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PubMed1991

Improving CD4+ lymphocyte counts in HIV-infected hemophilia patients. A favorable prognostic indicator?

CD4+ lymphocyte counts of 91 HIV+ hemophilia patients were monitored for a mean of 4 years (range: 15-69 months). CD4+ lymphocytes decreased in 55 but increased in 36 patients over time. The CD4+ cell increases were persistent in 5 patients, whereas they fluctuated in 31. Of the 36 patients with increasing CD4+ counts 3 developed AIDS and 1 LAS. The other 32 patients were clinically asymptomatic (CDC II), but had immunological abnormalities, such as increased serum neopterin (N = 18) and impaired in vitro T cell responses to pooled allogenic stimulator cells (N = 15) or mitogens (N = 18). In contrast, of the 55 patients whose CD4+ cells decreased, 24 developed AIDS and 5 ARC (P less than 0.0005). Only 2 of these 55 patients had normal mitogen stimulation in vitro and normal serum neopterin levels.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl.

OBJECTIVE: To assess rates of sexual activity, contraceptive use, genital infections and dysplasia, and other gynecologic symptoms among well-characterized populations of HIV-seropositive women enrolled in two Adult AIDS Clinical Trials Group (AACTG) randomized studies. METHODS: Gynecologic data were collected using standardized interview and examination forms from women enrolled in two protocols: ACTG 175, an antiretroviral trial (CD4+ lymphocyte counts 200-500 cells/microl) and ACTG 196, a Mycobacterium avium complex prophylaxis trial (CD4+ counts < or =100 cells/microl). RESULTS: Women enrolled in the two studies were similar in age, race, weight, and history of illicit or injection drug use, but women in ACTG 196 (n = 67) had lower median CD4+ counts (median, 35 cells/microl; range, 0-135 cells/microl versus median, 356 cells/microl; range, 131-620 cells/microl; p < .0005), were less likely to be antiretroviral naive (6% versus 38%; p < .0005), and were more likely to have a Karnofsky score <80 (28% versus 5%; p < .0001) than women in ACTG 175 (n = 185) at baseline. Recent changes in menstrual cycle were not different between groups. Women enrolled in ACTG 196 were less likely to be sexually active (40% versus 61%; p < .005), but both groups reported high levels of contraceptive use. Papanicolaou smear results in ACTG 196 and ACTG 175 respectively, were: normal, 38% and 50%, atypia, 24% and 39%, low-grade squamous intraepithelial lesions (SIL), 27% and 10%, and high-grade SIL, 11% and 0.7% (p < .001). CONCLUSIONS: Gynecologic complications are common among HIV-seropositive women with CD4+ lymphocyte counts < 500 cells/microl and are more common and severe among those with more advanced immunosuppression.

Adult↗

PubMed2006

Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia.

Absolute lymphocyte count (ALC) recovery postautologous stem cell transplantation is an independent predictor for survival in acute myelogenous leukemia (AML). The role of ALC recovery after induction chemotherapy (IC) in AML is unknown. We hypothesize that ALC recovery after IC has a direct impact on survival. We have now evaluated the impact of ALC recovery after IC on overall survival (OS) and leukemia-free survival (LFS) in 103 consecutive, newly diagnosed AML patients treated with standard IC and consolidation chemotherapy (CC) from 1998 to 2002. ALC recovery was studied at days 15 (ALC-15), 21 (ALC-21), 28 (ALC-28) after IC and before the first CC (ALC-CC). Superior OS and LFS at each time point were observed with an ALC-15, ALC-21, ALC-28, and ALC-CC > or = 500 cells/microl. Patients with an ALC > or = 500 cells/microl at all time points vs those who did not have superior OS and LFS (not reached vs 13 months, P<0.0001; and not reached vs 11 months, P<0.0001, respectively). Multivariate analysis demonstrated ALC > or = 500 cells/microl at all time points to be an independent prognostic factor for survival. Our data suggest a critical role of lymphocyte (immune) recovery on survival after IC in AML.

Adolescent↗

PubMed2005

Comparison of a new, affordable flow cytometric method and the manual magnetic bead technique for CD4 T-lymphocyte counting in a northern Nigerian setting.

We compared two techniques for CD4 T-lymphocyte counting: flow cytometry (Cyflow) and magnetic beads (Dynabead). Similar results with good correlation were obtained from the 40 adult blood samples counted (P=0.057, r=0.93). The Cyflow technique is more precise and cost-effective than the Dynabead method ($3 to $5 versus $12 to $22 per test, respectively), since as many as 200 samples can be measured per day.

Adult↗

PubMed2005

Genetic polymorphisms in CX3CR1 predict HIV-1 disease progression in children independently of CD4+ lymphocyte count and HIV-1 RNA load.

BACKGROUND: The impact of CX3CR1 polymorphisms on human immunodeficiency virus type 1 (HIV-1) pathogenesis is controversial, with conflicting reports of their role in disease progression in HIV-1-infected adults. METHODS: A cohort of 1055 HIV-1-infected children were genotyped for 2 CX3CR1 polymorphisms, V/I249 and T/M280, and their impact on HIV-1-related disease progression, including central nervous system (CNS) impairment, was evaluated. RESULTS: Children with the CX3CR1 I/I249 genotype experienced more-rapid disease progression (I/I249 vs. V/V249: relative hazard [RH], 2.19 [95% confidence interval {CI}, 1.30-3.68], P=.003; I/I249 vs. V/I249: RH, 1.77 [95% CI, 1.00-3.14], P=.05) and a trend toward more CNS impairment (I/I249 vs. V/V249: RH, 2.19 [95% CI, 1.00-4.78], P=.049; I/I249 vs. V/I249: RH, 2.02 [95% CI, 0.85-4.83], P=.11). Children with the V249-T280 haplotype experienced significantly less disease progression (RH, 0.42 [95% CI, 0.24-0.73]; P=.002) and CNS impairment (RH, 0.39 [95% CI, 0.39-0.22]; P=.001). Of note, these effects remained significant after CD4+ lymphocyte count and plasma HIV-1 RNA load at baseline were adjusted for and in a longitudinal, multivariate analysis. CONCLUSIONS: CX3CR1 genotypes and haplotypes impact HIV-1 disease progression independently of CD4+ lymphocyte count and plasma HIV-1 RNA load, suggesting that the fundamental role of CX3CR1 in the alteration of disease progression might be the recruitment of immunomodulatory cells responsible for the control of HIV-1.

CD4 Lymphocyte Count↗

PubMed1999

Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count.

IL-7 is produced by stromal cells and is the major lympho- and thymopoietic cytokine. IL-7 induces proliferation and differentiation of immature thymocytes, and protects thymocytes from apoptosis by induction of bcl-2 expression. The regulation of IL-7 production is poorly characterized, although down-regulation by transforming growth factor-beta (TGF-beta) has been described. We measured the serum levels of IL-7 before and after bone marrow transplant (BMT) in 32 children undergoing BMT for genetic diseases (severe combined immune deficiency (SCID) and thalassemia), aplastic anemia, and acute lymphoblastic and non-lymphoblastic leukemia (ALL and ANLL). Prior to BMT, the highest IL-7 levels were observed in patients with SCID and ALL, i.e. those patients with genetic or acquired lymphopenia. Patients with thalassemia and ANLL had normal levels of IL-7. Over the 8 weeks following BMT, the IL-7 levels of patients with SCID and ALL fell as the absolute lymphocyte count (ALC) increased. No detectable change in IL-7 levels was observed in the patients with thalassemia and ANLL. Levels of IL-7 were highest in the young infants with SCID compared to the age-matched controls. Together, the data demonstrate that serum levels of IL-7 in lymphopenic patients are inversely related to patient age and the absolute lymphocyte count (ALC). The inverse relationship to ALC suggests that there is either direct regulation of stromal production or more likely, binding of secreted IL-7 to lymphocytes expressing IL-7 receptors.

Adolescent↗

PubMed1999

Recombinant human gamma interferon in human immunodeficiency virus-infected children: safety, CD4(+)-lymphocyte count, viral load, and neutrophil function (AIDS Clinical Trials Group Protocol 211).

Nineteen children with human immunodeficiency virus (HIV) infection were treated with recombinant human gamma interferon (rIFN-gamma) (50 microg/m2 subcutaneously three times each week during weeks 1 through 12 and 100 microg/m2 subcutaneously three times each week during weeks 13 through 24) in a phase I/II clinical trial. All children continued to receive previously prescribed therapy with oral zidovudine or didanosine. Children were assessed clinically and with laboratory studies during 24 weeks of study treatment and for 12 weeks after completion of rIFN-gamma therapy. In general, rIFN-gamma therapy was well tolerated. There were two clinical or laboratory adverse events thought to be possibly or probably study drug associated. One child developed acute pancreatitis; another child developed granulocytopenia. Median CD4(+)-lymphocyte counts and plasma HIV RNA concentrations did not change significantly during therapy. In vitro neutrophil bactericidal activity against Staphylococcus aureus and superoxide production were not significantly affected by rIFN-gamma therapy. We conclude that rIFN-gamma therapy in HIV-infected children receiving single-agent antiretroviral therapy is safe and does not produce consistent changes in CD4(+)-lymphocyte count, plasma HIV RNA concentration, or in vitro neutrophil function.

Anti-HIV Agents↗

PubMed2006

Apheresis instrument settings influence infused absolute lymphocyte count affecting survival following autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin's lymphoma: the need to optimize instrument setting and define a lymphocyte collection target.

Autograft absolute lymphocyte count (A-ALC) is an independent prognostic factor for survival after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) for non-Hodgkin's lymphoma (NHL). Factors enhancing A-ALC collections are unknown. We hypothesize that apheresis instrument settings could affect A-ALC. Data from 127 NHL patients collected from 15 January 1999 to 30 July 2004 using a single apheresis instrument (COBE Spectra (SP), Baxter Amicus (AM), and CS3000 Plus (CS)) were analyzed. The primary end point of the study was to assess the correlation between apheresis instrument settings and A-ALC. The secondary end point was to determine the effect of apheresis instrument on survival post-APHSCT. Patients collected using SP achieved higher A-ALC compared to AM (with modified settings) or CS (P<0.05) and demonstrated superior overall (OS) and progression-free survival (PFS) (P<0.03). Multivariate analysis demonstrated A-ALC and not the apheresis instrument as an independent prognostic factor for OS and PFS, cancelling the prognostic effect of the apheresis instruments observed in the univariate analysis. The survival advantage observed by SP was from the higher A-ALC collected compared to AM and CS. These data suggest that apheresis instrument settings should be optimized to collect CD34(+) cells as well as an A-ALC target, with direct impact on survival post-APHSCT.

Adult↗

PubMed1998

Correlation among total lymphocyte count, absolute CD4+ count, and CD4+ percentage in a group of HIV-1-infected South African patients.

Depletion of CD4+ T cells is one of the hallmarks of progression of HIV-1 infection. However, measurement of the CD4+ T-cell count is expensive and often unavailable in less developed areas. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4+ T-cell count. To determine the relationship between TLC and CD4+ T-cell count in HIV-1-infected South African patients, 2777 HIV-1-seropositive patients visiting the Immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa from April 1991 to April 1997 were included in the study. In total, 3237 observations were used to determine sensitivity, specificity, and likelihood ratios, with 95% confidence intervals, of various cutpoints of the TLC to predict an absolute CD4+ T-cell count of <200 cells/mm3, CD4+ percentage <20%, and CD4+ percentage <15%. Spearman rank correlations were calculated between TLC and CD4+ T cells, CD4+ percentage and CD8+ T cells, as well as between CD4+ and CD8+ T cells. Results demonstrated that a TLC of 2 x 10(9)/L or less had a sensitivity of 90.3% to detect patients with a CD4+ T-cell count of <200 cells/mm3, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. For the observations as a group, a correlation (r = 0.704) between CD4+ T-cell count and TLC was demonstrated, but if the patients were divided into three groups according to their CD4+ T-cell count, this correlation weakened considerably. Therefore, although TLC shows a correlation with CD4+ T-cell count, it is not a good predictor of the CD4+ T-cell count in this population and should preferably not be used in the clinical care of HIV/AIDS patients.

Adolescent↗

PubMed1978

The response rate at chemotherapy in advanced Hodgkin's disease reflected by peripheral lymphocyte count.

Forty patients with advanced Hodgkin's disease stage III and IV were treated with combination chemotherapy. Absolute lymphocyte count in the peripheral blood was determined before start to chemotherapy. Higher levels of lymphocytes in the peripheral blood were associated with higher chemotherapy response rates. This difference was statistically significant (P less than 0.05).

Antineoplastic Agents↗

PubMed1977

Antagonistic effect of heparin and a water-soluble glucocorticoid on the peripheral lymphocyte count in mice.

The effect of heparin and prednisolone succinate on the peripheral white blood cell count of mice has been studied 3 hours after injecting the drugs. Heparin in low doses did not influence the cell count but in higher doses (20 to 400 U) elicited marked lymphocytosis. When prednisolone and heparin were administered together, heparin (5 to 10 U) markedly inhibited the prednisolone-induced lymphopenia. The effect on the lymphocyte count of prednisolone combined with a large dose of heparin depends on the doses of the drugs. The antagonism seems to be non-competitive in nature. The PMN count shows only minor changes and the reaction of eosinophils to heparin is less pronounced. The antagonistic effect was manifest on the spleen weight.

Animals↗

PubMed1980

Delayed cutaneous hypersensitivity and blood lymphocyte count in advanced Hodgkin's and non-Hodgkin's lymphomas.

Cell-mediated immune status was assessed in twenty patients of advanced and active lymphoreticular malignancies and twenty control subjects of comparable age and sex distribution by delayed cutaneous hypersensitivity responses to recall and contact antigens and peripheral blood lymphocyte counts. The results show depressed cellular immunity in both Hodgkin's and non-Hodgkin's lymphoma patients. However, the severity of immunological dysfunction as shown by anergy to skin antigens and lymphocytopaenia is remarkably less than what has been mostly reported in the literature.

Antigens↗

PubMed1995

A manual bead assay for the determination of absolute CD4+ and CD8+ lymphocyte counts in human immunodeficiency virus-infected individuals.

CD4+ T lymphocytes are currently the most common surrogate marker indicating disease progression in individuals infected with human immunodeficiency virus (HIV). Since the cost of enumerating lymphocyte phenotypes is quite high, an inexpensive bead assay analyzed by light microscopy (cytosphere assay; Coulter Corporation, Hialeah, Fla.) was developed as an alternative method for counting CD4+ and CD8+ T lymphocytes. To evaluate the reliability of the cytosphere assay, heparinized blood was collected from 117 HIV-infected individuals and tested for both CD4+ and CD8+ lymphocytes by flow cytometry and the cytosphere assay. The Pearson correlation coefficient of the cytosphere assay compared with that of flow cytometry for CD4+ T lymphocytes was 0.93, with mean values +/- standard deviations of 534 +/- 509 by flow cytometry and 499 +/- 477 by the cytosphere assay. The correlation coefficient for CD8+ T lymphocytes was 0.86, with mean values of 831 +/- 543 by flow cytometry and 746 +/- 472 by the cytosphere assay. The sensitivity and specificity of the cytosphere assay in determining absolute CD4+ T-lymphocyte counts of less than 200/microliters were 97.6 and 94.7%, respectively. The positive predictive value was 90.9%, and the negative predictive value was 98.6%. The cytosphere assay was highly correlative to flow cytometry in determining CD4+ and CD8+ T-lymphocyte counts among HIV-infected patients. The ease and limited resources needed to perform this test make it ideal in developing countries and other areas where technology and finances are limited.

CD4 Lymphocyte Count↗

PubMed2006

Should absolute lymphocyte count be used as a surrogate marker for CD4+ count in patients with HIV/AIDS?

The World Health Organization (WHO) has recommended the use of absolute lymphocyte count (ALC) as a potential marker for immunosuppression where CD4+ count is unavailable. However, there are conflicting reports on the usefulness of ALC as a surrogate marker for CD4+ counts in patients with HIV/AIDS, more so, in patients with HIV-associated tuberculosis (TB). To evaluate the usefulness of ALC as an alternative to CD4+ counts and to see whether TB affects the correlation of ALC with CD4+ counts in patients with HIV-associated TB. A total of 66 consecutive patients (33 with and 33 without TB) with a diagnosis of HIV infection were recruited into the study as cases. Another group of 66 subjects (33 subjects each) age- and sex-matched HIV-negative controls were recruited as controls and stratified in to two: a) HIV-negative PTB patients. b) apparently healthy HIV and PTB negative individuals. The age range was from 15-60 years (median: 32 years). The highest percentage (39%) of subjects fell in the age range of 25-29 years. The mean ALC for HIV-associated PTB was 3906 +/- 1092 cells/microl and for patients with HIV infection only. 4755 +/- 1049 cells/microl. There was no significant difference in mean ALC between males and females in both groups (P > 0.05). Patients with dual infection by M. tuberculosis and HIV had the lowest mean ALC (3906 +/- 1092 cells/microl). Healthy controls had mean ALC (+/- SD) of 5249 +/- 101 cells/microl. There was significant difference between the healthy controls and the other three groups. The observed difference was more in patients with HIV/ TB co-infection (P < 0.005) compared with patients with HIV alone (P < 0.05). No significant correlation was observed between CD4+ cell counts and ALC in all the age groups of the study population. When the CD4+ counts were divided into < 200 and > or = 200 cells/microl and the ALC into < 2000 and > or = 2000 cells/microl, the sensitivity, specificity and positive predictive values of the diagnostic usefulness of ALC in HIV-associated PTB were 52%. 56.3% and 78.8% while for HIV only patients the same values were 56.3%. 55.9% and 54.5%, respectively. We cannot recommend the use of ALC as a surrogate for CD4+ count in our environment as this study has clearly shown that the correlation between the two is weak. Patients with dual infection by HIV and M. tuberculosis are more likely to have lower CD4+ cell and AL counts than those with HIV infection occurring alone.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Assessment of the efficacy of total lymphocyte counts as predictors of AIDS defining infections in HIV-1 infected people.

BACKGROUND: The CD4 count is a dominant prognostic and predictive factor in HIV infection. This study assessed the utility of the total lymphocyte count (TLC) in place of the CD4 count to predict the development of AIDS defining opportunistic infections (ADOI). METHODS: The Chelsea and Westminster cohort was used to identify those people with a first episode of an ADOI. Corresponding CD4 and TLCs were recorded before diagnosis or at the time of first prescribing prophylaxis; patients without an AIDS defining opportunistic infection were defined as being at "risk" and receiver operating characteristic (ROC) curves were used to display the results of sensitivity and the false positive error rate of total lymphocyte and CD4 count groups. RESULTS: A significant linear correlation was seen between the log(10) CD4 count and log(10) TLC (Pearson's correlation coefficient = 0.70, p<0.001). The finer cut off value for TLC where false positive error rate is minimum and sensitivity maximum was 1500-2000 cells/mm(3). Patients with TLC 1000-1500 cells/mm(3) were estimated to be at 40% increased risk of developing an ADOI. The cut off value for CD4 counts measured 200 cells/mm(3) above which the risk developing an ADOI decreased. Patients with a CD4 count of 150-200 cells/mm(3) were at a 34% increased risk of developing an ADOI. The area under the ROC curve for TLC was 10% lower than that for CD4 count. CONCLUSIONS: The TLC is minimally less reliable than the CD4 count as a predictor of ADOIs. In the absence of expensive equipment for CD4 measurement, the TLC is a useful test.

AIDS-Related Opportunistic Infections↗

PubMed1992

CD4 lymphocyte count as an indicator of delay in seeking human immunodeficiency virus-related treatment.

BACKGROUND: As many as half of patients infected with the human immunodeficiency virus who are medically eligible for Pneumocystis prophylaxis and zidovudine treatment have not received these treatments. We used the CD4 lymphocyte count as an indicator of delay in seeking treatment among patients infected with human immunodeficiency virus and assessed whether insurance status was associated with the stage of illness when care is initiated. METHODS: Data from 96 patients who initiated medical care at a university acquired immunodeficiency syndrome clinic from August 1989 to January 1991 were retrospectively reviewed. RESULTS: Patients initiated care at a relatively late stage of illness (mean CD4 lymphocyte count, 0.37 x 10(9)/L [369/mm3]), and 29% were below the threshold for Pneumocystis prophylaxis. Patients with private insurance had significantly lower CD4 counts (mean, 0.27 x 10(9)/L) than did individuals with public insurance (mean, 0.46 x 10(9)/L). CD4 counts did not increase during the 18-month study period. CONCLUSIONS: The majority of patients infected with human immunodeficiency virus are eligible for medical therapy and could benefit by initiating care sooner. Private insurance was not associated with initiating early care, supporting anecdotal reports that some privately insured individuals may be reluctant to seek care for a human immunodeficiency virus-related condition.

Adult↗

PubMed1993

High complete remission rate from 2-chloro-2'-deoxyadenosine in previously treated patients with B-cell chronic lymphocytic leukemia: response predicted by rapid decrease of blood lymphocyte count.

PURPOSE: This study attempted to characterize the response of previously treated patients with B-cell chronic lymphocytic leukemia (CLL) to the purine analog 2-chloro-2'-deoxyadenosine (CdA) and to assess factors that predict response. PATIENTS AND METHODS: We treated 18 CLL patients with about-monthly courses of five daily 2-hour intravenous infusions of 0.12 mg CdA/kg. RESULTS: Complete remissions (CRs) were achieved in seven patients (39%), with a total response rate of 67%. CR patients received a median of 4.5 courses. One patient with CR relapsed and died 14 months from start of CdA treatment, whereas the other six patients with CR remain in remission following a mean observation period of 14 months. The median duration of partial remissions (PRs) was 9 months, with a median treatment-free interval of 15 months. Thrombocytopenia was the most common dose-limiting toxicity. Non-responding patients had a median survival of 3.5 months, and systemic fungal infections were the most common cause of death. Immunoglobulin (Ig) levels improved significantly in hypogammaglobulinemic patients during CdA treatment. Responses were predicted by a rapid decrease of blood lymphocyte counts following the first treatment course. CONCLUSION: A high CR rate was achieved with limited toxicity. A treatment strategy to enable high-quality response and limitation of treatment-related toxicity is provided.

Adult↗

PubMedDate not supplied

Total lymphocyte count in peripheral blood of peritoneal dialysis patients: relationship to clinical parameters and outcome.

BACKGROUND: Total lymphocyte count (TLC) is used as a nutritional status measurement. The impact of TLC on mortality in peritoneal dialysis (PD) patients is controversial. This study aimed at evaluating the effect of TLC on mortality, and assessing the relationship between TLC and nutritional status, anemia and erythropoietin (EPO) response, acute-phase response, dialysis adequacy and volume status in PD patients. METHODS: Seventy-three PD patients were monitored for 3 yrs from the beginning of the treatment. Data recorded for each patient included demographic features, comorbidity, TLC, blood biochemistry, systolic and diastolic blood pressures (BP), indices of dialysis adequacy and nutritional status, total fluid removal and mortality. Adjusted mortality risk for TLC was estimated using the Cox's regression models composed by TLC and one covariate having a value p<0.05 in univariate analysis. RESULTS: The 3-yr patient survival rates were significantly different among the TLC quartiles. The adjusted TLC was found, generally, to be a significant predictor of death in reduced Cox's models, except in models composed of TLC and total fluid removal or serum albumin. The receiver operating characteristics (ROC) analysis demonstrated that TLC provided a significant prediction of mortality. TLC correlated positively to total fluid removal, serum albumin, triglyceride and hematocrit, and negatively correlated to BP, high peritoneal transport and EPO-need. It did not correlate to other measures of nutritional status, dialysis adequacy and acute-phase response. Fluid removal and serum triglyceride were independent predictors of TLC in multivariate analysis. CONCLUSIONS: Our findings suggest that TLC can be used as a simple prognostic tool in PD patients; however, the association between TLC and mortality is confounded by other prognostic factors. Volume status could be a more important factor affecting the TLC than nutritional status.

Acute-Phase Reaction↗