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Dive into the research topics where Reggie Duerst is active.

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Featured researches published by Reggie Duerst.


Cancer | 1990

Pathogenesis of vertebral metastasis and epidural spinal cord compression.

Francisco Arguello; Reggie Duerst; Karen McQueen; Christopher N. Frantz; Raymond B. Baggs; Linda Johnstone

The authors have studied the sequential events in the process of vertebral metastasis that result in spinal cord compression. Different tumor cell lines were injected into the systemic arterial circulation of syngeneic or nude mice, and they were killed at timed intervals after injection or when they became paraplegic. The following observations were made. The tumor cells lodged and grew in the hematopoietic bone marrow of the vertebrae. Cancer cells in the vertebral marrow cavity invaded into the spinal canal through the foramina of the vertebral veins rather than destroying the cortical bone. Tumor cell lines that grew in an infiltrative fashion migrated toward a posterior location in the spinal canal, and compressed the spinal cord from a posterior direction. Tumor cell lines that grew as compact tumors formed a tumor mass at the same location from which the cells emerged from the vertebra, and compressed the cord predominantly from an anterior direction. Radiographic evidence of vertebral metastasis was a late event, and commonly associated with significant compression of the cord and extraosseous tumor. These experimental findings may help to establish better diagnostic and treatment strategies for patients with metastatic disease of the spine.


Journal of Clinical Oncology | 1999

Analysis of Factors That Correlate With Mucositis in Recipients of Autologous and Allogeneic Stem-Cell Transplants

Aaron P. Rapoport; Luc F. Miller Watelet; Tammy Linder; Shirley Eberly; Richard F. Raubertas; Joanna Lipp; Reggie Duerst; Camille N. Abboud; Louis S. Constine; Jessica Andrews; Mary Ann Etter; Linda Spear; Elizabeth Powley; Charles H. Packman; Jacob M. Rowe; Ullrich S. Schwertschlag; Camille L. Bedrosian; Jane L. Liesveld

PURPOSE To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK > or = 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK > or = 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P =.001); 24% of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P =.001). CONCLUSION Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.


The Lancet | 2004

Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children

David A. Jacobsohn; Reggie Duerst; William T. Tse; Morris Kletzel

BACKGROUND Transplantation of allogeneic haemopoietic stem cells can cure several non-malignant disorders in children. Transplantation with reduced intensity preparation might achieve the same goals but with less toxicity. We undertook a pilot study to determine engraftment rates, kinetics of engraftment, toxicity, and acute graft-versus-host disease (GVHD) associated with a uniform reduced intensity haemopoietic stem-cell transplant (HSCT) regimen for children with non-malignant diseases. METHODS We studied 13 paediatric patients with non-malignant disorders who underwent reduced intensity HSCT at Childrens Memorial Hospital from January, 2000, to February, 2004. Stem-cell sources included unrelated donor, matched-sibling peripheral blood stem cells, and unrelated cord blood. A uniform preparative regimen was used, consisting of fludarabine, busulfan, and anti-thymocyte globulin. Major endpoints were engraftment, transplant-related mortality at day 100, short-term toxicities, and incidence of acute GVHD. RESULTS 72% of evaluable patients achieved full donor engraftment. There was rapid reconstitution of platelets (median 13.5 days) and neutrophils (median 18 days). Short-term toxicities were minimal, as seen by a median length of hospital stay of 7 days (between days 0-100). Incidence of grade II-IV acute GVHD was 8%. Two patients died before day 100 from underlying disease and viral infection, respectively (day 100 transplant-related mortality of 15%). The 1-year overall survival was 84% (95% CI 64-100). Most patients with immunodeficiencies and metabolic disorders had excellent donor engraftment and disease resolution or stabilisation, but most of those with haemoglobinopathies rejected their graft. INTERPRETATION This reduced intensity regimen followed by HSCT provides a good alternative to myeloablative HSCT for children with non-malignant disorders, except for haemoglobinopathies, in which engraftment is poor. Even patients with unrelated donor haemopoietic stem-cell transplants had adequate engraftment with acceptable toxicities.


Bone Marrow Transplantation | 2005

Safety and efficacy of allogeneic PBSC collection in normal pediatric donors: The Pediatric Blood and Marrow Transplant Consortium Experience (PBMTC) 1996–2003

Michael A. Pulsipher; John E. Levine; Robert J. Hayashi; K. W. Chan; P. M. Anderson; Reggie Duerst; I. Osunkwo; V. Fisher; Biljana Horn; Stephan A. Grupp

Summary:The use of peripheral blood stem cells (PBSC) for allogeneic transplants in adults has greatly increased. This trend is reflected in pediatrics, where healthy children increasingly are donating PBSC or donor lymphocyte infusion (DLI) via apheresis for use by ill siblings. There is a potential concern that the risks of PBSC collection may differ for pediatric donors. However, no large studies have assessed safety issues in this population. To address this need, we reviewed 218 (213 PBSC, five DLI) collections in 201 normal pediatric donors (8 months to 17 years, median 11.8 years) at 22 institutions in the Pediatric Blood and Marrow Transplant Consortium. Donors received a median of 4 days of growth factor, and mean collection yield was 9.1 × 106 CD34+ cells/kg recipient weight. Younger age, days of apheresis, and male gender predicted increased yield of CD34+ cells/kg donor weight. Growth factor-induced pain was mild and reported in less than 15% of patients. Most donors <20 kg (23/25, 92%) required PRBC priming of the apheresis machine. This experience with over 200 collections demonstrates that PBSC collection is safe in normal pediatric donors and desired CD34 cell yields are easily achieved. Younger children utilize more medical resources and children <20 kg usually require a single blood product exposure.


Blood | 2016

Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure.

Paul G. Richardson; Marcie L. Riches; Nancy A. Kernan; Joel A. Brochstein; Shin Mineishi; Amanda M. Termuhlen; Sally Arai; Stephan A. Grupp; Eva C. Guinan; Paul L. Martin; Gideon Steinbach; Amrita Krishnan; Eneida R. Nemecek; Sergio Giralt; Tulio E. Rodriguez; Reggie Duerst; John Doyle; Joseph H. Antin; Angela Smith; Leslie Lehmann; Richard E. Champlin; Alfred P. Gillio; Rajinder Bajwa; Ralph B. D'Agostino; Joseph M. Massaro; Diane Warren; Maja Miloslavsky; Robin Hume; Massimo Iacobelli; Bijan Nejadnik

Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8;P= .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6;P= .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #.


Bone Marrow Transplantation | 1998

Autotransplantation for relapsed or refractory Hodgkin's disease : long-term follow-up and analysis of prognostic factors

Jeffrey E. Lancet; Aaron P. Rapoport; Ralph Brasacchio; Shirley Eberly; Richard F. Raubertas; Linder T; A. Muhs; Reggie Duerst; Camille N. Abboud; Charles H. Packman; John F. DiPersio; Louis S. Constine; Jacob M. Rowe; Jane L. Liesveld

Seventy consecutive patients with refractory or relapsed Hodgkin’s disease who received high-dose chemotherapy followed by autologous stem cell rescue were analyzed to identify clinically relevant predictors of long-term event-free survival. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine and cyclophosphamide (BEAC). The 5-year Kaplan–Meier event-free survival (EFS) for the entire cohort was 32% (95% confidence interval; 18–45%) with a median follow-up of 3.6 years (range 7 months–7.6 years). The most significant predictor of improved survival was the presence of minimal disease (defined as all areas ⩽2 cm) at the time of transplant: the 5 years EFS was 46 vs 10% for patients with bulky disease (P = 0.0002). Other independent predictors identified by step-wise regression analysis included the presence of non-refractory disease and the administration of post-transplant involved-field radiotherapy (XRT). Treatment-related mortality occurred in 13 of 70 patients: nine patients (13%) died within the first 100 days, mainly from cardiopulmonary toxicity. However, only one of 24 patients (4%) transplanted during the last 4.5 years died from early treatment-related complications. While high-dose therapy followed by autotransplantation led to long-term EFS of 50% for patients with favorable prognostic factors, a substantial proportion of patients relapsed, indicating that new therapeutic strategies are needed.


Bone Marrow Transplantation | 1997

Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors.

Aaron P. Rapoport; Lifton R; Louis S. Constine; Reggie Duerst; Camille N. Abboud; Jane L. Liesveld; Charles H. Packman; Shirley Eberly; Richard F. Raubertas; Martin Ba; Flesher Wr; Kouides Pa; John F. DiPersio; Jacob M. Rowe

One hundred and thirty-six patients autografted for relapsed or refractory non-Hodgkin’s lymphoma (NHL) were evaluated to assess long-term event-free survival and to identify important prognostic factors. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem cell rescue. The 5-year Kaplan–Meier event-free survival (EFS) for the entire cohort was 34% (95% confidence interval: 24–44%) with a median follow-up of approximately 3 years (range 0–7.5 years). For patients entering with minimal disease (defined as all areas ⩽2 cm), the 5-year EFS was 40 vs 26% for those entering with bulky disease (P = 0.0004). In the multivariate analysis, minimal disease on entry and administration of involved-field XRT post-transplant were significantly associated with improved EFS; the latter association was observed mainly in the cohort of patients with bulky disease. The overall 100-day treatment-related mortality rate was 4.4% (3% for the last 71 patients). New strategies are needed to reduce the high rate of relapse (50–60%) following autotransplantation for relapsed or refractory NHL.


Bone Marrow Transplantation | 2009

Challenges in the use of allogeneic hematopoietic SCT for ectodermal dysplasia with immune deficiency

J D Fish; Reggie Duerst; E W Gelfand; J S Orange; Nancy Bunin

Genetic mutations of proteins regulating nuclear factor of κ-light polypeptide gene enhancer in B lymphocyte (NF-κB) activation result in heritable diseases of development and immunity. Hypomorphic, X-linked mutations in the IKBKG gene (NF-κB essential modulator (NEMO) protein), and hypermorphic, autosomal dominant mutations in the IKBA gene (inhibitor of NF-κB (IκB)-α protein), are associated with a phenotype of immune deficiency and often ectodermal dysplasia (ED-ID). ED-ID predisposes patients to recurrent and life-threatening infections and is typically fatal within the first few years of life. Allogeneic hematopoietic SCT (HSCT) may correct the immune deficiency associated with NEMO or IκBα mutations, but there is very little published data. We gathered clinical data on three ED-ID patients that had undergone HSCT. Conditioning regimens were variable, as were the stem cell sources. All three patients experienced engraftment difficulties as well as post transplant complications. These cases suggest that patients with immune deficiencies caused by NEMO or IκBα mutations may have intrinsic barriers to successful engraftment, which require further investigation.


British Journal of Haematology | 2009

High WT1 gene expression before haematopoietic stem cell transplant in children with acute myeloid leukaemia predicts poor event-free survival.

David A. Jacobsohn; William T. Tse; Stanley Chaleff; Alfred Rademaker; Reggie Duerst; Marie Olszewski; Wei Huang; Pauline M. Chou; Morris Kletzel

WT1 gene expression has been proposed as a useful marker of minimal residual disease in leukaemia. Its utility in paediatric haematopoietic stem cell transplantation (HSCT) has not been studied. We studied the prognostic value of WT1 expression in peripheral blood prior to HSCT in 36 children with acute myeloid leukaemia (AML). Samples were obtained 2 weeks pre‐transplant to determine the level of WT1 expression. WT1 expression was normalized using K562 cells as a control and a relative value of 0·5 was chosen as the cut‐off point between high and low WT1 expression. The median level of pre‐transplant WT1 expression in the 36 patients was 0·09 (range 0·0001–11·0), with 11patients having WT1 ≥ 0·5 and 25, WT1 < 0·5. After HSCT, 76% of patients with high pre‐transplant WT1 expression relapsed, in contrast to 0% of the patients with low WT1 expression. Those with high WT1 expression had significantly lower 5‐year event‐free survival (EFS) (18%, 95% CI 0–40%) as compared to those with low WT1 expression (68%, 95% CI 50–86%, P = 0·007). Multivariate analysis showed that pre‐transplant WT1 level is the only significant prognostic factor for the difference in EFS. Our finding suggests that elevated WT1 gene expression before HSCT in paediatric AML predicts relapse and poor long‐term EFS. A larger prospective study is warranted to compare the value of high WT1 expression and other markers of minimal residue disease in predicting clinical outcomes after HSCT.


Transplantation | 2004

Eosinophilia correlates with the presence or development of chronic graft-versus-host disease in children

David A. Jacobsohn; Tali Schechter; Roopa Seshadri; Kimberly Thormann; Reggie Duerst; Morris Kletzel

Finding predictors of chronic graft-versus-host disease (cGVHD) in children would be extremely useful. Because of recent data suggesting that cGVHD may be a Th-2-mediated process, a theoretical foundation linking eosinophilia and cGVHD exists. While an association between eosinophilia and cGVHD has been described in adults, it has never been described in children. We studied 53 patients that received allogeneic hematopoietic stem cell transplants (SCT) between 1999 and 2002. Ten (19%) of these patients developed eosinophilia (absolute eosinophil count (AEC) > 500× 106/L) after day 100. Of these ten, eight either had or later developed cGVHD. We conclude that following the peripheral eosinophil count in children post-SCT is useful, and a rise in the AEC may herald the development of cGVHD. Taking the AEC into account with other risk factors (such as previous grade II-IV acute GVHD, human leukocyte antigen (HLA)-mismatch, and unrelated donor (URD) transplant) may improve our ability to predict cGVHD.

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David A. Jacobsohn

Children's National Medical Center

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William T. Tse

Children's Memorial Hospital

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Sonali Chaudhury

Children's Memorial Hospital

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Camille N. Abboud

Washington University in St. Louis

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