Este artículo no tiene resumen

Abstract: Background: Hematopoietic stem cell transplantation (HSCT) is currently the only clinical cure for thalassemia major (TM). Graft‐versus‐host disease (GVHD) and transplant‐related mortality (TRM) remain major barriers to clinical outcomes in TM‐unrelated donor transplantation (MUD‐HSCT). Aims: The role of Basiliximab in preventing acute graft‐versus‐host disease (aGVHD) after MUD‐HSCT in thalassemia major (TM) is still unknown. We performed a prospective, multicenter, open‐label, randomized controlled trial (RCT). The study is registered at www.clinicaltrials.gov as #NCT02342145.

PATIENTS AND METHODS:

Patients with TM with unrelated donor were randomly assigned to a basiliximab group (20 mg/kg basiliximab on days 0 and +4, respectively, plus tacrolimus [FK506], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (FK506, MTX, and MMF). The primary end point of this study was grade 2‐4 aGVHD on day 100. Results: From April 2015 and September 2021, a total of 205 TM patients were enrolled. The ratio of male to female was 123 to 82 with a median age of 7 years (range, 2‐19 years). Patients were randomly assigned to the basiliximab group of 102 and the control group of 103. Comparison of the basiliximab group and the control group, the cumulative incidence rate of grade 2‐4 aGVHD was 24.5% and 29.1%, respectively (P=0.456), and the cumulative incidence rate of grade 3‐4 aGVHD was 8.8% and 14.6% (P=0.201); the cumulative incidence rate of moderate or severe chronic GVHD was both 2.9%; median days of neutrophil engraftment were +11.8 and +11.6 days, respectively (P=0.701), platelets Implantation days were +15.4 and +13.5 days (P=0.126); TRM was 3.6% and 7.1% (P=0.249), over survival (OS) was 96.4% and 92.0% (P=0.188), respectively and thalassemia‐free survival (TFS) of the two groups was also the same as the OS. There was no significant difference between the basiliximab and control groups with regard to cytomegalovirus reactivation, Epstein‐Barr virus reactivation, and transplant‐related complications. Subgroup analysis according to the degree of HLA matching showed that the 9/10 mismatch group had significantly lower OS and TFS than the 10/10 matched group (both 82.6% v 96.5%, P=0.004). The 3‐year OS and TFS of the entire cohort (205 TM patients ) were 94.1% and 94.0%, respectively(Table 1, Fig 1).

CONCLUSION:

This first prospective randomized study showed basiliximab at a dose of 20 mg on day 0 and day+ 4 did not reduced the incidence of both aGVHD and cGVHD in patients with TM after MUD‐HSCT. The incidence of aGVHD in unrelated donor transplants for TM patients is still high, 9/10 mismatched unrelated donor transplants had poor result when comparing 10/10 matched donor transplants for TM patients. Unrelated donors are still a very good alternative source of donors. The TFS of TM patients treated by unrelated donor transplantation can reach 94.0%. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

This study assays therapy with basiliximab and different patterns of cyclosporin A (CsA) initiation in renal transplant (RT) recipients from expanded criteria donors (ECD) and at high risk of delayed graft function (DGF). A multicentre six-month open-label randomized trial with three parallel groups treated with basiliximab plus steroids, mycophenolate mofetil and different patterns of CsA initiation: early within 24 h post-RT at 3mg/kg/d (Group 1; n = 38), and at 5 mg/kg/d (Group 2; n = 40), or delayed after 7-10d at 5 mg/kg/d (Group 3; n = 36). There were no differences among groups in six months GFR (43.1 ± 12, 48.0 ± 14 and 47.2 ± 17 mL/min, respectively), DGF (Group1: 31%, Group 2: 37%, Group3: 42%), nor biopsy-proven acute rejection, although clinically treated and biopsy-proven acute rejection was significantly higher in Group 3 (25%) vs. Group 1 (5.3%, p< 0.05). At six months no differences were observed in death-censored graft survival or patient survival. Induction therapy with basiliximab and three CsA-ME initiation patterns in RT recipients from ECD and at high risk of DGF presented good renal function and graft survival at six months. Late onset group did not achieve improvement in DGF rate and showed a higher incidence of clinically treated and biopsy-proven acute rejection. © 2009 John Wiley & Sons A/S.

Abstract: Introduction: Severe graft‐versus‐host disease (GvHD) is a major barrier to the success of haploidentical stem cell transplantation (haplo‐SCT). However, there are no standard second‐line treatment for steroid‐resistant (SR) acute graft‐versus‐host disease (aGVHD) and causes poor overall survival (OS) in haplo‐SCT recipients. Mesenchymal stromal cells (MSCs) may be a potential efficacious therapy for SR aGVHD. Methods: We conducted a multicenter, randomized, open‐label trial to evaluate the efficacy and safety of MSCs combined with basiliximab as second‐line treatment for haplo‐SCT recipients with SR aGVHD. In both treatment groups, basiliximab was administered on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II, or showed no response after four doses. For patients assigned to the MSC group, MSCs were given in addition to basiliximab at a dose of 1.0×106/kg weekly for 4 weeks as a cycle, and further infusions of MSCs were based on the response of MSC. The primary endpoint was the rate of aGVHD complete response (CR) in week 4 after randomization. The key secondary endpoints were OS at the end of weeks 4/8/12/24/52 and the partial response (PR) rate in week 4. Safety analyses included evaluations of infusion toxicity, infections, hematologic toxicity, etc., and tumor relapse. Results: From February 2021 to May 2022, a total of 100 patients with SR aGVHD after haplo‐SCT were enrolled and randomized 1:1 to receive MSCs combined with basiliximab (MSC group, n=50) or basiliximab alone (control group, n=50) in 3 centers and all the enrolled patients were included in intention‐to‐treat (ITT) analysis. Among patients in MSC group, 3 withdrew informed consent and 3 discontinued MSC treatment before completing 4 MSC infusions due to patients’ decision after randomization, and so were not included in the safety analysis set. In the ITT population, the median age was 32 years (range, 18‐68), consisting 49 male patients. The median time from aGVHD diagnosis to basiliximab therapy was comparable between the two groups (4 days vs. 5days, P=0.92). The proportion of patients with grade 2‐4 SR aGVHD or grade 3‐4 SR aGVHD was comparable between the MSC group and the control group (82.0% (41/50) vs. 86.0% (43/50), P=0.585;38.0% (19/50) vs. 44.0% (22/50), P=0.542). For the primary endpoint, the rate of aGVHD CR in week 4 after randomization was significantly higher in the MSC group than in the control group (84.0% (42/50) vs. 60% (30/50), P=0.008) (Figure 1). Patients in the MSC group received higher 4‐week overall response rate (ORR) comparing to patients in the control group (96.0% (48/50) vs. 83.0% (41/50), P=0.025) (Figure 1A). However, for CR or ORR at week 8, week 16 and week 52, there was no significant difference between the two groups. In the ITT population, patients received the median of four doses of basiliximab (range, 2 to 8).And less patients in the MSC group used ≥ 6 doses of basiliximab (2%(1/50) vs. 16% (8/50), P=0.008).The 12‐week OS was significantly higher in the MSC group than in the control group (P=0.022). MSCs were well tolerated, and no infusion‐related toxicity was observed. There was no difference between the MSC and control groups in terms of infections, hematologic toxicity, or tumor relapse. Four patients in the MSC group and 5 patients in the control group died because of GVHD progression (n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function (n = 1). Conclusions: MSCs plus basiliximab is a safe and effective approach for treating SR aGVHD in patients who receive haplo‐SCT, decreases the dose of basiliximab without increasing relapse, is well‐tolerated and improves patients’ prognosis. Figure Legends: Figure 1A. A Overall response (OR) in week 4 after randomization; Figure 1B. The 12‐week OS was significantly higher in the MSC group [Formula presented] Disclosures: No relevant conflicts of interest to declare.

AIM:

The aim of this study was to report our single-center experience with the use of basiliximab, in combination with a steroid and tacrolimus-based regimen in adult to adult living-related liver transplantation (ALRLT) and in deceased donor liver transplantation (DDLT).

MATERIALS AND METHODS:

Seventy-seven consecutive ALRLT recipients (group 1) and 244 DDLT recipients (group 2) were analyzed. All patients received 2 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and a dose regimen of steroids. Follow-up ranged from 4-1972 days after transplantation in group 1 and from 1-2741 days in group.

RESULTS:

In group 1, 89.32% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.51% within 3 months. Actuarial patient survival rate at 3 years was 84.49%. In group 2, 86.07% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.04% within 3 months. Actuarial patient survival rate at 3 years was 87.69%. We observed 14 cases of hepatitis C virus (HCV) recurrence in group 1 (prevalence of 26.92%) and 80 cases in group 2 (prevalence of 54.05%).

CONCLUSION:

Basiliximab in association with tacrolimus and steroids is effective in reducing episodes of acute cellular rejection (ACR) and increasing ACR-free survival after ALRLT and DDLT. No difference in patient and graft survival was found between group 1 and 2, nor was there any difference in the incidence of ACR between the 2 groups. However, less risk of HCV recurrence was present in the LRLT group.

OBJECTIVES:

Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids.

MATERIALS AND METHODS:

We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses.

RESULTS:

During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group.

CONCLUSIONS:

High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

OBJECTIVES:

Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids.

MATERIALS AND METHODS:

We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses.

RESULTS:

During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group.

CONCLUSIONS:

High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Este artículo no tiene resumen

Este artículo no tiene resumen

Este artículo no tiene resumen