Factors Associated With Successful Discontinuation of Immune Suppression After Allogeneic Hematopoietic Cell Transplantation

Abstract

<h3>Importance</h3> Immune suppression discontinuation is routinely attempted after allogeneic hematopoietic cell transplantation (HCT) and under current practices may lead to graft-vs-host disease (GVHD)–associated morbidity and death. However, the likelihood and predictive factors associated with successful immune suppression discontinuation after HCT are poorly understood. <h3>Objectives</h3> To examine factors associated with successful immune suppression discontinuation and risk for immune suppression discontinuation failure under conventional HCT approaches and develop a practical tool to estimate successful immune suppression discontinuation likelihood at the clinical point of care. <h3>Design, Setting, and Participants</h3> Using long-term follow-up data from 2 national Blood and Marrow Transplant Clinical Trial Network studies (N = 827), a multistate model was developed to investigate the probability and variables associated with immune suppression discontinuation success. The study began in July 2015, and analyses were completed in August 2019. <h3>Main Outcomes and Measures</h3> Immune suppression discontinuation and immune suppression discontinuation failure. <h3>Results</h3> Of the 827 patients included in the analysis, 456 were men (55.1%). Median age at transplant was 44 (range, &lt;1-67) years. With median follow-up of 72 (range, 11-124) months, 20.0% of the patients were alive and not receiving immune suppression at 5 years. Older recipient age (adjusted odds ratio [aOR] of &gt;50 vs &lt;30 years, 0.27, 99% CI, 0.14-0.50;<i>P</i> &lt; .001), mismatched unrelated donor (aOR, mismatched unrelated vs matched related, 0.37; 99% CI, 0.14-0.97;<i>P</i> = .008), peripheral blood graft (aOR of peripheral blood graft vs bone marrow, 0.46; 99% CI, 0.26-0.82;<i>P</i> &lt; .001), and advanced stage disease (aOR of advanced vs early disease, 0.45; 99% CI, 0.23-0.86,<i>P</i> = 0.002), were significantly associated with decreased odds of immune suppression discontinuation. Failed attempts at immune suppression discontinuation (127 patients [37.1% of total immune suppression discontinuation events]) resulting in GVHD were significantly associated with use of peripheral blood stem cells (HR, 2.62; 99% CI, 1.30-5.29;<i>P</i> &lt; .001), prior GVHD, and earlier immune suppression discontinuation attempts. Earlier immune suppression discontinuation was not associated with protection from cancer relapse after HCT (adjusted hazard ratio for discontinuation vs not, 1.95; 99% CI, 0.88-4.31;<i>P</i> = .03).Dynamic prediction models were developed to provide future immune suppression discontinuation probability according to individual patient characteristics. <h3>Conclusions and Relevance</h3> Successful immune suppression discontinuation is uncommon in the setting of peripheral blood stem cell grafts. The data suggest earlier attempts at ISD conferred no long-term benefit, given frequent ISD failure, limited subsequent success after initial failed ISD attempt, and no evidence of relapse reduction. Using a risk model–based clinical application, physicians may be able to identify individual patients’ probability of successful immune suppression discontinuation.