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Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2019 08;25(8):1689-1694

Date

04/10/2019

Pubmed ID

30965140

DOI

10.1016/j.bbmt.2019.04.003

Scopus ID

2-s2.0-85065022222   18 Citations

Abstract

Corticosteroid-refractory graft-versus-host disease (SR-GVHD) remains a significant source of morbidity after allogeneic hematopoietic cell transplantation. No standard therapy exists in this setting; however, recent studies have demonstrated a very promising role for ruxolitinib, an oral Janus kinase 1/2 inhibitor. With increasing evidence of efficacy for SR-GVHD, limited data exist describing complications of ruxolitinib use, specifically infectious complications during use in SR-GVHD. In this study we report outcomes and infectious complications at our institution with ruxolitinib use. Overall, 43 patients were treated with ruxolitinib for SR-GVHD, 19 for acute SR-GVHD and 24 for chronic SR-GVHD. With respect to acute SR-GVHD, 15 patients had grade III acute GVHD and 4 patients had grade IV acute GVHD. At 28 days, a response rate of 84% was detected. With respect to chronic SR-GVHD, 16 patients had moderate refractory disease and 8 had severe refractory disease. At around 28 days, a 63% response rate was detected. Overall, 42% of patients (n = 18) treated with ruxolitinib had a documented infectious event. Infectious events were significantly more common among patients treated for acute SR-GVHD (P < .005). Among patients treated for acute SR-GVHD, both viral (n = 11) and bacterial (n = 10) events were frequently encountered. Cytomegalovirus reactivation was detected in 4 patients without organ involvement in any patient. Bacteremia was the most common bacterial event (n = 8), and 2 patients died after development of bacteremia. Only 5 of 24 patients treated with ruxolitinib for chronic SR-GVHD developed infectious complications after initiation of therapy. Nearly an even number of viral (n = 3) and bacterial (n = 4) were detected. This study supports the use of ruxolitinib in SR-GVHD, with impressive responses observed in both acute and chronic SR-GVHD. Infectious complications were particularly frequent among patients treated for acute SR-GVHD, and nearly all these patients were concurrently on high-dose steroids while on ruxolitinib. This study suggests careful monitoring for viral reactivation is required for patients initiated on ruxolitinib, supports the role of continuing prophylactic antimicrobial measures in ruxolitinib-treated GVHD patients, and raises the question of whether bacterial prophylaxis should be considered among patients initiated on ruxolitinib for acute SR-GVHD, particularly while on high-dose steroids.

Author List

Abedin S, McKenna E, Chhabra S, Pasquini M, Shah NN, Jerkins J, Baim A, Runaas L, Longo W, Drobyski W, Hari PN, Hamadani M

Authors

Sameem Abedin MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Saurabh Chhabra MD Associate Professor in the Medicine department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
James H. Jerkins MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
Lyndsey Runaas MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Disease
Adrenal Cortex Hormones
Aged
Allografts
Bacteremia
Chronic Disease
Cytomegalovirus
Cytomegalovirus Infections
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Middle Aged
Pyrazoles
Retrospective Studies
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a