scholarly journals 5700The delayed recovery of absolute lymphocyte count after induction therapy predicts cytomegalovirus viremia in heart transplantation

2017 ◽  
Vol 38 (suppl_1) ◽  
Author(s):  
M. Yoon ◽  
J. Oh ◽  
I.C. Kim ◽  
S.M. Kang
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Minjae Yoon ◽  
Jaewon Oh ◽  
Kyeong-Hyeon Chun ◽  
Chan Joo Lee ◽  
Seok-Min Kang

AbstractImmunosuppressive therapy can decrease rejection episodes and increase the risk of severe and fatal infections in heart transplantation (HT) recipients. Immunosuppressive therapy can also decrease the absolute lymphocyte count (ALC), but the relationship between early post-transplant ALC and early cytomegalovirus (CMV) infection is largely unknown, especially in HT. We retrospectively analyzed 58 HT recipients who tested positive for CMV IgG antibody and received basiliximab induction therapy. We collected preoperative and 2-month postoperative data on ALC and CMV load. The CMV load > 1200 IU/mL was used as the cutoff value to define early CMV infection. Post-transplant lymphopenia was defined as an ALC of < 500 cells/μL at postoperative day (POD) #7. On POD #7, 29 (50.0%) patients had post-transplant lymphopenia and 29 (50.0%) patients did not. The incidence of CMV infection within 1 or 2 months of HT was higher in the post-transplant lymphopenia group than in the non-lymphopenia group (82.8% vs. 48.3%, P = 0.013; 89.7% vs. 65.5%, P = 0.028, respectively). ALC < 500 cells/μL on POD #7 was an independent risk factor for early CMV infection within 1 month of HT (odds ratio, 4.14; 95% confidence interval, 1.16–14.77; P = 0.029). A low ALC after HT was associated with a high risk of early CMV infection. Post-transplant ALC monitoring is simple and inexpensive and can help identify patients at high risk of early CMV infection.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2552-2552
Author(s):  
Di Sun ◽  
Paul Elson ◽  
Michaela Liedtke ◽  
Bruno C. Medeiros ◽  
Marc Earl ◽  
...  

Abstract Abstract 2552 Long-term survival rates for adults with acute lymphoblastic leukemia (ALL) remain poor at 40% when compared with pediatric ALL pts. This is partly attributed to the lack of predictive markers for risk stratification in adult ALL. Childhood ALL studies have shown that higher absolute lymphocyte count (ALC) during or following induction predicts longer event free survival (EFS). We hypothesized that adult ALL patients with higher ALC following induction therapy will have prolonged EFS and overall survival (OS). Methods: We conducted a retrospective chart review of 230 adult pts (age 18–64 yrs) with de novo ALL diagnosed between 1993–2010 at the Cleveland Clinic and Stanford, 198 of whom were evaluable (112 Cleveland Clinic, 86 Stanford). Prior studies in the pediatric population identified an ALC of 350 cells/μL as a cutoff that was predictive of outcome; we assessed this cutoff as well as other ALC metrics including day 1, 3, 7, 11, 14, 17, 20, 25, and 28 counts, nadirs and area under the curves at various time points, and the rate of ALC decline. We also evaluated the impact of gender, age at diagnosis, cytogenetics (CG), WBC at diagnosis, and transplant. The Kaplan-Meier method was used to summarize OS and EFS and the log-rank test was used for univariable analysis. The Cox proportional hazards model, stratified by institution, was used for multivariable and univariable analyses of measured factors. Patient characteristics: Median age: 38 yrs (range 18–64); Gender: 58% (114) male; CG risk: 62 (31%) poor, 46 (23%) miscellaneous, 54 (27%) normal, 36 (19%) no growth or not done; 178 (90%) B-cell lineage; median WBC at diagnosis 9.5 K/μL (range 0.5–760). Eighty-three percent of pts (165) achieved a CR with induction chemotherapy. The majority of pts (178, 90%) received a vincristine/prednisone/anthracycline-based induction regimen. Four pts (2%) received double-induction on trial S0333 (induction 1: vincristine/prednisone/anthracycline; induction 2: high dose cytarabine/mitoxantrone); eight pts (4%) hyperCVAD; and eight pts (4%) high dose cytarabine/mitoxantrone. Twenty-one pts (11%) received imatinib in combination with chemotherapy. Forty-six pts (23%) received an allogeneic transplant in CR1. Results: The median OS and EFS for this cohort were 29.5 and 24.9 mos, respectively. A number of the metrics were found to be associated with outcome; however we found that ALC at day 28 with a cut-point of <350 cells/μL was the strongest predictor of OS and EFS. The median ALC at Day 28 was 300 cells/μL (range 0–4000 cells/μL). Patients with ALC ≥350 cells/μL had a median OS of 47.4 mos compared to 17.6 mos for patients with ALC <350 cells/μL (HR=1.98, p=.007, Figure 1). Similarly, among pts who achieved a CR, median EFS for those with ALC ≥350/μL on day 28 was 42.1 mos compared to 13.9 mos in pts with ALC <350 cells/μL (HR=2.08, p=.006). Other factors associated with OS and EFS in univariable analyses were age at diagnosis, CG, WBC at diagnosis, and subsequent transplant (all p≤.04). In multivariable analysis the ALC on day 28 (<350 cells vs ≥350 cells/μL, p≤.0004 for OS and EFS) along with WBC at diagnosis (≤6.0 or >50.0 K/μL vs >6.0–50 K/μL, p≤.002 for OS and EFS) and CG (abnormal vs normal, p=.002 for OS and p=.02 for EFS) were independent prognostic factors of both outcomes. Combining these three factors by counting the number of poor features present yields a 3-group risk stratification: favorable (0–1 poor feature, 30% of pts, median OS and EFS not yet reached); intermediate (2 poor features, 45% of pts, estimated median OS and EFS 47.4 and 66.0 mos, respectively); unfavorable (3 poor features, 26% of pts, median OS and EFS 9.0 and 6.5 mos, respectively). Conclusion: By identifying an additional prognostic marker—ALC—this study aims to optimize the current adult ALL treatment protocol by risk stratification. As an indicator of bone marrow recovery, ALC following induction therapy may demonstrate the body's immune surveillance against malignant cells. Further characterization of higher risk pts allows for modifications to therapeutic regimens, which may translate into improvements in long-term survival. In addition, this data suggests that targeting the immune system to improve ALC may be a worthwhile strategy in ALL. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1472-1472 ◽  
Author(s):  
Jonathan A Rose ◽  
Tamara J. Dunn ◽  
Michaela Liedtke ◽  
Paul Elson ◽  
Matt Kalaycio ◽  
...  

Abstract Abstract 1472 Introduction: Despite significant advances in survival rates for pediatric Acute Lymphoblastic Leukemia (ALL) patients (pts), long-term survival rates for adults with ALL have remained below 40%. An absolute lymphocyte count (ALC) < 350/μL at Day 28 of induction therapy is predictive of poor outcome [event-free survival (EFS) and overall survival (OS)] in adults with newly diagnosed ALL. It is unknown, however, whether ALC at Day 28 is also predictive of outcome in those patients who undergo allogeneic HCT in CR1. We hypothesized that the prognostic impact of ALC at Day 28 might be nullified by HCT in CR1 due to the graft versus leukemia effect. Methods: We conducted a retrospective chart review of 90 adult pts (≥ 18 yrs of age) with de novo ALL who underwent HCT while in CR1 during the years 1998–2011 at the Cleveland Clinic and Stanford, 66 of whom were evaluable for data analysis. Institutional review board approval was obtained at each institution. Prior studies identified an ALC of 350/ μL at Day 28 of induction therapy as a cut-off predictive of outcome. Therefore, we evaluated this number as well as other cut-offs. Cytogenetic (CG) risk was ascribed by CALGB criteria. We also evaluated the impact of gender, age at diagnosis, CG, and WBC at diagnosis. The Kaplan-Meier method was used to summarize OS and EFS, which were measured from HCT to death and the first of relapse/death, respectively. The log-rank test was used for univariable analysis of categorical factors and the Cox proportional hazards model, stratified by institution, was used for multivariable analysis and univariable analysis of measured factors. Patient characteristics: Median age: 38 yrs (range 19–66); Gender: 58% (38) male; CG risk: 57 (86%) poor, 5 (8%) miscellaneous, 4 (6%) normal; 64 (97%) B-cell lineage; median WBC at diagnosis 18.1 K/μL (range 0.9–432); median Day 28 ALC 440/μL (range 0–2450). The majority of pts (50, 76%) received a vincristine/prednisone/anthracycline-based induction regimen, with the remainder receiving a high-dose cytarabine based regimen. The median interval between the start of induction and CR was 28 days and the median interval from CR to HCT was 3.2 months (0.2–10.8). Results: Median EFS and OS have not been reached; 1-year EFS is estimated to be 57% ± 6%, and 2-year OS 57% ± 7%. In univariable analyses age > 50 (EFS) and WBC at diagnosis ≥ 40 K/μL (EFS and OS) were associated with worse outcomes (all p ≤ 0.04). A Day 28 ALC < 250/μL (but not < 350/μL) was also associated with decreased EFS [HR 2.27 (1.08–4.79), p=0.03] (Figure 1) with a trend towards worse OS [HR 1.89 (0.89–4.04), p=0.10]. WBC and Day 28 ALC remained statistically significant prognostic factors for RFS on multivariable analysis; HRs 2.89 (1.38–6.05), p=0.005 and 2.25 (1.06–4.78), p=0.04, respectively. Conclusion: ALC at Day 28 remains prognostic for outcome in newly diagnosed ALL pts undergoing HCT in CR1. Further characterization of the lymphocytes in pts with high ALCs and their potential role in preventing relapse is needed. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5178-5178
Author(s):  
Jieun Jang ◽  
Yu Ri Kim ◽  
Hyunsoo Cho ◽  
Haerim Chung ◽  
Soo-Jeong Kim ◽  
...  

Background: The recurrent translocation t(8;21) represents approximately 12% of adult AML cases, and it involves the AML1 gene on chromosome 21 and the ETO gene on chromosome 8, which generates an AML1-ETO fusion protein. Previous studies have shown that t(8;21) AML with AML1-ETO fusion has a high complete remission rate with standard chemotherapy and a prolonged survival when sequential high-dose cytarabine is administered. However, prognosis of AML with t(8;21) is heterogeneous. Method: In order to under the relationship between clinical characteristics and prognosis, we retrospectively analyzed data of 68 t(8;21) AML patients who diagnosed at the two centers of South Korea between November 2005 and September 2016. Results: Median age was 56 (range, 17 to 82) and median follow up duration was 99.8 months (range, 278 to 150.8). Among 65 patients who achieved CR after induction therapy, 24 patients (37%) received allogeneic stem cell transplantation (allo-SCT). The median absolute lymphocyte count (ALC) at diagnosis was 2,093 × 106/L (range, 400-7,200), with higher ALC (≥ 2,205 x 106/L) being detected in 31 (45.6%) patients. Higher ALC at diagnosis was defined by an ALC cut-off of ≥ 2,205 x 106/L determined by receiver operating characteristic analysis and this cutoff value discriminated (in terms of sensitivity and specificity) between survival and death (area under curve [AUC] = 0.740, P = 0.001). In univariate analysis, lower CD19 expression (≥ 35%), higher BM blast (≥ 55%) and higher ALC at diagnosis were significantly associated with poor overall survival (OS) and leukemia-free survival (LFS) rate. The 5-year OS and the 5-year LFS of patients with higher ALC were 26.2% and 26.7%, respectively, while those of patients with lower ALC were 83.9 % and 73.6%, respectively. Of note, when we analyzed OS of 139 patients with normal karyotype according to ALC, there was not significant difference of survival rate and the 5-year OS of higher ALC in normal karyotype AML patients was 21.2%. Both groups according to ALC in t(8;21) AML patients were comparable for age, sex and clinical features at diagnosis as well as the proportion of patients who received allo-SCT. WBC count (> 20,000 x 109/L), ANC (> 1,500 x 106/L), additional cytogenetic abnormality, and C-kit mutation at diagnosis have not significant impact on survival. Minimal residual disease (MRD) after the first consolidation therapy did not affect the survival rate. Interestingly, among the patients who achieved CR after induction therapy, patients in higher ALC group showed MRD after the first consolidation therapy with higher incidence (91.3% vs. 60.6%, P = 0.012). In multivariate analysis, higher BM blast (HR 3.97, P = 0.004) and higher ALC (HR 11.59, P < 0.001) remained independent prognostic factors for poor OS rates. Higher BM blast (HR 4.42, P = 0.001) and higher ALC (HR 7.37, P < 0.001) were also independent factors for worse LFS rates. Conclusion: Higher ALC was a significant prognostic factor for LFS and OS in AML patients with t(8;21). Further study for the correlation of ALC and the mechanism of adverse prognosis are needed. Disclosures No relevant conflicts of interest to declare.


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