Introduction: allogenic hematopoietic stem cell transplantation (HSCT) is the only currently available curative treatment for a number of high-risk hematologic malignancies and for a range of inherited and acquired non-malignant diseases. Haploidentical (HI) HSCT is a valid option for patients who lack an HLA-identical brother. Objective: to describe the results obtained with HI HSCT in pediatrics. Method: in 2005 an HI HSCT program was started at the Pediatric Hemato-Oncological Department of the Centro Hospitalario Pereira Rossell, for patients who lack an HLA-matched related donor. Results: Thirty two patients were transplanted, 24 of them with hematological malignancies and 8 with non-malignant diseases. Two strategies were used to prevent the Graft-Versus-Host-Disease (GVHD), in- vitro T-cell depletion (28 patients) and in-vivo depletion of aloreactives T-cells with high-dose post-transplantation cyclophosphamide (4 patients). Successful engraftment occurred in 27 patients (84%), with full-donor chimerism. Incidence of acute and chronic GVHD was 26.9% and 11.8% respectively. One year non-relapsed mortality was 21.9%. With a median follow-up of 32 months, the overall survival was 52.4%. Conclusions: HI HSCT has proved to be a feasible option in our country for those patients without an HLA-identical donor. The results obtained are comparable to those obtained with other alternative donors and costs are more reasonable. Today, Uruguay is in a better position to offer a HSCT to patients who need it.
Introduction Predictive value of donor specific antibody (DSA) for the ocurrence of antibody mediated rejection (AMR) and graft loss in the individual patient is variable. In Uruguay, these techniques for detecting antibodies began to be implemented since 2016.The objective of this study was to assess the impact of presenting pre-formed antibodies in the first year of kidney transplantation outcome. Materials and Methods Retrospective multi-centric study, which included adult patients who received a kidney transplant with a cadaveric donor between 1/1/16 and 4/30/17, in the 3 transplant centers of Uruguay. All patients underwent study of HLA class I and II antibodies and specificity study for determination of DSA, performed by solid-phase technique, Luminex. At the transplant, they had a negative cross-test due to microliphocytotoxicity. Comparison off the incidence of acute rejection (AR) and survival of grafts and patients were calculated between the groups of patients with and without preformed antibodies. Results Of 125 patients analyzed, 73% did not present preformed antibodies, while 27% were sensitized with the presence of anti-HLA antibodies both class I and/or class II. Of this 27% of patients, 11% had anti-HLA antibodies pre-transplant positive, both class I and/or class II without DSA, and 16% had DSA. Patients were divided into 3 groups, according to absence of antibodies (G1), presence of antibodies but without DSA-positive (G 2) and presence of antibodies with DSA-positive (G3). G2 and G3 had a significantly higher percentage of females (p = 0.002), retransplants (p = 0.001), time on dialysis (p = 0.01), higher PRA (p = 0.001) as well as a higher number of transfusions (p = 0.02), versus G1 patients. The 3 groups did not have induction differences nor maintenance immunosuppression. There was a significant difference in perioperative desensitization, with infusion of gamma globulin (G3 75% versus G1 and G2 4.6% and 8%, p = 0.001). Month follow-up of the groups was of G1, G2 and G3, 11 ± 5.12 ± 5 and 9 ± 5.5 months of mean respectively. The incidence of AR in G2 and G3 was 46% and 45% versus 15% G1, (p = 0.001). Diagnosis of AR was performed at 19 ± 17.16 ± 26 and 18 ± 32 days post transplant for groups G1, G2 and G3 respectively, without differences. Patients survival was similar between groups, with 1 death in each group, all due to sepsis. Censored by death graft survival at one year was 95% G1, 100% G2 and 93% G3 (p = ns). Conclusion Patients transplanted with preformed antibodies, were most frequently females, retransplant and had more time on dialysis. Although this group mostly received desensitization treatment, at 3 months it presents a higher acute rejection rate, but with similar renal graft survival at 1 year.
The humoral response after SARS-CoV-2 vaccination and boosters in kidney transplant recipients (KTRs) is heterogeneous and depends on immunosuppression status. There is no validated immune measurement associated with serological response in clinical practice. Multicolor flow cytometric immunophenotyping could be useful for measuring immune response. This study aimed to study B- and T-cell compartments through Standardized EuroFlow PID Orientation after SARS-CoV-2 vaccination and their association with IgG SARS-CoV-2 seropositivity status after two doses or boosters.We conducted a multicenter prospective study to evaluate humoral response after SARS-CoV-2 vaccination in KTRs. Heterologous regimen: two doses of inactivated SARS-CoV-2 and two boosters of BNT162b2 mRNA (n=75). Homologous vaccination: two doses of BNT162b2 mRNA and one BNT162b2 mRNA booster (n=13). Booster doses were administrated to KTRs without taking into account their IgG SARS-CoV-2 seropositivity status. Peripheral blood samples were collected 30 days after the second dose and after the last heterologous or homologous booster. A standardized EuroFlow PID Orientation Tube (PIDOT) and a supervised automated analysis were used for immune monitoring cellular subsets after boosters.A total of 88 KTRs were included and divided into three groups according to the time of the first detected IgG SARS-CoV-2 seropositivity: non-responders (NRs, n=23), booster responders (BRs, n=41), and two-dose responders (2DRs, n=24). The NR group was more frequent on mycophenolate than the responder groups (NRs, 96%; BRs, 80%; 2DRs, 42%; p=0.000). Switched memory B cells in the 2DR group were higher than those in the BR and NR groups (medians of 30, 17, and 10 cells/ul, respectively; p=0.017). Additionally, the absolute count of central memory/terminal memory CD8 T cells was higher in the 2DR group than in the BR and NR groups. (166, 98, and 93 cells/ul, respectively; p=0.041). The rest of the T-cell populations studied did not show a statistical difference.switched memory B cells and memory CD8 T-cell populations in peripheral blood were associated with the magnitude of the humoral response after SARS-CoV-2 vaccination. Boosters increased IgG anti-SARS-CoV-2 levels, CM/TM CD8 T cells, and switched MBCs in patients with seropositivity after two doses. Interestingly, no seropositivity after boosters was associated with the use of mycophenolate and a lower number of switched MBCs and CM/TM CD8 T cells in peripheral blood.
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