Renal allograft procurement from living unrelated donors in Iran: What falls under the eclipse

Renal transplantation is the treatment of choice for end stage kidney disease.However,despite all the efforts to expand the donor pool,the shortage of donors is increasing and as a consequence,there has been a significant increase in the number of patients on transplant waiting lists globally.Societies worldwide have employed different methods to address this,each with specific ethical concerns surrounding them.Over three decades ago,a governmentally regulated program of kidney transplantation from living unrelated donors was introduced in Iran and since practiced which has been the subject of hot debate in the literature.Nevertheless,despite all these extensive discussions and publications,several key aspects of the program have still not been properly elucidated and addressed.In this article,the author aims to illuminate some dark corners related to this issue that have largely escaped the notice of ethicists.

Successful transplantation of double unit umbilical-cord blood from unrelated donors in high risk leukemia with a long follow-up

Umbilical-cord blood (UCB) is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children. But the low cell dose severely limits the application of unrelated umbilical-cord blood transplantation (UCBT) in adult patients, particularly in those with high body weight. We hypothesized that the combined transplantation of two partially matched UCB units would improve engraftment without crossed immunological rejection. Since May 2000, six adult patients with high risk leukemia have been transplanted in this study.

Outcomes of peripheral blood stem cell transplantation in patients from human leukocyte antigen matched or mismatched unrelated donors

Background AIIogeneic peripheral blood stem cell transplantation from unrelated donors （UR-PBSCT） is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen （HLA）-identical sibling donors. This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT. Methods Patients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated. They were divided into three groups according to high-resolution molecular typing. SPSS version 17.0 was used to analysis and compare the statistics of engraftment, incidence of GVHD, other complications and survival among the groups. Results One hundred and eleven patients received UR-PBSCT, 60 of them with an HLA matched donor （10/10）, 36 of them with a one locus mismatched donor （9/10）, and 15 of them with a two loci mismatched donor （8/10）. Similar basic characteristics were found in the three groups. No differences were found in engraftment of myeloid cells or platelets in the three groups （P〉0.05）. Two-year cumulative incidence of relapse, overall survival （OS） and disease-free survival （DFS） among those three groups were similar （P〉0.05）. The cumulative incidence of 100-day Ill-IV aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group （3.3%, 8.6%, and 26.7%, P=0.009）. The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups （26.67%, 52.78%, and 41.18%, P=0.035）. The cumulative incidence of 100-day and 2-year transplantation related mortality （TRM） in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group, （8.4%, 11.8% and 33.3%, P=0.016） and （12.3%, 18.7% and 47.5%, P=0.002）. Conclusions HLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT, but two mismatched HLA loci may increase the cumulative incidence of severe aGVHD and TRM. Chin Med J 2014;127 （14）： 2612-2617

Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies： a single-institute analysis

Background Umbilical cord blood （UCB） has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival （LFS） and some primary results, such as hematologic recovery, risk of graft-versus-host disease （GVHD）, relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source. Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood （UCBT） as a primary unrelated stem cell source （n=38）, bone marrow （UBMT n=28, transplanted before January 2003）, or peripheral blood stem cells （UPBSCT n=46, transplanted after January 2003） between July 2000 and July 2008 were analyzed. Results Except that the patients were much younger in the UCBT group （median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT）, other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti- thymocyte globulin （ATG） used for the UBMT patients （2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000）. Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower （87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000） for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease （aGVHD） was much higher in the UBMT group but did not differ among the other groups （51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000）. The occurrence of extensive chronic GVHD （cGVHD） was significantly decreased for recipients of UCBT （4%） compared with that of UPBSCT （39.1%） and UBMT （49.1%, P=0.000）, although the rates of whole cGVHD were not significantly different （30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively）. The patients had a similar rate of CMV infection （21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively）, while the HC occurrence was lower after UCBT （7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively）. As of August 2012, there was no apparent difference in 5-year overall survival （OS）, LFS, or the relapse rate for each graft source （52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT）. Conclusion These data support the use of UCB donors as an alternative allogeneic donor.

Changing landscape in living kidney donation in Greece

Patients with end-stage renal disease in Greece are facing long waiting times to receive a kidney transplant from a deceased donor.Living kidney donation offers a valuable alternative that provides optimal outcomes and significantly expands the donor pool but still remains relatively underutilised.Developments around the world in the field of kidney transplantation mandate a change in current practice to include additional options for living donation through paired exchange,antibody-incompatible transplantation and other strategies,following careful consideration of the cultural and ethical factors involved in these complex clinical decisions.An increase in living donation rates may be achieved in several ways,including targeted campaigning to overcome potential barriers.Educating clinicians on transplantation will prove as equally important as informing patients and prospective donors but requires training and resources.Adoption of established practices and implementation of new strategies must be tailored to the needs of the Greek donor and recipient population.Local beliefs about donation,perception of associated risk and other social characteristics must be considered in the design of future strategies.Facilitating living donation in a safe environment with appropriate donor and recipient education will form the solid foundation of a new era of kidney transplantation in Greece.

Long-term outcomes in adults with leukemia treated with transplantation of two unrelated umbilical cord blood units

Background Wide application of umbilical cord blood transplantation （UCBT） in adult patients is limited by low cell-dose available in one umbilical cord blood （UCB） unit. The aim of this study was to investigate the safety and long-term outcomes of UCBT from unrelated donors in adult and adolescent patients with leukemia. Methods Thirteen patients with leukemia received double-unit UCBT with human leukocyte antigen （HLA） mismatched at 0-2 loci. We analyzed the engraftment, graft-versus-host disease （GVHD） and survival. Results Twelve evaluable patients （92.3%） had neutrophil and platelet engraftment at a median of 21 days （range, 16-38 days） and 34 days （range, 25-51 days）, respectively. At day 30, engraftment was derived from one donor in 8 patients （66.7%, 95% Cl 40.0%-93.4%）, and from both donors in 4 patients （33.3%, 95% CI 6.7%-60.0%） with 1 unit predominated. Unit with larger nucleated cell （NC） dose would predominate in engraftment （P=-0.039）, whereas CD34~ cell dose or HLA-match failed to demonstrate any relationship with unit predominance. Only one patient developed grade II acute graft-versus-host disease （aGVHD）. Chronic GVHD （cGVHD） was observed in 2 of 11 patients who survived more than 100 days, and both were limited. The median follow-up after transplantation for the 13 patients was 45 months （range 1.5-121.0 months） and 72 months （range 41.0-121.0 months） for the 8 alive and with full donor chimerism. The 5-year cumulative disease free survival （DFS） was （61.5±13.5）%. Of the 13 patients, 5 patients died in 1 year and 1-year transplantation related mortality （TRM） was 23.1% （95% Cl 0.2%-46.0%）. Conclusion Double-unit UCBT from unrelated donors with HLA-mismatched at 0-2 loci may overcome the cell-dose barrier and be feasible for adults and adolescents with leukemia.

A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia

Objective To evaluate the efficacy of unrelated do-nor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT).for children and adolescents with severe aplastic anemia(SAA).Methods Clinical data of34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015.According to the source of donor,the