Impact Of Prophylaxis With Defibrotide On The Occurrence Of Acute GvHD In Allogeneic HSCT

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4591-4591
Author(s):  
Selim Corbacioglu ◽  
Simone Cesaro ◽  
Maura Faraci ◽  
Bernd Gruhn ◽  
Jaap J Boelens ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Controlled Study ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Adjusted Risk ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
And Control ◽  
The Impact

Background Acute GvHD (aGvHD) remains one of the most significant complications of allogeneic hematopoietic stem cell transplantation (HSCT) with a persistently high incidence despite a plethora of prophylactic approaches. The medical need for effective drugs to prevent aGvHD remains substantial. Methods A prospective, randomized, open-label controlled study has been conducted in 356 children at high-risk for hepatic VOD post-HSCT to demonstrate efficacy of prophylaxis with defibrotide (DF) to reduce the incidence of VOD (180 in the DF arm and 176 in the control arm [Corbacioglu, Lancet 2012]). A secondary objective of the study was to analyze the impact of DF prophylaxis on the incidence and severity of aGvHD. Among children undergoing allogeneic HSCT (allo-subset) 122 patients received DF prophylaxis and 117 were in the control arm. Results Demographic and baseline characteristics were similar in the DF and control arm of the allo-subset. Mean age (± SD) was 6.47±5.28 and 6.54±5.49 in DF arm and in the controls respectively, with 29% and 30% being <2 years; 64% and 58%, respectively, were males. Busulfan was used in conditioning in 62% and 64% of patients in the two arms, and melphalan in 60% and 53%, respectively. Grafts were from related donors in 40% and 30%, respectively, in DF and control arm. Prophylaxis with DF was shown to significantly reduce the occurrence and severity of aGvHD. At day+100 post-HSCT the incidence of aGvHD was 47% in the DF arm vs. 65% in the control group (p=0.0046). DF did not seem to affect the incidence of aGvHD grade I (25% vs 28%, respectively). However, Defibrotide showed a consistent reduction of the more severe grade II–IV aGvHD from 37% to 22% (p=0.0130). Of note the use of corticosteroids was significantly lower in patients receiving DF prophylaxis (37% vs 48% in control arm, p=0.0363), likely reflecting the lower incidence of aGvHD in the DF arm. This has also previously been observed in the treatment studies [Richardson, ASH 2012]. Standard GvHD prophylaxis was allowed according to best practice and was generally comparable (cyclosporine A: 81% vs. 89%; methotrexate: 46% vs. 56%; in DF and control arm, respectively). However, there was a difference in patients who received antithymocyte globulin (ATG) in the DF arm compared to controls (55% vs 70%). Exploratory analysis performed adjusting for ATG as covariate confirmed the significant effects of defibrotide [Adjusted Risk Difference (DF vs control) for aGvHD grade II–IV: -0.1470 (95%CI: -0.2618; -0.0322), p =0.0121]. Defibrotide did not seem to interfere with a graft-versus-leukemia effect. Relapse rates of combined leukemias were 8% (ALL 1.5%, AML 5%, others 1.5%) in DF group compared with 10% (ALL 3%, AML 7%) in controls by day +100; while 10% (ALL 1.5%, AML 7%, others 1.5%) patients in DF group relapsed by day +180 compared with 13% (ALL 8%, AML 5%) in the control arm. Conclusions The study shows that DF prophylaxis can reduce the incidence and severity of aGvHD in children undergoing allogeneic HSCT. This reduction observed with defibrotide is additional to standard GvHD prophylaxis that was fully implemented in these patients. Defibrotide has been reported to protect endothelial cells from damage as well as to downregulate heparanase activity. These clinical data would therefore suggest a benefit of defibrotide to reduce the incidence and severity of aGvHD. Further studies may be conducted to strengthen preclinical and clinical evidence for the role of defibrotide in aGvHD prevention. Ref: Corbacioglu S et al, Lancet 2012; 379:1301-9. Richardson PG et al, Blood 2012; 120:738. Disclosures: Corbacioglu: Gentium : Consultancy. Cesaro:Pfizer SpA: Honoraria; Gilead: Honoraria; Merck: Honoraria. Tudone:Gentium : Employment. Ballabio:Gentium : Employment. Heringa:Gentium S.p.A.: Employment.

scholarly journals Role of Extracorporeal Photopheresis in Prevention of Graft-Versus-Host Disease in Patients Treated with Allogeneic Hematopoietic Stem Cell Transplantation: A Randomized Controlled Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 102-102
Author(s):  
Maryan M Ali ◽  
Tobias Gedde-Dahl ◽  
Marit B Veierød ◽  
Geir E Tjønnfjord ◽  
Per Ole Iversen
Keyword(s):  
Hematological Malignancy ◽  
Intervention Group ◽  
Study Groups ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Randomized Controlled ◽  
Gvhd Prophylaxis ◽  
One Year ◽  
And Control

Abstract Introduction In many patients diagnosed with a hematological malignancy, the disease cannot be totally eradicated by conventional therapeutic approaches, and for them allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option. A major complication of allo-HSCT is graft-versus-host disease (GvHD), affecting about 50% of transplant recipients. In addition to increased risk of death and long-lasting debilitating conditions, severe GvHD also impairs health-related quality of life. High-dose systemic steroids is the first line treatment for GvHD, but treatment failure is common, and steroid-refractoriness is a major cause of non-relapse mortality after allo-HSCT. While there is no established second line GvHD-treatment, extracorporeal photophoresis (ECP) has emerged as an attractive and increasingly applied alternative, partly due to its favourable safety profile. However, the use of ECP in preventing GvHD is sparse and data are inconclusive due to lack of randomized controlled trials (RCT). We therefore conducted a RCT to study if ECP given post transplantation could prevent the development of GvHD. Methods Between June 2017 and February 2020, we enrolled 157 patients (&gt; 18 years) diagnosed with a hematological malignancy and treated with an allo-HSCT in first remission into an intention-to-treat open RCT. Ethical and IRB approvals were granted, and the RCT was registered with Clinical Trials (ID NCT03204721). The sample size (76 in intervention group and 81 controls) was calculated based on a reduction of 25% in the total number of patients diagnosed with any form of GvHD within the first year of allo-HCST (primary end-point) as clinically relevant. The patients were stratified according to whether they received myeloablative or reduced intensity conditioning (Table 1), and they were given GvHD prophylaxis as shown in Table 1. ECP (Therakos Cellex ®, Mallinckrodt Pharm., NJ) was initiated when patients had engrafted (i.e. leukocytes &gt; 1 x 10 9/L and platelets &gt; 20 x 10 9/L), and, according to the study protocol, we planned for ECP on two consecutive days/week for two weeks, then weekly for four weeks to a total eight treatments for each patient in the intervention group. Chi-square test was used to test differences between the two study groups. Results Table 1 shows that patient characteristics were well balanced among the two study groups. Four patients did not receive ECP while 39 received all the eight treatments. One year after allo-HCST, the proportion of GvHD was 45/76 (59%) in the intervention group and 52/81 (64%) in the controls (p=0.52). There were no significant differences between the intervention and control group regarding development of acute (45% vs. 48%) or chronic (39% vs. 40%) GvHD. Neither did we detect any statistical differences between the two study groups regarding organ involvement or severity of the GvHD manifestations (data not shown). During the one-year observation period, 16/76 (21%) and 10/81 (12%) relapsed in the intervention and control group, respectively (p=0.14). The corresponding numbers of deaths were 12/76 (16%) and 16/81 (20%), respectively (p=0.52). Six patients in the intervention group experienced mild to moderate temporary, adverse events that could possibly be related to the ECP-procedure. Conclusion In this first RCT addressing ECP as GvHD prophylaxis in allo-HSCT for hematological malignancy, we found no significant difference in the numbers, types, organ involvement, or severity of GvHD between the intervention and the control group. Thus, our study does not support the use of ECP as an adjunct to GvHD-prophylaxis based on cyclosporine and methotrexate, mycophenolate mofetil, or sirolimus. However, ECP did not seem to be harmful in this setting. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Extended Use of Ciprofloxacin Markedly Decreases the Incidence of Severe BK Virus-Associated Hemorrhagic Cystitis In Allogeneic HSCT Recipients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2317-2317
Author(s):  
Ashley N Miller ◽  
Ashley S Glode ◽  
Kathy Hogan ◽  
Christine Schaub ◽  
Robert K Stuart ◽  
...  
Keyword(s):  
Viral Replication ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Bk Virus ◽  
Control Group ◽  
Control Groups ◽  
Hematopoietic Stem ◽  
Cox Regression Analysis ◽  
Allogeneic Hsct ◽  
And Control

Abstract Abstract 2317 Introduction: The polyoma virus BK is present in the urothelial tract of the majority of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Urothelial damage by the conditioning regimen triggers early viral replication and subsequent immune mediated damage to the urothelium. Clinical manifestations of BK virus-associated hemorrhagic cystitis (BKHC), with typical onset in the first 100 days after HSCT, range from asymptomatic microscopic hematuria to massive life threatening blood loss and urinary obstruction. There is no standard prophylaxis or treatment for BKHC. The antibacterial fluoroquinolones have been shown in vitro to inhibit BK viral replication by direct inhibition of the BK encoded DNA gyrase. Therefore, we hypothesized that extended prophylaxis with the fluoroquinolone ciprofloxacin might decrease the incidence of severe BKHC after HSCT. Methods: In March 2009 we began prescribing prophylaxis for BKHC with ciprofloxacin 500 mg orally twice daily from day 0 until day 60 after transplantation in all allograft recipients (except patients allergic to ciprofloxacin). Patient and transplant variables, as well as incidence of severe BKHC, were collected retrospectively for all consecutive patients undergoing allogeneic HSCT between June 2006 and July 2010. Severe BKHC was defined as grades 3 or 4 hemorrhagic cystitis with evidence of urinary excretion of BK virus by polymerase chain reaction. We estimated the incidence of severe BKHC and the survival free of severe BKHC for patients receiving (ciprofloxacin group) or not (control group) prophylaxis. Additionally, we performed a multivariate analysis to assess the independent role of ciprofloxacin prophylaxis in preventing episodes of severe BKHC. Results: Eighty-one consecutive patients were included in the analysis, of which 33 received ciprofloxacin prophylaxis. Median age of patients was 50 years (range 19–70) and 37% were female. Overall 47% of patients received a myeloablative conditioning regimen and 60% had an alternative (not HLA-matched sibling) donor. Median follow up for patients in the ciprofloxacin and control groups were respectively 180 (range 33–504) and 515 days (range of 29–1645). There was no difference in overall survival between ciprofloxacin and control groups. Episodes of severe BKHC occurred after a median of 60 days (range 27–118) after transplantation and were less frequent in the ciprofloxacin than in the control group (2.9% vs. 22.9%, chi-square test P= 0.01). Survival free of severe BKHC was also significantly superior in the ciprofloxacin group (Log-rank test P=0.04; Figure). In a multivariate Cox-regression analysis including age, gender, intensity of the conditioning regimen, use of mesna during conditioning and alternative donor, only the use of ciprofloxacin prophylaxis was significantly associated with the endpoint survival free of severe BKHC (P=0.01). There were no complications associated with prolonged use of ciprofloxacin, in particular no increase in Clostridium difficile associated diarrhea. Conclusion: Ciprofloxacin prophylaxis appears safe and effective in reducing the incidence of severe BKHC after allogeneic HSCT. This finding requires confirmation with a prospective randomized trial. Disclosures: Off Label Use: Ciprofloxacin- prevention of BK associated hemorragic cystitis.

Matched HLA Haplotype Contributes to Reduce Sever Acute GVHD with Conserving GVL Effect in HLA-Mismatched Cord Blood Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4140-4140
Author(s):  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Seiko Kato ◽  
Toshiro Kawakita ◽  
Arinobu Tojo ◽  
...  
Keyword(s):  
Cord Blood ◽  
Acute Gvhd ◽  
Adult Patients ◽  
The Other ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Matched Group ◽  
Other Hand ◽  
The Impact

Abstract Abstract 4140 Study purpose: The cell dose of graft is the primary factor to select for cord blood (CB) unit and most of adult patients choose human leukocyte antigen (HLA)-mismatched CB graft. We have performed more than 7,500 CB transplantation (CBT) in Japan. Almost two-third of them has been using 2-loci HLA-mismatched CB unit. The degree of HLA disparity between patient and graft is known to be associated with risks of poor graft function and of graft-versus-host disease (GVHD) on allogeneic hematopoietic stem cell transplantation. On the other hand, those risks of transplant-related complications are not equivalent even among the donor-recipient pairs who have same number of mismatched HLA antigens. The mismatched HLA haplotype could be responsible for post-transplant adverse events because of incompatibility of non-HLA polymorphic genes. Recently, HLA haplotype matching effect on GVHD has been demonstrated in unrelated bone marrow transplantation (S Morishima, et al. Blood 2010). In this study, we have performed the single institutional analysis to determine the impact of HLA haplotype matching in HLA-mismatched CBT. Patients and Methods: We studied the clinical outcomes of 170 consecutive adult patients who received unrelated CBT between August 1998 and January 2011 in the institute of medical Science, University of Tokyo. Patients received previous allogeneic transplants were excluded from this study. All patients received myeloablative regimens including 12 Gy of total body irradiation, cyclosporine plus short term methotraxate for GVHD prophylaxis and almost same supportive care by the institutional protocol. By low-resolution typing method for HLA-A, -B and -DR loci, 6 patients received matched grafts, 57 received 1 antigen-mismatched and 107 received 2 antigens-mismatched grafts in the graft-versus-host (GvH) direction. We have determined the HLA haplotype based on common haplotypes in Japanese population referred from the 11th International Histocompatibility Workshop and other previous reports. We evaluated the impact of haplotype matching on cumulative incidences of hematopoietic recovery, of GVHD, of relapse and of non-relapse mortality (NRM) using the Pepe and Mori's test. Estimates of overall and disease-free survivals were calculated using the Kaplan-Meier method and analyzed by the log-rank test. Results: Thirty-three among all 170 pairs were defined as the haplotype-matched pairs sharing same haplotypes in both grafts and recipients. The age, sex, cytomegalovirus serological status, diagnosis, risk of the disease at the transplant, numbers of total nucleated cells and CD34+ cells at the cryopreserved were not significantly different between both groups with and without matched haplotypes. Engraftment of platelet after CBT tended to be earlier in haplotype-matched group compared with control group among the 1 antigen-mismatched pairs in the host-versus-graft direction (median: 38 days versus 44 days) and among the 2 antigens-mismatched pairs (median: 38 days versus 42 days), but those were not significant. The cumulative incidences of grades III and IV acute GVHD in patients with haplotype-matched (7%) were significantly lower than non-matched group (9%) among 2 antigens-mismatched pairs in the GvH direction (P=0.033). Notably, cumulative incidences of relapse tended to be lower in haplotype-matched patients among this group (3 years cumulative incidences were 7% in haplotype-matched patients versus 21% in non-matched patients, P=0.086). The haplotype matching effects were not observed in survival rates, cumulative incidences of NRM among any HLA-mismatched pairs. Conclusion: Those data suggest that untyped variation carried on the HLA haplotytpe might be better to be matched. The haplotype matching seemed to effect on lower risk of sever acute GVHD, on the other hand, graft-versus-leukemia effect was conserved in the setting of HLA-mismatched CBT. Disclosures: No relevant conflicts of interest to declare.

Immunotherapy with Autologous Anti-CD19 Chimeric Antigen Receptor T Cells Followed By Allogeneic Hematopoietic Stem Cell Transplantation Has Remarkably Improved Leukemia-Free Survival in Refractory/Relapsed B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 829-829
Author(s):  
Yan-Li Zhao ◽  
Tong Wu ◽  
De-Yan Liu ◽  
Jian-Ping Zhang ◽  
Zhi-Jie Wei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Control Group ◽  
Control Groups ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Time Period ◽  
And Control

Abstract Introduction: The prognosis of refractory/relapsed acute lymphoblastic leukemia (ALL) is poor with chemotherapy or even allogeneic hematopoietic stem cell transplantation (HSCT). Although our immunotherapy with autologous anti-CD19 chimeric antigen receptor T cells (CART) has resulted in 88.6% complete remission (CR) in refractory/relapsed B-cell ALL (B-ALL), many patients relapsed at around 2 months after CART therapy (unpublished data). Our current strategy is to perform HSCT for refractory/relapsed B-ALL in CR by CART therapy to attain continuous leukemia-free survival (LFS). However, majority of the patients with CART therapy developed cytokine release syndrome which may increase transplant-related mortality (TRM). Moreover, all patients with CART therapy have very tough diseases which could result in higher relapse rate after transplant. Objective: In current study, the safety and efficacy of HSCT for refractory/relapsed B-ALL after CART therapy were investigated. The patients with B-ALL who received HSCT during the same time period without CART therapy were as control. Patients and Methods: Between July 2015 and May 2016, consecutive 22 patients with refractory/relapsed CD19+ B-ALL in CR by CART therapy followed by allogeneic HSCT in our hospital were analyzed as CART group; and consecutive 89 patients with B-ALL in CR who received allogeneic HSCT in our hospital during the same time period but without previous CART therapy were as control group. Clinical characteristics between two groups was comparable except more CR1 (22.7% vs. 57.3%) in control group and more CD3+ cells infused (1.93x108/kg vs. 1.46 x108/kg, p=0.026) in CART group. The median age was 8 (2-44) years, 15 (2-52) years in CART and control groups (p=0.147). The median disease course was 19.1 (3.9-53.7) months, 10.6 (3.7-123.0) months in CART and control groups (p=0.385). The median time from CART therapy to HSCT was 86 (31-172) days. Disease status was 22.7% cases in CR1, 54.5% in CR2, 18.2% in CR3 and 4.5% in CR4 in CART group; and 57.3% cases in CR1, 36.0% in CR2 and 6.7% in CR3 in control group (p=0.08). Minimal residual disease pre-conditioning by flow cytometry was positive in 22.7%, 31.5% patients in CART and control groups (p=0.422). Donor source was identical sibling (IS) in 13.6%, unrelated (UR) in 31.8% and haploidentical (HI) in 54.5% in CART group; and IS in 14.6%, UR in 16.9% and HI in 68.5% in control group (p=0.313). Myeloablative conditioning regimens were administered with either total body irradiation (TBI) plus cyclophosphamide (Cy)/ fludarabine (Flu)-based in 90.9% cases or busulfan (Bu) plus Cy/ Flu-based in 9.1% cases in CART group; and TBICY/Flu-based in 85.4% cases or BuCy/Flu-based in 14.6% cases in control group (p=0.498). Antithymocyte globulin was used in UR and HI transplants. Cyclosporine, short-term methotrexate, and mycophenolate mofetil were employed for GVHD prophylaxis. Results: The median time to neutrophil engraftment was similar between two groups (14 days vs. 13 days, p=0.196), but platelet engraftment was slower in CART group (14 days vs. 12 days, p=0.031). Cumulative incidence of grade II-IV acute GVHD (aGVHD) was higher in CART group (57.6% vs. 33.1%, p=0.009), which may related to higher CD3+ cells infused in CART cohort; but the incidences of grade III-IV aGVHD were no statistical significance (25.1% vs. 15.7%, p=0.564) in two groups. No remarkable differences were seen in CMV reactivation (45% vs. 51.7%, p=0.601) and transplant-associated thrombotic microangiopathy (13.6% vs. 9.0%, p=0.514) in two groups. No significant difference was found in TRM between CART and control groups (7.1% vs. 15.2%, p=0.808). Relapse rates were similar in two groups (5.0% vs. 6.9%, p=0.888). With a median follow-up 9 (2-12) months, LFS was comparable in CART and control groups (84.8% vs. 80.9%, p=0.937). Conclusions: Our preliminary results have shown that the strategy with CART therapy followed by allogeneic HSCT in refractory/relapsed B-ALL is very safe and effective with similar outcomes in TRM, relapse rate and LFS compared with control group. CART therapy has resulted in very good CR in refractory/relapsed B-ALL and allowed the patients to achieve continuous LFS by subsequent allogeneic HSCT, which is revolutionary modality for those patients who have otherwise incurable diseases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Dual T-Cell Depletion with a Very Low Dose of ATG and Ptcy Provides an Effective Control of Acute Gvhd in PBSC RIC Allo-HSCT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5669-5669
Author(s):  
Maria Queralt Salas ◽  
Arjun Law ◽  
Wilson Lam ◽  
David Loach ◽  
Zeyad Al-Shaibani ◽  
...  
Keyword(s):  
Low Dose ◽  
Acute Gvhd ◽  
Effective Control ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Grade Ii ◽  
The Impact

Introduction As has been described by Dr. Viswabandya et al, the combination of anti-thymoglobulin (ATG), post-transplant cyclophosphamide (PTCy) and cyclosporine (CsA) provides an effective control of graft-versus host disease (GVHD) in peripheral blood (PB) allo-HSCT. We aim to report our experience in reduced intensity conditioning (RIC) allo-HSCT using a novel GVHD prophylaxis composed by a very low dose of ATG, PTCy and CsA for GVHD prophylaxis. Patients and methods Between May 2018 and April 2019, 106 adult patients underwent RIC allo-HSCT with the present GVHD prophylaxis. All these recipients were included in the study. RIC regimen was composed by fludarabine, busulfan, and 200cGy of total body irradiation. For GVHD prophylaxis all recipients received a total dose of 2mg/kg of rabbit-ATG on day -3 (0.5mg/kg) and -2 (1.5mg/kg), PTCy 50mg/m2/day on day +3 and +4, and CsA since day +5. Data was collected retrospectively and updated on July 2019. The median follow-up was 7.6 months (range: 0.4-14.6) and survival percentages were calculated at 6 months. The cum.Inc of GVHD was assessed accounting relapse and death as competing events. Results The main baseline and post-transplant information is summarized in the Table 1 and 2. The cum.Inc of grade II-IV and III-IV acute GVHD at day +100 was 19% and 7.7%. The cum.Inc of grade II- IV was not significantly affected by donor type (P=0.787). However, the cum.Inc of grade III-IV was significantly higher in those recipients who received haploidentical or 9/10 matched unrelated donor (MUD) grafts (p=0.048). Rates of CMV and EBV reactivation were respectively 62.3% and 68.9%. No patients were diagnosed with CMV disease. Biopsy proven post-transplant lymphoproliferative disorder was diagnosed in only 1 recipient and successfully resolved after rituximab. Thirty-two (30.2%) recipients died and 16 (15.1%) relapsed during the follow-up. Main causes of death were relapse 13 (12.3%) and infection 6 (5.7%). The main outcome information is reported in the Table 2 and Plot 1 and 2. Those recipients who received grafts from matched related and unrelated donors had a significant better non-relapse mortality (NRM) (P=0.001), overall survival (OS) (P=0.02), relapse-free survival (RFS) (P=0.03) and GVHD-free/RFS (P=0.006). Table 3 shows the impact of risk factors in transplant outcomes. Those recipients with an HCT-CI score ≥3 had a significant worse OS (HR 2.5; P=0.024) and RFS (HR 2.5; P=0034). Those recipients who received grafts from 9/10 MUD and haploidentical donors had a significant worse RFS (HR 2.1; P=0.049). Disease risk index was not a significant risk factor for OS or RFS. Lastly, those recipients who received grafts from haploidentical donors had a significant worse GRFRS (HR 2.9; P=0.04). Conclusion The dose of ATG for GVHD prophylaxis is not well established. The combination of ATG (2mg/kg), PTCy, and CsA is safe and provides an effective acute GVHD prophylaxis in PB RIC allo-HSCT. Further investigations are required to analyze the effect of this prophylaxis in chronic GVHD to better state long-term outcome conclusions and to improve post-transplant outcomes in those recipients who received grafts from mismatched donor sources (haploidentical and 9/10 matched unrelated donors). Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

The Impact of Sex Steroids Inhibiter on Thymic Function Following Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4599-4599
Author(s):  
Xiaodan Luo ◽  
Qifa Liu ◽  
Zhiping Fan ◽  
Yu Zhang ◽  
Juan Ning
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Thymic Function ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
The Impact

Abstract Objective To evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT). Methods Established model of allogenic murine HSCT (C57BL/6→BALB/c). The severity of acute graft-versus-host-disease (GVHD) was assessed by a clinical scoring system that incorporates five clinical parameters: weight loss, posture, activity, fur texture and skin integrity. The intra-cellular levels of interferon-γ (INFγ), tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) in thymocyte were analyzed by protein array and thymic function was evaluated by quantification of signaljoint TCR rearrangement excision circles (sjTRECs). Results Recipients in group A (allogenic mice), B( allogenic LHRH castrated-mice) and C (syngenic mice) all attained hematopoiesis reconstitution. White blood cell counts of mice in groups A, B and C were over 1.0×109/L on day (10.60±1.34), day (9.40±0.55) and day (9.40±0.89), respectively. There was no significant difference among the time of hematopoiesis reconstitution in three groups. The time of acute GVHD occuring was on day +11±0.5 and +14±0.5 posttransplantation, respectively, in groups A and B, and all mice had acute GVHD with the incidence of 100% in groups A and B. The average scores of acute GVHD in groups A and B were (1.56±0.51) and (0.92±0.49), respectively. Acute GVHD scores in group A was significantly higher than that in group B (P=0.000). The levels of INFγ, TNFα and IL-1β in control groups were 1.67±1.76 ng/ml, 1.69±1.07 pg/ml and 5.55±3.56 pg/ml, respectively. The levels of INFγ in groups A, B and C were (10.74±2.55) ng/ml,(6.81±2.33) ng/ml and (5.52±3.96) ng/ml, respectively. The levels of TNFα were (7.51±2.89) pg/ml, (4.30±0.63) pg/ml and (3.36±2.31) pg/ml, respectively. The levels of IL-1β were (25.83±8.91) pg/ml, (19.33±3.03) pg/ml and (11.94±4.00) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P=0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those of control group (P 0.010,0.037,0.000). The levels of INFγ in group C were significantly higher than those of the control group (P=0.044). Among groups A, B and C, there were significant differences in the levels of INFγ, TNFα and IL-1β (P=0.001,0.000,0.000). The levels of INFγ and TNFα in group A were significantly higher than those in group B (P=0.041,0.013). The levels of INFγ, TNFα and IL-1β in group A were significantly higher than those in group C (P=0.009, 0.002, 0.000). The analysis of linear regression showed that the average levels of INFγ paralled with aGVHD scores (r2 0.363,P=0.038). The average sjTRECs copies/1000 PBMNCs were (39.41±44.68) in the control group and (12.29±13.02), (58.01±71.82) and (19.61±14.59) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P=0.575). Conclusion INFγ ATNFα and IL-1β might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intracellular levels of INFγ and TNFα in thymocyte.

Graft-Versus-Host Disease (GVHD) After Double-Unit Cord Blood Transplantation (DCBT) Is Associated with Unique Clinical Features Including a Higher Incidence of Grade III-IV Acute GVHD in Children

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3044-3044
Author(s):  
Doris M Ponce ◽  
Anne Marie Gonzales ◽  
Marissa N Lubin ◽  
Hugo Castro-Malaspina ◽  
Sergio A Giralt ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Treatment Response ◽  
Acute Gvhd ◽  
High Rate ◽  
Hematopoietic Stem ◽  
Systemic Corticosteroids ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Unit Unit ◽  
Grade Iii

Abstract Abstract 3044 While the GVHD incidence after unrelated donor CBT is lower than expected for the degree of human leukocyte antigen (HLA)-mismatch, GVHD can be a serious complication and at our center has been the second most common cause of transplant-related mortality after DCBT. However, relatively little is known about DCBT GVHD manifestations, treatment response, and risk factors. Therefore, we evaluated 108 DCBT recipients (median 37 years, range 0.9–69) transplanted for hematologic malignancies. The majority had acute leukemia and high-risk disease. Patients received either myeloablative (n = 81) or non-myeloablative (n = 27) conditioning and 4–6/6 HLA-matched grafts. GVHD prophylaxis consisted of a calcineurin-inhibitor with mycophenolate mofetil, and no patient received anti-thymocyte globulin (ATG). With a median follow-up of 28 months (range 9–64), the cumulative incidences of day 180 grade II-IV and III-IV acute GVHD (aGVHD) were 52% (95%CI :42–62) and 24% (95%CI :15–32), respectively. The median onset was 40 days (range 14–161); the gut was most commonly affected (43/54, 80%) followed by skin (35/54, 65%). Twenty-five patients with mainly grade II gut aGVHD were treated with budesonide alone, 26 patients with predominantly grade III-IV aGVHD received systemic corticosteroids, and complete or partial treatment response was achieved in over 80% by day 56 of therapy. However, 41 patients had active GVHD after day 100 with the majority (25/41, 61%) having aGVHD (persistent, recurrent or late onset), particularly of the gut. Overlap syndrome and classical chronic GVHD were uncommon. Only 1 patient had oral ulceration, and no patient had moderate or severe ocular or sclerotic skin involvement, joint, or pulmonary GVHD manifestations. Univariate analysis of the association between patient/ graft characteristics and grade III-IV aGVHD showed the only significant factor associated with a higher severe aGVHD incidence was age 0–15 years (Figure). Diagnosis, patient ancestry, cytomegalovirus seropositivity, conditioning intensity, and infused cell doses/kg (total graft and engrafting-unit nucleated cell, CD34+ and CD3+) were not significant. A higher engrafting unit-recipient HLA-match of 8–9/10 was associated with a lower incidence of severe aGVHD, and a better unit-unit HLA-match of 6–10/10 was associated with a higher incidence of severe aGVHD, although these differences were not significant (p = 0.128 and 0.266, respectively). To further investigate these findings multivariate Cox regression analysis was performed (Table). Younger age was independently associated with a higher incidence of severe aGVHD (p = 0.042) whereas better engrafting unit-recipient match at 8–9/10 HLA-alleles was protective (p = 0.053). There was a trend toward better unit-unit HLA-match being associated with a higher incidence of grade III-IV aGVHD, but, surprisingly, total infused TNC/kg had no relationship. The 2-year PFS of 72% (95%CI :51–94) in children was higher than the 56% (95%CI :45–66) in adults despite their greater incidence of severe aGVHD. Nine patients (all adult) have died of GVHD including 5 patients initially treated with systemic corticosteroids and 4 with budesonide. We conclude that aGVHD after DCBT is common in the absence of ATG, predominantly affects the gut, and has a high rate of treatment response. Furthermore, GVHD after day 100 frequently has acute features. While the GVHD incidence does not preclude a high rate of survival, improved prophylaxis and treatment are needed. Notably, in contrast to single-unit CBT and adult hematopoietic stem cell transplantation, children receiving DCBT are at a higher risk for severe disease. A possible approach to reduce aGVHD in pediatric DCBT recipients with adequate CB units doses would be to prioritize high resolution HLA-match. Moreover, our data does not currently support an upper limit of infused TNC/kg in DCBT recipients. Further investigation of the biology underlying these unique observations (including the role of specific cellular subsets) should be a major priority. Disclosures: Off Label Use: Mycophenolate Mofetil as GvHD prophylaxis.

A Matched Controlled Analysis of Post-Transplant Cyclophosphamide (CY) Versus Tacrolimus and Mini-Dose Methotrexate in Matched Sibling and Unrelated Donor Transplant Recipients Receiving Reduced-Intensity Conditioning: Post-Transplant CY Is Associated with Higher Rates of Acute Gvhd

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4200-4200 ◽  
Author(s):  
Amin M. Alousi ◽  
Rima M Saliba ◽  
Julianne Chen ◽  
Borje S Andersson ◽  
Issa Khouri ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Control Group ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Matched Sibling ◽  
And Control

Abstract Abstract 4200 Graft-vs.-Host Disease (GVHD) remains a common complication following matched sibling and unrelated donor hematopoietic cell transplantation (HCT). Standard GVHD prophylaxis calls for prolonged immune suppression, typically with a calcineurin-inhibitor. Recently, post-transplant cyclophosphamide (CY) has been studied as sole prophylaxis in matched related and unrelated bone marrow (BM) transplant recipients following an ablative conditioning regimen with busulfan (Bu) and CY and demonstrated comparable rates of acute GVHD and lower rates of chronic GVHD as traditional GVHD prophylaxis regimens. We recently conducted a phase II study of post-transplant CY following a reduced-intensity conditioning (RIC) regimen of Busulfan (Bu) and Fludaribine (Flu) in matched related and unrelated donor transplants and performed a matched-control analysis comparing their results with patients who received traditional GVHD prophylaxis with tacrolimus and mini-dose methotrexate (MTX) during the same time period. Forty-nine (49) patients were enrolled onto this study. They received Flu at a dose of 40mg/m2 over 1hour followed by intravenous Bu over 3 hours targeting a daily AUC of 4,000 microMol-min on days –6 to –3. Recipients of unrelated transplants received ATG on days –3 to –1 (total dose 4 mg/kg). CY was given as sole GVHD prophylaxis at a dose of 50 mg/kg on days +3 and +4. During the same period of time, 133 patients received a RIC regimen with intravenous Bu/Flu or Flu and melphalan (Mel) and received GVHD prophylaxis with tacrolimus plus mini-dose MTX (10mg/m2 on day +1, 5mg/m2on days +3, +6, +11). Unrelated donor transplants also received ATG. A computer generated algorithm was used to identify a comparable control group from our departmental database matching, in order of priority, on age, diagnosis, disease status, donor (matched-related versus unrelated) and graft source (PB versus BM). Matched controls (control group) were successfully identified for 37 study patients (Post-Cy group). Results: The median age for the Post- CY group and control group was 61 (range, 39–72) and 62 years (range, 37–72). Eight-one (81) % of patients in both groups had AML or MDS, 3% had ALL and 16% had NHL or CLL. Fifty-nine (59) % of patients in both groups had unrelated donors and received ATG in the conditioning. Disease status for the Post-CY and control groups respectively were CR1: 14 and 14%, CR2: 8 and 11%, >CR2: 38 and 32% and Primary Induction Failure / Untreated: 40 and 32%. Seventy (70) % of the post-CY group received BM versus 48% of the control group, whereas sex mismatching (Male donor for Female patient) occurred in 22% of the post-Cy and 8% of the control group. The cumulative incidence of grade II-IV acute GVHD and chronic GVHD in the post-CY and control groups were: 46% versus 19% (Hazard Ratio (HR): 2.8, 95% CI, 1.1–6.7; p=0.02) and 14% versus 21% (HR: 0.8, 95% CI, 0.2–2.6, p=0.7). Grades III/IV acute GVHD occurred in 14% (95% CI, 6–32) of the patients in the post-CY group whereas there were no cases of grade III/IV in the control group (p=0.02). Overall, progression-free and non-relapse mortality at 2-years are shown in the table below. Conclusion: Post-transplant CY following RIC is associated with higher rates of acute GVHD, with resultant trends for higher non-relapse mortality and lower overall survival when compared to tacrolimus and mini-dose MTX. The use of post-transplant CY as a sole GVHD prophylaxis regimen should be avoided following RIC transplant in matched-related and unrelated donors. Disclosures: Off Label Use: azacitidine: off-label use as maintenance therapy following allogeneic stem cell transplant for MDS/AML.

scholarly journals A Role for Antimicrobial Stewardship in Clinical Sepsis Pathways: a Prospective Interventional Study

2017 ◽  
Vol 38 (9) ◽  
pp. 1032-1038 ◽  
Author(s):  
John Burston ◽  
Suman Adhikari ◽  
Andrew Hayen ◽  
Heather Doolan ◽  
Melissa L. Kelly ◽  
...  
Keyword(s):  
Antimicrobial Stewardship ◽  
Tertiary Care ◽  
Controlled Study ◽  
Control Group ◽  
Case Review ◽  
Suspected Sepsis ◽  
Clinical Sepsis ◽  
Adjusted Risk ◽  
Antibiotic Management ◽  
The Impact

OBJECTIVETo evaluate the impact of early infectious diseases (ID) antimicrobial stewardship (AMS) intervention on inpatient sepsis antibiotic management.DESIGNInterventional, nonrandomized, controlled study.SETTINGTertiary-care referral hospital, Sydney, Australia.PATIENTSConsecutive, adult, non–intensive care unit (non-ICU) inpatients triggering an institutional clinical sepsis pathway from May to August 2015.INTERVENTIONAll patients reviewed by an ID Fellow within 24 hours of sepsis pathway trigger underwent case review and clinic file documentation of recommendations. Those not reviewed by an ID Fellow were considered controls and received standard sepsis pathway care. The primary outcome was antibiotic appropriateness 48 hours after sepsis trigger.RESULTSIn total, 164 patients triggered the sepsis pathway: 6 patients were excluded (previous sepsis trigger); 158 patients were eligible; 106 had ID intervention; and 52 were control cases. Of these 158 patients, 91 (58%) had sepsis, and 15 of these 158 (9.5%) had severe sepsis. Initial antibiotic appropriateness, assessable in 152 of 158 patients, was appropriate in 80 (53%) of these 152 patients and inappropriate in 72 (47%) of these patients. In the intervention arm, 93% of ID Fellow recommendations were followed or partially followed, including 53% of cases in which antibiotics were de-escalated. ID Fellow intervention improved antibiotic appropriateness at 48 hours by 24% (adjusted risk ratio, 1.24; 95% confidence interval, 1.04–1.47; P=.035). The appropriateness agreement among 3 blinded ID staff opinions was 95%. Differences in intervention and control group mortality (13% vs 17%) and median length of stay (13 vs 17.5 days) were not statistically significant.CONCLUSIONSepsis overdiagnosis and delayed antibiotic optimization may reduce sepsis pathway effectiveness. Early ID AMS improved antibiotic management of non-ICU inpatients with suspected sepsis, predominantly by de-escalation. Further studies are needed to evaluate clinical outcomes.Infect Control Hosp Epidemiol 2017;38:1032–1038

Jin Shin Jyutsu® Self-Help Reduces Nurse Stress: A Randomized Controlled Study

2020 ◽  
pp. 089801012093892
Author(s):  
Julia Millspaugh ◽  
Catherine Errico ◽  
Sunnie Mortimer ◽  
Mildred Ortu Kowalski ◽  
Stephanie Chiu ◽  
...  
Keyword(s):  
Stress Reduction ◽  
Controlled Study ◽  
Control Group ◽  
Randomized Controlled ◽  
Education Group ◽  
Self Help ◽  
Personal Stress ◽  
Jin Shin Jyutsu ◽  
And Control ◽  
The Impact

Purpose: The purpose of this research was to explore the impact of Jin Shin Jyutsu (JSJ) Self-Help on personal stress and the caring efficacy of nurses. Design: A randomized, controlled comparison study, with crossover design was conducted. Method: Stress and caring efficacy were measured via surveys at baseline, posteducation, and again 30 to 40 days after completion of the JSJ educational intervention. Self-reported stress was the primary endpoint as measured with the validated Personal and Organizational Quality Assessment–Revised 4 Scale (POQA-R4) survey. Caring Efficacy was measured using the Coates Caring Efficacy Scale. Findings: A total of 41 nurses consented and completed the study; 18 were in the education group and 23 were in the control group. Changes in stress were sustained in the education group for the POQA-R4. Changes observed in the control group were not sustained. Statistical differences were observed when comparing education and control from baseline to final surveys for measures of emotional vitality and buoyancy. Increases in nursing caring efficacy were observed in both groups. Scores were consistently higher in the education group. Statistically significant differences were observed from baseline to final measure for the education group. Conclusions: Results show JSJ as a viable option for stress reduction in nurses.

Sign in / Sign up

Export Citation Format

Share Document