections. More prospective studies and meta-analyses are warranted

Atelier d’harmonisations 2019 : indications et organisation d’une microtransplantation de cellules souches hématopoïétiquesIndications and management of hematologic microtransplantation: Recommendations of the French Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC)

Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete remission rates and longer disease free survival and overall survival have been reported. Safety seems acceptable. The most frequent adverse event is non-severe cytokine release syndrome. Risk of GVHD remains very low. Here, we summarize the published data and detail the practical aspects of the procedure. Current data are not strong enough to provide recommendations on indications. Nevertheless, it seems reasonable to propose MT to patients with AML or HR-MDS, regardless of age, presenting an indication for allogeneic stem cell transplantation but ineligible for it. MT is still under investigation and rather be proposed within clinical trials