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Similar efficacy outcomes with peripheral blood stem cell versus bone marrow for autologous stem cell transplantation in acute myeloid leukemia: Long-term follow-up of the EORTC-GIMEMA randomized AML-10 trial
Baron, F., Efficace, F., Cannella, L., Stevens-Kroef, M., Amadori, S., de Witte, T., Lübbert, M., Venditti, A., Suciu, S.
American journal of hematology. 2024
Abstract
We report here the long-term follow-up of the only prospective randomized trial of autologous hematopoietic stem cell transplantation (auto-HSCT) with peripheral blood stem cells (APBSCT) versus auto-HSCT with bone marrow (ABMT) in acute myeloid leukemia (AML) patients in first remission (CR). We observed that among patients alive and still in CR 5 years after planned auto-HSCT, approximately 10% of the patients died in the following 10 years. This stresses the need for long-term close surveillance of AML patients after auto-HSCT. Further, long-term follow-up of the trial confirms that APBSCT was comparable to ABMT in term of disease-free-survival and overall survival.
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Stem cell yield and transplantation in transplant-eligible newly diagnosed multiple myeloma patients receiving daratumumab + bortezomib/thalidomide/dexamethasone in the phase 3 CASSIOPEIA study
Hulin, C., Offner, F., Moreau, P., Roussel, M., Belhadj, K., Benboubker, L., Caillot, D., Facon, T., Garderet, L., Kuhnowski, F., et al
Haematologica. 2021
Abstract
Not available.
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Superior GVHD-free, relapse-free survival for G-BM to G-PBSC grafts is associated with higher MDSCs content in allografting for patients with acute leukemia
Fan, Q., Liu, H., Liang, X., Yang, T., Fan, Z., Huang, F., Ling, Y., Liao, X., Xuan, L., Xu, N., et al
Journal of hematology & oncology. 2017;10(1):135
Abstract
BACKGROUND Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1). METHODS Totally 101 adult leukemia in CR1 undergoing HLA-identical sibling transplants were randomized into G-BM or G-PBSC group. The primary study endpoint was GVHD-free/relapse-free survival (GRFS). RESULTS Both the engraftment of neutrophil and platelet were 2 days later in G-BM than in G-PBSC group (P=0.412, P=0.39). G-BM group showed significantly lower II-IV acute GVHD (aGVHD) and similar III-IV aGVHD compared with G-PBSC group (12.2% vs 28.8% for II-IV, P=0.048; 4.1% vs 9.6% for III-IV aGVHD, P=0.267, respectively). The overall cumulative incidence of chronic GVHD (cGVHD) at 3 years were 22.3%+/-6.3% and 44.8%+/-7.6% (P=0.026), respectively, and extensive cGHVD were 4.5%+/-3.1% and 15%+/-5.3% (P=0.08), respectively, in G-BM and G-PBSC groups. Two groups had similar 3-year relapse, transplant-related mortality (TRM), overall survival (OS), and disease-free survival (DFS) (all P>0.05). G-BM group showed significantly higher probability of GRFS than G-PBSC group (73.5%+/-6.3% vs 55.8%+/-6.9% at 1 year, P=0.049; 69.0%+/-6.7% vs 49.7%+/-7.0% at 2 and 3 years, P=0.03, respectively). Graft content analysis revealed statistically higher frequency of myeloid-derived suppressor cells (MDSCs) in the G-BM than in G-PBSC grafts (P<0.01), and recipients received statistically higher numbers of MDSCs in G-BM than in G-PBSC group (P=0.045). Numbers of MDSCs infused to patients were negatively correlated with the severity of aGVHD (P=0.032, r=-0.214). Multivariate analysis showed that MDSC cell dose below the median (HR=3.49, P<0.001), recipient age (HR=2.02, P=0.039), and high risk of disease (HR=2.14, P=0.018) were independent risk factors for GRFS. CONCLUSIONS G-BM grafts lead a better GRFS and less GVHD associated with a higher MDSCs content compared with G-PBSC grafts.
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Immunologic Autograft Engineering and Survival in Non-Hodgkin Lymphoma
Porrata, L. F., Burgstaler, E. A., Winters, J. L., Jacob, E. K., Gastineau, D. A., Suman, V. J., Inwards, D. J., Ansell, S. M., Micallef, I. N., Johnston, P. B., et al
Biology of Blood & Marrow Transplantation. 2016;22(6):1017-23
Abstract
Retrospective studies have reported that the collected and infused autograft absolute lymphocyte count (A-ALC) affects clinical outcomes after autologous peripheral hematopoietic stem cell transplantation (APHSCT). We hypothesized that manipulation of the apheresis machine to target a higher A-ALC dose would translate into prolonged progression-free survival (PFS) in patients with non-Hodgkin lymphoma (NHL) undergoing APHSCT. Between December 2007 and October 2010, we performed a double-blind, phase III, randomized study randomly assigning 122 patients with NHL to undergo collection with the Fenwal Amicus Apheresis system with our standard settings (mononuclear cells offset of 1.5 and RBC offset of 5.0) or at modified settings (mononuclear cells offset of 1.5 and RBC of 6.0). The primary endpoint was PFS. Neither PFS (hazard ratio [HR] of modified to standard, 1.13; 95% confidence interval [CI], .62 to 2.08; P = .70) nor overall survival (OS) (HR modified to standard, .85; 95% CI, .39 to 1.86; P = .68) were found to differ by collection method. Collection of A-ALC between both methods was similar. Both PFS (P = .0025; HR, 2.77; 95% CI, 1.39 to 5.52) and OS (P = .004; HR, 3.38; 95% CI, 1.27 to 9.01) were inferior in patients infused with an A-ALC < .5 x 10(9) lymphocytes/kg compared with patients infused with an A-ALC > .5 x 10(9) lymphocytes/kg, regardless of the method of collection. We did not detect significant differences in clinical outcomes or in the A-ALC collection between the modified and the standard Fenwal Amicus settings; however, despite physician discretion on primary number of collections and range of cells infused, higher A-ALC infused dose were associated with better survival after APHSCT. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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Comparison of Patient-Reported Outcomes in 5-Year Survivors Who Received Bone Marrow vs Peripheral Blood Unrelated Donor Transplantation: Long-term Follow-up of a Randomized Clinical Trial
Lee, S. J., Logan, B., Westervelt, P., Cutler, C., Woolfrey, A., Khan, S. P., Waller, E. K., Maziarz, R. T., Wu, J., Shaw, B. E., et al
JAMA Oncology. 2016;2(12):1583-1589
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Abstract
Importance: Bone marrow or peripheral blood from unrelated donors may be used for hematopoietic cell transplantation. Information about the relative success of transplantation with these 2 graft sources would help physicians and patients choose between them. Objective: To compare patient-reported outcomes between patients randomized to receive 1 of 2 graft types for unrelated donor transplantation. Design, Setting, and Participants: This follow-up of a randomized clinical trial included English- or Spanish-speaking patients 16 years or older participating in a multicenter randomized clinical trial of unrelated donor bone marrow (BM) vs peripheral blood (PB) (N=551) in hematopoietic cell transplantation for hematologic neoplasms. Patient-reported outcomes were collected from patients at enrollment and 0.5, 1, 2, and 5 years after transplantation. Interventions: Unrelated donor BM or PB hematopoietic cell transplantation. Main Outcomes and Measures: Functional Assessment of Cancer Therapy-Bone Marrow Transplant, Mental Health Inventory, occupational functioning, Lee Chronic Graft-vs-Host Disease Symptom Scale. Results: At 5 years after transplantation, 102 BM and 93 PB participants were alive and eligible for assessment (age >40 years or older: 104 [53.5%] male: 101 [51.8%]). The mean (SE) Mental Health Inventory Psychological Well-Being scores (78.9 [1.7] vs 72.2 [1.9]; P=.01; higher better) and Lee chronic graft-vs-host disease symptom scores (13.1 [1.5] vs 19.3 [1.6]; P=.004; lower better) were significantly better for BM recipients, adjusting for baseline scores and missing data. Recipients of BM were also more likely to be working full or part-time than recipients of PB (odds ratio, 1.5; 95% CI, 1.2-2.0; P=.002), adjusting for work status before transplantation. With a median follow-up of 73 months (range, 30-121 months) for survivors, no differences in survival (40% vs 39%; P=.84), relapse (32% vs 29%; P=.47), or treatment-related mortality (29% vs 32%; P=.44) between BM and PB were observed. Conclusions and Relevance: Recipients of unrelated donor BM had better psychological well-being, less burdensome chronic GVHD symptoms, and were more likely to return to work than recipients of PB at 5 years after transplantation. Bone marrow should be the standard of care for these types of transplant procedures. Trial Registration: clinicaltrials.gov Identifier: NCT00075816.
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Prospective randomized and crossover comparison of two apheresis machines for peripheral blood stem cell collection: a multicenter study
Ikeda, K., Minakawa, K., Muroi, K., Fujiwara, S. I., Yamada-Fujiwara, M., Fujimori, Y., Tanosaki, R., Ohto, H., Study Group for Peripheral Blood Stem Cell Collection, Cell Therapy Committee The Japan Society of Transfusion Medicine, Cell, Therapy
Transfusion. 2016;56(11):2839-2847
Abstract
BACKGROUND Improving apheresis technology may lead to an efficient and safe peripheral blood stem cell (PBSC) collection. Recently, the Spectra Optia (Optia, Terumo BCT) was introduced as an automated apheresis instrument, but comparisons with other instruments have been few. This is the first randomized multicenter and crossover comparison of the Optia with the automated program of the established apheresis instrument, the Spectra (Spectra-Auto, Terumo BCT). STUDY DESIGN AND METHODS A total of 233 apheresis procedures performed in 46 autologous patients and 108 allogeneic donors were investigated. Apheresis performed in the first day for all subjects using the Spectra-Auto (n=79) and the Optia (n=75) were evaluated as first-day analysis. Seventy-nine subjects, who required another session on the second day, underwent apheresis using the other instrument than the first-day instrument and were compared with each other in a paired crossover analysis. RESULTS The two instruments processed similar volumes with comparable run times and volumes of acid-citrate-dextrose used. The volumes of collected products were greater in the Optia. Yields of mononuclear cells and CD34+ cells were not different, but collection efficiencies were higher in the Optia (p=0.008 in CE1 of crossover analysis). Spectra-Auto-collected products contained more contaminating red blood cells (RBCs), whereas there was a trend of more contaminating platelets (PLTs) in the Optia-collected products. Slight reductions were noted in the RBC or PLT counts of subjects who underwent apheresis with the Spectra-Auto or the Optia, respectively. CONCLUSION The Optia is safe and more efficient in the PBSC collection compared with the Spectra-Auto. Copyright © 2016 AABB.
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Peripheral-blood stem cells versus bone marrow from unrelated donors
Anasetti, C., Logan, B. R., Lee, S. J., Waller, E. K., Weisdorf, D. J., Wingard, J. R., Cutler, C. S., Westervelt, P., Woolfrey, A., Couban, S., et al
New England Journal of Medicine. 2012;367(16):1487-96
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Practice changing study
Abstract
BACKGROUND Randomized 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. METHODS We 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). RESULTS The 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. CONCLUSIONS We 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.).
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Anticoagulation in large-volume leukapheresis: comparison between citrate- versus heparin-based anticoagulation on safety and CD34 (+) cell collection efficiency
Dettke, Markus, Buchta, Christoph, Wiesinger, Helfried, Maas, Jens-Holger, Strate, Alexander, Chen, Ying
Cytotherapy. 2012;14(3):350-8
Abstract
BACKGROUND AIMS Little is known of the effect of anticoagulation on peripheral blood progenitor cell (PBPC) harvest during large-volume leukapheresis (LVL). Because of the interaction of heparin with stromal cell-derived factor (SDF)-1alpha, it has been proposed that a heparin-based anticoagulation may result in an increased PBPC collection efficiency compared with standard citrate-based anticoagulation. METHODS We conducted a prospective randomized trial to address the effect of both anticoagulation regimes on safety, subjective comfort and CD34 (+) collection efficiency in 90 adult patients undergoing standardized LVL. Anticoagulation consisted of either citrate (group C) or a combination of heparin and low-dose citrate (group H). RESULTS The overall incidence of adverse reactions (AR) during LVL was 17%. AR consisted only of citrate-related AR; no bleeding complications were observed. Determination of parameters of the acid-base balance revealed a higher frequency of metabolic alkalosis in group C. Analysis of serum SDF-1alpha revealed no differences in SDF-1alpha plasma levels. There were no differences in the CD34 (+) cell collection efficiency, resulting in the harvest of equal CD34 (+) cell yields independent of the anticoagulation used. CONCLUSIONS Our data show no clinical relevant effect of a heparin containing anticoagulation in terms of an increased overall CD34 (+) cell collection during LVL, although this regime shows some benefits in terms of the incidence and subjective tolerance towards AR. Based on our results the decision between a citrate- and heparin-substituted anticoagulation for LVL should be driven by patient-related factors, and should concern potential contraindications of both methods.
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Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study
Vellenga, E., van Agthoven, M., Croockewit, A. J., Verdonck, L. F., Wijermans, P. J., van Oers, M. H., Volkers, C. P., van Imhoff, G. W., Kingma, T., Uyl-de Groot, C. A., et al
British Journal of Haematology. 2001;114(2):319-26
Abstract
The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT). Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n = 166; Hodgkin's disease n = 38) were, after induction treatment with the DHAP-VIM (cisplatin, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate) regimen, randomly (2:1) assigned to the harvest of granulocyte-macrophage colony-stimulating factor-mobilized stem cells after the second DHAP course or autologous bone marrow cells before the second DHAP course. These stem cells were reinfused following high-dose myeloblative chemotherapy. After induction, 118 patients obtained a partial or complete response and were eligible for randomization. In the PSCT arm (n = 76) significantly faster engraftment of neutrophils [> or = 0.1 and > or = 0.5 x 10(9)/l: 10.7 d (7-36, median, range), 15 (9-45) versus 13 (8-25) and 26 (14-80), P < 0.01] and thrombocytes [> or = 20 x 10(9)/l: 13 d (7-51) versus 18 (11-65), P < 0.01] were observed. In addition, significantly fewer transfusions of red blood cells [6 (0-23) versus 8 (2-24), P < 0.01] and platelets [4 (0-60) versus 8 (2-55), P = 0.01] were required in the PSCT arm. These findings were associated with a significant reduction in the median days of intravenous antibiotics in patients with fever [8.5 (0-30) versus 14 (0-34), P = 0.04] and hospital stay [27 (8-51) versus 34 (24-78), P < 0.05]. Quality of life demonstrated a significant difference in favour of the PSCT arm. Total transplantation costs were significantly lower in the PSCT arm [$13,954 ($4913- 29,532) versus $17 668 ($10,170-44,083) P < 0.05], as a result of the reduced hospital stay and lower antibiotic costs. In summary, these results indicate that PSCT is superior to ABMT with regard to engraftment, supportive care, quality of life and cost.