Results of the First Clinical Study in Humans That Combines Hyperbaric Oxygen Pretreatment with Autologous Peripheral Blood Stem Cell Transplantation.

Autor: Abdelhakim H; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Shune L; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Bhatti S; Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS., Cantilena AR; University of Kansas School of Medicine, Kansas city, KS; Cardiovascular Research Institute, University of Kansas School of Medicine, Kansas City, KS., Baran A; Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY., Lin TL; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Ganguly S; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Singh AK; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Abhyankar S; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Divine C; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Lipe B; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., McGuirk J; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS., Allin D; Emergency Department, University of Kansas Medical Center, Kansas City, KS., Aljitawi OS; Division of Hematologic Malignancies and Cellular Therapy, Internal Medicine Department, University of Kansas Medical Center, Kansas city, KS; Division of Hematology and Bone Marrow Transplantation Program, University of Rochester Medical Center, Rochester, NY. Electronic address: Omar_aljitawi@urmc.rochester.edu.
Jazyk: angličtina
Zdroj: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2019 Sep; Vol. 25 (9), pp. 1713-1719. Date of Electronic Publication: 2019 Jun 03.
DOI: 10.1016/j.bbmt.2019.05.028
Abstrakt: Patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation (auto-HCT) are at risk for multiple morbidities, including mucosal inflammation and neutropenic fever, both related to neutropenia. Evidence from our preclinical work in an umbilical cord blood (UCB) transplantation murine model suggests that treatment with hyperbaric oxygen (HBO) before UCB infusion improves UCB CD34 + cell engraftment by reducing erythropoietin levels. A pilot clinical trial using HBO in patients undergoing UCB transplantation showed improvement in kinetics of blood count recovery. In this study, we evaluated HBO in combination with auto-HCT. Our primary aim was to determine the safety of HBO in this setting and secondarily to determine its efficacy in reducing time to neutrophil and platelet engraftment compared with matched historic controls. Patients with multiple myeloma, non-Hodgkin lymphoma, and Hodgkin disease eligible for auto-HCT were included. On day 0, patients received HBO treatment consisting of exposure to 2.5 atmosphere absolutes for a total of 90 minutes, in a monoplace hyperbaric chamber, breathing 100% oxygen. Six hours after the start of HBO, peripherally mobilized stem/progenitor cells were infused and patients were followed daily for toxicity and blood count recovery. All patients received daily granulocyte colony-stimulating factor starting on day +5 and until absolute neutrophil count (ANC) of ≥1500 or ANC of 500 for 3 consecutive days. A matched historic cohort of 225 patients who received auto-HCT between January 2008 and December 2012 was chosen for comparison and matched on sex, age, conditioning regimen, and disease type. We screened 26 patients for this study; 20 were treated and included in the primary analysis, and 19 completed the HBO therapy and were included in the secondary analysis. Although the median time to neutrophil count recovery was 11 days in both the HBO and control cohorts, the Kaplan-Meier estimates of the full distributions indicate that the time to neutrophil recovery was generally about 1 day sooner for HBO versus historical controls (log-rank P = .005; range, 9 to 13 for HBO patients and 7 to 18 for controls). The median time to platelet count recovery was 16 days (range, 14 to 21) for HBO versus 18 days (range, 11 to 86) for controls (log-rank P < .0001). In the secondary analysis comparing the HBO cohort who completed HBO therapy (n = 19) with our historical cohort, we evaluated neutropenic fever, growth factor use, mucositis, day +100 disease responses, and blood product use. HBO was associated with less growth factor use (median 6 days in HBO cohort versus median 8 days in controls, P < .0001). Packed RBC and platelet transfusion requirements were not statistically different between the 2 cohorts. Mucositis incidence was significantly lower in the HBO cohort (26.3% in HBO cohort versus 64.2% in controls, P = .002). HBO therapy appears to be well tolerated in the setting of high-dose therapy and auto-HCT. Prospective studies are needed to confirm potential benefits of HBO with respect to earlier blood count recovery, reduced mucositis, and growth factor use, and a cost-benefit analysis is warranted. © 2019 American Society for Blood and Marrow Transplantation.
(Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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