High Incidence of Transient Monoclonal Gammopathies after Allogeneic Hematopoietic Stem Cell Transplantation in Non-Myeloma Patients
Authors: Widmer Corinne C , Schanz Urs , Theocharides Alexandre PA 
Published: October 2019

Abstract
Background
The clinical and biological relevance of a monoclonal gammopathy (MG) that newly arises after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in non-myeloma patients is unknown. In healthy subjects, the incidence of monoclonal gammopathy of undetermined significance (MGUS) ranges from 3-9% and significantly increases with age. In these individuals, the absolute risk of progression to plasma cell myeloma at 20 years is 5-58%, depending on the MGUS subtype. The aim of this study was to investigate the incidence, the course and the clinical relevance of post-allo-HSCT MG.
Methods
We retrospectively analyzed a cohort of 403 non-myeloma patients (median age: 48y, range: 18-69y, 57% men, 43% women) who underwent allo-HSCT at the Division of Hematology of the University Hospital Zurich between January 2004 and December 2014. In these patients, a serum electrophoresis and an immunofixation was performed every 3-6 months post allo-HSCT. Patients with a MGUS before allo-HSCT were excluded from the study. The immunoglobulin subtype and the light chain restriction of the MG were determined by immunofixation. The most frequent indications for allo-HSCT were acute leukemia (AL, n=305), chronic myeloid leukemia (CML, n=30), myelodysplastic syndrome (MDS, n=24), and myeloproliferative neoplasm (MPN, n=20).
Results
The incidence of a MG after allo-HSCT (56/403 patients, 14%) was higher than the reported incidence of MGUS in age-matched healthy subjects (estimated prevalence of MGUS in 50y old men: 3.2%) and in contrast to healthy subjects did not correlate with age. The majority of patients carried a IgG paraprotein (80%), while IgM paraproteins were detected in 12.5% of patients. Rarely, two types of paraproteins were identified simultaneously in the same patient. In most patients (44/56, 79%), the MG appeared within the first year after allo-HSCT and was transient with a median duration of 5.8 months (range 2.5 - 43.9 months). However, in 7/56 (13%) patients, the MG persisted until the end of the observation period (median duration 33 months, range 12-45.6 months). Only one patient showed a very late (7y post allo-HSCT) but also transient appearance of a MG. Development of plasma cell myeloma was not observed in patients with post allo-HSCT MG. Conditioning regimen, GvHD, immunoglobulin treatment and cessation of immunosuppressive therapy did not predict the appearance of post allo-HSCT MG.
Conclusions
Our study reveals a high incidence of a transient MG after allo-HSCT that is not related to age of the recipient and follows the expected immunoglobulin subtype distribution. Importantly, patients with post allo-HSCT were not at increased risk of developing plasma cell myeloma as observed for MGUS in otherwise healthy subjects inferring a distinct pathogenetic mechanism. The transient nature of MG early after allo-HSCT suggests an association with the immune reconstitution process and future studies will determine whether expansion of a specific plasma cell clone can occur during engraftment of donor-derived hematopoiesis.

Disclosures
Theocharides: Novartis: Consultancy, Honoraria.