Post-Transplantation Sinusoidal Obstruction Syndrome in Adult Patients with B Cell Acute Lymphoblastic Leukemia Treated with Pretransplantation Inotuzumab.

Autor: Agrawal V; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Pourhassan H; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Tsai NC; Department of Computational and Quantitative Medicine, Beckman Research Institute at City of Hope, Duarte, California., Ngo D; Department of Pharmacy, City of Hope Comprehensive Cancer Center, Duarte, California., Koller P; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Malki MMA; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Salhotra A; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Ali H; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Aribi A; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Sandhu KS; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Arslan S; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Ball B; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Otoukesh S; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Amanam I; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Artz A; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Singh D; Department of Gastroenterology, City of Hope Comprehensive Cancer Center, Duarte, California., Becker PS; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Stewart FM; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Smith EP; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Curtin P; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Stein AS; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Marcucci G; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Forman SJ; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Nakamura R; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Pullarkat V; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California., Aldoss I; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, California. Electronic address: ialdoss@coh.org.
Jazyk: angličtina
Zdroj: Transplantation and cellular therapy [Transplant Cell Ther] 2023 May; Vol. 29 (5), pp. 314-320. Date of Electronic Publication: 2023 Jan 19.
DOI: 10.1016/j.jtct.2023.01.017
Abstrakt: Sinusoidal obstruction syndrome (SOS) is a potentially life-threatening complication that can be observed after allogeneic hematopoietic cell transplantation (HCT). Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody-drug conjugate that has demonstrated high efficacy in relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) but is associated with an increased risk of SOS in HCT recipients. Here we aimed to examine the incidence and outcomes of SOS in 47 adult patients with R/R ALL who received inotuzumab therapy and subsequently underwent HCT at our institution. All patients received prophylactic therapy with ursodiol, and continuous low-dose heparin also was administered to patients receiving myeloablative conditioning (MAC). SOS occurred in 12 patients (26%) post-HCT, at a median onset of 11 days (range, 3 to 41 days). SOS was graded as very severe in 50% (n = 6), severe in 25% (n = 3), and mild in 25% (n = 3). All patients diagnosed with SOS received treatment with defibrotide for a median of 21 days (range, 3 to 34 days), with resolution of SOS occurring in 8 patients (67%). Mortality from SOS was 33% (n = 4) and occurred at a median of 10 days from diagnosis (range, 3 to 31 days) in patients graded as very severe (n = 3) or severe (n = 1). There were no significant differences between patients who developed SOS and those who did not develop SOS in the median time from the last dose of inotuzumab to transplantation (46 days versus 53 days; P = .37), use of an MAC regimen (42% versus 49%; P = .75), number of lines of therapy prior to inotuzumab (P = .79), median number of administered cycles of inotuzumab (2 versus 2; P = .14), or receipt of inotuzumab as the last therapy prior to HCT (67% versus 66%; P = 1.0). Sirolimus-based graft-versus-host disease (GVHD) prophylaxis was used more frequently in the SOS group (75% versus 29%; P < .01), but there was no between-group difference in the peak sirolimus level (P = .81) or the median time to peak sirolimus level (7 days versus 3.5 days; P = .39). In univariable analysis, only the use of sirolimus-based GVHD prophylaxis was significantly associated with an increased risk of SOS (hazard ratio [HR], 7.50; 95% confidence interval [CI], 1.7 to 33.6; P < .01). In the SOS group, the 100-day mortality rate was 33% (n = 4), and median overall survival (OS) post-HCT was 4.3 months (range, 0.2 to 57.2 months). In the group without SOS, the 100-day mortality rate was 14% (n = 5) and the median OS post-HCT was 10.7 months (range, .52 to 39.6 months). In this study cohort, SOS was prevalent in HCT recipients who had been treated with inotuzumab prior to transplantation, and sirolimus-based GVHD prophylaxis was a risk factor for SOS in inotuzumab recipients.
(Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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