Monocytosis in the Peripheral Blood At First Relapse/Progression Predicts Poorer Overall and Progression-Free Survival After Autologous Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma
Authors: Toft-Petersen Marie , Kamper Peter , Albertsen Signe , Secher Louise , Segel Erik Kay , Clausen Michael , d'Amore Francesco 
Published: October 2019

Abstract
Abstract 1559

Background:
Lymphocytopenia and absolute leukocytosis are included in the seven prognostic factors of the International Prognostic Score (IPS) for advanced Hodgkin's lymphoma (HL). Recent studies suggest that a high number of tumor-associated macrophages (TAMs) in pre-therapeutic tumor biopsies correlate with poorer outcome in classical HL. TAMs are derived from circulating monocytes and are thought to play a role in the tumor microenvironment of HL by promoting tumor growth. Therefore, the aim of the present study was to investigate whether a complete blood count (CBC) and counts of white blood cell (WBC) subpopulations could predict outcome also in patients with relapsed/refractory HL. For the purpose of the present study, we limited our analysis to younger HL patients undergoing high dose therapy (HDT) followed by autologous hempoietic stem cell transplantation (ASCT) as part of their salvage treatment strategy.

Design and methods:
The data from 68 relapsed/refractory HL patients (classical HL n=63; nodular lymphocytic predominance HL n=5) diagnosed and treated at the Department of Hematology, Aarhus University Hospital, in the period 1989 to 2009 were analyzed. The cohort had a median age at relapse/progression of 31 years (range 16–67 years). All patients received HDT and ASCT due to biopsy-verified relapse or primary refractory disease occurred after standard treatment regimen with adriamycin, bleomycin, vinblastin, dacarbazin. CBC and WBC differentials were performed on all patients at time of first relapse or just prior to salvage chemotherapy in cases of refractory disease. Using the log rank test and univariate analysis we studied the effect of CBC and WBC differentials on overall survival (OS) and progression-free survival (PFS). PFS was calculated from the date of autologous stem cell re-infusion to the date of relapse or death by any cause. Due to a limited number of events a backward stepwise selection model was used to select covariates for a multivariate analysis (significance level p≤0.05).

Results:
The median follow up for the entire study cohort was 5 years. Consistent with the factors of the IPS in the pre-therapeutic setting, also in relapsed/refractory HL we found that absolute leukocytosis was associated with decreased OS (50% vs. 81%; HR 3,0; p=0,048) and PFS (27% vs. 72%; HR 3,7; P=0,005), and that lymphocytopenia also correlated with poorer outcome, however limited to OS (65 vs. 85%; HR 3,8; p=0,02). Interestingly, the analysis also revealed that both neutrophil granulocytosis and monocytosis (for both parameters: > normal upper limit) were significantly associated with higher risk of relapse/progression post-transplant and consequently poorer outcome in terms of lower OS and PFS. If present, neutrophil granulocytosis was associated with a 5-yr OS of 52% as opposed to 84% in patients with normal neutrophil count (HR 2,88; p=0,04); the corresponding values for PFS were 35% and 74% (HR 3,0; p=0,014). Similarly, patients with monocytosis at relapse/progression had a 5-yr OS post-transplant of 55% as opposed to 84% for patients with a normal monocyte count (HR 3,4; p=0,018); the corresponding PFS values were 39% and 74% (HR 3,4; p=0,006). A subsequent multivariate analysis showed that only monocytosis retained an independent predictive impact on both OS (p=0.02) and PFS (p=0.04). Lymphocytopenia was co-selected as independent factor for OS alone (p=0.02) and absolute leukocytosis for PFS alone (p=0.04).

Conclusions:
The influence of monocytosis, along with lymphocytopenia and absolute leukocytosis, on post-transplant outcome in relapsed/refractory HL is a novel finding. If confirmed, it will provide a useful, cheap and readily available tool to optimize treatment strategies in this subset of HL patients.

Disclosures:
No relevant conflicts of interest to declare.