CD4 Cell Count of More Than 250/Microl in the Peripheral Blood Is Associated with Improved Overall Survival in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Independent of the aaIPI

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3775-3775
Author(s):  
Hossein Borghaei ◽  
Mitchell Smith ◽  
Michael Millenson ◽  
Tianyu Li ◽  
Danielle Shafer ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Cd4 T Cell ◽  
Cancer Center ◽  
Large B Cell Lymphoma ◽  
Cd4 T Cell Count

Abstract Background: Interaction between lymphoma and the host immune system may influence patient outcomes. The predictive value of lymphocyte subsets in the peripheral blood of patients with DLBCL on survival has not been reported. We retrospectively reviewed the flow cytometry (FCM) data of the peripheral blood in patients with DLBCL and analyzed the effect of lymphocyte subsets on overall survival from the time of FCM. Patients and Methods: Multicolor FCM was performed on 103 patients with DLBCL treated at Fox Chase Cancer Center (during 1996–2006). All pathology specimens were centrally reviewed. About half of these patients were treated by various regimens before referral to our center. Sixty-one males and 42 females with a median age of 64 years (19–89) were studied. Absolute lymphocyte count (ALC), NK cell (CD56+CD3−), CD3+CD4+ T cell and CD3+CD8+ T cell subsets were calculated. Median overall survival (OS) from time of FCM in all evaluable patients (91) was 22 months (range: 3 to 126 months). Median cell counts were as follows: NK cells 140, CD4+= 355, CD8+=224 and the ALC= 1064. Univariate analysis was done via Kaplan-Meier estimation and multivariate analysis via Cox proportional hazard model. Results: We found, in univariate analysis, that OS from the date of initial FCM was significantly correlated with increased CD4+ T cell count and ALC, with cutoffs of 250 and 1000 cells/microL, respectively. No significant cut-off was found for CD56+ or CD8+ cells. The hazard ratio for OS by CD4+ T cell-count is 0.240 (95% CI 0.099–0.581; p = 0.0015) and for ALC is 0.44 (95% CI: 0.217–0.905; p = 0.0256). In multivariate analysis, for patients with either lower risk aaIPI (0–1) or higher risk (2–3), the only significant predictor of OS, based on FCM data, is the CD4+ T cell-count (p =0.0098 hazard ratio 0.251, 95% CI 0.0088 to 0.716). Conclusion: In patients with diffuse large B-cell lymphoma referred for management at a tertiary cancer center regardless of prior therapy, CD4+ T cell levels of more than 250/microl predict improved overall survival independent of the IPI.

A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted R EPOCH Regimen

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4213-4213
Author(s):  
Hasmukh Jain ◽  
Manju Sengar ◽  
Hari Menon ◽  
Tanuja Shet ◽  
Epari Sridhar ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Count ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd4 T Cell ◽  
Survival Outcomes ◽  
High Grade ◽  
Cd4 T Cell Count

Abstract Background- High grade B-cell NHL's are 200 fold more common in seropositive as compared to seronegative patients. It includes diffuse large B cell lymphoma (DLBCL) (50%), Burkitt's (BL)(40%) and others such as plasmablastic lymphoma(PBL). They are biologically different from their seronegative counterparts with higher incidence of extranodal involvement, advanced stage and poor response to conventional therapy. In addition, they are at a higher risk of chemotherapy side effects and poorly tolerate dose intense regimens. To add to the complexity, social stigma and financial constraints decrease the compliance to therapy. R-EPOCH is designed to provide a balance between efficacy and safety. We report on our cohort of patients who were treated with this protocol. Methods- We retrospectively analysed HIV-associated de-novo high grade B-cell NHL patients who were treated with R EPOCH regimen at Tata Memorial Centre from 2011 till 2015. Patients aged ≥18 years who had received at least 1 cycle were included in the analysis. R EPOCH is an infusional regimen in which the dose of cyclophosphamide is adjusted depending on the baseline CD4+ T cell count and tolerance. The primary objective was the 3-year overall survival(OS), secondary objectives were response rates, the incidence of grade3/4 toxicities, dose intensity and correlation of OS with CD4 count, IPI, duration of HIV, Cyclophosphamide dose intensity (CDI). Demographic features, HIV related details (CD4 count at diagnosis, ART regimen), histological diagnosis, stage, bulky disease, extranodal sites, treatment details (number of cycles, dose administered), response, toxicity and status at last follow up were recorded. Descriptive statistics were summarised with median and range, survival outcomes were analysed with Kaplan meier method and impact of CD 4 count, CDI, IPI and duration of HIV on survival was assessed using log rank test. Results- A total of 40 patients(31males) with a median age-40 years (24-65 years) were treated. B symptoms were present in 19(48%). The cohort comprised of DLBCL-19 (48%), BL-16(40%), High grade B-Cell Lymphoma-Unclassifiable-4 (10%) and PBL 1 (2.5%). 16 (40%) patients had co-morbidities, including co-existent Hepatitis C in 5 and Hepatitis B in 2. HIV infection was detected at the time of lymphoma diagnosis in 18 (45%). The median CD4+ T cell count was 202 cells/mm3, 6 patients (15%)had count of <100/mm3 All patients received HAART while on chemotherapy, NNRTI plus 2 NRTI combination being the commonest regimen-33(82%) patients. Performance status (ECOG) ≤2 was seen in 36(90%) patients. 38 (95%) had stage III/IV disease and bulky disease (defined as size ≥7cm) was seen in 29(72%) patients. Extranodal involvement was seen in 36(90%) patients. Haemoglobin level ≤11g/dL in 10(25%) patients (range- 8.2-15.6 g/dL), serum albumin <4g/dL in 23(58%) patients, serum LDH ≥ upper normal limit -38 (95%)patients. Atleast 4 cycles of chemotherapy were administered to 35 (93%)patients, with 28 (70%) receiving 6 cycles. Cyclophosphamide dose escalation was possible in 18(45%) patients. CNS prophylaxis was administered with intrathecal methotrexate (median number-6) to 36(90%) patients. High dose methotrexate was given to 5 patients. Rituximab was not administered to 5 patients (3 due to CD4 count <100, 2 due to CD20 negativity). Responses were assessed using 18FDG PET-CT scan with complete response-32(80%), partial response-1(3%), disease progression-4(10%) and not evaluable- 4 (7%). Grade ¾ toxicities were seen in 33(83%) patients, with febrile neutropenia-26(65%), mucositis-10(25%) and peripheral neuropathy in5(13%) patients. Out of the 210 cycles administered, there were 41(20%) episodes of hospitalisation (duration ranged from 2-51 days). There were 11(28%) deaths (progression-7, toxicity-2, Not known-2) and 7(18%) patients had progression (4- on treatment progression, 3- relapses). With a median follow-up of 29 months, estimated 3-year OS is 71% (Figure 1) and 3-year progression free survival is 79%. There was no difference in survival based on IPI, CD 4+ T cell count, CDI or duration of HIV. Conclusions- R-EPOCH is a highly effective regimen in seropositive high-grade B-cell lymphoma even in the presence of adverse features (advanced stage, extranodal sites, CNS involvement, low CD4+ T cell count). The emphasis should now be on further reducing the toxicities. Figure Overall survival outcomes Figure. Overall survival outcomes Disclosures No relevant conflicts of interest to declare.

scholarly journals Therapeutic Prediction of HIV-1 DNA Decay: A Multicenter Longitudinal Cohort Study

2020 ◽  
Author(s):  
Yongsong Yue ◽  
Yijia Li ◽  
Yizhi Cui ◽  
Nidan Wang ◽  
Yunda Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Predictive Model ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cd4 T Cell ◽  
Peripheral Blood Mononuclear ◽  
Treatment Naïve ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract Background: Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions.Methods: Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, and 288 weeks after combined antiretroviral therapy (cART) initiation in 607 treatment-naïve patients with chronic HIV-1 infection were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART.Results: The total HIV-1 DNA rapidly decreased from baseline [mean = 3.04 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (mean = 2.51 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (<100 copies/106 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log10 copies/106 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%.Conclusions: The derived model based on baseline total HIV-1 DNA and CD4+ T cell count provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART.

Early Immune Recovery Predicts Overall and Disease-Free Survival After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2222-2222
Author(s):  
Jenna D. Goldberg ◽  
Junting Zheng ◽  
Juliet Barker ◽  
Farid Boulad ◽  
H.R. Castro-Malaspina ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Count ◽  
Cox Model ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Cd4 T Cell ◽  
Immune Recovery ◽  
Hematopoietic Stem ◽  
Cd4 T Cell Count

Abstract Abstract 2222 Poster Board II-199 Background: Immune recovery is an important determinant of outcome after allogeneic hematopoietic stem cell transplantation (alloHSCT). Previous studies have demonstrated that early recovery of absolute lymphocyte count (ALC) predicts overall (OS) and disease free survival (DFS) in conventional and partially T-cell depleted (TCD) alloHSCT. Recipients of conventional and especially TCD alloHSCT can have prolonged recovery of their immune systems, which may extend beyond one year. We have previously shown that the rate of CD4+ T cell recovery after TCD alloHSCT correlates with the risk of opportunistic infections. However, the impact of lymphocyte subset recovery on relapse and long-term survival following alloHSCT remains an important unknown. Methods: We conducted a retrospective study on 353 consecutive patients (median age 39, range 2-68) who received a fully TCD alloHSCT at MSKCC between January 1997 and December 2005. We excluded patients transplanted after 2005, because they received KGF for which pre-clinical data suggest an effect on immune recovery. Diseases included ALL (85), AML (146), CML (43), MDS (31), NHL (47), and undifferentiated leukemia (1). We excluded patients who died or did not have stable engraftment by 30 days. Immune recovery data, including ALC through day 90 and lymphocyte subsets through one year were grouped by quartile of cohort (table). The primary endpoints were OS and DFS. The score statistic from the Cox proportional hazards model defined the association of these endpoints with the values of ALC, CD4+ and CD8+ T cells, and NK cells. Subsequent to individual score tests, the Cox model determined the values associated with survival endpoints, in addition to prognostic clinical factors. Because markers were measured post-HSCT, a landmark analysis explored their prognostic significance. The landmark times were 1, 2, 3, 6, 9, and 12 months post-HSCT. Additional factors in the Cox model were: patient sex, age, number of remissions, stem cell source, and donor-recipient HLA match. The Kruskal-Wallis test evaluated if the diagnoses were associated with lymphocyte recovery. Results: In univariate analysis, high ALC at day 30 (ALC 30, p < 0.001) and day 60 (ALC 60, p = 0.015) were associated with improved OS. High ALC 30 was also associated with improved DFS (p = 0.005). Multivariate analysis demonstrated that high ALC 30 was independently associated with improved OS (p = 0.011). NK cell count at day 60 was associated with improved OS and DFS by univariate (p = 0.014, 0.010) and multivariate (p = 0.007, 0.002) analysis. Similarly, CD4+ T-cell count at 6 and 12 months predicted survival. By univariate analysis, CD4+ T-cell count at 6 and 12 months predicted OS (p = 0.007, p < 0.001) and DFS (p= 0.032, 0.002). This relationship remained with multivariate analysis. CD4+ T-cell count at 6 and 12 months independently predicted OS (p = 0.013, 0.007) and DFS (p = 0.059, 0.043). There was no association of CD8+ T cell count with OS or DFS. Other predictors of improved survival included younger age, higher degree of HLA match, peripheral blood as stem-cell source, and transplant in 1st remission. Diagnosis did not differentiate clinical outcomes except for CML patients, who had decreased DFS (but not OS) secondary to increased relapse with TCD. Finally, diagnosis was not associated with post transplant immune recovery. Discussion: We demonstrate that several measures of immune recovery, including time points as early as day 30, are important predictors of OS and DFS after fully TCD alloHSCT. Our finding that ALC 30 predicts OS in the TCD setting is consistent with prior studies in the conventional and partially TCD settings. We further demonstrate that reconstitution of NK cells and, later, CD4+ T cells predicts survival and relapse in the TCD setting. Finally, we show there is no relationship between diagnosis and immune recovery. It is likely that these findings will also apply to conventional alloHSCT given the concordance of our ALC 30 outcomes. These results may help identify patients most likely to benefit from interventions to enhance post-alloHSCT immune reconstitution. Disclosures: Castro-Malaspina: Alexion: Consultancy, Honoraria.

scholarly journals Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP-treated patients with diffuse large B-cell lymphoma

2017 ◽  
Vol 7 (4) ◽  
pp. e558-e558 ◽  
Author(s):  
Y Kusano ◽  
M Yokoyama ◽  
Y Terui ◽  
N Nishimura ◽  
Y Mishima ◽  
...  
Keyword(s):  
B Cell ◽  
Peripheral Blood ◽  
Blood Lymphocyte ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd4 T Cell ◽  
Large B Cell Lymphoma ◽  
Cd4 T Cell Count ◽  
Large B Cell

Abstract The absolute peripheral blood lymphocyte count at diagnosis is known to be a strong prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but it remains unclear as to which peripheral blood lymphocyte population is reflective of DLBCL prognosis. In this cohort, 355 patients with DLBCL treated with R-CHOP from 2006 to 2013 were analyzed. The low absolute CD4+ T-cell count (ACD4C) at diagnosis negatively correlated with the overall response rate and the complete response rate significantly (P<0.00001). An ACD4C<343 × 106/l had a significant negative impact on the 5-year progression-free survival and the overall survival as compared with an ACD4C⩾343 × 106/l (73.7% (95% confidence interval (CI)=66.7–79.5) versus 50.3% (95% CI=39.0–60.6), P<0.00001 and 83.3% (95% CI=77.1–88.0) versus 59.0% (95% CI=47.9–68.5), P<0.00000001, respectively). Multivariate analysis revealed that the ACD4C was an independent prognostic marker (hazard ratio=2.2 (95% CI=1.3–3.7), P<0.01). In conclusion, a low ACD4C at diagnosis served as an independent poor prognostic marker in patients with DLBCL.

scholarly journals PD‐1 expression on the surface of peripheral blood CD4 + T cell and its association with the prognosis of patients with diffuse large B‐cell lymphoma

2016 ◽  
Vol 5 (11) ◽  
pp. 3077-3084 ◽  
Author(s):  
Wei Zhang ◽  
Jie‐Fei Bai ◽  
Meng‐Xuan Zuo ◽  
Xin‐Xin Cao ◽  
Miao Chen ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd4 T Cell ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Therapeutic Prediction of HIV-1 DNA Decay: A Multicenter Longitudinal Cohort Study

2020 ◽  
Author(s):  
Yongsong Yue ◽  
Yijia Li ◽  
Yizhi Cui ◽  
Nidan Wang ◽  
Yunda Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Predictive Model ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cd4 T Cell ◽  
Peripheral Blood Mononuclear ◽  
Treatment Naïve ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract Background: Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions.Methods: Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, and 288 weeks after combined antiretroviral therapy (cART) initiation in 607 treatment-naïve patients with chronic HIV-1 infection were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART.Results: The total HIV-1 DNA rapidly decreased from baseline [mean = 3.04 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (mean = 2.51 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (<100 copies/106 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log10 copies/106 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%.Conclusions: The derived model based on baseline total HIV-1 DNA and CD4+ T cell count provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART.

scholarly journals Therapeutic prediction of HIV-1 DNA decay: a multicenter longitudinal cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yongsong Yue ◽  
Yijia Li ◽  
Yizhi Cui ◽  
Nidan Wang ◽  
Yunda Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Predictive Model ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cd4 T Cell ◽  
College Hospital ◽  
Plasma Rna ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract Background Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions. Methods Two sets of study populations were included: 490 China AIDS Clinical Trial (CACT) participants (Training cohort, followed up for 144 to 288 weeks) and 117 outpatients from Peking Union Medical College Hospital (PUMCH) (Validation cohort, followed up for more than 96 weeks). All patients were chronically HIV-1-infected and achieved successful HIV-1 plasma RNA suppression within week 48. Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, 144 and 288 weeks after combined antiretroviral therapy (cART) initiation were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART. Results The total HIV-1 DNA rapidly decreased from baseline [median = 3.00 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (median = 2.55 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 plasma RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (< 100 copies/106 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log10 copies/106 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%. Conclusions Baseline total HIV-1 DNA and CD4+ T cell count are two independent predictors of total HIV-1 DNA after treatment. The derived model based on these two baseline factors provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART.

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