IKZF1 Deletion Is Strongly Associated with Risk of Relapse in Intermediate Risk Group in JACLS ALL02 Cohort

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1455-1455 ◽  
Author(s):  
Daisuke Asai ◽  
Toshihiko Imamura ◽  
Souichi Suenobu ◽  
Daiichiro Hasegawa ◽  
Takao Deguchi ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Point Mutation ◽  
Peripheral Blood ◽  
Risk Group ◽  
Current Therapy ◽  
Intermediate Risk ◽  
Rt Pcr ◽  
Over Expression ◽  
Cell Counts ◽  
Risk Of Relapse

Abstract Abstract 1455 Introduction: Despite the progress of the current therapy, approximately 20 % of pediatric patients with B-cell-presursor (BCP)-ALL experience relapse who had no conventional adverse prognostic factor. Recently, alteration of the IKZF1 gene has been reported to be associated with a poor outcome in pediatric BCP-ALL without BCR-ABL. In addition, it is also reported that a significant proportion of these cases with the alteration of IKZF1 shared the point mutation of JAK2 and over-expression of cytokine receptor-like factor 2 (CRLF2). Herein, in order to assess the prognostic value of these genetic abnormalities in Japanese cohort, we conducted genetic analysis of IKZF1, JAK2 and CRLF2 in pediatric BCP-ALL. Materials and Methods: Diagnostic bone marrow or peripheral blood samples of 215 pediatric BCP-ALL patients treated according to Japan Association of Childhood Leukemia Study (JACLS) ALL02 protocol from April, 2002 to May, 2008 were examined in this study. All patients were categorized into high risk (HR) group defined as follows;(1) initial white blood cell counts more than 10,000 /μl, (2) age at diagnosis is > 10 years and (3) good response to initial predonisolone (PSL) treatment ( blast counts in peripheral blood is less than 1,000 /μl after one week PSL treatment). Ph+ALL and infantile ALL patients were excluded in this protocol. The patients with Down syndrome were also excluded in this genetic analysis. The deletion of IKZF1 was determined using multiplex ligation-dependent probe amplification (MLPA) in 212 patients whose diagnostic DNA samples were available. The expression of isoform of IKZF1 was determined by RT-PCR in 113 patients whose diagnostic RNA samples were available. The expression level of CRLF2 was also determined by real time RT-PCR in 112 patients and over-expression was defined as over ten times more than median expression value. The presence of P2RY8-CRLF2 fusion was examined by RT-PCR or MLPA in the patients with CRLF2 over-expression or IKZF1 deletion. JAK2 mutations were also determined by direct sequencing of the exon 16, 20 and 21 in the patients with IKZF1 deletion. Results: The deletion of IKZF1 gene was present in 19 of 212 (9.0 %) patients. In detail, the mono-allelic deletion of entire IKZF1 gene was present in 10 of 19 patients. On the other hand, the expression of dominant-negative IK6 isoform was present in 9 of 112 (8.0%) patients including 12 patients with IKZF1 deletion. The expression of IK6 was present in 4 of 12 (33.3%) IKZF1 deleted patients. Interestingly, 5 of 9 patients with IK6 expression had no alteration of IKZF1 gene. In terms of CRLF2, over-expression was detected in 16 of 112 patients (14.3 %). However, P2RY8-CRLF2 fusion was not detected in these 16 patients with altered CRLF2 expression. Strikingly, none of the patients with IKZF1 deletion (n=19) had either P2RY8-CRLF2 fusion or JAK2 exon 16, 20 and 21 mutation. Patients with IKZF1 gene deletion had significantly worse relapse rate than those without IKZF1 deletion (7/19 vs 22/193, p<0.01). On the contrary, none of the patients with IK6 expression experienced relapse. Discussions: This study confirmed that the presence of IKZF1 deletion was strongly correlated with risk of relapse in intermediate risk group in JACLS ALL02 cohort. Thus, we expect that IKZF1 deletion is an independent predictor of treatment outcome and represents a candidate of prognostic marker to be integrated in future algorithms for early risk stratification in pediatric BCP-ALL. Strikingly, point mutation of JAK2 exon 16, 20 and 21 or P2RY8 -CRLF2 fusion was rarely present even in BCP-ALL patients with IKZF1 deletion. There might be unrevealed class I mutation cooperating with IKZF1 alteration in Japanese BCP-ALL cohort. Disclosures: No relevant conflicts of interest to declare.

Role of Minimal Residual Disease Monitoring in Acute Promyelocytic Leukemia Treated with Arsenic Trioxide in Frontline Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 941-941
Author(s):  
Ezhilarasi Chendamarai ◽  
Poonkuzhali Balasubramanian ◽  
Biju George ◽  
Kavitha M Lakshmi ◽  
Auro Viswabandhya ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Residual Disease ◽  
Risk Group ◽  
High Risk Group ◽  
Promyelocytic Leukemia ◽  
Rt Pcr ◽  
Time Points ◽  
Kinetics Of ◽  
Minimal Residual ◽  
Time Point

Abstract Abstract 941 Algorithms for relapse risk prediction, kinetics of hematological relapse (HR) following a molecular relapse (MR) and intervention based on these results have been well studied for patients with acute promyelocytic leukemia (APL) treated with conventional all-trans retinoic acid (ATRA) plus chemotherapy based regimens. It is recognized that the kinetics of leukemia clearance with the use of arsenic trioxide (ATO) in induction is significantly different from that of ATRA alone or ATRA plus chemotherapy combinations. Extrapolation of data generated from ATRA plus chemotherapy regimens may potentially not be valid when applied to regimens that use ATO in up front therapy. At our center we undertook a prospective minimal residual disease (MRD) detection study in APL treated with ATO. 151 patients who achieved hematological remission (CR) were followed up serially for MRD detection by peripheral blood RT-PCR. All patients achieved a molecular remission (CRm) prior to starting maintenance therapy. Figure 1 summarizes the time points for analysis, compliance and RT-PCR positivity. An RT-PCR was positive in 90 (64%) at the end of induction which was associated with a significant increase in the risk of relapse. On a multivariate analysis after adjusting for conventional risk factors that predict relapse, an RT-PCR positivity at this time point was the only parameter that retained statistical significance (RR=3.82; 95%CI=1.2–12.8; P-value=0.03). The event free survival (EFS) and cumulative incidence of relapse (CIR) for those who were RT-PCR positive was significantly worse than those who were negative as illustrated in figure 2. Further analysis revealed that none of the low risk patients (WBC count at diagnosis <5 × 109/Lt and platelet count >20 × 109/Lt) who were RT-PCR negative at the end of induction relapsed while 4 (10%) of the high risk group patients who were RT-PCR negative, at this time point, relapsed. There were a total of 31 (20.5%) hematological relapses, only 3 of these relapses were beyond 3 years from completion of maintenance. An RT-PCR was positive in the 3–4 months period prior to a HR in 15/31 (48.3%), negative in 10/31 (32.2%) and was not done in this time frame in 6/31 (19.3%). An additional 7/151 (4.6%) were transiently RT-PCR positive but did not have a HR at a median follow up of 50 months (range: 21–87) from a positive test. The overall sensitivity, specificity and positive predictive value of using an RT-PCR for successful MRD detection prior to a frank HR was 62.5%, 93.3% and 65.2% respectively. Retrospective RQ-PCR analysis at the same time points revealed that with an RQ-PCR the sensitivity would be further improved to 83.3%. The data generated is with a single agent ATO based regimen as reported by us previously (J Clin Oncol 2010;28:3866); it could potentially apply to other regimens with ATO used up front. The data suggests that a positive peripheral blood RT-PCR at the end of induction predicts relapse and could potentially be used to risk stratify patients for intensification of the currently used low intensity regimen. High risk group patients and those who remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring using peripheral blood RT-PCR and this should probably be done up to 3 years after completion of therapy. Disclosures: No relevant conflicts of interest to declare.

Differences In Clinical Characteristics and Prognostic Features Between Patients with Myelodysplastic Syndromes (MDS) From Korea, Japan, and Germany

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1882-1882
Author(s):  
Andrea Kuendgen ◽  
Je-Hwan Lee ◽  
Akira Matsuda ◽  
Kyoo Hyung Lee ◽  
Jung-Hee Lee ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Clinical Characteristics ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Asian Countries ◽  
Cell Counts ◽  
Blast Count ◽  
K 12

Abstract Abstract 1882 Evidence exists for differences between eastern and western type MDS. However, for the development of the IPSS Score, 6 of the participating study groups were European or US, while only one group originated from Japan. In order to find out more about the differences in MDS patients (pts) from separate ethnic groups we performed an analysis of 1048 pts from Dusseldorf, Germany (G), 242 pts from Seoul, Korea (K), and 143 pts from Saitama, Japan (J). Initially, we compared clinical characteristics. Then we evaluated the influence of important prognostic factors. For all pts included at least the parameters needed to determine the IPSS had to be available. For survival analyses pts who received induction chemotherapy or allogeneic transplantation were excluded. Median age was 66 yrs in Germany, 54 in Korea, and 68 in Japan. The distribution of gender, with a male preponderance, was comparable in all cohorts. Median blast count was <5% in all groups. Median cell counts were significantly lower in the Japanese and Korean, when compared to the German pts. However, although Asian pts tended to have more severe cytopenias regarding all 3 lineages, they also had a significantly higher percentage of refractory cytopenias with unilineage dysplasia (21% (K) and 36% (J) compared to 7% (G)). MDS with del5q was significantly more frequent in German pts (9 vs 0 vs 1%) as well as RCMD (40 vs 22 vs 18%), while the frequency of RAEB I/II was comparable. Due to the high incidence of pancytopenia Asian pts rarely had a low risk IPSS (2% (K), 12% (J) vs 27% (G)), while the int I risk group was larger and int II and high risk groups were of almost the same size. Regarding karyotype (KT) risk according to IPSS, the intermediate risk group was smaller, and the low risk group was larger in Asian pts. To evaluate the relevance of different prognostic factors we first compared the whole cohorts of not intensively treated pts. Since the result was all factors analyzed were important in German while many were not in Asian pts we decided to look at a smaller subgroup of German pts to compare similar sizes. Pts were chosen by chance to avoid any kind of bias by matching. The results are presented in table 1. Already survival was very different in the 3 groups: 31 months (ms) (G) vs 43 ms (K) vs 157 ms (J). In univariate analysis in German pts variables with significant influence on survival were Hb, sex, age, LDH, platelets, blast count, KT, and IPSS, while in the Korean and Japanese pts the 3 different cytopenias and LDH had no influence on survival (except a borderline influence of Hb in Japanese pts). Very striking was the importance of gender in the 2 Asian countries. In both men lived for a median of only about 2 years, comparable to German pts, while women had a very long survival with median not reached. Regarding KT risk, the intermediate risk group had in the Asian countries a significantly longer survival than in Germany (nr vs 24 ms), possibly due to a high frequency of +8. The IPSS divided, again in both Asian countries, 2 different risk groups, but not 4. Multivariate analysis identified Hb, platelets, blasts, LDH, age, and KT as independent risk factors for German pts, compared to ANC, blast count, and age in Korean, and blast count plus KT in Japanese pts. It is established that survival of Asian MDS pts is longer than that of European, but it remains unclear why there is such a strong difference between Korean and Japanese pts although the former are younger and most other features are very comparable between the two. The most striking features of Asian MDS are the strong influence of gender, as well as the lesser importance of cytopenias compared to European pts. This, together with a slight difference in the survival according to KT, leads to an inferior separation of risk groups by the IPSS. The most important factor with equal relevance in all MDS pts remains blast count. Disclosures: No relevant conflicts of interest to declare.

Prolonged Administration of the Telomerase Vaccine GRNVAC1 Is Well Tolerated and Appears to Be Associated with Favorable Outcomes In High-Risk Acute Myeloid Leukemia (AML)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2190-2190 ◽  
Author(s):  
H. Jean Khoury ◽  
Robert H. Collins ◽  
William Blum ◽  
Lori Maness ◽  
Patrick Stiff ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Disease Free Survival ◽  
Catalytic Subunit ◽  
Patient Specific ◽  
Major Protein ◽  
Intermediate Risk ◽  
Prolonged Administration ◽  
Early Relapse ◽  
Risk Of Relapse

Abstract Abstract 2190 Background: Telomerase activity in leukemic blasts is frequently increased in high-risk AML patients, and the major protein catalytic subunit of telomerase (hTERT) includes immunogenic epitopes which can stimulate generation of hTERT-specific cytotoxic T cells. Methods: We evaluated the feasibility, safety, and immunologic effects of telomerase catalytic subunit (hTERT)-expressing autologous dendritic cells (DC) in adult AML patients. GRNVAC1 (VAC1) was produced at a central facility from patient-specific leukapheresis harvests. Immature DCs from monocyte-enriched PBMCs were electroporated with an mRNA construct encoding hTERT and a lysosomal targeting sequence (LAMP-1). Further culture with cytokines induced a mature DC phenotype. AML patients were eligible if in CR1 and with intermediate or high risk cytogenetics or in CR2. PBMCs were harvested after induction, and before or after completion of planned consolidation cycles. Patients in ongoing CR or early relapse (<20% marrow blasts) were vaccinated. Vials of VAC1 containing 1 × 107 cells were administered by intra-dermal injections weekly × 6, followed by 4 weeks off, then as boost vaccinations every other week × 6. In cases where additional vials were available, injections could then continue on a q28 day extended boost schedule. This abstract summarizes safety of administering VAC1 up through the extended boost schedule. Results: Between September 2007 and December 2009, 33 patients with a median age 61yrs (range, 30–75) were enrolled and leukapheresed. 21 patients received VAC1 vaccinations, 19 in CR (16 in CR1 and 3 in CR2) and 2 in early relapse. Eight of 16 in CR1 were at intermediate risk of relapse and 8 were at high risk of relapse. A median of 17 (6-32) vaccinations were administered to those 19 patients. VAC1 was well tolerated with no toxicities with the exception of one patient who developed ITP after 6 vaccinations. Local transient erythema at the site of injection was common in all patients. With a median follow-up of 10.5 months (range, 1.2–27.2) months, 4/19 relapsed and 7 continue to receive VAC1. The Kaplan-Meier estimate of disease free survival (DFS) at 12 months, measured from beginning with the first vaccination of VAC1, was 79% for the 19 CR patients (95% CI: 52%-91%), 75% (31%-93%) for the eight patients in the intermediate risk group, and 81% for the 11 patients in the high risk group. Median DFS was not reached. Conclusions: Prolonged administration of VAC1, up to 32 vaccinations (the maximum number administered so far), is well tolerated in patients with AML, and associated with favorable DFS, especially in high-risk patients. Disclosures: DiPersio: Genzyme: Honoraria.

The Detection of Minimal Residual Disease By Multiparameter Flow Cytometry Predicts a Higher Risk of Relapse in Patients with ELN Intermediate Risk Acute Myeloid Leukemia Where Molecular Markers Are Not Available

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2882-2882
Author(s):  
Erika Borlenghi ◽  
Mirko Farina ◽  
Marco Chiarini ◽  
Viviana Giustini ◽  
Cinzia Lamorgese ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Risk Group ◽  
Risk Groups ◽  
Multiparameter Flow Cytometry ◽  
Intermediate Risk ◽  
Rt Pcr ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract INTRODUCTION: Over the last years multiparameter flow cytometry (MFC) has proven an effective method for the detection of minimal residual disease (MRD) not only in Acute Lymphoblastic Leukemia but also in Acute Myeloid Leukemia (AML) (Inaba, JCO 2012) providing powerful independent prognostic information (Loken, Blood 2012; Freeman, JCO 2013) in addition to molecularly-based approaches. It is unclear if it should be useful in all AML patients (pts) with a detectable leukemia associated immune-phenotype (LAIP) or just in pts without a molecular marker. Herein we report the results obtained in a consecutive series of pts followed at our institution. METHODS: Between July 2010 and March 2016, we analyzed MRD by MFC in 144 AML pts treated according to NILG AML study (Bassan, Blood 2003) at diagnosis and at the following subsequent time points (TP): achievement of complete remission (CR) after 1 or 2 courses of induction therapy (TP1), after the first consolidation course (TP2) and at the end of the treatment program (TP3). Bone marrow samples were analyzed by eight/six-colours MFC, the cut-off value used for MRD was 0.1% and 0.035% at TP1 (Al-Mawali, 2009) and 0.035% at TP2 and TP3 (Buccisano, Blood 2010). Molecularly based real-time quantitative PCR (RT-PCR) methods were used to monitor CBF in 10 pts and NPM1 in 25 pts (Gorello, Leukemia 2006). The pts median age was 56 years (19-73y), the F/M 59/85; de-novo AML 125/144 (86.8%) and secondary AML (s-AML) were 19/144 (13.2%). Most pts belonged to the intermediate (int) cytogenetic risk group (MRC favorable n=12, 8.3%, int n=105, 73%, adverse n=27, 18.7%), while the distribution according to ELN risk group was 51 favorable (35.4%), 47 int-I (32.6%), 19 int-II (13.2%) and 27 adverse (18.8%), respectively. RESULTS: At diagnosis 120/144 pts (83.3%) had a LAIP. There were no differences in clinical or biologic characteristics between pts with or without a LAIP, except that in the no-LAIP group the s-AML and adverse risk ELN were more represented (25% vs 10.7% and 25% vs 16.6%, respectively). In pts with LAIP, after a median follow-up of 23 months (ms), the CR rate was 88.3%, median relapse free survival (RFS) was 49%+/-7 ES, at 5y and median overall survival (OS) was 57.9 ms, with no differences compared to no-LAIP pts. Distribution among cytogenetic and molecular risk groups was as follows: for MRC favorable n=10 (8.3%), int n=90 (75%), adverse n=20 (16.7%); according to ELN risk: 43 favorable (35.8%), 40 int-I (33.3%), 17 int-II (14.2%), and 20 adverse (16.7%). The ELN risk classification stratified both for OS (p=0.004) and for RFS (p=0.0095), while MRC classification did not (p=0.33 and p=0.36, respectively). In the LAIP group we serially analyzed marrow cells at the different TP: 106/120 at TP1 (10 pts did not reach CR, 4 inadequate sample), 99 at TP2, while 66 were evaluable at TP3. MRD negativity was achieved at TP1 in 52/106 (49%) and in 21/106 (19.8%) pts with a threshold of 0.1% and 0.035%, respectively; at TP2 in 35/99 (35.4%) and at TP3 in 19/66 (24.2%). According to risk classification, at TP1 MRD positivity by MFC predicted relapse in int-I and int-II ELN risk groups, both with a threshold of 0.035% (p=0.018), and of 0.1% (p=0.0013) (Figure 1). The median of time to relapse was 11.9 ms in MRD positivity and 14.4 ms in MRD negativity pts. In the other ELN risk group there was no difference in relapse rate according to MRD negativity (p=0.19 and p=0.9 in favorable and p=0.16 and p=0.7 in adverse, respectively, according to 2 threshold). In the favorable ELN group the comparison of MRD results obtained by MFC with those obtained by RT-PCR was possible in 25 pts with NPM-mutated AML who achieved CR in 100% and relapsed in 20% of cases. MRD by MFC resulted detectable in 2 pts (8%) at TP1, in 7 pts at TP2 (28%), and in 13 of 25 pts (53%) at TP3, with no correlation with relapse risk. MRD positivity by RT-PCR predicted the relapse at TP2 (p=0.07) and at TP3 (p=0.0058) (Figure 2). CONCLUSION: Methods for determining MRD in AML may differ in their accuracy. Our study confirms that while in pts with favorable ELN risk AML, molecular methods may be considered the gold standard, in pts without a molecularly evaluable marker, the use of MFC may be useful for predicting relapse. Promising results of MFC MRD determination were achieved in the subset of AML at ELN intermediate risk where it is clinically most helpful in supporting the difficult choice among different postremission treatment strategy. Disclosures No relevant conflicts of interest to declare.

AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3832-3840 ◽  
Author(s):  
Nicolas Mounier ◽  
Michele Spina ◽  
Jean Gabarre ◽  
Martine Raphael ◽  
Giuliano Rizzardini ◽  
...  
Keyword(s):  
Risk Group ◽  
Cox Model ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Intermediate Risk ◽  
Intensive Chemotherapy ◽  
Poor Risk ◽  
Cell Counts ◽  
Risk Patients ◽  
Good Risk

We aimed to compare AIDS risk–adapted intensive chemotherapy in AIDS-related lymphoma (ARL) patients before and after the advent of highly active antiretroviral therapy (HAART). A total of 485 patients aged from 18 to 67 years were randomly assigned to chemotherapy after stratification according to an HIV score based on performance status, prior AIDS, and CD4+ cell counts below 0.10 × 109/L (100/mm3). A total of 218 good-risk patients (HIV score 0) received ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) or CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone); 177 intermediate-risk patients (HIV score 1), CHOP or low-dose CHOP (Ld-CHOP); and 90 poor-risk patients (HIV score 2-3), Ld-CHOP or VS (vincristine and steroid). The 5-year overall survival (OS) in the good-risk group was 51% for ACVBP versus 47% for CHOP (P = .85); in the intermediate-risk group, 28% for CHOP versus 24% for Ld-CHOP (P = .19); and in the poor-risk group, 11% for Ld-CHOP versus 3% for VS (P = .14). The time-dependent Cox model demonstrated that the only significant factors for OS were HAART (relative risk [RR] 1.6, P < .001), HIV score (RR 1.7, P < .001), and the International Prognostic Index (IPI) score (RR 1.5, P < .001) but not chemotherapy regimen. Our findings indicate that in ARL patients, HIV score, IPI score, and HAART affect survival but not the intensity of the CHOP-based chemotherapy.

scholarly journals Comparison of leucocyte profiles between healthy children and those with asymptomatic and symptomatic Plasmodium falciparum infections

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Diana Ahu Prah ◽  
Linda Eva Amoah ◽  
Matthew P. Gibbins ◽  
Yaw Bediako ◽  
Aubrey J. Cunnington ◽  
...  
Keyword(s):  
T Cells ◽  
Plasmodium Falciparum ◽  
Peripheral Blood ◽  
Parasite Load ◽  
Study Groups ◽  
Healthy Children ◽  
Peripheral Cell ◽  
Peripheral Blood Leucocyte ◽  
Cell Counts ◽  
Significant Difference

Abstract Background The immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood. Several studies have been carried out to characterize the associations between disease outcomes and leucocyte numbers. However, the majority of these studies have been conducted in adults with acute uncomplicated malaria, despite children being the most vulnerable group. Methods Peripheral blood leucocyte subpopulations were characterized in children with acute uncomplicated (symptomatic; n = 25) or asymptomatic (n = 67) P. falciparum malaria, as well as malaria-free (uninfected) children (n = 16) from Obom, a sub-district of Accra, Ghana. Leucocyte subpopulations were enumerated by flow cytometry and correlated with two measures of parasite load: (a) plasma levels of P. falciparum histidine-rich protein 2 (PfHRP2) as a proxy for parasite biomass and (b) peripheral blood parasite densities determined by microscopy. Results In children with symptomatic P. falciparum infections, the proportions and absolute cell counts of total (CD3 +) T cells, CD4 + T cells, CD8 + T cells, CD19 + B cells and CD11c + dendritic cells (DCs) were significantly lower as compared to asymptomatic P. falciparum-infected and uninfected children. Notably, CD15 + neutrophil proportions and cell counts were significantly increased in symptomatic children. There was no significant difference in the proportions and absolute counts of CD14 + monocytes amongst the three study groups. As expected, measures of parasite load were significantly higher in symptomatic cases. Remarkably, PfHRP2 levels and parasite densities negatively correlated with both the proportions and absolute numbers of peripheral leucocyte subsets: CD3 + T, CD4 + T, CD8 + T, CD19 + B, CD56 + NK, γδ + T and CD11c + cells. In contrast, both PfHRP2 levels and parasite densities positively correlated with the proportions and absolute numbers of CD15 + cells. Conclusions Symptomatic P. falciparum infection is correlated with an increase in the levels of peripheral blood neutrophils, indicating a role for this cell type in disease pathogenesis. Parasite load is a key determinant of peripheral cell numbers during malaria infections.

Presenting White Blood Cell Count and Kinetics of Molecular Remission Predict Prognosis in Acute Promyelocytic Leukemia Treated With All-Trans Retinoic Acid: Result of the Randomized MRC Trial

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4131-4143 ◽  
Author(s):  
Alan K. Burnett ◽  
David Grimwade ◽  
Ellen Solomon ◽  
Keith Wheatley ◽  
Anthony H. Goldstone
Keyword(s):  
Retinoic Acid ◽  
Promyelocytic Leukemia ◽  
Rt Pcr ◽  
Blood Cell Count ◽  
Relapse Risk ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
To Receive ◽  
Risk Of Relapse

Abstract All-trans retinoic acid (ATRA) is an essential component of the treatment of acute promyelocytic leukemia (APL), but the optimal timing and duration remain to be determined. Molecular characterization of this disease can refine the diagnosis and could be potentially useful in monitoring response to treatment. Patients defined morphologically to have APL were randomized to receive a 5-day course of ATRA before commencing chemotherapy or to receive daily ATRA commencing with chemotherapy and continuing until complete remission (CR). The chemotherapy was that used in current MRC Leukaemia Trials. Outcome comparisons were by intention to treat with additional analysis for relevant risk factors. Patients were characterized by molecular techniques for the fusion products of the t(15;17) and monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) during and after treatment. Two hundred thirty-nine patients were randomized. Treatment with extended ATRA resulted in a superior remission rate (87% v 70%, P &lt; .001), due to fewer early and induction deaths (12% v 23%, P = .02), and less resistant disease (2% v 7%, P = .03), which was associated with a significantly more rapid recovery of neutrophils and platelets. Extended ATRA reduced relapse risk (20%v 36% at 4 years, P = .04) and resulted in superior survival (71% v 52% at 4 years, P = .005). Presenting white blood cell count (WBC) was a key determinant of outcome. The 70% of patients who presented with a WBC less than 10 × 109/L had a better CR (85% v62%, P = .0001) and reduced relapse risk (22% v42%, P = .002) and superior survival (69%v 43%, P &lt; .0001). Within the low count group, extended ATRA resulted in a better CR (94% v 76%, P= .001), reduced relapse risk (13% v 35%, P = .04), and improved survival (80% v 57%, P = .0009). There was no evidence of benefit in patients presenting with a higher WBC (&gt;10 × 109/L). Molecular monitoring after the third chemotherapy course had a correlation with risk of relapse. The relapse risk was 57% if the RT-PCR was positive versus 27% if the RT-PCR was negative (P = .006). APL patients who present with a low WBC derive substantial benefit from combining ATRA with induction chemotherapy until remission is achieved, whereas patients with a higher WBC did not benefit. Molecular characterization of disease can improve diagnostic precision and a positive RT-PCR after consolidation identifies patients at a higher risk of relapse.

Over-expression of IL-6 coding gene in the peripheral blood of migraine with aura patients

2021 ◽  
pp. 1-5
Author(s):  
Mahdi Ramezani ◽  
Alireza Komaki ◽  
Mohammad Mahdi Eftekharian ◽  
Mehrdokht Mazdeh ◽  
Soudeh Ghafouri-Fard
Keyword(s):  
Migraine With Aura ◽  
Peripheral Blood ◽  
Healthy Subjects ◽  
Migraine Without Aura ◽  
P Value ◽  
Healthy Controls ◽  
Over Expression ◽  
Significant Difference ◽  
Male Patients ◽  
Years Lived With Disability

Migraine is a common disorder which is placed among the top ten reasons of years lived with disability. Cytokines are among the molecules that contribute in the pathophysiology of migraine. In the current study, we evaluated expression levels of IL-6 coding gene in the peripheral blood of 120 migraine patients (54 migraine without aura and 66 migraine with aura patients) and 40 healthy subjects. No significant difference was detected in expression of IL-6 between total migraine patients and healthy controls (Posterior beta = 0.253, P value = 0.199). The interaction effect between gender and group was significant (Posterior beta =-1.274, P value = 0.011), therefore, we conducted subgroup analysis within gender group. Such analysis revealed that while expression of this gene is not different between male patients and male controls (Posterior beta =-0.371, P value > 0.999), it was significantly over-expressed in female patients compared with female controls (Posterior beta = 0.86, P= 0.002). Expression of IL-6 was significantly higher in patients with aura compared with controls (Posterior beta = 0.63, adjusted P value = 0.019). However, expression of this cytokine coding gene was not different between patients without aura and healthy subjects (Posterior beta = 0.193, adjusted P value = 0.281). Therefore, IL-6 might be involved in the pathophysiology of migraine among females and migraine with aura among both sexes.

scholarly journals Athletes Drive Distinctive Trends of COVID-19 Infection in a College Campus Environment

2021 ◽  
Vol 18 (14) ◽  
pp. 7689
Author(s):  
Austin T. Hertel ◽  
Madison M. Heeter ◽  
Olivia M. Wirfel ◽  
Mara J. Bestram ◽  
Steven A. Mauro
Keyword(s):  
Risk Group ◽  
Temporal Trends ◽  
Rapid Identification ◽  
College Campus ◽  
Surveillance Program ◽  
Institutions Of Higher Education ◽  
Rt Pcr ◽  
Campus Environment ◽  
Incidence Risk ◽  
Academic Year

The COVID-19 pandemic forced most institutions of higher education to offer instruction and activities offsite, impacting millions of people. As universities consider resuming normal operations on campus, evidence-based guidance is needed to enhance safety protocols to reduce the spread of infectious disease in their campus environments. During the 2020/2021 academic year, Gannon University in Erie, PA, USA, was able to maintain most of its operations on campus. Part of Gannon’s disease mitigation strategy involved the development of a novel in-house, real-time RT-PCR-based surveillance program, which tested 23,227 samples to monitor the presence of COVID-19 on campus. Temporal trends of COVID-19 infection at Gannon were distinct from statewide data. A significant portion of this variance involved student athletes and associated staff, which identified as a higher incidence risk group compared with non-athletes. Rapid identification of athlete driven outbreaks allowed for swift action to limit the spread of COVID-19 among teammates and to the rest of the campus community. This allowed for successful completion of instruction and a modified season for all sports at Gannon. Our findings provide insights that could prove useful to the thousands of institutions seeking to resume a more traditional presence on campus.

Predictive Value of Gross Extranodal Extension for Differentiated Thyroid Carcinoma Persistence/Recurrence

2021 ◽  
pp. 019459982110231
Author(s):  
Ying Kou ◽  
Guohua Shen ◽  
Zhuzhong Cheng ◽  
Anren Kuang
Keyword(s):  
High Risk ◽  
Thyroid Carcinoma ◽  
Risk Group ◽  
Differentiated Thyroid Carcinoma ◽  
Individual Risk ◽  
Intermediate Risk ◽  
Entire Cohort ◽  
Gene Group ◽  
Extranodal Extension ◽  
Disease Persistence

Objective We systematically investigated the predictive value of gross extranodal extension (gENE) for differentiated thyroid carcinoma persistence/recurrence. Study Design Retrospective study. Setting A tertiary care hospital. Methods This study was divided into 2 groups according to gENE status: the gENE group and non-gENE group. We compared the disease persistence/recurrence rates of these 2 groups in the entire cohort and by individual risk group (intermediate/high risk), analyzed whether gENE was an independent risk factor for disease persistence/recurrence, and explored the impact of gENE-specific features on disease persistence/recurrence. Results There were 989 patients who satisfied the inclusion criteria: 57 patients in the gENE group and 932 in the non-gENE group. The disease persistence/recurrence rate of the gENE group was higher than that of the non-gENE group in the entire cohort and by individual risk group ( P < .05 for each). Unexpectedly, the outcomes of the gENE group with intermediate risk were similar to those of the non-gENE group with high risk ( P = .72). For the entire cohort, gENE was an independent predictor for disease persistence/recurrence (odds ratio, 2.89; 95% CI, 1.39-6.00; P = .005). Specific features of gENE ( P > .05 for each) were not related to disease persistence/recurrence. Conclusion Patients with gENE and intermediate risk might be regraded as high risk. Specific features of gENE have no impact on disease persistence/recurrence.

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