Factors Affecting Early Immune Recovery after Autologous Transplantation and Its Clinical Significance - a Prospective Analysis of Patients with Non-Hodgkin Lymphoma
Authors: Valtola Jaakko , Varmavuo Ville , Ropponen Antti , Selander Tuomas , Kuitunen Hanne , Keskinen Leena , Vasala Kaija , Nousiainen Tapio , Mäntymaa Pentti , Pelkonen Jukka , Jantunen Esa 
Published: October 2019

Abstract
Introduction
Early immune recovery after autologous transplantation has in various studies been reported to be of clinical significance in non-Hodgkin lymphoma (NHL) patients. Especially the recovering of lymphocytes 15 days post-transplant (ALC-15) has previously been reported to predict outcome and disease-free survival. However, these results have not been detected in all studies. There is currently limited data available on the factors affecting the course and speed of the early immune recovery. Further, most of these results are somewhat controversial and usually from retrospective studies.
Patients and methods
Seventy-two patients with NHL were included into this prospective study. There were 35 males and 37 females with a median age of 62 years. The most common histology was diffuse large B-cell lymphoma (DLBCL) (44%) and 79% of the patients were in first complete or partial remission at the time of the auto-SCT. Patients with either the histology of DLBCL, T cell lymphoma or one patient with Burkitts (transformation from follicular lymphoma) were considered having aggressive lymphoma histology. All patients were mobilized with chemotherapy plus G-CSF. In addition, plerixafor was given for 24 poorly mobilizing patients. Cryopreserved graft samples from each collection were analyzed with flow cytometry for CD34+ cells, T and B lymphocytes and NK cells. Complete blood counts were evaluated at +15 days and 1 month post-transplant and a flow cytometry of lymphocyte subsets (T, NK, B) was performed one month after the graft infusion. Associations of various factors (age, gender, histology, disease status, use of plerixafor or rituximab, graft CD34+ counts and lymphocyte subsets) to various cut-off levels of ALC15, ALC30 and lymphocyte subsets at 1 month post-transplant were evaluated. Uni- and multivariate as well as survival analysis was performed.
Results
In multivariate analysis, ALC-15³ 0.5 x 109/L was found to associate with the higher number of CD34+ (p = 0.015) and primitive CD34+ CD133- CD38- cells (p = 0.005) in the infused grafts as well as the use of plerixafor (p = 0.004). Diagnosis of mantle cell or follicular lymphoma was associated with decreased probability of ALC-15³ 0.5 x 109/L. In the whole patient cohort the mean PFS of patients with of ALC-15³ 0.5 x 109/L was 897 days compared to. 606 days in patients with ALC-15 < 0.5 x 109/L (p = 0.252) and the mean OS was 957 days vs. 618 days (p = 0.021), respectively. In patients with aggressive histology, the mean PFS was 915 days in patients with ALC-15 ³ 0.5 x 109/L vs. 404 days in patients with ALC-15 < 0.5 x 109/L (p = 0.030), the mean OS was 987 days vs. 427 days (p = 0.002), respectively
Conclusions
Our prospective results verify the importance of early immune recovery in respect to outcome in transplanted NHL patients. Therefore the evaluation of the early immune recovery seems to be of clinical significance and also an easy and affordable method for individual disease-related risk analysis. Patients with aggressive histology and slow immune recovery may need additional post-transplant treatment to prevent relapse or disease progression.
Figure 1. Figure 1. Figure 2. Figure 2.

Disclosures
Valtola: Sanofi: Honoraria. Varmavuo:Roche: Consultancy; Celgene: Consultancy. Keskinen:TEVA: Consultancy. Jantunen:Sanofi: Honoraria; Genzyme: Honoraria; Genzyme: Consultancy.