scholarly journals Hematopoietic Recovery after in-Vivo T-Cell Depleted Allogeneic Stem Cell Transplant- Effects of ABO Incompatibility, Rhesus Incompatibility and Acute Gvhd

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5745-5745
Author(s):  
Usama Gergis ◽  
Naima Ali Al-Mulla ◽  
Segovia Javier ◽  
Rania Hafez ◽  
Adrienne A. Phillips ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Allogeneic Transplantation ◽  
Host Disease ◽  
Post Transplant ◽  
Abo Incompatibility ◽  
Hematopoietic Recovery ◽  
Graft Vs Host Disease ◽  
Rhesus Incompatibility ◽  
Acute Graft

Abstract Background: Transfusion needs after allogeneic transplantation are closely associated with morbidity, cost of transplantation and may also be associated with long-term outcome. In an effort to better predict determinants of recovery after reduced intensity conditioning, we analyzed 214 consecutive patients who received allogeneic hematopoietic stem cell transplantation (HSCT) at our institution from January 2012 to December 2013. Patients and Methods: We excluded patients who experienced early (in the first 4 months) relapse (n=28), non-relapse mortality (n=28) or who experienced prolonged hospital stay before day 100 for transplant related complications (n=51). One hundred and seven patients had uneventful recovery until day 100 and met the inclusion criteria. The majority of patients received Fludarabine and melphalan conditioning (87%). Approximately one third each of the patients had HLA-identical related, HLA-matched unrelated donors or underwent haplo-cord transplantation. Recipients of HLA-identical related or unrelated donor transplant received alemtuzumab and post-transplant tacrolimus. Haplo-cord recipients received thymoglobulin and post-transplant tacrolimus and mycophenolate. Patients and transplant characteristics are summarized in table 1. T-tests were used for comparison between groups. Results: In our analysis of 107 patients who underwent T cell depleted allogeneic transplantation and fared well at day 100, the determinants of prolonged anemia were ABO incompatibility (p=0.006), rhesus incompatibility (p=0.01) and acute graft versus host disease (aGVHD) (p=0.02). Whereas prolonged thrombocytopenia was only associated with the development of any grade aGVHD (p=0.04). At day 100, the hematopoietic recovery of haplo-cord grafts is similar to matched related and unrelated grafts. Conclusion: ABO incompatibility, rhesus incompatibility and occurrence of acute graft vs host disease are the major determinants of red blood cell recovery. Occurrence of acute graft vs host disease is a major determinant of platelet recovery. Of interest, the use of umbilical cord blood grafts combined with haplo-identical grafts is associated with recovery of red blood cells and platelets that is similar to that of adult donor grafts. Disclosures No relevant conflicts of interest to declare.

Thymic Recovery among Pediatric Stem Cell Recipients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1422-1422
Author(s):  
Helena Olkinuora ◽  
Tanja Kaartinen ◽  
Sanna Siitonen ◽  
Kimmo Talvensaari ◽  
Ulla Pihkala ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Real Time Quantitative Pcr ◽  
Stem Cell Rescue ◽  
Autologous Stem Cell Rescue ◽  
Acute Graft

Abstract BACKGROUND: Thymic recovery is an essential part of immune reconstitution post stem cell transplantation. The process is affected by the age of the recipient, use of radiotherapy in conditioning and graft versus host disease. The duration of impaired T cell function depends mainly on thymic recovery and is associated with an increased risk of complications such as infections. The aim of this study was to evaluate thymic recovery post-transplant in pediatric patients. And also to detect differencies in thymic recovery between recipients of autologous stem cell rescue and those of allogeneic grafts from sibling and unrelated donors MATERIAL AND METHODS: Between 8/2001–8/2005 a total of 66 patients with a mean age of 7 yrs with either a malignant or non-malignant disease were studied. 31 received a matched unrelated, 21 a sibling graft and 14 were given autologous stem cell rescue. Thymic function was evaluated by quantifying TREC (T cell receptor excision circles) levels in peripheral blood mononuclear cells by real time quantitative PCR once prior to transplant and once every three months during the first year and at 18 months post-transplant. FOXP3 levels were evaluated simultaneously with those of TREC by real time quantitative PCR. The data was related to the clinical status of patients and the recovery of peripheral blood T cell numbers. In 29% (6/21) of the recipients of sibling grafts and 65% (20/31) of recipients of unrelated grafts had clinically significant (Gr II–IV) acute graft versus host disease. About 30 % in both groups developed chronic graft versus host disease. RESULTS: Comparison of TREC levels in children following SCT indicated that thymic recovery was brisk among recipients of autologous stem cell rescue by the 6 months and within the allogeneic group the recovery was significantly better in recipients of sibling grafts than in recipients of unrelated grafts (Figure 1.0). There was an significant negative association between the values of TREC and the occurrence of chronic graft versus host disease from 6 months to 18 months post-transplant. Children with low (below median) TREC values had increased mortality. Patients with low TREC experienced more infections during first six months post-transplant than children with high (above median) TREC values. Blood numbers of CD4 naive cells (CD45RA+) and CD27+ cells correlated significantly with TREC values. FOXP3 values were associated at three months post-transplant with acute graft versus host disease and with its chronic form at 12 and 18 months post-transplant. FOXP3 correlated with blood CD4 naive cells (CD45RA+) and CD27+ cells at 12 and 18 months post-transplant. There was a significant correlation between levels of TREC and FOXP3 at 12 and 18 months post stem cell transplant. CONCLUSIONS: Our data may indicate a difference in the kinetics of thymic recovery post-transplant between recipients of sibling and URD grafts and those of autologous stem cell rescue. Chronic GVHD seems to associate with thymic dysfunction and herpesviral infections with the pace of thymic recovery. Figure Figure

scholarly journals 2569. The Gut Microbiome and Acute Graft vs. Host Disease Risk in Hematopoietic Stem Cell Transplantation Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S892-S893
Author(s):  
Emma E Ilett ◽  
Joanne Reekie ◽  
Mette Jørgensen ◽  
Daniel D Murray ◽  
Marc Noguera ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Gut Microbiome ◽  
Conditioning Regimen ◽  
Clinical Factors ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Vs Host Disease ◽  
Gene Richness ◽  
Acute Graft

Abstract Background 16S rRNA gene-based studies report that allogeneic hematopoietic stem cell transplant (aHSCT) recipients with low bacterial diversity and certain bacteria close to engraftment have increased risk of developing acute graft-vs.-host disease (aGvHD). Using shotgun metagenomic data, we aim to confirm and extend these observations in a larger cohort. Methods Adult aHSCT recipients with stool samples collected days −30 to +100 relative to aHSCT, but prior to aGvHD, were included. One sample was selected per patient and time point: pre-aHSCT (T1), post-aHSCT pre-engraftment (T2). Complete ascertainment of aGvHD (grades ≥ 2) until day +100 was performed. Bacterial microbiome factors (α-diversity, gene richness and 16 a priori bacteria) and clinical factors were tested for associations with aGvHD across T1:2 in univariable models. Significant factors (P < 0.1) were included in a multivariable model. Results Of 147 aHSCT recipients, 35 developed aGvHD a median of 35 days (IQR 24–51) post-aHSCT. We found that higher gene richness was significantly associated with lower aGvHD risk in T2, but not T1, samples (OR 0.65 (95% CI 0.42–1.00), P = 0.04 vs. OR 1.14 (95% CI 0.67–1.94), P = 0.64 per doubling of unique genes). A decreased abundance of Akkermansia muciniphila, Proteobacteria, Blautia and Gammaproteobacteria was observed in those that developed aGvHD, again in T2 samples only (Figure 1). Among clinical factors, donor sex, donor/recipient (related/unrelated) and conditioning regimen (adjusted OR = 0.34 for non-myeloablative vs myeloablative (95% CI 0.15–0.77)) were significantly associated with aGvHD. Conditioning regimen was also strongly associated with microbiome changes; myeloablative recipients had lower gene richness and differences in bacterial abundance, including decreased abundance of aforementioned bacteria, compared with non-myeloablative recipients at T2 (Figures 2and 3). Conclusion Post-aHSCT pre-engraftment was a crucial timepoint where microbial changes, including lower gene richness and abundance of certain bacteria, were associated with development of aGvHD. Myeloablative regimes were also associated with both aGvHD and microbiome changes, suggesting that intense conditioning may affect aGvHD risk through perturbation of the gut microbiome. Disclosures All authors: No reported disclosures.

Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3479-3482 ◽  
Author(s):  
Joseph H. Antin ◽  
Daniel Weisdorf ◽  
Donna Neuberg ◽  
Roberta Nicklow ◽  
Shawn Clouthier ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 1 ◽  
Double Blind ◽  
Host Disease ◽  
Double Blind Placebo ◽  
Graft Versus Host ◽  
Acute Graft

Acute graft-versus-host disease (GVHD) is thought to derive from direct T-cell injury of target tissues through perforin/granzyme, Fas/FasL interactions, and the effects of inflammatory cytokines. Animal models and some clinical trials support the notion that inhibition of inflammatory mediators such as interleukin-1 (IL-1), tumor necrosis factor α, and interferon γ may ameliorate or prevent GVHD. We hypothesized that blockade of IL-1 during the period of initial T-cell activation would reduce the risk of severe GVHD. We tested this hypothesis in a double-blind, placebo-controlled randomized trial of recombinant human IL-1 receptor antagonist (IL-1Ra) in 186 patients undergoing allogeneic stem cell transplantation. Randomization was stratified by degree of histocompatibility and stem cell source. All patients were conditioned with cyclophosphamide and total body irradiation. GVHD prevention consisted of cyclosporine and methotrexate in all patients. Recombinant human IL-1Ra or saline placebo was given from day −4 to day +10. Randomization was stratified according to GVHD risk. The 2 groups were well-matched for pretreatment characteristics. Moderate to severe GVHD (grades B-D) developed in 57 (61%) of 94 patients receiving IL-1Ra and in 51 (59%) of 86 patients on placebo (P = .88). There was no difference in hematologic recovery, transplantation-related toxicity, event-free survival, or overall survival. We conclude that blockade of IL-1 using IL-1Ra during conditioning and 10 days immediately after transplantation is not sufficient to reduce GVHD or toxicity or to improve survival.

Radiotherapy-Based Conditioning Is Effective Immunosuppression for Patients Undergoing Transplantation with T-Cell Depleted Stem Cell Grafts for Severe Aplasia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1819-1819
Author(s):  
Nicolas Novitzky ◽  
Valda Thomas ◽  
Helen Stubbings ◽  
Geoff Hale ◽  
Herman Waldmann
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Aplastic Anaemia ◽  
Graft Failure ◽  
Haematological Toxicity ◽  
Mucosal Damage ◽  
Cell Number ◽  
Post Transplantation ◽  
Host Disease ◽  
Graft Vs Host Disease

Abstract The combination of cyclophosphamide and ALG is highly effective in inducing engraftment in patients with aplastic anaemia undergoing allogeneic stem cell transplantation. However, the incidence of graft vs. host disease remains substantial. We studied the outcome of individuals with aplastic anaemia conditioned with a radiation containing regimen followed by the infusion of stem cell grafts that had been depleted of lymphocytes with CAMPATH-1H. The conditioning regime consisted of fractionated (f) total body irradiation 8 Gy followed by f total nodal irradiation 6 Gy. Additionally, patients received cyclophosphamide 60 mg/kg on 2 consecutive days. Cytokine mobilised peripheral blood grafts from HLA identical siblings were T-cell depleted with CAMPATH-1H “in the bag”. Cyclosporin was commenced on day -1 and continued until day +90. Seventeen heavily transfused patients with aplastic anaemia with a median age of 18 years (range 14–56) were studied. Median time from diagnosis to transplantation was 172 days (range 34–443). The median CD34+ cell number infused was 3.47 x106/kg (range 1.03–18.4). All patients engrafted. Recovery was fast and patients reached 0.5 x 109/L polymorphs by median day 11 (range 9–17) days. Toxicity from the conditioning included grade 4 haematological toxicity in all. Other major toxicity was gastrointestinal mucosal damage, which exceed grade 2 in only 2 instances. 1 patient developed thrombotic thrombocytopenic purpura which responded to substitution of cyclosporin with tacrolimus and plasmapheresis. Another, who had normal blood counts died of infection on day 241. Chimerism studies at 6 months post transplantation confirmed donor origin of haematopoiesis in all 7 patients tested. None of the patients developed acute or chronic graft vs. host disease. There was no delayed graft failure and 94% of patients survive disease free, at a median of 1303.5 days (range 216–2615) from graft infusion. In this cohort of multiply transfused patients, the radiation containing schedules described in this study led to universal engraftment with limited toxicity despite T-cell depletion. No patient developed graft vs. host disease or late graft failure. Lower doses of radiation containing conditioning should be explored further.

Sign in / Sign up

Export Citation Format

Share Document