The Experts below are selected from a list of 110853 Experts worldwide ranked by ideXlab platform
Haydar Frangoul - One of the best experts on this subject based on the ideXlab platform.
-
Engraftment syndrome following unrelated cord blood transplant in pediatric patients
Blood, 2008Co-Authors: Jennifer Domm, Cassie Calder, Becky Manes, Li Wang, Haydar FrangoulAbstract:Engraftment syndrome or hyper-acute graft versus host disease like syndrome describes a constellation of symptoms that occur prior or during neutrophil recovery after both allogeneic and autologous stem cell transplant. The usual symptoms are high grade fever and diffuse erythematous rash. There are no prior published reports describing the incidence and clinical implications of Engraftment syndrome in recipients of unrelated cord blood transplant. There were 326 patients ≤ 18 years of age with malignant (N=229) or non-malignant (N=97) diseases enrolled on a prospective National Heart Lung Blood Institute (NHLBI) sponsored cord blood transplant study between 1999 and 2003. Dataset was abstained after signed agreement with the NHLBI and local IRB approval. All patients received myeloablative preparative regimen with either total body irradiation or busulfan based regimens with cyclosporine and prednisone GVHD prophylaxis. All patients received anti-thymocyte globulin as part of their conditioning regimen. ES was defined as high grade fever and diffuse erythematous rash without documented infections. The median age was 4.65 years (range 0.04 – 17.90) with 127 (60%) male, 264 (81%) had a performance status of ≥ 90. Two hundred twenty eight (70%) of the patients had malignant diseases and 179 (55%) received a cord blood unit matched at 3/6 or 4/6 HLA antigens and 147 (45%) received a cord blood unit matched at 5/6 or 6/6 HLA antigens. The median total nucleated cell dose per kg infuses was 6.94 x 107/kg (range 0.08–809.4 x 107/kg). Sixty-four patients (20%) developed Engraftment syndrome at a median of 10 days (range 5–24) post transplant. All patients developed Engraftment syndrome prior to Engraftment and were treated with high dose steroids. Patients who developed Engraftment syndrome had a median age of 2.47vs. 5.57 years, 48% had nonmalignant disease versus 25%, compared to those who did not develop Engraftment syndrome respectively. The median pre-cyopreserved total nucleated cells infused was 8.58x107/kg (range 1.54x107 to 27.49 x107) in those who developed Engraftment syndrome compared to 6.68x107/kg (range 0.08 x107 to 80.91x107) to those who did not. A multivariable analysis using Cox regression analysis using Engraftment syndrome as a time dependent co-variable was performed including patients age, sex, performance status (
Joanne Kurtzberg - One of the best experts on this subject based on the ideXlab platform.
-
total colony forming units are a strong independent predictor of neutrophil and platelet Engraftment after unrelated umbilical cord blood transplantation a single center analysis of 435 cord blood transplants
Biology of Blood and Marrow Transplantation, 2011Co-Authors: Kristin Page, Lijun Zhang, Adam Mendizabal, Stephen Wease, Shelly L Carter, Tracy Gentry, Andrew E Balber, Joanne KurtzbergAbstract:Graft failure occurs in approximately 20% of patients after unrelated umbilical cord blood transplantation (UCBT). This could be because of inadequate potency of the cord blood unit (CBU). To this end, we investigated the impact of graft characteristics on Engraftment and survival of 435 primarily pediatric (median age: 5.3 years) patients receiving a single-unit unrelated UCBT after myeloablative conditioning from 2000 to 2008. Pre-cryopreservation (pre-cryo) graft characteristics were provided by the banks. Post-thaw parameters were measured on dextran/albumin-washed grafts. Post-thaw recovery of the colony-forming unit (CFU), a biological assay reflecting functional viability of the cord blood cells was the lowest percent age (median 21.2%, mean 36.5%) of the pre-cryo value, regardless of the bank of origin. The cumulative incidences of neutrophil and platelet Engraftment were 76.9% (95%, confidence interval [CI], 71.3%-82.5%) and 55% (95% CI, 49.3%-60.7%), respectively. Univariate and separate multivariate models using pre-cryo and post-thaw datasets including clinical parameters identified predictors of Engraftment and survival. In multivariate modeling, higher CFU dosing was the only pre-cryo graft characteristic predictive of neutrophil (P = .0024) and platelet Engraftment (P = .0063). In the post-thaw model, CFU dose best predicted neutrophil and platelet Engraftment (both P < .0001). Comparatively, CD34(+) and total nucleated cell (TNC) were only weakly predictive in post-thaw neutrophil and platelet Engraftment models, respectively. In conclusion, CFU dose is a strong independent predictor of Engraftment after unrelated UCBT and should be used to assess potency when selecting CBUs for transplantation.
-
Splenectomy and partial splenectomy improve hematopoietic stem cell Engraftment in hypersplenic mice.
Journal of pediatric surgery, 2010Co-Authors: Elisabeth T. Tracy, Lindsay J. Talbot, Joanne Kurtzberg, Henry E. RiceAbstract:Abstract Background Hematopoietic stem cell (HSC) Engraftment is delayed after transplantation in children with hypersplenism, increasing the morbidity and costs of care. Preliminary clinical data suggest that splenectomy before HSC transplantation may improve HSC Engraftment, although this observation has not been tested in an animal model. Methods We performed total splenectomy (n = 22), partial splenectomy (n = 16), or sham laparotomy (n = 21) on erythrocyte protein 4.2 knockout mice, a murine model of hereditary spherocytosis with hypersplenism. After 10 days, we lethally irradiated the mice, transplanted 3 × 10 6 allogeneic bone marrow cells, and then assessed Engraftment using serial complete blood counts. Successful engraftmen t was defined as recovery of hemoglobin, neutrophil, or platelet counts. We compared Engraftment rate using χ 2 test and time to Engraftment using Student's t test analysis, with significance defined as P Results Total splenectomy increased the rate of successful HSC Engraftment and decreased the interval to HSC Engraftment compared with controls. Similarly, partial splenectomy decreased the interval to HSC Engraftment, with a nonsignificant trend toward improved overall rate of successful HSC Engraftment. Conclusion Partial or total splenectomy before HSC transplantation improves HSC Engraftment in hypersplenic mice. This model supports consideration of splenic resection in hypersplenic children requiring HSC transplantation.
Judith A. Shizuru - One of the best experts on this subject based on the ideXlab platform.
-
Fine mapping of the Bmgr5 quantitative trait locus for allogeneic bone marrow Engraftment in mice
Immunogenetics, 2013Co-Authors: Yuanyuan Wang, Xinjian Chen, Schickwann Tsai, Alun Thomas, Judith A. Shizuru, Thai M. CaoAbstract:To identify novel mechanisms regulating allogeneic hematopoietic cell Engraftment, we used forward genetics and previously described identification, in mice, of a bone marrow (BM) Engraftment quantitative trait locus (QTL), termed Bmgr5 . This QTL confers dominant and large allele effects for Engraftment susceptibility. It was localized to chromosome 16 by quantitative genetic techniques in a segregating backcross bred from susceptible BALB.K and resistant B10.BR mice. We now report verification of the Bmgr5 QTL using reciprocal chromosome 16 consomic strains. The BM Engraftment phenotype in these consomic mice shows that Bmgr5 susceptibility alleles are not only sufficient but also indispensable for conferring permissiveness for allogeneic BM Engraftment. Using panels of congenic mice, we resolved the Bmgr5 QTL into two separate subloci, termed Bmgr5a (Chr16:14.6–15.8 Mb) and Bmgr5b (Chr16:15.8–17.6 Mb), each conferring permissiveness for the Engraftment phenotype and both fine mapped to an interval amenable to positional cloning. Candidate Bmgr5 genes were then prioritized using whole exome DNA sequencing and microarray gene expression data. Further studies are warranted to elucidate the genetic interaction between the Bmgr5a and Bmgr5b QTL and identify causative genes and underlying gene variants. This may lead to new approaches for overcoming the problem of graft rejection in clinical hematopoietic cell transplantation.
-
Pathways analysis of differential gene expression induced by engrafting doses of total body irradiation for allogeneic bone marrow transplantation in mice
Immunogenetics, 2013Co-Authors: Xinjian Chen, Yuanyuan Wang, Schickwann Tsai, Alun Thomas, Qiuxia Li, Judith A. ShizuruAbstract:A major challenge in allogeneic bone marrow (BM) transplantation is overcoming Engraftment resistance to avoid the clinical problem of graft rejection. Identifying gene pathways that regulate BM Engraftment may reveal molecular targets for overcoming Engraftment barriers. Previously, we developed a mouse model of BM transplantation that utilizes recipient conditioning with non-myeloablative total body irradiation (TBI). We defined TBI doses that lead to graft rejection, that conversely are permissive for Engraftment, and mouse strain variation with regards to the permissive TBI dose. We now report gene expression analysis, using Agilent Mouse 8x60K microarrays, in spleens of mice conditioned with varied TBI doses for correlation to the expected Engraftment phenotype. The spleens of mice given engrafting doses of TBI, compared with non-engrafting TBI doses, demonstrated substantially broader gene expression changes, significant at the multiple testing-corrected P
Alexandra H Filipovich - One of the best experts on this subject based on the ideXlab platform.
-
cytokine profile of Engraftment syndrome in pediatric hematopoietic stem cell transplant recipients
Biology of Blood and Marrow Transplantation, 2016Co-Authors: Pooja Khandelwal, Najibah Rehman, Kristi Smiley, Joyce Villanueva, Rebecca A Marsh, Michael Grimley, Stella M Davies, Sabine Mellorheineke, Adam Lane, Alexandra H FilipovichAbstract:The biology of Engraftment syndrome is poorly understood, and the degree of overlap with acute graft-versus-host disease (GVHD) is unclear. To understand Engraftment syndrome better, plasma cytokine profiles were evaluated in 56 pediatric allogeneic bone marrow transplant recipients before transplant, on the day of stem cell infusion, and weekly until day +100. Patients were divided into 4 groups: those with isolated Engraftment syndrome (n = 8), acute GVHD (n = 12), both Engraftment syndrome and acute GVHD (n = 4), and neither Engraftment syndrome nor acute GVHD (n = 32). Engraftment syndrome was observed a median of 13.5 days (range, 10 to 28) after transplant, whereas acute GVHD was diagnosed a median of 55 days (range, 19 to 95) after transplant. Four patients developed both Engraftment syndrome at a median of 10.5 days (range, 10 to 11) and acute GVHD at a median of 35 days (range, 23 to 56) after stem cell infusion. Median plasma levels of IL-1β, IL-6, IL-12, IL-4, and IL-13 were significantly elevated in patients with isolated Engraftment syndrome when compared with isolated acute GVHD. A rise of proinflammatory cytokines (IL-1β, IL-6, and IL-12) was followed by surge in anti-inflammatory cytokines (IL-4 and IL-13) in patients with isolated Engraftment syndrome. The observation of elevated IL-1β suggests that Engraftment syndrome could be an inflammasome mediated phenomenon.
Nobuyoshi Arima - One of the best experts on this subject based on the ideXlab platform.
-
Successful treatment with combined chemotherapy of two adult cases of hemophagocytic lymphohistiocytosis in recipients of umbilical cord blood cell transplantation
International Journal of Hematology, 2011Co-Authors: Akiko Fukunaga, Fumiaki Nakamura, Noriyoshi Yoshinaga, Shojiro Inano, Wataru Maruyama, Hirokazu Hirata, Nobuyoshi ArimaAbstract:Hemophagocytic lymphohistiocytosis (HLH), which occurs during the early period following allogeneic hematopoietic stem cell transplantation (HSCT), is often difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. Here, we summarize the cases of two patients who experienced Engraftment failure and subsequently developed hematopoietic stem cell transplantation-hemophagocytic lymphohistiocytosis (HSCT-HLH). Both patients had high-risk hematological malignancies for which they underwent umbilical cord blood transplantation (UCBT) at our institution. Based on the presence of massive hemophagocytosis in their bone marrow specimens and the results of chimerism analysis, diagnosis of HSCT-HLH was made in both cases. A single infusion of low-dose etoposide was administered immediately to each patient. Four days after the injection, therapeutic efficacy was evaluated. As both cases showed an insufficient response to etoposide, we added vincristine and a medium dose of prednisolone. Clinical symptoms rapidly improved and stable Engraftments were observed within a week. The first and second patients were alive 1008 and 232 days after UCBT, respectively. The combined use of low-dose etoposide and vincristine plus prednisolone appears to be a promising treatment option for HSCT-HLH, without serious adverse side effects.