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H M Lazarus - One of the best experts on this subject based on the ideXlab platform.

  • Blood and marrow transplantation in elderly acute myeloid leukaemia patients – older certainly is not better
    Bone Marrow Transplantation, 2007
    Co-Authors: T L Kiss, H M Lazarus, W Sabry, J H Lipton

    Acute myeloid leukaemia in the elderly is a disease with distinct biological properties, commonly associated with leukaemic cell treatment resistance and with an increased number of high-risk features, including concomitant myelodysplasia and poor-risk cytogenetic abnormalities such as monosomy 5 and 7. Complete remission rates after standard induction chemotherapy in patients above age 60 years are less than 50%, with long-term survival rates below 10%. Post-remission stem cell transplant therapies have not been studied extensively. Autologous Transplants can result in an acceptable 3-year leukaemia-free survival rate of up to 47%, yet this procedure is applicable only to a small minority of patients. Myeloablative allogeneic Transplants similarly show feasibility in selected few patients and in general are very toxic. Non-myeloablative allogeneic Transplants are associated with reduced toxicity, but are plagued by an increased relapse rate. The latter strategy appears promising, but must be validated in larger, multi-centre prospective trials, in which outcomes are compared to non-transplant approaches.

  • Should we be performing more combined hematopoietic stem cell plus solid organ Transplants?
    Bone Marrow Transplantation, 2003
    Co-Authors: K Y Chiang, H M Lazarus

    Both bone marrow and solid organ Transplants (SOTs) can be life saving for a wide variety of diseases. We reviewed the literature and summarized the experiences of dual Transplants. In total, 37 patients received a SOT for organ failure after a previous hematopoietic stem cell transplant. In all, 12 subjects received SOTs followed by a bone marrow transplant, while three patients received simultaneous SOTs and bone marrow Transplants. Of these 52 patients, 37 were alive at the time of the original report at follow-up times ranging from 3 months to 8 years. A special registry for data collection may prove helpful for obtaining long-term follow-up data and providing outcome information that may improve future patient survival.

Raphaël Gaisne - One of the best experts on this subject based on the ideXlab platform.

  • Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome
    Journal of the American Society of Nephrology, 2019
    Co-Authors: Julien Zuber, Marie Frimat, Sophie Caillard, Nassim Kamar, Philippe Gatault, Florent Petitprez, Lionel Couzi, Noemie Jourde-chiche, Valérie Châtelet, Raphaël Gaisne

    Background Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country. Methods To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016. Results The first study included 126 kidney Transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney Transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the Transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients. Conclusions Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

E Gluckman - One of the best experts on this subject based on the ideXlab platform.

  • History of cord blood transplantation
    Bone Marrow Transplantation, 2009
    Co-Authors: E Gluckman

    Since the first human cord blood transplant, performed 20 years ago, cord blood banks have been established worldwide for the collection and cryopreservation of cord blood for allogeneic hematopoietic stem cell transplant. A global network of cord blood banks and transplant centers has been established for a common inventory and study of clinical outcomes. Results of unrelated allogeneic cord blood Transplants in malignant and nonmalignant diseases, in adults and children, show that, compared with HLA-matched unrelated BM transplant, cord blood has several advantages, including prompt availability of the transplant, decrease of GVHD and better long-term immune recovery resulting in a similar long-term survival. Several studies have shown that the number of cells is the most important factor for engraftment, although some degree of HLA mismatches is acceptable. Developments are expected to facilitate engraftment, including ex vivo expansion of stem cells, intrabone injection of cord blood cells and double cord blood Transplants. In addition to hematopoietic stem cells, cord blood and placenta contain a large number of nonhematopoietic stem cells. In the absence of ethical concern, the unlimited supply of cells explains the increasing interest of using cord blood for developing regenerative medicine.

Meijie Zhang - One of the best experts on this subject based on the ideXlab platform.

  • risk factors for acute gvhd and survival after hematopoietic cell transplantation
    Blood, 2012
    Co-Authors: Madan Jagasia, Mukta Arora, Mary E D Flowers, Nelson J Chao, Philip L Mccarthy, Corey Cutler, Alvaro Urbanoispizua, Steven Z Pavletic, Michael Haagenson, Meijie Zhang

    Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell Transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD Transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD Transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD Transplants and 33% (95% CI, 31%-35%) with URD Transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients.

  • outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia a comparison study
    The Lancet, 2007
    Co-Authors: Mary Eapen, Meijie Zhang, Pablo Rubinstein, Cladd E Stevens, Joanne Kurtzberg, Andromachi Scaradavou, Fausto R Loberiza, Richard E Champlin, John P Klein, Mary M Horowitz

    Summary Background Although umbilical cord blood is an accepted alternative to bone marrow for transplantation, allele-matched bone marrow is generally regarded as the preferred graft source. Our aim was to assess leukaemia-free survival after transplantations of these alternatives compared with present HLA-matching practices, and to assess the relative effect of cell dose and HLA match, and their potential interaction on leukaemia-free survival after cord-blood transplantation. Methods Outcomes of 503 children ( Findings In comparison with allele-matched bone-marrow Transplants, 5-year leukaemia-free survival was similar to that after Transplants of umbilical cord blood mismatched for either one or two antigens and possibly higher after Transplants of HLA-matched umbilical cord blood. Transplant-related mortality rates were higher after Transplants of two-antigen HLA-mismatched umbilical cord blood (relative risk 2·31, p=0·0003) and possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood Transplants (1·88, p=0·0455). Relapse rates were lower after two-antigen HLA-mismatched umbilical-cord-blood Transplants (0·54, p=0·0045). Interpretation These data support the use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord blood in children with acute leukaemia who need transplantation. Because better HLA matching and higher cell doses significantly decrease the risk of transplant-related mortality after umbilical-cord-blood transplantation, greater investment in large-scale banking is needed to increase HLA diversity.

Rainer W G Gruessner - One of the best experts on this subject based on the ideXlab platform.

  • Survival Benefit of Solid-Organ Transplant in the United States
    JAMA Surgery, 2015
    Co-Authors: Abbas Rana, Bruce Kaplan, Angelika C. Gruessner, Vatche G. Agopian, Zain I Khalpey, Irbaz Bin Riaz, Karim J. Halazun, Ronald W. Busuttil, Rainer W G Gruessner

    Importance The field of transplantation has made tremendous progress since the first successful kidney transplant in 1954. Objective To determine the survival benefit of solid-organ transplant as recorded during a 25-year study period in the United Network for Organ Sharing (UNOS) database and the Social Security Administration Death Master File. Design, Setting, and Participants In this retrospective analysis of UNOS data for solid-organ transplant during a 25-year period (September 1, 1987, through December 31, 2012), we reviewed the records of 1 112 835 patients: 533 329 recipients who underwent a transplant and 579 506 patients who were placed on the waiting list but did not undergo a transplant. Main Outcomes and Measures The primary outcome was patient death while on the waiting list or after transplant. Kaplan-Meier survival functions were used for time-to-event analysis. Results We found that 2 270 859 life-years (2 150 200 life-years from the matched analysis) were saved to date during the 25 years of solid-organ transplant. A mean of 4.3 life-years were saved (observed to date) per solid-organ transplant recipient. Kidney transplant saved 1 372 969 life-years; liver transplant, 465 296 life-years; heart transplant, 269 715 life-years; lung transplant, 64 575 life-years; pancreas-kidney transplant, 79 198 life-years; pancreas transplant, 14 903 life-years; and intestine transplant, 4402 life-years. Conclusions and Relevance Our analysis demonstrated that more than 2 million life-years were saved to date by solid-organ Transplants during a 25-year study period. Transplants should be supported and organ donation encouraged.

  • Short- and long-term outcome for living pancreas donors
    Journal of Hepato-Biliary-Pancreatic Sciences, 2010
    Co-Authors: Jason F. Reynoso, David E R Sutherland, Christine E. Gruessner, Rainer W G Gruessner

    The advantages of living donor pancreas Transplants for the recipient include good HLA matching, lower immunologic risk, less immunosuppression, lower risk of infection and of posttransplant malignancies, and shorter pancreas graft preservation time. In 2008, a total of 155 segmental pancreas Transplants using living donors were reported to the International Pancreas Transplant Registry from six countries. Pancreas living donors need to undergo a thorough pretransplant endocrinologic workup in order to minimize the risk of metabolic complications. The pretransplant workup has evolved over time, after initial reports showed that up to 25% of living donors had elevated hemoglobin A_1c levels after donation. Avoiding obesity after donation diminishes the risk of long-term metabolic complications. The risk of surgical complications for the donor (such as pancreatitis, pancreatic leak or fistula, pancreatic abscess, and pancreatic pseudocyst) is less than 5%. If both the donor and recipient operations are technically successful, the long-term graft survival rate is significantly higher for living (versus deceased) donor pancreas transplant recipients. Future long-term studies of metabolic function in living donors are warranted to determine whether living donor pancreas Transplants can safely be applied more widely and whether living donors can be used for islet Transplants.

  • technical failures after pancreas Transplants why grafts fail and the risk factors a multivariate analysis
    Transplantation, 2004
    Co-Authors: Abhinav Humar, Raja Kandaswamy, Angelika C. Gruessner, Rainer W G Gruessner, Thigarajan Ramcharan, David E R Sutherland

    Background. Technical failure (TF) rates remain high after pancreas Transplants; while rates have decreased over the last decade, more than 10% of all pancreas grafts continue to be lost due to technical reasons. We performed a multivariate analysis to determine causes and risk factors for TF of pancreas grafts. Results. Between 1994 and 2003, 937 pancreas Transplants were performed at our center in the following transplant categories: simultaneous pancreas-kidney (SPK) (n=327), pancreas after kidney (PAK) (n=399), and pancreas transplant alone (PTA) (n=211). Of these, 123 (13.1%) grafts were lost due to technical reasons (thrombosis, leaks, infections). TF rates were higher for SPK (15.3%) versus PAK (12.2%) or PTA (11.4%), though this was not statistically significant. Thrombosis accounted for 52.0% of all TFs. Other causes were infections (18.7%), pancreatitis (20.3%), leaks (6.5%), and bleeding (2.4%). Thrombosis was the most common cause for TF in all three transplant categories. By multivariate analysis, the following were significant risk factors for TF of the graft: recipient body mass index (BMI) >30 kg/m 2 (relative risk [RR] =2.42, P=0.0003), preservation time >24 hr (1.87, P=0.04), cause of donor death other than trauma (RR=1.58, P=0.04), enteric versus bladder drainage (1.68, P=0.06), and donor BMI >30 kg/m 2 (1.66, P=0.06). Not significant were donor or recipient age, a retransplant, and the category of transplant. Conclusions. TFs remain significant after pancreas Transplants. In SPK recipients, TF represents the most common cause of pancreas graft loss. For isolated pancreas Transplants, TF is second only to rejection as a cause of graft loss. Increased preservation times and donor or recipient obesity seem to be risk factors. Minimizing these risks factors would be important to try to decrease TF.