Early Lymphocyte Recovery Predicts Superior Disease Free Survival and Overall Survival after High Dose Chemotherapy and Autologous Stem Cell Transplantation in Non-Hodgkin Lymphoma Patients
Authors: Borelli Walter G , Otero Cristina , Landoni Ana Ines , Magariños Alicia , Zamora Mercedes , De Lisa Elena , Ferrando Martín , Rosanna De Giuda , Claudia Martínez , Prado Ana , Vazquez Alberto , Gabus Raul 
Published: October 2019

Abstract
Introduction. An early absolute lymphocyte count (ALC) recovery after high dose therapy (HDT) and autologous hematopoietic stem cell transplantation (HSCT) in non Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma and acute leukemia patients has been related with an improved outcome due to a better immune restoration. In this retrospective study we analyze a population of NHL patients to evaluate ALC recovery after autologous HSCT and its relation with post-transplant survival.
Patients and methods. Fifty-three consecutive adult NHL patients received HDT followed by autologous HSCT in a single center between 2000 and 2012. Only individuals with at least 6 months post-transplant follow up were included. All patients received the same conditioning regimen (BEAM: carmustine, etoposide, cytarabine and melphalan) followed by peripheral blood stem cells previously collected by leukapheresis. Median CD34+ cell dose was 4.13 x 106/kg (1.62 – 12.58). Patients were divided into two groups: ALC at day +15 inferior than 500/mm3 (group 1) and ALC at day +15 superior or equal than 500/mm3 (group 2). Differences between groups were analyzed using t-Student and Chi-Square tests, with statistical significance determined at p<0.05. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan Meier method. Differences in survival between the two groups were determined by log-rank test.
Results. No differences were observed between groups regarding gender, histology, disease status at transplant and cell dose. Patients into group 1 were older and more heavily pre-treated. Neutrophil and platelet engraftment were significantly faster in group 2 (Table 1). After a median follow-up of 56 months, progression-free survival (PFS) and overall survival (OS) were superior in group 2 patients. Median PFS was 47 months and not reached (p=0.013) and OS was 51 months and not reached (p=0.016) in groups 1 and 2 respectively (figures 1 and 2).
Discussion. An early ALC recovery after autologous HSCT is associated with a better PFS and OS in NHL patients. Patients with ALC major or equal than 500/mm3 had a shorter time to neutrophil and platelet recovery and a shorter stay at transplant unit. In this study, CD34+ cell dose does not appears as a determinant factor for lymphocyte recovery. The extent of pre-transplant chemotherapy may influence ALC recovery after transplant. These results confirm the association between lymphocyte recovery and outcome in NHL patients after autologous HSCT. Table 1.Patient characteristics and comparison between groups 1 and 2.Group 1Group 2pALC< 500 /mm3> 500/mm3N2528Age, median (range)57 (29 - 66)41 (15 - 65)0.008Female gender (n)1214NSHistology (n)DLBCL1316 NSFollicular lymphoma62Mantle cell lymphoma32Peripheral T cell lymphoma13Indolent lymphoma12Others13Individuals who received two or more lines of pre-transplant treatment (n)1180.01Disease status at transplant (n)Complete remission711 NSPartial remission1613Progressive disease21CD34+ cells dose, median (range) (10E6/kg)3.45 (1.62 - 9.12)4.40 (2.28 - 12.58)NSMononuclear cells dose, median (range) (10E8/kg)8,84 (3,55 - 18,74)6,7 (1,94 - 27)NSDays to achieve ANC > 500/mm3, median (range)11 (7 - 30)8 (3 - 16)0.034Days to achieve platelets > 20.000/mm3, median (range)9 (2 - 49)5 (1 - 10)0.003Length of stay in transplant unit, days, median (range)30 (20 - 59)24 (20 - 35)0.001
Figure 1. PFS and ALC on day +15. Group 1: patients with ALC < 500/mm3 (dotted line); group 2: patients with ALC > 500/mm3 (solid line). Figure 1. PFS and ALC on day +15. Group 1: patients with ALC < 500/mm3 (dotted line); group 2: patients with ALC > 500/mm3 (solid line).
Figure 2. Figure 2. OS and ALC on day +15. Group 1: patients with ALC < 500/mm3 (dotted line); group 2: patients with ALC > 500/mm3 (solid line).

Disclosures
No relevant conflicts of interest to declare.