CD4 lymphopenia to identify end-of-life metastatic cancer patients

https://doi.org/10.1016/j.ejca.2012.11.003Get rights and content

Abstract

Background

Cancer patients with CD4 lymphopenia have an increased risk of severe toxicity after administration of cytotoxic chemotherapy. The impact of CD4 lymphopenia on long term overall survival (OS) of cancer patients was explored in this work.

Patients and methods

The first prospective series (test series) included 219 patients with solid tumours, lymphomas or myelomas receiving chemotherapy within an oncology department in 1999 and 2000. A phenotypic analysis of lymphocyte subsets by flow cytometry was performed before chemotherapy on day 1. The prognostic value of total, CD4, CD8 and CD56 lymphocyte count for OS was tested in a multivariate analysis. The prognostic value of low CD4 counts was then tested in a validation series of 269 patients with metastatic solid tumours in second line treatment included in a prospective observational study in the Centre Leon Berard.

Results

In the test series, all patients with metastatic cancers and CD4 lymphopenia ⩽200/μL (12% of metastatic patients) died within 18 months with a median OS of 5.9 months. CD4 count was an independent prognostic factor for OS and PFS in multivariate analysis. In the validation series, 83 (30%) of patients had CD4 count ⩽200/μL: their median overall survival was 3.9 months with an 18-month survival rate of 6%. CD4 count was also an independent prognostic factor for overall survival in this series.

Conclusions

CD4 lymphopenia <200/μL is frequent in advanced cancer patients and associated with a very short life expectancy. These patients should be proposed for specific treatment and research approaches.

Introduction

Lymphopenia is frequently observed in patients with advanced cancers, and may result from chemotherapy, host characteristics such as age, tumour stage and tumour biology 1, 2, 3, 4. Lymphopenia has been studied as a prognostic factor for a variety of patient populations 5, 6 including patients with cancer 7, 8, 9, 10, 11, 12, 13. Lymphopenia before and during the administration of chemotherapy is a powerful predictor of chemotherapy-induced toxicity 8, 14, 15, 16, 17, 18, 19, 20, 21, 22, early death 8, 18, 23 and overall survival 7, 8, 9, 10, 11, 12, 13. In selected lymphopenic patients, preventive measures using granulocyte and erythrocyte growth factors reduced the incidence of febrile neutropenia and red blood cell transfusion respectively, but failed to improve survival in two randomised trials 21, 22.

The lymphopenia of cancer patients is observed for most lymphocyte subsets, including CD4, CD8, CD56 and CD19+ lymphocytes 18, 24, 25. Low CD4 count was found to be an independent risk factor for early death (<30 days) and febrile neutropenia [18]. However, it remains unclear whether lymphopenia on specific lymphocyte subsets influences long term outcome, in particular progression free survival (PFS) or overall survival (OS), in patients with solid tumours and lymphomas.

To explore this question, the prognostic value of CD4 lymphocyte counts for long term PFS and OS was investigated on a prospective cohort of 219 patients treated in 1999–2000 with a minimum 10 years of follow up, and validated on a prospective validation study of 269 patients.

Section snippets

Test series

This series has been previously described [18]. This is the prospectively collected cohort of all patients treated by chemotherapy within a single oncology department in the Centre Léon Bérard (Lyon, France) between April 1999 and November 2000. Patients were proposed for the quantification of CD4, CD8, CD56 and CD19 phenotype of peripheral blood lymphocytes prior to the initiation of the new line of chemotherapy. The study was performed in agreement with the French laws at that time. All

Results

Table 1 describes the baseline characteristics of the patients and the incidence of lymphopenia in different subgroups of the test series. Among the 219 included patients, 85 (39%) had lymphomas, 13 (6%) had myelomas, 58 (26%) had sarcomas, 20 (9%) had breast cancers and 43 (20%) had other cancers. Most patients were analysed while naïve of treatment (n = 136, 62%). Eighty-three (38%) were in second or later line of cytotoxic treatment. Female, lymphoma and PS >1 patients had lower absolute

Discussion

The prognostic impact of low CD4 lymphocyte counts, and other subsets, on the long term survival of cancer patients had not been examined previously. In this study, we analysed the long-term outcome of lymphopenic cancer patients in two series of patients, a training set and a validation set, one with a minimum follow up of 12 years, the other with a minimum follow-up of 6 years.

These series gathered patients at different stages of their disease. CD4 lymphopenia was however observed in 17% and

Novelty and impact statement

The frequency and prognostic significance of CD4 lymphopenia in patients with advanced cancer were not known. The work presented in this report shows that CD4 lymphopenia ⩽200/μL is observed in 10% to 45% of the patients in the different subgroups and that these patients have consistently a very short life expectancy, regardless of the histological subtype. These patients could be proposed for specific treatment approaches, including innovative strategies for immune restoration.

Conflict of interest statement

None declared.

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