Impact of autologous blood transfusion after bone marrow harvest on unrelated donor's health and outcome: a CIBMTR analysis.
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ABSTRACT:
SUBMITTER: Farhadfar N
PROVIDER: S-EPMC7606543 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRandomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.MethodsWe conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).ResultsThe overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.ConclusionsWe did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).
| S-EPMC3816375 | biostudies-literature
Project description:This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18?mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), ?-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.
| S-EPMC6231388 | biostudies-other
Project description:Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections, it was .2 in both arms; and for fungal/parasitic infections, it was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts.
| S-EPMC4716871 | biostudies-literature
Project description:Results of 2 parallel phase 2 trials of transplantation of unrelated umbilical cord blood (UCB) or bone marrow (BM) from HLA-haploidentical relatives provided equipoise for direct comparison of these donor sources. Between June 2012 and June 2018, 368 patients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were randomly assigned to undergo UCB (n = 186) or haploidentical (n = 182) transplant. Reduced-intensity conditioning comprised total-body irradiation with cyclophosphamide and fludarabine for both donor types. Graft-versus-host disease prophylaxis for UCB transplantation was cyclosporine and mycophenolate mofetil (MMF) and for haploidentical transplantation, posttransplant cyclophosphamide, tacrolimus, and MMF. The primary end point was 2-year progression-free survival (PFS). Treatment groups had similar age, sex, self-reported ethnic origin, performance status, disease, and disease status at randomization. Two-year PFS was 35% (95% confidence interval [CI], 28% to 42%) compared with 41% (95% CI, 34% to 48%) after UCB and haploidentical transplants, respectively (P = .41). Prespecified analysis of secondary end points recorded higher 2-year nonrelapse mortality after UCB, 18% (95% CI, 13% to 24%), compared with haploidentical transplantation, 11% (95% CI, 6% to 16%), P = .04. This led to lower 2-year overall survival (OS) after UCB compared with haploidentical transplantation, 46% (95% CI, 38-53) and 57% (95% CI 49% to 64%), respectively (P = .04). The trial did not demonstrate a statistically significant difference in the primary end point, 2-year PFS, between the donor sources. Although both donor sources extend access to reduced-intensity transplantation, analyses of secondary end points, including OS, favor haploidentical BM donors. This trial was registered at www.clinicaltrials.gov as #NCT01597778.
| S-EPMC7819761 | biostudies-literature
Project description:Peripheral blood (PB) and bone marrow (BM) from unrelated donors can serve as a graft source for hematopoietic cell transplantation (HCT). Currently, PB is most commonly used in roughly 80% of adult recipients. Determining the long-term impact of graft source on outcomes would inform this decision. Data collected by the Center for International Blood and Marrow Transplant Research from 5200 adult recipients of a first HCT from an 8/8 or 7/8 HLA antigen-matched unrelated donor for treatment of acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome between 2001 and 2011 were analyzed to determine the impact of graft source on graft-versus-host disease (GVHD) relapse-free survival (GRFS), defined as freedom from grade III/IV acute GVHD, chronic GVHD requiring immunosuppressive therapy, relapse, and death, and overall survival. GRFS at 2 years was superior in BM recipients compared with PB recipients (16%; 95% confidence interval [CI], 14% to 18% versus 10%; 95% CI, 8% to 11%; P <.0001) in the 8/8 HLA-matched cohort and 7/8 HLA-matched cohort (11%; 95% CI, 8% to 14% versus 5%; 95% CI, 4% to 7%; P?=?.001). With 8/8 HLA-matched unrelated donors, overall survival at 5 years was superior in recipients of BM (43%; 95% CI, 40% to 46% versus 38%; 95% CI, 36% to 40%; P?=?.014). The inferior 5-year survival in the PB cohort was attributable to a higher frequency of deaths while in remission compared with the BM cohort. For recipients of 7/8 HLA-matched grafts, survival at 5 years was similar in BM recipients and PB recipients (32% versus 29%; P?=?.329). BM grafts are associated with improved long-term GRFS and overall survival in recipients of matched unrelated donor HCT and should be considered the unrelated allograft of choice, when available, for adults with acute leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome.
| S-EPMC6339839 | biostudies-literature
Project description:Sickle cell disease (SCD) is a monogenic red blood cell (RBC) disorder with high morbidity and mortality. Here, we report, for the first time, the impact of SCD on the bone marrow (BM) vascular niche, which is critical for hematopoiesis. In SCD mice, we find a disorganized and structurally abnormal BM vascular network of increased numbers of highly tortuous arterioles occupying the majority of the BM cavity, as well as fragmented sinusoidal vessels filled with aggregates of erythroid and myeloid cells. By in vivo imaging, sickle and control RBCs have significantly slow intravascular flow speeds in sickle cell BM but not in control BM. In sickle cell BM, we find increased reactive oxygen species production in expanded erythroblast populations and elevated levels of HIF-1α. The SCD BM exudate exhibits increased levels of proangiogenic growth factors and soluble vascular cell adhesion molecule-1. Transplantation of SCD mouse BM cells into wild-type mice recapitulates the SCD vascular phenotype. Our data provide a model of SCD BM, in which slow RBC flow and vaso-occlusions further diminish local oxygen availability in the physiologic hypoxic BM cavity. These events trigger a milieu that is conducive to aberrant vessel growth. The distorted neovascular network is completely reversed by a 6-week blood transfusion regimen targeting hemoglobin S to <30%, highlighting the plasticity of the vascular niche. A better insight into the BM microenvironments in SCD might provide opportunities to optimize approaches toward efficient and long-term hematopoietic engraftment in the context of curative therapies.
| S-EPMC7273832 | biostudies-literature
Project description:BackgroundAutogenous Iliac Crest Bone Graft (ICBG) has been the "gold standard" for spinal fusion. However, bone graft harvest may lead to complications, such as chronic pain, numbness, and poor cosmesis. The long-term impact of these complications on patient function and well-being has not been established but is critical in determining the value of expensive bone graft substitutes such as recombinant bone morphogenic protein. We thus aimed to investigate the long-term complications of ICBG. Our second aim was to evaluate the psychometric properties of a new measure of ICBG morbidity that would be useful for appropriately gauging spinal surgery outcomes.MethodsProspective study of patients undergoing spinal fusion surgery with autologous ICBG. The SF-36v2, Oswestry Disability Index, and a new 14-item follow-up questionnaire addressing persistent pain, functional limitation, and cosmesis were administered with an 83% response rate. Multiple regression analyses examined the independent effect of ICBG complications on physical and mental health and disability.ResultsThe study population included 170 patients with a mean age of 51.1 years (SD = 12.2) and balanced gender (48% male). Lumbar fusion patients predominated (lumbar = 148; cervical n = 22). At 3.5 years mean follow-up, 5% of patients reported being bothered by harvest site scar appearance, 24% reported harvest site numbness, and 13% reported the numbness as bothersome. Harvest site pain resulted in difficulty with household chores (19%), recreational activity (18%), walking (16%), sexual activity (16%), work activity (10%), and irritation from clothing (9%). Multivariate regression analyses revealed that persistent ICBG complications 3.5 years post-surgery were associated with significantly worse disability and showed a trend association with worse physical health, after adjusting for age, workers' compensation status, surgical site pain, and arm or leg pain. There was no association between ICBG complications and mental health in the multivariate model.ConclusionChronic ICBG harvest site pain and discomfort is reported by a significant percentage of patients undergoing this procedure more than three years following surgery, and these complications are associated with worse patient-reported disability. Future studies should consider employing a control group that does not include autologous bone graft harvest, e.g., a group utilizing rhBMP, to determine whether eliminating harvest-site morbidity does indeed lead to observable improvement in clinical outcome sufficient to justify the increased cost of bone graft substitutes.
| S-EPMC2693524 | biostudies-literature
Project description:We conducted an animal experiment and used total RNA sequencing (RNA-Seq) to identify novel RNA markers to detect autologous blood transfusion (ABT) doping within red blood cells (RBCs) as a pilot study before human trials. The total RNA-Seq and bioinformatics were performed using rat RBCs that were stored 10- and 20-day periods with citrate–phosphate–dextrose solution with adenine (CPDA) at 4°C In the results, we identified three significant genes whose expression levels were drastically decreased according to the storage period. Our novel insights may allow future studies to develop a test method for ABT doping.
2022-07-14 | GSE205806 | GEO
Project description:We report a comparison of time to recovery, side effects, and change in blood counts from baseline to after donation from unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network phase III randomized, multicenter trial (0201) in which donor-recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) were from international centers (145 German and 9 Canadian). PBSC donors recovered in less time, with a median time to recovery of 1 week compared with 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months after donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time after donation compared with BM donors (hazard ratio, 2.08; 95% confidence interval [CI], 1.73 to 2.50; P < .001). Other characteristics that significantly increased the likelihood of complete recovery were being an international donor and donation in more recent years. Donors of BM were more likely to report grades 2 to 4 skeletal pain, body symptoms, and fatigue at 1 week after donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 after collection of BM donors) could be analyzed, no variable was significantly associated with grades 2 to 4 skeletal pain, including product donated (BM versus PBSC; odds ratio, 1.13; 95% CI, .74 to 1.74; P = .556). Blood counts were affected by product donated, with greater mean change from baseline to after donation for white blood cells, neutrophils, mononuclear cells, and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as product donated was independent of physician bias or donor preference.
| S-EPMC4867293 | biostudies-literature