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Prognostic value of lymphopenia in early breast cancer: learnings from the prospective CANTO cohort.

BACKGROUND: Lymphopenia has been associated with poor outcomes in metastatic breast cancer (BC), but its prognostic relevance in early-stage disease remains unclear. This study aimed to evaluate the prognostic value of baseline lymphopenia in patients with non-metastatic BC using data from the prospective French CANTO cohort (NCT01993498). METHODS: 10,854 patients with baseline absolute lymphocyte count (ALC) were analysed. Lymphopenia was defined as ALC&#x2009;<&#x2009;1.0&#x2009;&#xd7;&#x2009;10&#x2079; cells/L, measured before any cancer treatment. Relapse-free survival (RFS), overall survival (OS), and treatment-related toxicities were assessed using Kaplan-Meier estimates, piecewise-Cox regression models, and cause-specific hazard analyses considering pre-specified time periods. RESULTS: Baseline lymphopenia was observed in 342 patients (3.1%). It was associated with ECOG performance status&#x2009;>&#x2009;0, hypoalbuminemia, and prior neoplasia. Lymphopenia correlated with inferior 5-year RFS (89.1% vs. 92.9%) and OS (92.5% vs. 96.4%). In multivariable analyses, lymphopenia was associated with increased risk of early relapse during the first 24 months (HR&#x2009;=&#x2009;2.11; 95%CI: 1.28-3.48; p&#x2009;=&#x2009;0.003), but not beyond, and no independent prognostic impact on OS was observed. No significant differences were found in surgical complications or chemotherapy dose intensity, though granulocyte colony-stimulating factor use was higher among lymphopenic patients. CONCLUSION: Baseline lymphopenia is uncommon in early BC but may serve as a marker of early relapse risk. Although it does not independently predict long-term survival, its presence could reflect underlying tumour aggressiveness or patient frailty. These findings support further investigation of lymphocyte subpopulations to refine prognostic stratification in early BC. TRIAL REGISTRATION: Approved by French ethics committee in 2011 (ID-RCB:2011-A01095- 36,11-039 /NCT01993498 [20FEB2012]).

Adult

Lymphopenia in systemic lupus erythematosus. Clinical, diagnostic, and prognostic significance.

One hundred fifty-eight patients with active, untreated systemic lupus erythematosus (SLE) were studied from the time of diagnosis. Lymphopenia was present in 75%, and another 18% of those patients developed lymphopenia subsequent to disease reactivation. Lymphopenia of less than 1500 cells/microliter occurred more frequently than any of the preliminary criteria for the classification of SLE, and it was the most prevalent initial laboratory abnormality. Lymphocyte counts were significantly lower in lupus than in the other connective tissue diseases except mixed connective tissue disease and polymyositis.

Adolescent

Lymphopenia and lymphocyte transformation in alcoholics.

The basis of peripheral blood lymphopenia observed in patients with chronic alcoholism and liver disease was investigated by examining the effect of sera of these patients on in vitro transformation of normal human peripheral blood lymphocytes. A positive correlation was demonstrated between the serum inhibition of phytohaemagglutinin- and pokeweed mitogen-induced transformation and the degree of lymphopenia. Thus serum factors may contribute to the observed lymphopenia by inhibiting lymphocyte production in vivo.

Alcoholism

Prognostic significance of lymphopenia in sarcoidosis.

During 1959--67, sarcoidosis were diagnosed in a series of 140 patients. All were followed up and 22 developed chronic sarcoidosis. In 134 patients (20 with chronic course) the initial granulocyte, monocyte and lymphocyte counts were known. No differences in granulocyte values were seen between different groups of sarcoidosis patients. Patients with erythema nodosum had significantly increased monocyte levels. Lymphopenia below 1 000/microliter was seen in only 7.5% of the patients. Lymphocyte counts below 1 500 microliter were a common finding, especially in patients developing chronic sarcoidosis. Significantly decreased lymphocyte values were also seen in patients older than 40 years at the time of diagnosis, in patients negative to 10 TU of PPD and in those with a disease requiring treatment with corticosteroids. A correlation was found between initial lymphopenia and less favourable prognosis, 85% of the patients having a very good prognosis. Patients with initial lymphopenia must be carefully followed up. The initial presence of erythema nodosum does not always guarantee a good prognosis.

Adult

Lymphopenia caused by cranial irradiation in children receiving craniospinal radiotherapy.

The peripheral blood changes were studied in 67 children who received craniospinal irradiation for posterior fossa tumors. At the completion of a cranial dose of about 3500 rad to the whole brain port, the lymphocytes were reduced to 858/mm3 rom 3084/mm3 preoperatively. The counts of the remaining leukocytes stayed at a level somewhat higher than preoperatively; the eosinophils rose to 288/mm3 from 125/mm3. With the initiation of the spinal field irradiation, which included a large proportion of the total bone marrow, the numbers of all the leukocytes decreased rapidly; the observed leukopenia was mainly secondary to neutropenia. A mechanism that was operating to restore the number of leukocytes became manifest immediately after the completion of radiotherapy, though the number of lymphocytes had not been totally restored to the preoperative level 6 years later. Irradiation of the lymphocytes that circulate through the vascular bed can explain the lymphopenia observed during cranial radiotherapy. Mild leukopenia observed in patients receiving radiotherapy through a relatively small port may be secondary to lymphopenia, and this does not necessarily indicate impaired bone marrow reserves.

Adolescent

Prognostic significance of lymphopenia in pulmonary sarcoidosis.

Since BOTTGER (1966, 1969) AND HOFFBRAND (1968) had described the absolute lymphopenia in pulmonary sarcoidosis as a sign of immune deficiency there were several authors who tried to elucidate different problems of sarcoidosis (RACOVEANU et al. 1970, STOJAN et al. 1971, OSODA et al. 1972). One of these problems is the effort to correlate absolute lymphopenia to prognostic parameters. Three controlled therapeutic trials were performed and compared: 59 cases with clinically and histologically proven sarcoidosis with spontaneous regression and 180 cases with different regimens of prednisolone: --a steady increase of the absolute number of lymphocytes in cases without and with treatment is a prognostically good sign, --no increase or even decrease is a poor sign, -- a very low and unchanged number is worst. This seems to confirm--among other things--that course and prognosis of sarcoidosis really may not be affected by time-limited corticotherapy.

Humans

Lymphopenia in acute nitrofurantoin pleuropulmonary reactions.

Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.

Adult

Analysis of treatment in childhood leukaemia. III. Independence of lymphopenia induced by irradiation and by chemotherapy.

Lymphopenia induced by treatment for acute lymphoblastic leukaemia is analysed and discussed in relation to the type and incidence of infection occurring in those patients during complete remission. Blood lymphocytes can be placed into three largely independent groups: (1) those lymphocytes susceptible to long-term depletion following irradiation; (2) those lost from the blood during and for a short period after maintenance chemotherapy with methotrexate and 6-mercaptopurine; and (3) the remainder which are not depleted by irradiation or maintenance chemotherapy. The number of cells in each compartment varies from child to child and probably with age but on average is about 1.2 x 10(9)/1. for group 1, 0.7 x 10(9)/1. for group 2 and 0.4 x 10(9)/1. for group 3. Conventional lymphocyte typing crosses these barriers in that: Group 1 consists mainly of E-rosetting cells and cells which show a mitotic response to phytohaemagglutinin; Group 2 also contains E-rosetting cells but contains a major proportion of blood lymphocytes with surface immunoglobulin and essentially all antibody dependent cytotoxic lymphocyte (K-cell) activity; Group 3 comprises E-rosetting cells and a few immunoglobulin-staining cells.

Antimetabolites, Antineoplastic

[Lymphopenia and variations in T and B lymphocytes appearing immediately after irradiation (author's transl)].

Immunity tests were conducted in 21 patients with cancer, before and two months after irradiation. T and B lymphocyte counts were normal before irradiation when compared to a control group. Lymphopenia was present after irradiation affecting mainly the T lymphocytes (P = 0.005), whereas changes in B lymphocytes were not significant. These results suggest that irradiation has an immunosuppressive effect which should be studied in greater detail to establish possible therapeutic applications.

Adult

Harmonic dwarfism, lymphopenia, deficit of IgA and IgE in a 6-year old boy.

A six-year old boy who had suffered from the age of two with chronic diarrhea has been found to be severely retarded in statural growth. Examinations discovered marked lymphopenia with a T lymphocyte defect accompanied by absent IgA and IgE. In contrast with other cases described in literature, in this case the immunodeficiency was not accompanied by bone or cartilage alterations. The only factor apparently responsible for his lack of growth was the malabsorption.

Child

Dependence of the postirradiation lymphopenia and hypersegmentation of neutrophil nuclei on the therapeutic irradiation exposure in patients with breast carcinoma--some ways of its use for biological detection of irradiation.

In the work, changes are presented of the numbers of lymphocytes and hypersegmented neutrophils after therapeutic irradiation of women after mastectomy. The values found were evaluated statistically by the decision method. It was found that in the course of irradiation the lymphopenia and increase in the number of neutrophils with hypersegmented cellular nuclei occurred. This contraversory course of the values showed an increasing tendency with increasing exposure. An attempt was made, whether the values found could serve for the biological detection if irradiation, when completing the response of the organism to irradiation based on changes of one parameter by a response from changes of second parameter examined. The values were used as training material for the statistical decision method. The results are represented in the from of a diagram for reading off the magnitude of the damage in practice by stimultaneous evaluation of both parameters. A further approach is shown in the biological dosimetry by simultaneous examination of several independent paramters statistically treated by a suitable method.

Breast Neoplasms

Lymphopenia and lymph node histology following repetitive extracorporeal irradiation of blood in normal and thymectomized calves.

Repetitive extracorporeal irradiation of the circulating blood (RECIB) in normal or thymectomized calves and RECIB plus Imuran were used for comparative studies on the depletion of blood and lymph node lymphocytes. Elimination of the easily mobilizable pool of lymphocytes was almost complete within approximately 6 days after commencing RECIB and was reflected by a reduction of approximately 50% in the numbers of paracortical lymphocytes. Blood lymphocyte counts were reduced to approximately 1/3 to 1/4 of the pre-irradiation values. Thymectomized calves had lower pre-irradiation blood lymphocyte counts than non-operated controls, however, the reduction in the number of blood lymphocytes was proportionally similar. Continuation of RECIB beyond one week did not result in a further depletion of blood lymphocytes. The lymphocyte counts in the follicular cortex and in the medulla of lymph nodes were not significantly changed by the various procedures. RECIB of 8-16 days duration did not alter the number of germinal centers in non-thymectomized calves, however, in thymectomized animals treated with Recib, the number of germinal centers was reduced.

Animals

Corticosteroid-induced lymphopenia, immunosuppression, and body defense.

The apparent paradox of heightened adrenal corticosteroid levels associated with reduction in the competence of the body's defensive apparatus to cope with exposure to new microbial antigens is considered. The question is asked how this lowered defensive capability, which occurs in the face of a threat to body integrity, is consistent with Cannon's principals of the "wisdom of the body." The suggestion is offered that the immunologic response to self-antigens exposed by disease or trauma may be suppressed by corticosteroid to offset the likelihood of autoimmune attack.

Adrenal Cortex Hormones