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BACKGROUND: Allogeneic hematopoietic stem cell transplantation is still the only cure method for acquired severe aplastic anemia. How to select patients for treatment has become a research hotspot in recent years. OBJECTIVE: To review the progress of allogeneic hematopoietic stem cell transplantation from three aspects: HLA full-phase matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT), unrelated cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (HID-HSCT). METHODS: Literatures on allogeneic hematopoietic stem cell transplantation for severe aplastic anemia collected in PubMed, CNKI full-text database and WanFang database from 2000 to 2018 were retrieved with the keywords “unrelated donor; haploidentical; unrelated cord blood; severe aplastic anemia” in Chinese and English. RESULTS AND CONCLUSION: MSD-HSCT is the first-line treatment for severe aplastic anemia, but in view of China’s special national conditions, HLA matched donor is not easy to find. As an important alternative treatment, MUD-HSCT is close to MSD-HSCT. However, the incidence of graft versus host disease and severe infection after MUD-HSCT is still higher than that after MSD-HSCT. It is still necessary to consider multiple factors when choosing MUD-HSCT treatment. Umbilical cord blood hematopoietic stem cells are widely used because of their abundant sources and high match success rate. The probability of UCBT is very high when the amount of pre-frozen total nucleated cells is more than 3.9×107/kg. However, in view of the delay of UCBT and immune function reconstruction, unless other transplantation methods are not feasible in clinical treatment of severe aplastic anemia and immunosuppressive therapy fails in the first course of treatment, UCBT should not be considered. HID-HSCT has the advantages of easy access and good compliance of donors and is close to full-matched transplantation. It has become an important alternative to transplantation. The use of baliximab and/or antithymocyte globulin is expected to reduce the incidence of graft versus host disease and expand the clinical application of HID-HSCT.
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Background: Kidney transplantation is the best treatment for end stage kidney disease. The allograft allocation system considers immunological factors and time in waiting list, but not the age of donors or recipients, in spite that both have prognostic relevance. Aim: To study the fairness of the allograft allocation system considering the age of donors and recipients. Material and Methods: Based in the age distribution of donors and waiting list of patients for kidney transplantation, we constructed probability functions for receiving a graft as an allocation system based on age changes from a strict to a more lax criteria. Finally, we compared our model with the real transplants performed during 2012. Results: The probability distribution for receiving a kidney transplantation is displaced to the right compared with the age distribution of graft donors. This gap increases as the procuring hospitals enlist progressively older graft candidates without accepting older donors in parallel. An allocation system that maintains age parity between donors and recipients is fairer that other that allows lax criteria for the same allocation. This phenomenon is attenuated if the procurement acceptance criterion allows older donors. Conclusions: It is necessary to reduce the gap between donor and recipient ages for kidney transplantation to improve the fairness of the graft allocation system.
Subject(s)
Adolescent , Adult , Aged , Humans , Middle Aged , Young Adult , Age Factors , Donor Selection/standards , Kidney Transplantation , Patient Selection , Waiting Lists , Age Distribution , Graft SurvivalABSTRACT
Hematopoietic stem cell transplantation has been successfully used to treat the pediatric population with malignant and non-malignant hematological diseases. This paper reports the results up to 180 days after the procedure of all unrelated hematopoietic stem cell transplantations in pediatric patients that were performed in one institution.METHODS: A retrospective review was performed of all under 18-year-old patients who received unrelated transplantations between 1995 and 2009. Data were analyzed using the log-rank test, Cox stepwise model, Kaplan-Meier method, Fine and Gray model and Fisher's exact test.RESULTS: This study included 118 patients (46.8%) who received bone marrow and 134 (53.2%) who received umbilical cord blood transplants. Engraftment occurred in 89.47% of the patients that received bone marrow and 65.83% of those that received umbilical cord blood (p-value < 0.001). Both neutrophil and platelet engraftments were faster in the bone marrow group. Acute graft-versus-host disease occurred in 48.6% of the patients without statistically significant differences between the two groups (p-value = 0.653). Chronic graft-versus-host disease occurred in 9.2% of the patients with a higher incidence in the bone marrow group (p-value = 0.007). Relapse occurred in 24% of the 96 patients with malignant disease with 2-year cumulative incidences of 45% in the bone marrow group and 25% in the umbilical cord blood group (p-value = 0.117). Five-year overall survival was 47%, with an average survival time of 1207 days, and no significant differences between the groups (p-value = 0.4666).CONCLUSION: Despite delayed engraftment in the umbilical cord blood group, graft-versus-host disease, relapse and survival were similar in both groups...
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Child , Cord Blood Stem Cell Transplantation , Hematologic Diseases , Hematopoietic Stem Cell Transplantation , Stem Cell Transplantation , Unrelated DonorsABSTRACT
Background: There is a gap between the number of patients requiring a renal allograft and the number of potential deceased donors (DD). One alternative is using allografts from non-related living donors (NRLD). Aim: To compare survival and complications of renal allograft recipients from DD, related living donors (RLD) and NRLD. Material and Methods: Observational study of a cohort of renal allograft recipients. Of 253 transplants performed in a Chilean region between 1981 and 2003, 20 patients received and allograft from a NRLD. Graft and patient survival of these patients were compared with those of 93 patients receiving an allograft from a related living donor and 140 receiving it from a DD. Patients were followed for 10 years or until death or dialysis requirement. Results: No significant differences between groups in graft and patient survival, deaths with a functioning graft or return to dialysis were observed. Receptors of DD had more hospital admissions during the first years after receiving the graft, usually due to infections. Also a delayed graft function was more common among them. Glomerular filtration rate ten years after the graft was similar among the three groups. Conclusions: No differences in graft or patient survival was observed between patients receiving a renal allograft from NRLD, RLD or DD.
Subject(s)
Animals , Female , Mice , Rats , Analgesics , Anti-Inflammatory Agents, Non-Steroidal , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Amides/pharmacology , Carrageenan , Dipyrone/pharmacology , Edema/chemically induced , Edema/drug therapy , Formaldehyde , Hot Temperature , Isomerism , Motor Activity/drug effects , Pain Measurement/drug effects , Picolinic Acids/pharmacology , Poly(ADP-ribose) Polymerases/antagonists & inhibitors , Postural Balance/drug effects , Rats, WistarABSTRACT
Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.
Subject(s)
Child, Preschool , Humans , Middle Aged , Hematopoietic Stem Cell Transplantation/methods , Transplantation, Homologous/methods , Unrelated Donors , Anemia, Diamond-Blackfan/surgery , Blood Banks , Fetal Blood/transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Treatment OutcomeABSTRACT
BACKGROUND: Lung transplantation (LTx) is an effective treatment for end stage lung disease. However, the shortage of donor lungs has been a major limiting factor to increase the number of LTx. Ex vivo lung perfusion (EVLP) is a currently approved method to evaluate lung function and to repair donor lung with poor function. The purpose of this study was to develop EVLP system in pig model and to maintain lung function during 4 hours of EVLP. METHODS: Bilateral lung blocks were harvested from five 40 kg pigs. These blocks were applied in EVLP perfused with 37degrees C Steen solution. We performed arterial blood gas (ABG) analyses before death and also every 1 hour for 4 hours after application of EVLP and calculated oxygen capacities (OC) using the results of ABG. We also calculated pulmonary vascular resistance (PVR) and peak airway pressure (PAP) every 1 hour for 4 hours. After EVLP procedure, we excised specimens for pathologic review. RESULTS: We found that OC gradually decreased during the 4 hour period of EVLP; however, no statistically significant difference was obtained. PVR declined sharply after 1 hour of EVLP (P=0.031) and then remained constant for 3 hours. PAP significantly increased after 3 hours (P<0.0001). Pathologic investigations revealed various findings from normal lung to severe pulmonary edema. CONCLUSIONS: On the results of this study, we could preserve the lung function for 4 hours using EVLP. We conclude that application of EVLP in clinical setting can make more donor lungs available for LTx. However, we also understand that more studies and training are needed in clinical practice.
Subject(s)
Humans , Lung , Lung Diseases , Lung Transplantation , Organ Preservation , Oxygen , Perfusion , Swine , Tissue Donors , Unrelated Donors , Vascular ResistanceABSTRACT
Objective To assess the impact of HLA-A,HLA-B,HLA-DRB1 matching on the prognosis of hematopoietic stem cell transplantation from unrelated donors.Methods A total of 81 patients with hematological malignancies including leukemia,myelodysplastic syndrome(MDS)and lymphoma who underwent hematopoietic stem cell transplantation from unrelated donors from 2007 to 2012 in our department were included in this retrospective analysis.Patients were classified into HLA match group(n=53)and HLA mismatch group(n=28)according to the HLA high-resolution matching.The overall survival (OS),treatmentrelated mortality(TRM),relapse rate(RR),graft-versus-host disease(GVHD)incidence were analyzed.Results The 81 patients were analyzed with a median follow-up of 11.9 months(0.3 to 57.4 months).The OS (66.0％vs 46.4％,P=0.031)and TRM(17.0％vs 42.9％,P=0.017)were significantly different between the HLA match group and HLA mismatch group,while the RR had no significant difference(14.3％vs 32.1％,P=0.111).Multivariate analysis showed HLA matching was an independent prognostic factor of TRM,but not OS.There's no significant difference of aGVHD(22.9％vs 40.9％,P=0.122)and cGVHD (40.0％vs 46.7％,P=0.655)incidence between the two groups,but the incidence of severe aGVHD in HLA match group were much lower(4.2％vs 25.0％,P=0.005)than HLA mismatch group.Conclusion the high-resolution matching of HLA-A,-B,DRB1 affect OS,TRM and the incidence of severe aGVHD in unrelated hematopoietic stem cell transplantation,but not affect RR,the incidence of aGVHD and cGVHD.
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Objective To assess the impact of antithymocyte globulin (ATG) on the incidence of graft-vs-host disease (GVHD) in hematopoietic stem cell transplantation from unrelated donors.Methods A total of 92 patients with hematological malignancies including leukemia,myelodysplastic syndrome (MDS) and lymphoma who underwent hematopoietic stem cell transplantation from unrelated donors from January 1999 to December 2011 were included in this retrospective analysis.Patients were classified into ATG group (n =66)and non-ATG group (n =26) according to the GVHD prophylaxis regimen.The incidence of acute GVHD (aGVHD) and chronic GVHD (cGVHD),risk factors of aGVHD and cGVHD and impact of ATG on the overall survival (OS),treatment related mortality (TRM) and relapse rate were analyzed.Results Grade Ⅱ-Ⅳ aGVHD (26.7 ％ vs 44.0 ％,P=0.12) or grade Ⅲ-Ⅳ aGVHD (13.3 ％ vs 8.0 ％,P =0.74) were not significantly different between ATG and non-ATG group.However,the incidence of cGVHD in the ATG group was significantly lower (34.0 ％ vs 72.2 ％,P =0.005) than non-ATG group.The incidence of extensive cGVHD was also significantly reduced (10.0 ％ vs 44.4 ％,P =0.005) compared to non-ATG group.In multivariate analysis,the use of ATG prophylaxis significantly decreased the cGVHD (RR =0.22,95 ％CI 0.081-0.599,P =0.003) while one allele mismatch of human leukocyte antigen (HLA) was associated with increased risk of cGVHD (RR =3.25,95 ％ CI 1.39-7.61,P =0.007).As to the extensive cGVHD,the use of ATG was the only independent factor (RR =0.05,95 ％ CI 0.009-0.240,P ＜ 0.001).With a median follow-up of 12 months (1-84 months),ATG prophylaxis had no impact on OS rate (60.4 ％ vs 43.1％,P =0.41),TRM rate (19.8 ％ vs 34.3 ％,P =0.43) and relapse rate (40.6 ％ vs 33.6 ％,P=0.54).Conclusion In hematopoietic stem cell transplantation from unrelated donors,ATG prophylaxis total dose of 6 mg/kg may significantly decrease the incidence of cGVHD and extensive cGVHD without increase of TRMand relapse rate and impairment of OS.