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.

The Impact of HLA Haplotype Matching for Mismatched Cord Blood Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1206-1206
Author(s):  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Nobuhiro Tsukada ◽  
Seiko Kato ◽  
Aki Sato ◽  
...  
Keyword(s):  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Graft Function ◽  
Matched Pair ◽  
Control Group ◽  
Graft Versus Host ◽  
Matched Group ◽  
Blood Transplantation ◽  
The Impact

Abstract Abstract 1206 Poster Board I-228 [Study purpose] With the increased number of cord blood transplantation (CBT) for adults, more human leukocyte antigen (HLA)-mismatched grafts are selected as alternative donor. In Japan, we have performed more than 5,500 CBT and almost two-third of them has been using 2-loci HLA-mismatched grafts. Slow engraftment and high risk of graft failure should be solved to improve the clinical results. In general, the degree of HLA disparity is known to be associated with risks of poor graft function and of graft-versus-host disease (GVHD). On the other hand, those risks of transplant-related complications are not equivalent even in the donor-recipient pairs who have same number of mismatched HLA antigens. There might be “haplotype matching effect” because novel undetected major histocompatiblility antigen (MHC) resident variation encoded on HLA haplotypes and those mismatching could be responsible for post-transplant risks. In this study, we have analyzed the impact of HLA haplotype matching in HLA-mismatched CBT using the same method in the single institute. [Patients and Methods] We studied the clinical outcomes of 149 consecutive adult patients who received unrelated CBT between August 1998 and June 2009 in the institute of medical Science, University of Tokyo. Patients received previous allogeneic tranplants 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 the same supportive care. By low-resolution typing method for HLA-A, -B and –DR loci, 9 patients received matched grafts, 46 received 1 antigen-mismatched and 94 received 2 antigens-mismatched grafts in the host-versus-graft (HvG) direction. In the graft-versus-host (GvH) direction, 7 patients received matched grafts, 51 received 1 antigen-mismatched and 91 received 2 antigens-mismatched grafts. When we looked at the maximum number of mismatched antigens for both directions, 38 patients received 1 antigen-mismatched and 111 received 2 antigens-mismatched grafts respectively, but there was no matched pair. Common haplotypes in Japanese population were referred from the 11th International Histocompatibility Workshop and other previous reports. Median numbers of leukocytes and CD34+ progenitor cells before freezing of cord blood grafts were 2.4×107/kg and 0.9×105/kg, respectively. Median follow-up was 39 months. 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 survival were calculated using the Kaplan-Meier method and analyzed by the log-rank test. [Results] Thirty (11 of 38 one antigen-mismatched and 19 of 111 two antigens-mismatched) among all 149 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. Among the 1 antigen-mismatched pairs in the HvG direction, early engraftment of neutrophil after CBT occurred in haplotype-matched group compared with control group (median: 20.5 days versus 23 days, P=0.01). The haplotype matched group had better platelet engraftment in the 1 antigen-mismatched pairs (cumulative incidence on day 120: 86% versus 62%; median: 41 days versus 53 days), but this is not significant (P=0.29). Such correlation between engraftment and haplotype matching was not observed in 2 antigens-mismatched pairs. The cumulative incidences of grades II to IV acute GVHD were not significantly different between haplotype matched and control groups, however, those of grades III and IV in patients with matched-haplotype tended to be lower among 1 antigen-mismatched pairs in GvH direction (P=0.10) and were significantly lower among 2 antigens-mismatched pairs (P=0.02). Those haplotype matching effects were not observed in survival rates, cumulative incidences of relapse and NRM among any HLA mismatched pairs. [Conclusion] Those data suggest that untyped variation carried on the HLA haplotytpe might be better to be matched and the haplotype matching might effect on better engraftment and lower risk of sever acute GVHD after HLA-mismatched CBT. Disclosures: No relevant conflicts of interest to declare.

Unrelated Cord Blood Transplantation: Comparison After Single Unit Cord Blood Intrabone Injection and Double Unit Cord Blood Transplantation In Patients with Hematological Malignant Disorders. A Eurocord-EBMT Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 223-223 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Marina Podestà ◽  
Dolores Caballero ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Myeloablative Conditioning ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
The Impact

Abstract Abstract 223 The use of single cord blood unit for transplantation in adult patients is limited due to the high risk of graft failure and delayed neutrophil and platelet recoveries. The limited hematopoietic progenitors in UCB grafts and their homing after IV injection, have prompted investigators to study the design of delivering CB grafts directly into the bone marrow (BM) space (IBCBT) or to use double cord blood transplantation (dUCBT) to improve engraftment. To evaluate the impact of IBCBT, we made a retrospective based registry comparison with dUCBT performed in the same time period (2006-2010) and reported to Eurocord-EBMT. We included 87 and 149 patients who received either IBCBT or dUCBT, respectively, after a myeloablative conditioning regimen for malignant disorders. IBCBT was performed in 8 EBMT centers whereas dUCBT was performed in 56 EBMT centers. Majority of patients in both groups had acute leukemia. IBCBT patients were older (p<0.001), more frequently received an autologous graft (p<0.001) and had positive CMV serology (p<0.001), and importantly had more advanced disease at transplantation (p=0.04). Median number of infused (after thawing) nucleated cells injected intrabone was 2.5×107/kg and it was 3.9×107/kg in dUCBT (p<0.001). In 72% of both groups, CB grafts were HLA 4/6 (the highest HLA disparity was taken into consideration in dUCBT). Other differences were regarding GVHD prophylaxis that was based on CSA+MMF in 100% of IBCBT and in 62% of dUCBT cases; ATG was used in all IBCBT and 40% of dUCBT. Median follow-up time was 18 months in IBCBT and 17 months in dUCBT. At day 30, cumulative incidence (CI) of neutrophil recovery (ANC >500) was 83% after IBCBT and 63% after dUCBT, and at day 60, it was 90% in both groups; the median time to reach ANC>500 was 23 and 28 days after IBCBT and after dUCBT (p=0.001) respectively. At Day-180 CI of platelets recovery was 81% after IBCBT and 65% after dUCBT (p<0.001) with a median time of 36 days and 49 respectively (p=0.002). At day 100, CI of acute GVHD (II-IV) was 19% and 47% (p<0.001) and chronic GVHD 34% and 37% respectively (p=NS) respectively. Unadjusted 2 years-CI of NRM and RI were 31% and 23% after IBCBT and 35% and 28% after dUCBT, respectively (p=NS). Unadjusted 2 y-DFS estimation was 47% after IBCBT and 37% after dUCBT (p=NS). In multivariate analysis adjusting for statistical differences between 2 groups (such as status of the disease at transplant, age, CMV, previous transplants, GVHD prophylaxis), recipients of IBCBT had improved DFS (HR: 1.64, p=0.035), faster platelet recovery (HR:2.13, p<0.001) and decreased acute GVHD (HR:0.31; p<0.001) compared to dUCBT recipients. We did not find a cut-off value of number of nucleated cells after IBCBT or dUCBT that could be associated with outcomes after both approaches. In conclusion, both strategies have extended the use of CB transplants to adults in need of cord blood transplantation. Therefore, IBCBT is an option to transplant adult patients with single CB units after myeloablative conditioning regimen and may impact the total costs of cord blood transplantation. Based on these results, intra-bone technique may disclose new transplant potentialities also with other HSC sources. Disclosures: No relevant conflicts of interest to declare.

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.

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.

Development of BK Virus-Associated Hemorrhagic Cystitis (HC) Is Associated with Decreased Survival Post-Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1933-1933
Author(s):  
Vivien Bautzer ◽  
Fernanda NC Santos ◽  
Erika AF Oliveira ◽  
Erika Maria Macedo ◽  
Fabio R. Kerbauy ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Bk Virus ◽  
Pcr Assay ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
The Impact ◽  
Time Varying Covariates ◽  
Cmv Reactivation

Abstract Abstract 1933 Introduction: Infection by BK virus in the allo-HSCT setting is associated with the development of HC, which is a major cause of morbidity. There are few studies evaluating the impact of BK virus-associated HC on survival post allo-HSCT. Objectives: To evaluate the incidence of HC by BK virus in patients after allo-HSCT and its impact on survival. Methods: We retrospectively reviewed the medical charts of 107 patients who underwent allo-HSCT at Hospital Israelita Albert Einstein from July 2007 until November 2011. HC was defined by the presence of any degree of unexplained hematuria and positivity for BK virus in a urine sample by quantitative polymerase chain reaction (PCR) assay. CMV reactivation was defined as positivity in the antigenemia assay or greater than 165 copies in a quantitative PCR assay. Three patients were excluded because PCR results for BK virus were inconclusive, with 104 patients being analyzed in the final cohort. Cumulative incidence (CI) of HC, CMV reactivation and acute graft-versus-host disease (GVHD) were estimated taking into account the competing risk of death. Overall survival (OS) was estimated by the Kaplan-Meier method. Gray model was used for regression analysis of factors associated with the development of HC. Hazard ratios (HRs) were estimated by a Cox multivariable proportional hazards model, considering HC, CMV reactivation and acute GVHD as discrete time-varying covariates. Results: Median age was 28 years (range 6 months–76 years), and 60.5% of patients were male. About 37% had high-risk disease (refractory leukemia/lymphoma or 2nd-transplantation). Source of HSCs included matched related donors (37%), 10/10 HLA-matched unrelated donors (24%) and cord blood/haploidentical donors in 39%. The conditioning regimen was myeloablative in 81% of cases. The median follow-up of the whole cohort was 450 days (range 9–1624 days). At 1 year, the cumulative incidence of HC was 30.5% (95% confidence interval [CI] 21.8%–39.7%). The 1-year incidence of CMV reactivation and acute GVHD (all grades) was 57.1% and 39.7%, respectively. In a multivariate analysis taking into account age, sex, risk of disease, source of HSCs, intensity of conditioning, CMV reactivation and acute GVHD, only receiving cells from cord blood/haploidentical donors was associated with an increased incidence of HC (subhazard ratio 4.04, 95% CI 1.31–12.49, p = 0.015). The 1 year-OS of the whole cohort was 55% (95% CI 44–62%). Patients who developed HC had an inferior OS (1 year: 18% vs. 70%; HR= 4.40, p <0.0001; 95% CI 2.37–8.14). In the multivariate Cox analysis for OS, after adjusting for age, sex, disease risk, source of HSCs, intensity of conditioning, CMV reactivation and development of acute GVHD, development of HC was associated with an increased mortality (table). Conclusion: In this cohort, the development of CH was associated with an inferior OS in patients undergoing allogeneic HSCT. Even after adjusting for several variables, including development of acute GVHD and CMV reactivation, HC still remained an important factor associated with decreased survrival. It is possible that HC is not the direct cause of the increased mortality, but is rather a surrogate marker of a state of severe immunosuppression and increased risk of dying in the post-transplant setting. Nonetheless, our results suggest that the development of BK virus-associated HC in allo-HSCT patients is associated with inferior survival and future studies should confirm this finding and seek strategies to prevent this complication. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of Neurofeedback on Clinical Signs of Children That Have Attention Deficit Disorder and Hyperactivity

2017 ◽  
Vol 9 (2) ◽  
pp. 48
Author(s):  
Samaneh Hedayati Manesh ◽  
Azam Alikhademi
Keyword(s):  
Attention Deficit ◽  
Attention Deficit Disorder ◽  
Clinical Signs ◽  
The Other ◽  
Control Group ◽  
Wait List ◽  
Other Hand ◽  
Adhd Children ◽  
The Impact ◽  
Experimental Group

This study was an attempt to examine the impact of Neurofeedback on clinical signs of Children that have attention deficit disorder and hyperactivity. The participants of this study 24 boys (6-11) that afflicted to ADHD. The participants of the study randomly divided into two groups and were selected to participate in the study. The experimental group received the Neurofeedback treatment (8 weeks, three sessions in a week). The control group, on the other hand was placed in a wait list. After treatment, CBCL, IVA, QEEG were administered between two groups. The analysis of data revealed that Nero feedback has a significant impact on ADHD children. Moreover, Neurofeedback treatment leads to improve attention deficit disorder and decrease impulsivity in ADHD children.

Mesenchymal Stem Cells Derived from Different Donors as Salvage Therapy for Resistant Severe Acute Graft-Versus-Host Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4364-4364
Author(s):  
Jianyu Weng ◽  
Xin Du ◽  
Peng Xiang ◽  
Suijin Wu ◽  
Zesheng Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Partial Response ◽  
Acute Gvhd ◽  
Response Rate ◽  
Complete Response ◽  
The Other ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
The Third ◽  
Acute Graft

Abstract Severe Acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT), especially severe intestinal aGVHD, is associated with a high morbidity and mortality rate and is a major threat to a successful outcome. Currently, corticosteroids are still the first-line treatment for established aGVHD with a response rate of 30–50%; however, patients who fail on standard therapy have poor outcome, and therapeutic options avail able for them are limited. Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into different tissues and also have immunomodulatory effects, inhibit T-cell proliferation in mixed lymphocyte cultures, prolong skin allograft survival. Recently, Le Blanc and Fan B et al. respec tively reported their experience of using vitro expanded MSCs to treat severe, resistant aGVHD of the gut and liver, and the results showed rapid improvement after infusion of MSC. Thus, MSC may be used for the treatment of severe acute GVHD. The purpose of our study was to evaluate further the efficacy of ex vivo expanded MSC as the salvage therapy for severe refractory acute GVHD. Between February, 2006, and July, 2007, four patients with gastrointestinal grade III to IV acute GVHD after sibling HLA-identical hematopoietic stem cell transplantation, who didn’t respond to steroid therapy (≥2mg per kg per day) for more than seven days, or with progression at least within 72 hours were treated with MSC. The study was approved by the Ethics Committee at Guangdong Provincial People’s Hospital. All patients and the MSC donors gave them written informed consent. Eleven infusions of MSCs were given Fone patient had one infusion, others had two or more infusions. All of them, the first-infusion MSCs were derived from their HLA-identical sibling donors, and the second or more MSCs were derived from different HLA-mismatched unrelated donors. The median dose given to patients was 0.5×106 cells per kg(range: 0.3 to 0.8×106 cells per kg). Median time from tansplantation of haemopoietic stem cells to infusion of MSCs was 58 days (range 28–63days). No patients had acute side-effects either during or after infusion. Total response rate was 100%. Two patients achieved complete response and the others achieved partial response. Four patients with gut aGVHD, two of them achieved complete response after the first dose infusion, and the other two achieved partial response and good partial response after the second and the third infusion, respectively. Otherwise, two of four patients with liver aGVHD, achieved partial response and complete response after the second and the third infusion. The median time from first infusion of MSCs to primary response time and fully response time was 3 days and 23 days(range: 2 to 5 days; 10 to 72 days) after MSC transfusion, respectively. Two patients had died of multiple cerebral infarction and the other one died of multiorgan failure. Just case 2 was alive and developed gut chronic GVHD. At last follow-up (July 31, 2008), the patient was in stable state and his immunosuppressive therapy is being tapped. In conclusion, our preliminary results support the hypothesis that MSC derived from either bone marrow or umbilical cord blood, HLA-identical or HLA-mismatched, single donor’s or multiple donors’ MSCs can be used safely and has encouraging efficacy in the treatment of patients with severe acute GVHD who was refractory to conventional immunosuppressive threapy, although our result may have been influenced by the small number of patients studies and the short observation period, however, in view of the dismal outcome in patients with grades III–IV acute GVHD, MSC seems promising.

Reconstitution of Regulatory T Cells Involves in the Development of Acute Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2204-2204
Author(s):  
Shuhei Karakawa ◽  
Kazuhiro Nakamura ◽  
Keiichi Hara ◽  
Yoko Mizoguchi ◽  
Mizuka Miki ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Regulatory T Cells ◽  
Cd4 T Cells ◽  
Acute Gvhd ◽  
The Other ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Self Tolerance

Abstract Graft-versus-host disease (GVHD) is a significant complication in hematopoietic stem cell transplantation (SCT). On the other hand, graft-versus-tumor (GVT) effect has been known to be concerned with the prevention of relapses in various hematological or non-hematological malignant disorders. The regulation of GVHD without suppressing GVT effect is a pivotal role in the success of hematopoietic SCT. Recently CD4+CD25+regulatory T cells have been recognized to regulate the maintenance of self-tolerance, and associate with several autoimmune diseases. In transplant immunity, CD4+CD25+regulatory T cells have been reported to regulate GVHD without suppressing GVT effect in several animal studies. Natural killer T (NKT) like cells also have been recognized to associated with the maintenance of self-tolerance by inducing CD4+CD25+regulatory T cells through the production of IL-2. In this study, we examined the roles of CD4+CD25+regulatory T cells and NKT like cells in cases underwent hematopoietic SCT. Blood samples from patients underwent SCT in our institution during past 3 years (7 months through 26 years of age, n =19) were obtained every two weeks until day 90 after SCT. Primary disorders of patients were non-malignant hematological disease such as aplastic anemia (n=3), chronic granulomatous disease (n=8) and malignant disease such as leukemia (n=5), and solid tumors (n=3). Pre-conditioning regimens used in this study were myeloablative regimens in 10 cases and reduced intensity regimens in 9 cases, respectively. The frequencies of CD4+CD25+regulatory T cells were assessed by the expression of CD4 and CD25, and those of NKT like cells were assessed by the expression of CD3, CD16, and CD56 using flow cytometry. The mRNA expression of FOXP3 in purified CD4+CD25+regulatory T cells were determined by quantitative real-time PCR method. In 13 patients who had none or Grade 1 acute GVHD, the frequency of CD4+CD25+regulatory T cells in CD4+ T cells was increased up to 25–90% at early period after SCT and normalized below 20% after day 45 post SCT. On the other hand, four of 6 patients who had acute GVHD (more than Grade 2) showed that the frequency of CD4+CD25+regulatory T cells in CD4+ T cells persisted below 20%. In other one patient, the development of acute GVHD (Grade 2) was associated with decreasing the frequency of CD4+CD25+regulatory T cells (30 to 10%) and the recovery of GVHD was found with increasing CD4+CD25+regulatory T cells (10 to 30%). The mean frequency of CD4+CD25+regulatory T cells in CD4+ T cells on day 15 after SCT was 44% in patients without GVHD and 21% in patients with GVHD (p=0.07). No difference in the expressions of FOXP3 mRNA in purified CD4+CD25+regulatory T cells was noted between patients with GVHD and those without GVHD. The reconstitution pattern of CD3+CD16+CD56+ NKT like cells after SCT was not associated with the development of GVHD. These results suggest that the development of acute GVHD may be strongly associated with the reconstitution of donor derived CD4+CD25+regulatory T cells in CD4+ T cells. The measurement of CD4+CD25+regulatory T cells in CD4+ T cells might lead to the early diagnosis and the prevention of acute GVHD. (Future studies will be needed to examine the association between the frequency of regulatory T cells and GVT effect.)

Tregs In Graft-Versus-Host Disease: A Task Force In Trouble?.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3748-3748
Author(s):  
Sya N. Ukena ◽  
Jens Grosse ◽  
Stefanie Buchholz ◽  
Michael Stadler ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Peripheral Tolerance ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
The Impact

Abstract Abstract 3748 Graft-versus-host disease (GvHD) remains the major clinical complication in hematopoietic stem cell transplantation (SCT) resulting in severe morbidity and significant mortality. This alloreactive immune response is mainly induced by donor T cells transplanted with the graft. Regulatory T cells (Tregs) play an essential role in the induction and maintenance of peripheral tolerance. In addition, data from murine models have shown that Tregs can prevent GvHD while preserving the graft-versus-leukemia effect. In order to functionally and dynamically characterize human Tregs after allogeneic SCT, we analyzed CD4+CD25highCD127dim T cells isolated from the peripheral blood of more than 80 patients with hematological malignancies every 30 days over half a year following SCT. Patients were divided into the following clinical groups: (A) no signs of acute or chronic GvHD, (B) acute GvHD, (C) chronic GvHD and (D) acute GvHD passed into chronic GvHD. Human peripheral blood lymphocytes were separated by Ficoll gradient and CD4+CD14−CD25highCD127dim T cells were isolated by MoFlow cell sorting. Isolated RNA was pooled and microarray analysis was performed by using Affymetrix HG_U133_Plus2.0 Arrays. Results were verified by using quantitative realtime RT-PCR. Additionally, Tregs were phenotypically analyzed by FACS. We monitored a continous but slower recovery of Tregs in GvHD within the first 6 months following PBSCT. Manifestation of acute and chronic GvHD correlated with significantly reduced frequencies of peripheral Tregs in the first month after PBSCT compared to patients without GvHD. Microarray data revealed a high stability of the Treg transcriptome in the first half year representing the most sensitive time window for tolerance induction. Moreover, comparison of the Treg gene expression profiles from patients with and without GvHD point to a reduced suppressive function of Tregs with diminished migration capacity to the target organs likely contributing to the development of GvHD. Our findings corroborate the impact of human Tregs in the pathophysiology of GvHD and identify novel targets for the manipulation of Tregs to optimize strategies for prophylaxis and treatment of life-threatening GvHD. Disclosures: No relevant conflicts of interest to declare.

Impact of HLA Haplotype Matching On Engraftment in Reduced Intensity Cord Blood Transplantation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3043-3043
Author(s):  
Kazuya Ishiwata ◽  
Hikari Ota ◽  
Aya Nishida ◽  
Masanori Tsuji ◽  
Hisashi Yamamoto ◽  
...  
Keyword(s):  
High Resolution ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Post Transplant ◽  
Matched Group ◽  
Blood Transplantation ◽  
The Impact ◽  
Reduced Intensity

Abstract Abstract 3043 Introduction HLA-mismatched unrelated cord blood transplantation (UCBT) is feasible and, in retrospective comparative analyses, allows survival rates similar to conventional unrelated HLA-matched adult-derived grafts. Although it is clear that the degree of UCB HLA mismatch in patients has a negative effect on outcomes, the biologic implications of HLA haplotype itself have not been explored for UCBT. In unrelated bone marrow transplantation, an effect of HLA haplotype matching on GVHD has been clarified. (S.Morishima. et al. Blood 2010). This study was conducted to determine the impact of HLA haplotype matching in reduced intensity UCBT. Patients and Methods To determine the impact of HLA haplotype matching with outcomes after UCBT, We retrospectively reviewed patients with hematologic malignancies who underwent reduced intensity CBT at Toranomon Hospital from August 2006 and December 2010 consecutively. Patients who had prior history of transplantation, were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. Then, the remaining 164 consecutive patients were reviewed. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. DNAs of 164 pairs were analysed for HLA-A, -B, and -DRB1 based on High Resolution typing, and we have determined the HLA haplotype based on Japanese common HLA haplotypes referred from the previous reports. Results For A, B, DR based on high resolution typing the following mismatch occurred: no mismatch 3(2%), one mismatch 12(7%), two mismatch 58(35%), three mismatch 60(37%), four mismatch 28(17%), five mismatch 3(2%) in the GvH direction, and: no mismatch 2(1%), one mismatch 16(10%), two mismatch 55(34%), three mismatch 56(34%), four mismatch 32(20), five mismatch 3(2%) in the HvG direction. Then 37 among 164 pairs were defined as the HLA haplotype matched group. The number of total nucleated cells and CD34+ cells were not significantly different between HLA haplotype matched group and non-matched group. The cumulative incidence of neutrophil recovery was higher in HLA haplotype matched group than in non-matched group.( 94.6% vs. 80.3% up to day 60, p=0.0027). Lower incidence of pre-engraftment immune reaction(PIR) and acute GVHD were observed in haplotype matched group (37.8 % vs. 47.9 % up to day 60 post-transplant, P = 0.32), III to IV acute GVHD( 18.9% vs. 27.7% up to day 100 post-transplant, p=0.29). The cumulative incidences of relapse tended to be lower in haplotype matched group than in non-matched group (21.5% vs. 31.5%, P=0.28).Overall survival (OS) was estimated as 36.0 % at 3 years post-transplant. There were no significant differences between mathed and non-matched group in the cumulative incidence of OS (36.8 % vs. 34.3% at 3 years post-transplant, P = 0.84). Conclusion HLA haplotype matching in UCBT was found to have a significant impact on engraftment in this analysis. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document