Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS

Geertiena Van Der Wal,Gustaaf W Van Imhoff,Mar Bellido,Anouschka Biswana,Laura Bungener,Laurence M C Kok,Geertruida H De Bock

doi:10.1007/s13577-019-00297-7

Geertiena Van Der Wal, Gustaaf W Van Imhoff + Show 5 more

Open Access

https://doi.org/10.1007/s13577-019-00297-7

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Abstract

Moderate to severe chronic graft-versus-host disease (cGVHD) is associated with high morbidity, hospital dependency and poor quality of life. In this study, we analyzed a well-defined consecutive series of 98 patients with acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) who received allogeneic stem cell transplantation with non-myeloablative (NMA) conditioning to determine risk factors associated with the severity of cGVHD. cGVHD was defined according to the 2005 National Institute of Health consensus criteria. Transfusions before transplantation, presence of HLA antibodies, composition of the graft (CD3+, CD19+, CD34+ cells), sibling or matched unrelated donor, female donor to male recipient, CMV serology and the development of acute GVHD (aGVHD), were considered potential risk factors. Multivariate Cox regression analysis identified the number of CD19+ 106/kg (HR 2.79; 95% CI 1.35–5.74), CD3+ 106/kg (HR 2.18; 95% CI 1.04–4.59) infused cells and the presence of patient HLA antibodies before transplantation (HR 2.34; CI 1.11–4.95) as significant risk factors for the development of moderate to severe cGVHD. In summary, we identified in a small, but well-defined cohort, 3 risk factors associated with the severity of cGVHD that should be validated in a larger multi-center study.

Highlights

AlloSCT is a standard treatment for patients with AML/ MDS with high risk of relapse [1,2,3]
The factors related with a high percentage of relapses in the group with no-GVHD may be related to early immunological factors which avoid tolerance and recognize residual leukemic cells avoiding relapses in patients who develop moderate to severe cGVHD [18]. In this well-defined unselected series of patients diagnosed with AML and/or MDS who consecutively received a peripheral blood T-cell repleted NMA AlloSCT, moderate or severe chronic graft-versus-host disease was associated with high morbidity, hospital dependency and poor quality of life as compared to mild cGVHD [6, 7]
The goal of this study was to identify risk factors associated with severity, i.e., with the development of moderate to severe cGVHD in this population

Summary

Introduction

AlloSCT is a standard treatment for patients with AML/ MDS with high risk of relapse [1,2,3]. Moderate to severe cGVHD is associated with high morbidity, hospital dependency and poor quality of life as compared to mild cGVHD [6, 7]. Patients who develop moderate to severe cGVHD are treated with high-dose systemic steroids for months and often years, whereas mild cGVHD can be treated with topical steroids [8, 9]. Long-term steroid treatment impairs immune function and can, increase the risk of opportunistic infections. Other steroid therapy-related complications include osteoporosis, avascular necrosis, glucose intolerance, cataract, muscle atrophy, hypertension, and disturbance of mood and sleep [10]

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