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