Chimerism Analyses in Stem Cell Recipients with Non Hodgkin Lymphoma
Authors: Iwanski Gabriela Bernadeta , Ocheni Sunday , Hartwig Maite , Fehse Boris , Zabelina Tatjana , Muth Alexander , Zeschke Silke , Lehmann Friederike , Zander Axel R. , Kroeger Nicolaus , Bacher Ulrike 
Published: April 2020

Abstract
Increasing numbers of patients with Non Hodgkin Lymphoma receive allogeneic stem cell transplantation (SCT) due to progressive disease or relapse after standard therapy protocols or after autologous stem cell transplantation. However, depending on the entity, variable proportions of lymphoma patients develop relapse after SCT. For the earliest detection of relapse with respect to immunotherapeutic approaches, monitoring of chimerism provides an option, but most studies were performed in patients with acute leukemias. This retrospective single-center analysis evaluated the performance of chimerism as assessed either by restriction length fragment polymorphisms (RFLP) or by quantitiative real-time PCR for nine different genetic polymorphisms (Alizadeh et al., 2001) and for Y-specific sequences (Fehse et al., 2001) in thirteen patients with mantle cell lymphoma after SCT. Allo-SCT was performed from related and unrelated donors (Jan 2000–Dec 2006) at the Interdisciplinary Clinic for Stem Cell Transplantation of the University of Hamburg, Germany. Thirteen patients received fourteen allo-SCTs (in one case due to relapse after allogeneic SCT being followed by a second SCT from a second donor). One patient received a stem cell boost after graft failure following SCT. There were eleven males and two females (median age: 52 years; range: 36–62 years). Four patients had Ann-Arbor Stage IIIA, eight had stage IVA–B (in one case the previous stage was unknown). Before allo-SCT, three cases were in complete remission, six in partial remission, two had progressive disease, and one case showed stable disease (data missing in one case). Four allo-SCTs were from related donors, nine from unrelated donors. Donors and recipients showed HLA-match in eleven transplantations and mismatch in two SCTs. At the time of this report, six patients were alive and in complete remission (6/13; 46%), four died due to transplant related mortality (TRM) (31%), and three due to relapse/progression of the lymphoma (23%). Median overall survival (OS) was 460 days (range 53–1380 days); median disease free survival (DFS) was 210 days (range: 49–1380 days). After SCT, all thirteen stem cell recipients achieved complete donor chimerism (being defined by &gt;99.9% of donor cells). In eleven cases chimerism was stable, in seven cases in association to stable long-time remissions with a median of 145 days (range 36–1380 days). Five patients developed relapse with a median interval of 132 days after SCT (range 49–924 days), and one further patient achieved partial remission only. Four relapse cases maintained complete donor chimerism; only one of the five relapse patients had a significant decrease of donor chimerism on day +38 from 100% to 70%, while relapse was diagnosed on day +49. The patient with partial remission had complete loss of donor chimerism on day +171. This study points to the conclusion that measurement of chimerism as single diagnostic method in patients with NHL who undergo allogeneic SCT might not be as effective for early detection of relapse when compared to other hematological malignancies such as acute leukemias. Although the limited sample size of this study has to be considered, it should be investigated whether the combination of chimerism analyses with minimal residual disease detection as the specific reciprocal rearrangements e.g. BCL1-IgH in MCL might improve the early detection of relapse after SCT.