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PubMed1998

Changes in lymphocyte subsets in human immunodeficiency virus-positive persons with < 5 CD4 T lymphocytes/mm3.

All patients seen at the Royal Free Hospital, London, who had at least one CD4 T lymphocyte count of < 5 cells/mm3 (n = 166) were prospectively followed to assess changes in their total T lymphocyte and CD8 T lymphocyte counts over time. While overall there were no clear trends towards a drop or increase in either count, persons who died during the study experienced a rapid drop in both CD8 T lymphocyte and total T lymphocyte levels in the months preceding death. Multivariate Cox proportional hazards models revealed that both the total T lymphocyte count and CD8 T lymphocyte count provided important prognostic information for survival. Despite almost a complete absence of CD4 T lymphocytes, lymphocyte subset monitoring is useful in identifying decreasing CD8 T lymphocyte levels that predict short-term prognosis.

CD4-Positive T-Lymphocytes↗

PubMed2003

Lymphocyte-rich gastric cancer: associations with Epstein-Barr virus, microsatellite instability, histology, and survival.

Lymphocyte-rich gastric carcinomas may have a better prognosis than cancers without a pronounced host inflammatory response. Two subsets of gastric cancer-Epstein-Barr virus-positive and microsatellite instability high-have been associated with a lymphocyte-rich phenotype. We assessed relationships between tumor-infiltrating lymphocytes, Epstein-Barr virus status, microsatellite instability status, and cancer-specific survival in 110 resected gastric cancers. Seven patients had Epstein-Barr virus-positive cancer, including 4 (3.7%) of 107 consecutive patients. Tumors from 17 patients (16%) were designated microsatellite instability high on the basis of negative immunohistochemical staining for MLH1; all tumors had intact expression of MSH2 and MSH6. Epstein-Barr virus-positive cancers had increased tumor-infiltrating lymphocytes compared with Epstein-Barr virus-negative cancers (median 450/10 HPF versus 21/10 HPF, P <.001). Microsatellite instability-high cancers also had increased tumor-infiltrating lymphocytes compared with non-microsatellite instability-high cancers (median 150/10 HPF versus 20/HPF, P <.001). Microsatellite instability-high cancers affected older patients and were more likely to be intestinal in the Lauren classification and expanding in the Ming classification. By univariate analysis, decreased risk of death from gastric cancer was significantly associated with low tumor stage, expanding growth pattern, increasing tumor-infiltrating lymphocyte count, and microsatellite instability-high status. High tumor-infiltrating lymphocyte count and microsatellite instability-high status retained statistical significance as favorable prognostic factors after adjustment for tumor stage in multivariate analysis. Tumor-infiltrating lymphocyte count retained statistical significance as a favorable prognostic factor after adjustment for microsatellite instability-high status; but microsatellite instability-high status did not remain a significant independent prognosticator after adjustment for tumor-infiltrating lymphocyte count. The association between microsatellite instability-high cancers and high tumor-infiltrating lymphocyte counts may account for the association of microsatellite instability-high gastric cancers with improved survival.

Adenocarcinoma↗

PubMed2005

Evaluation of a new single-parameter volumetric flow cytometer (CyFlow(green)) for enumeration of absolute CD4+ T lymphocytes in human immunodeficiency virus type 1-infected Thai patients.

Use of the standard dual-platform flow cytometric method for determination of CD4(+) T-lymphocyte counts, which needs both a flow cytometer (FCM) and hematological analyzer, would inevitably lead to increased variability. The development of new single-platform (SP) FCMs that provide direct CD4(+) T-lymphocyte counts for improved assay precision and accuracy have recently attracted attention. This study evaluated one of those systems, CyFlow(green) (Partec), a single-parameter SP volumetric FCM. The performance of CyFlow(green) was compared with those of two reference standard SP microbead-based technologies of the three-color TruCOUNT tube with the FACScan FCM and a two-color FACSCount system (Becton Dickinson Biosciences). Absolute CD4(+) and CD8(+) T-lymphocyte counts in 200 human immunodeficiency virus type 1-seropositive blood specimens were determined. Statistical analysis for correlation and agreement were performed. A high correlation of absolute CD4 counts was shown when those obtained with CyFlow(green) were compared with those obtained with the bead-based three-color TruCOUNT system (R(2)=0.96; mean bias, -69.1 cells/microl; 95% confidence interval [CI], -225.7 to+87.5 cells/microl) and the FACSCount system (R(2)=0.97; mean bias, -40.0 cells/microl; 95% CI, -165.1 to+85.1 cells/microl). The correlation of the CD4(+) T-lymphocyte counts obtained by the two bead-based systems was high (R(2)=0.98). Interestingly, CyFlow(green) yielded CD4(+) T-lymphocyte counts that were 21.8 and 7.2 cells/microl lower than those obtained with the TruCOUNT and the FACSCount systems, respectively, when CD4(+) T-lymphocyte counts were <250 CD4(+) T-lymphocyte counts/microl range or 17.3 and 5.8 cells/microl less, respectively, when CD4(+) T-lymphocyte counts were <200 cells/microl. The single-parameter CyFlow(green) volumetric technology performed well in comparison with the performance of the standard SP bead-based FCM system. However, a multicenter comparative study is needed before this FCM machine is implemented in resource-limited settings.

Adult↗

PubMed1985

Lymphocyte fluctuation in bronchoalveolar lavage fluid in normal volunteers.

In an attempt to understand the widely varying bronchoalveolar lavage lymphocyte counts reported in normal subjects, we performed bronchoalveolar lavage in 42 healthy nonsmokers. The mean (SD) lymphocyte percentage in this first lavage was 9.6% (7.7%). The values did not fit a normal distribution. Five subjects had more than 20% of lymphocytes, and when they were excluded the distribution of lymphocyte counts was normal. Bronchoalveolar lavage was repeated once or twice in these five subjects 47 days or more after the previous lavage and the lymphocyte count decreased below 14% in four. Eight volunteers with an initial lymphocyte percentage less than 20% also had repeat lavages; two presented a transient increase of lymphocyte count above 20%. These data show that the percentage of lymphocytes in lavage fluid fluctuates significantly in normal subjects and suggest that lymphocyte counts counts higher than 14% should not be considered as normal.

Adult↗

PubMed2001

Phase IB study on prevention of surgery-induced immunodeficiency with preoperative administration of low-dose subcutaneous interleukin-2 in gastric cancer patients.

BACKGROUND AND OBJECTIVES: Low count of total and T helper lymphocytes predicts a poor prognosis in cancer patients and surgical trauma can worsen cancer-related immunodeficiency. Aim of this phase IB study is to verify toxicity and biological effects of interleukin-2 (IL-2) at 9 million IU/day subcutaneously (sc.) administered one, two or three preoperative days in patients with gastric cancer undergoing radical surgery. METHODS: Absolute value of total and T-helper (CD4) lymphocytes were measured at baseline and at 7th, 14th, and 50th postoperative days in 12 gastric cancer patients, who preoperatively received IL-2 at 9 million IU/day sc. as follows: group A (4 pts) 1-day; group B (4 pts) 2-days; group C (4 pts) 3-days administration. T and total lymphocytes count were recorded and retrospectively analyzed in a historical control-group of 22 consecutive patients, age and stage-matched. RESULTS: Toxicity consisted of fever grade I. In group A (1 day) T helper lymphocytes count decreased at 7th and at 14th postoperative day; in group B (2 days) and group C (3 days) no decrease of neither total nor T helper lymphocyte count occurred postoperatively, whereas in the historical group these parameters decreased significantly postoperatively and recovered only at 50th day. CONCLUSIONS: Two- and three-day schedules of sc. IL-2 preoperative administration at 9 million IU/daily prevented postoperative lymphocytopenia, whereas one-day administration did not. Since the IL-2 dose was so tolerable, that it could be given safely as outpatient, based on the previous results on survival observed in colorectal cancer patients with 3-days schedule we suggest that a 3-day schedule of Interleukin-2 as outpatient preoperative treatment seems advisable for further studies in gastric cancer patients.

Adenocarcinoma↗

PubMed2004

FTY720 exerts differential effects on CD4+ and CD8+ T-lymphocyte subpopulations expressing chemokine and adhesion receptors.

BACKGROUND: FTY720 (FTY), a novel immunomodulator with the potential to improve immunosuppressive therapy after organ transplantation, is currently under clinical investigation. Previous experimental animal studies have shown that FTY has a unique mechanism of action associated with altered lymphocyte recirculation. METHODS: Participating in a phase I clinical trial, we studied the pharmacodynamic effects of FTY in stable renal allograft recipients. We analysed the effect of FTY on surface marker expression on T-cell subpopulations by flow cytometry. RESULTS: A single oral dose of FTY (0.25-3.5 mg) significantly reduced peripheral lymphocyte counts by 30-70%. FTY reduced all T-lymphocyte subsets, CD4(+) cells more than CD8(+) cells. However, we observed that lower doses of FTY (0.25-2 mg, n = 11) did not affect peripheral CD4(+)CCR5(+) T-lymphocyte counts, while the highest FTY dose of 3.5 mg (n = 2) exerted a rapid reduction of CD4(+)CCR5(+) cells. Peripheral CD8(+)CCR5(+) T-lymphocyte counts were reduced by either low (0.25-2 mg) or high (3.5 mg) doses of FTY. In contrast to CCR5(+) cells, cells expressing CD62L were preferentially reduced after administration of FTY. In particular, CD4(+)CD62L(+) T cells declined after treatment. CD4(+) and CD8(+) T-lymphocyte subpopulations expressing the other chemokine and adhesion receptors (CXCR4, CD11a and CD49d) were reduced to a similar extent as compared with overall CD4(+) or CD8(+) T-lymphocyte counts. CONCLUSIONS: Despite the limited number of patients, especially in the placebo (n = 3) and the high-dose groups (n = 2), our observations suggest that FTY exerts differential effects on T-cell subpopulations. FTY predominantly reduces CD4(+)CD62L(+) cells in the peripheral blood suggesting increased migration into lymph nodes. It seems that only FTY doses above 2 mg are able to reduce peripheral CD4(+)CCR5(+) T lymphocytes, which are potentially capable of infiltrating into the allograft during rejection.

Cell Culture Techniques↗

PubMed2000

Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda.

BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.

AIDS-Related Opportunistic Infections↗

PubMed2007

[Apoptosis of circulating lymphocyte in surgical critically ill patients associated with poor outcome].

OBJECTIVE: To investigate the role and mechanism of lymphocyte apoptosis in post-operative critically ill patients and to determine the effects of lymphocyte apoptosis on the outcome of post-operative critically ill patients. METHODS: Thirty-nine consecutive post-operative patients admitted to the intensive care unit (ICU) were included in the prospective study. In addition, 30 healthy blood donors were involved for comparison. Early signs of apoptosis were investigated using flow cytometric measurement of Annexin-V binding to the cell surface of peripheral lymphocytes. In patients, absolute lymphocyte counts were measured on day 1, 3 and 5. The correlations of secondary infection and ICU stay duration with lymphocyte apoptosis and lymphocyte counts were determined. RESULTS: Post-operative critically ill patients exhibited higher rate of lymphocyte apoptosis than controls [(10.82+/-3.32)% vs. (2.89+/-1.17)%, P<0.01]. Meanwhile, lymphocyte counts were decreased significantly in patients compared with healthy individuals [(1.41+/-1.26) x 10(9)/L vs. (2.58+/-0.62) x 10(9)/L, P<0.01]. In patients group, rate of lymphocyte apoptosis was significantly higher in patients with secondary infection compared with those without secondary infection [(12.67+/-3.11)% vs. (9.24+/-2.63)%, P<0.01], and lymphocyte counts had no difference on day 1, while on day 3 and day 5 were decreased significantly in patients with secondary infection compared with those without secondary infection [(0.68+/-0.35) x 10(9)/L vs. (1.30+/-1.33) x 10(9)/L, (0.72+/-0.40) x 10(9)/L vs. (1.34+/-1.11) x 10(9)/L, respectively, stay duration of post-operative patients was positively correlated with rate of lymphocyte apoptosis (r=0.412, P=0.009) and negatively correlated with day 1, 3 and 5 lymphocyte counts, significantly correlated with day 1 and day 5 (r(1)=-0.333, r(5)=-0.361, both P<0.05). CONCLUSION: Lymphocyte apoptosis is enhanced in peripheral blood of post-operative critically ill patients and leads to a profound and persistent lymphopenia associated with poor outcome such as secondary infection and delay of ICU stay duration. Further studies are required to examine whether intervention to prevent lymphocyte apoptosis might alter the patients' outcome.

Apoptosis↗

PubMed1996

Hematotoxicity among Chinese workers heavily exposed to benzene.

Benzene is a well-established hematotoxin. However, reports of its effects on specific blood cells have been somewhat inconsistent and the relative toxicity of benzene metabolites on peripheral blood cells in humans has not been evaluated. We compared hematologic outcomes in a cross-sectional study of 44 workers heavily exposed to benzene (median: 31 parts permillion [ppm] as an 8-hr time-weighted average [TWA] and 44 age and gender-matched unexposed controls from Shanghai, China. All hematologic parameters (total white blood cells [WBC], absolute lymphocyte count, platelets, red blood cells, and hematocrit) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume (MCV), which was higher among exposed subjects. In a subgroup of workers who were not exposed to more than 31 ppm benzene on any of 5 sampling days (n = 11, median 8 hr TWA = 7.6 ppm, range = 1-20 ppm), only the absolute lymphocyte count was significantly different between exposed workers (mean [sd]1.6 [0.4] x 10(3) mu L) and controls (1.9 [0.4] x l0(3) uL, p = 0.03). Among exposed subjects, a dose response relationship with various measures of current benzene exposure (i.e., personal air monitoring, benzene metabolites in urine) was present only for the total WBC count, the absolute lymphocyte count, and the MCV. Correlations between benzene metabolites and hematologic parameters were generally similar, although hydroquinone was somewhat more strongly associated with a decrease in the absolute lymphocyte count, and catechol was more strongly associated with an increase in MCV. Morphologic review of peripheral blood slides demonstrated an excess of red blood cell abnormalities (i.e., stomatocytes and target cells) only in the most heavily exposed workers, with no differences in granulocyte, lymphocyte, or platelet morphology noted. Although benzene can affect all the major peripheral blood elements, our results support the use of the absolute lymphocyte count as the most sensitive indicator of benzene-induced hematotoxicity.

Adult↗

PubMed1986

T-cell subsets and natural killer cell activity in patients with gestational trophoblastic neoplasia.

Lymphocyte counts, T-cell counts, B-cell counts, helper T-cell counts, and suppressor-cytotoxic T-cell counts were performed in 38 patients with gestational trophoblastic neoplasia and 38 normal control subjects. Natural killer cell activity was also assayed in 30 patients and 30 control subjects. The percentage and count of lymphocytes and the absolute counts (but not the percentages) of T cells, helper T cells, and suppressor-cytotoxic T cells in patients with gestational trophoblastic neoplasia were significantly lower than those of normal control subjects. In high-risk patients with gestational trophoblastic neoplasia, there was also a significant reduction of the helper T cell to suppressor-cytotoxic T-cell ratio in comparison with that in normal control subjects. There was no significant difference in the B-cell counts or natural killer cell activity. The measurement of these parameters was not useful in predicting the response to chemotherapy.

Adult↗

PubMed1992

Application of the World Health Organization system for HIV infection in a cohort of homosexual men in developing a prognostically meaningful staging system.

OBJECTIVE: Validation of a modified version of the recently proposed World Health Organization (WHO) staging system for HIV infection and disease in a cohort of homosexual men. METHODS: Five hundred and thirty HIV-positive men followed for a median of 51 months (range, 1-98 months) were eligible for analysis. Subjects were classified into stages at their first seropositive visit and at all subsequent visits. RESULTS: As of 1 April 1991, 136 subjects (26%) had progressed to stage IV of the modified WHO system on the basis of their CD4 lymphocyte counts, and 78 subjects (15%) had died. Kaplan-Meier estimates for progression to stage IV from stages I, II and III were 52.8 +/- 7.5% over 6.6 years, 58.1 +/- 7.1% over 5.9 years and 66.5 +/- 9.7% over 5.7 years (log-rank P = 0.0001). Estimated median times to stage IV were 6.4, 5.3 and 3.8 years from stages I, II and III, respectively. Estimated median times to death were 10.9, 8.2, 6.3 and 1.7 years from stages I to IV, respectively. Results remained unchanged when CD4 lymphocyte count was replaced with lymphocyte count in the laboratory axis of the staging system. CONCLUSIONS: The proposed staging scheme, based on the WHO system, provides a prognostically meaningful classification for HIV infection in a cohort of homosexual men. Furthermore, the use of absolute lymphocyte count as a valid alternative for CD4 lymphocyte count has implications for the applicability of this system in many parts of the world where diagnostic resources are limited.

CD4-Positive T-Lymphocytes↗

PubMed1994

Brain parenchymal infection in bone marrow transplantation patients: CT and MR findings.

OBJECTIVE: The purpose of this study was to assess the MR and CT appearance of brain infection after bone marrow transplantation and to correlate the appearances with laboratory and pathologic findings. MATERIALS AND METHODS: We retrospectively reviewed the records of seven bone marrow transplant recipients with radiologic evidence of brain infection. RESULTS: Forty-one lesions were detected in seven patients with proved infectious foci outside the brain before brain infection was suspected clinically. Six patients had low total WBC or lymphocyte counts and one patient had normal total WBC and lymphocyte counts. Most lesions in patients with low total WBC or lymphocyte counts showed no appreciable edema or contrast enhancement. However, all lesions detected in the patient with normal total WBC and lymphocyte counts showed marked vasogenic edema and ring enhancement. CONCLUSION: Brain infection in bone marrow transplant recipients during immunosuppression exhibited MR characteristics different from those typically seen in immunocompetent patients. This appearance may be related to a diminished immunologic/inflammatory response.

Adult↗

PubMed1988

Moderately virulent African swine fever virus infection: blood cell changes and infective virus distribution among blood components.

Blood samples of pigs infected with a moderately virulent African swine fever virus (ASFV) isolate, obtained from the Dominican Republic (DR-II), were monitored temporally for viremia, infective ASFV association with major blood components, differential changes in blood cell composition, and plasma antibodies to ASFV. After intranasal/oral virus inoculation, pigs underwent acute infection and illness that resolved. Acute illness began on postinoculation day (PID) 4 and continued to PID 11, and pigs were febrile, with maximal infective ASFV titers detected in blood. By PID 11, initial antibody titers to ASFV antigens were detected in plasma. The WBC numbers were maintained near preinoculation counts; however, lymphocyte counts decreased slightly with a compensatory increment in neutrophil and monocyte numbers. From PID 11 to PID 25, rectal temperatures gradually returned to preinoculation values, titers of viremia began to decrease, plasma antibody to ASFV antigens increased to peak titers, and WBC numbers increased slightly. Percentages of lymphocytes returned to preinoculation values, neutrophil percentages decreased to slightly below preinoculation values, monocyte percentages were mildly increased, and eosinophil percentages were unaffected. From PID 25 to PID 46, titers of viremia further decreased, and plasma titers of antibodies to ASFV antigens remained high. In pigs with DR-II viremia (PID 4 to PID 46), most viral infectivity (greater than 95%) was RBC associated. Plasma contained less than 1% infectivity, and less than 0.1% of virus was in the WBC fraction (monocytes, lymphocytes, and granulocytes). After PID 46, viremia was no longer detectable.

Acute Disease↗

PubMed1994

Profound reversible CD4+ T lymphocytopenia in a severely uremic patient.

We report a human immunodeficiency virus antibody-negative, profoundly uremic patient who presented with a CD4+ T lymphocyte count of 133/mm3, a CD8+ T lymphocyte count of 77/mm3, and a CD3+ T lymphocyte count of 259/mm3. These values decrease significantly below reported levels in other lymphopenic uremic patients. High-efficiency chronic hemodialysis resulted in correction of these cytopenias to a normal range within 12 weeks.

Adult↗

PubMed1999

Recovery from lymphocytopenia following extracorporeal circulation: simple indicator to assess surgical stress.

This study investigated whether the lymphocyte count is a useful indicator to assess surgical damage following extracorporeal bypass. In Study 1, to investigate the correlation between extracorporeal circulating time (ECCT) and lymphocyte counts, 40 elective CABG patients were studied retrospectively. The lymphocyte recovery ratio (LRR), which represented the actual lymphocyte count divided by the preoperative lymphocyte count, was determined preoperatively, and on postoperative day (POD) 1, POD 3, and POD 5. In Study 2, the correlation between the interleukin-8 (IL-8) level and LRR was examined prospectively in elective CABG patients (n = 20). We measured the LRR and serum IL-8 levels preoperatively and during extracorporeal circulation (ECC) at 5 min, at the end of ECC, and 1, 3, and 12 h following ECC termination. Study 1 showed that the LRR decreased until POD 1 and gradually increased thereafter. The LRR had a negative correlation with the ECCT. In Study 2, the IL-8 level demonstrated a time course opposite to that of the LRR; it increased until 3 h after ECC termination and declined thereafter. There was a significant negative correlation between the LRR on POD 3 and the IL-8 level at 3 h after ECC termination. In summary, long-term ECC induced significant and prolonged lymphocytopenia. The LRR had a negative correlation with IL-8. These results indicated that the LRR may represent the degree of surgical stress following ECC; therefore, the counting of lymphocytes can be a quite useful bedside monitor to assess surgical damage and prognosis.

Coronary Artery Bypass↗

PubMedDate not supplied

Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastatic solid tumors.

The evidence of lymphocytopenia has been demonstrated to predict a poor prognosis in terms of survival in advanced cancer patients. This finding is not surprising because of the fundamental role of lymphocytes in mediating tumor cell destruction. Despite the importance of lymphocytes in the pathogenesis of cancer, there are only few data about the profile and the function of lymphocytes during the various antitumor therapies, and in particular the relation between lymphocyte pretreatment number and response to chemotherapy remains to be established. The present study was performed to evaluate whether the evidence of lymphocytopenia before the onset of treatment may influence the efficacy of chemotherapy in metastatic cancer patients affected by the most frequent tumor types. The study included 183 patients (lung cancer: 89; colorectal cancer: 63; breast cancer: 31), 95 of whom had been previously treated with chemotherapy. The chemotherapeutic regimens consisted of oxaliplatin plus 5-fluorouracil and folates in untreated colorectal cancer, weekly irinotecan in pretreated colorectal cancer, cisplatin plus gemcitabine or etoposide in untreated lung cancer, weekly vinorelbine in pretreated lung cancer, and taxotere in breast cancer patients who had been previously treated with anthracyclines. Lymphocyte count was considered to be abnormally low for values below 1500/mm3. Lymphocytopenia was found in 79/183 (43%) patients, without any significant differences in relation to tumor histology. A complete response (CR) was achieved in 6/104 patients with a normal lymphocyte count and in none of the 79 lymphocytopenic patients. A partial response (PR) was obtained in 39 patients with a normal lymphocyte count and in only eight patients with a low lymphocyte count prior to therapy. Therefore, irrespective of the type of chemotherapy, the objective tumor response rate (CR + PR) in lymphocytopenic patients was significantly lower than in patients with normal pretreatment lymphocyte counts (8/79 vs 45/104; p < 0.001). This study shows that the evidence of lymphocytopenia prior to chemotherapy is associated with a lower efficacy of treatment in terms of objective tumor regression rates in patients with metastatic solid tumors, and suggests that the action of chemotherapy may depend at least in part on an interaction with the antitumor immunity. Pretreatment lymphocyte count may represent a new, simple biological marker to be taken into consideration by oncologists in the chemotherapeutic treatment of metastatic cancer.

Adult↗

PubMedDate not supplied

Phase-II randomized study of preoperative IL-2 administration in radically operable gastric cancer patients.

BACKGROUND/AIMS: Surgery has appeared to induce lymphocytopenia and this decrease in host defenses during postoperative period could promote both the proliferation of possible micrometastases and the implantation of surgically disseminated tumor cells. The aim of this study is to evaluate if the preoperative subcutaneous injection of IL-2 (interleukin-2) may be able to abrogate surgery-induced immunosuppression in radically operable gastric cancer and to assess its toxicity. METHODOLOGY: This phase II study included 39 consecutive patients with histologically proven gastric adenocarcinoma (M/F 26/13; mean age 68; range 48-82) who underwent radical surgery from October 1999 to December 2000. Patients were randomized to be treated with surgery alone as controls (20 patients) or surgery plus preoperative treatment with recombinant human IL-2 (19 patients). IL-2 was administered subcutaneously, at a dose of 9,000,000 IU, for three consecutive days, followed by surgery within 36 hours from IL-2 withdrawal. We considered the total lymphocyte count and lymphocyte subset (CD4, CD4/CD8) during the preoperative period, before IL-2 administration, and on the 14th and 50th day. RESULTS: Two groups were well matched for type of surgery and extent of disease. All the patients underwent radical surgery plus D2 lymphadenectomy. At baseline, there were no significant differences in total lymphocyte and lymphocyte subsets between groups. The control group showed a significant decrease of total lymphocytes, CD4 cells, and CD4/CD8 ratio at the 14th postoperative day relative to the baseline value. Among the 22 patients evaluated in the control group 13 had a decreased of CD4 under 500 cells/mm3 (65%). Instead in the IL-2 group a significant increase was observed over the control group values of total lymphocytes and CD4 cells (14th ly total and CD4: IL-2 vs. control p<0.05). Moreover in this group only 3 patients had CD4 under 500 cells/mm3 (15%). This difference in CD4 count, is significant at the 50th postoperative day too (p=0.006). No anesthesiologic or surgical complication was seen in IL-2 treated group, with low grade of toxicity (WHO grade:1): the main effect was fever (14/19) easily manageable, with no cardiovascular complications. Furthermore, IL-2 group showed lower postoperative complications (p<0.05) and higher lymphocyte/eosinophil infiltration into the tumor (p<0.002). CONCLUSIONS: This phase II study would suggest that a preoperative immunotherapy with IL-2 is a well tolerated treatment able to prevent surgery induced lymphocytopenia. IL-2 seems to neutralize the immunosuppression induced by operation and so to stimulate the host reaction against tumor tissue (lymphocytes/eosinophils infiltration). Next randomized clinical trials could investigate the prognostic impact of IL-2 on the clinical course.

Adenocarcinoma↗

PubMed2002

The association of serum lactate dehydrogenase level with selected opportunistic infections and HIV progression.

BACKGROUND: The purpose of this study was to determine the association of serum lactate dehydrogenase (LDH) levels with certain opportunistic infection and to determine an association between LDH levels and CD4+ lymphocyte counts. METHOD: We studied 352 patients retrospectively with HIV infection and one of the following infections: histoplasmosis; toxoplasmosis; tuberculosis (pulmonary and disseminated); bacterial pneumonia; Pneumocystis carinii pneumonia. Demographic and clinical data were obtained from the Adult Spectrum of Diseases (ASD) database in New Orleans. Bivariate and multivariate analysis were used to determine the association between LDH levels and opportunistic infections and CD4+ lymphocyte counts. RESULTS: Patients with a serum LDH level <225 IU/L had a mean CD4+ lymphocyte count of 159/dl (SE 19.3) as compared to patients with a serum LDH level > or =225 IU/L, who had a mean CD4+ lymphocyte count of 58/dl (SE 6.9) (P<0.01). Non-Caucasian race, a diagnosis of histoplasmosis, disseminated tuberculosis or Pneumocystis carinii pneumonia, and CD4+ lymphocyte count were significantly associated with a serum LDH level > or =225 IU/L in the bivariate analysis. In a multivariate analysis, after controlling for race and CD4+ lymphocyte count, the only diagnoses that were significantly associated with the serum LDH level were definitive Pneumocystis carinii pneumonia and toxoplasmosis. Having a higher LDH level was not associated with early mortality. CONCLUSIONS: Although not diagnostic, serum LDH levels could be used as an adjunctive marker in certain opportunistic infections. There is an inverse relationship between serum LDH levels and CD4+ lymphocyte counts in this group.

AIDS-Related Opportunistic Infections↗