Targeting the αv integrin-TGF-β axis improves natural killer cell function against glioblastoma stem cells Running title-GBM induce NK cell dysfunction via integrin-TGF- axis

Objective:Sticky platelet syndrome (SPS) is an inherited condition that leads to arterial and venous thrombosis. There is scant information about the association between SPS and obstetric complications. This study aimed to assess the relationship between SPS and fetal loss at a single institution.Materials and Methods:The obstetric histories of all consecutive female patients prospectively studied in a 324-month period at a single institution with a history of thrombosis and a clinical marker of primary thrombophilia were reviewed.Results:Between 1989 and 2016, 268 consecutive patients with a clinical marker of primary thrombophilia and a history of arterial or venous thrombosis were studied; of these, 108 were female patients. Within this subset of thrombophilic females, 77 (71%) had been pregnant at some point. Twenty-eight of these 77 patients (37%) had had a spontaneous abortion and 24 of those (86%) were found to have SPS. On the other hand, in a subset of 73 female patients with SPS who had been pregnant, 32% had miscarriages. These figures are significantly higher than the prevalence of spontaneous abortions in the general Mexican population of pregnant women, which is 12%-13% (chi-square: 7.47; p=0.0063). Accordingly, the relative risk of having a miscarriage is 2.66 times higher in female patients with SPS than in the general population (p=0.0014).Conclusion:In Mexico, female patients with SPS experience significantly more spontaneous abortions than the general population. Since the treatment of SPS is simple and effective and could in turn prevent adverse obstetric outcomes, its investigation in women treated for obstetric complications may be useful and deserves further research.

Background: With the goal of immune system reset, autologous hematopoietic stem cell transplantations have been done in patients with multiple sclerosis (MS). Material and methods: 131 consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSC) on an outpatient basis and conditioning with cyclophosphamide (Cy) and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. The PBSC mobilization schedule was done with Cy and filgrastim (G-CSF). Intravenous Cy (50 mg/Kg) was delivered on days - 11 and - 10. Subcutaneous G-CSF (10 ug / Kg / bid) was delivered on days - 9 to - 1.. The apheresis procedure was performed on day - 2. The apheresis objective was to reach at least 1 x 106 viable CD34+ cells/Kg. As outpatients and after collecting the PBSC, intravenous Cy (50 mg / Kg) was delivered along a 120 minute period, on days - 2 and - 1 followed by MESNA (1000 mg/m2 along a 180-minute period). After the intravenous Cy, oral ondansetron), oral cotrimoxazole, oral fluconazole and oral acyclovir were used in all patients until granulocytes were greater than 0.5 x 109/L. After the recovery of the granulocytes, patients were given rituximab (375 mg/m2 along a 3 h period) and subsequently rituximab (100 mg) every two months along a 12-month period. The cumulative dose of Cy is 200 mg/Kg. Results: 80 females and 51 males were included; median age was 47 years. All procedures were started on an outpatient basis and two persons were admitted to the hospital during the procedure. In order to obtain at least 1 x106 / Kg viable CD34 cells, one to four apheresis were performed (median 1). Total number of viable CD34+ cells infused ranged between 1 and 9.6 x106 / Kg (median 2.2). Patients recovered above 0.5 x109/L absolute granulocytes on median day 9 (range 6 to 12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant related deaths, the 120-month overall survival being 100%. In a subset of 25 persons followed for 5 months or more the EDSS was assessed three months after the graft and means diminished from 5.4 to 4.9. The EDSS score improved in 11 patients (44%), remained stable in 7 (28%) and worsened in 7 (28%). A tendency to diminish the EDSS score as a function of time after the autograft was observed in this subset of individuals. Conclusions: It is possible to conduct autotrasplants for patients with MS employing non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS. Disclosures No relevant conflicts of interest to declare.

NAFLD should be considered as a cause of mild thrombocytopenia. Our initial observation has been confirmed and defined more precisely. Additional studies are needed to further define more features of the thrombocytopenia of NAFLD, as well as its mechanisms.

Background: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). Material and Methods: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. Results: One hundred and ninety-four females and 92 males were included; the median age was 47. All procedures were started on an outpatient basis and only 8 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1 × 10⁶/kg viable CD34 cells, 1-4 aphereses were performed (median 1). The total number of viable CD34+ cells infused ranged between 1 and 19.2 × 10⁶/kg (median 4.6). Patients recovered above 0.5 × 10⁹/L absolute granulocytes on median day 8 (range 0-12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant-related deaths and the 128-month overall survival of the patients is 100%. In 82 persons followed up for 3 or more months, the Expanded Disability Status Scale diminished from a mean of 5.2-4.9, the best results being obtained in relapsing-remitting and primary progressive MS. Conclusions: It is possible to conduct autotransplants for patients with MS employing non-frozen PBSCs and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS.