First Results of a Prospective Study on Erythropoietin Biosimilar (Epoetin zeta) Use in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

Abstract Introduction: Anemia is the most common hematological abnormality in patients with cancer and hematological malignancies, and is associated with poor prognosis and outcomes that have a detrimental impact on the patient's condition and quality of life (QOL). Erythropoiesis-stimulating agents (ESA) represent a good treatment option in order to increase the hemoglobin level in patients with anemia. Anemia can also be treated by red blood cell transfusion, but this has a transient effect and is associated with risks such as exposure to infectious agents, iron overload, or transfusion-related acute lung injury. ESA also have safety concerns, including the established increased risk of venous thromboembolic events. However, they are currently the only therapeutic alternative to transfusions. We performed a prospective observational study in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological malignancies, with the primary objective of evaluating the effect of a new ESA biosimilar, epoetin zeta (Hospira) on patient QOL. Secondary objectives included hemoglobin (Hb) and platelet (Pt) recovery, safety, overall survival (OS) and relapse incidence. Results of this study were compared to two reference populations, one receiving epoetin beta (Roche) and one control group not treated with ESA. Here, we present preliminary results for the secondary objectives. Materials and methods: The study included adult patients with Hb level ≤11g/dl occurring after all types of allo-HSCT for any hematological disease (Table 1). Epoetin zeta (30,000 IU) was administered s.c. once per week for up to 6 months, and Hb levels were monitored weekly. Injections were stopped once the Hb level reached 12g/dl without transfusion. If after 4 injections, no improvement was observed, doses were doubled, and if after 8 injections, no improvement was observed, the patient was withdrawn from the study. The QOL was measured at baseline and at 1, 2, 3 and 6 months by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Epoetin zeta responders were defined as having Hb level ≥12g/dl (complete response, CR) or a ≥2g/dl increase (partial response, PR) compared with baseline value, in the absence of transfusion. Patients receiving epoetin zeta (group 1) were compared to a similar population receiving epoetin beta with the same procedures (group 2) and to a matched population not treated with ESA (group 3), taking into account the following variables: sex, age, diagnosis, disease status at allo-HSCT, conditioning regimen and HSC source. Results: Between December 2011 and September 2014, 58 patients (from 168 screened) were included in group 1, and compared to 59 patients in group 2 and 65 patients in group 3. The main exclusion criteria were ESA contra-indication and patient refusal. Patients in group 1 had lower Hb baseline levels compared to group 2; patient characteristics for each group are summarized in Table 1. The median number of injections/patient was 10 (range: 6-14) in group 1 and 8 (range: 2-28) in group 2. The cumulative incidence of CR was 80% in group 1 and 71% in group 2. The median time to achieve CR was 48 days (range: 35-70) in group 1, and 39 days (range: 14-180) in group 2. Eight patients withdrew due to ESA inefficacy in group 1 and 8 in group 2. Adverse events were all thromboembolic: 2 events in group 1 and 5 events in group 2, compared to 2 events in group 3 (p=0.34). The multivariate analysis studying different confounding factors on the cumulative incidence of CR showed a significant positive impact of younger age (p=0.001), and a negative impact of being female or having major ABO incompatibility. We did not find any significant difference in terms of OS and relapse rate between the 3 groups. Conclusion: We describe here, for the first time, preliminary data for ESA biosimilar epoetin zeta (Hospira) in allo-HSCT patients showing comparable efficacy and safety to an existing ESA, epoetin beta (Roche) with no impact on OS and relapse incidence, compared to a control group. The QOL and transfusion evaluations as well as a cost-effectiveness study are ongoing and results will be presented. Disclosures Nicolini: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Download Full-text

AML-CM Score Predicts Prognosis in Hemato-Geriatric Patients with New-Onset Acute Myeloid Leukemia (AML) Who Receive Hypomethylating Agents (HMA)

Blood ◽

10.1182/blood-2019-130630 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2617-2617

Author(s):

Giovanni Marconi ◽

Roberta di Nicola ◽

Chiara Sartor ◽

Mariachiara Abbenante ◽

Jacopo Nanni ◽

...

Keyword(s):

Adverse Events ◽

Board Of Directors ◽

Advisory Committees ◽

Group 4 ◽

Group A ◽

Group 3 ◽

Group 2 ◽

Group B ◽

Idh2 Mutation ◽

Group 1

Background Although much efforts have been made to precisely define fitness of AML patients, in patients who are not candidate to chemotherapy, there is no prognostic model and the respective weight of AML biology and patient fitness are not well established. Here we test AML-CM score (Sorror, JAMA 2018), that is validated in fit population, in a set of old AML patients who received HMAs. Methods We retrospectively collected data of consecutive patients who received HMAs in our institution from 1st Jan 2008 with an age > 65 years at AML diagnosis. AML-CM score was applied to all the patients. Patients were divided in 4 groups (score 1-4: group 1, score 5-6: group 2; score 7-9: group 3, score > 9: group 4) and in 2 macro-groups (score 1-6: group A and score > 6 group B) for the analyses. Descriptive data are presented as median with interquartile ranges (IQR). Adverse events are graded according to CTCAE v4.03. Survival analysis was conducted with Kaplan-Meyer and are presented as 95% confidence intervals (C.I.) and differences in overall survival (OS) were tested with 2-side log rank test. Fisher exact test and Person's chi squared test were used whenever appropriate. Results At data cut-off, 1st Jan 2019, 60 consecutive patients received decitabine or azacytidine as 1st line therapy for AML. Median age of the population was 75.94 years (IQR 72.53-80.38). Most of the patients (37/62, 59.7%) had de novo AML, 19/62 (30.6%) had AML secondary to previous myeloid disorders and 6/62 (9.7%) had AML secondary to chemotherapy or radiotherapy. Most of the patients were smokers (19/33, 57.57%, 29 no data), and few were usual drinkers (4/16, 25.00%, 46 no data). In our set, out of 62 patients, 2 patients (3.2%) had inv(3), 1 (1.6%) a translocation involving 11q23, 1 (1.6%) del(5q), 4 (6.4%) mon(7) or del (7q), 1 (1.6%) del(17p), 15 (24.2%) complex karyotype, 27 (43.5%) normal karyotype, 4 (6.5%) other alterations and 5 were not evaluable; 3/17 (17.65%, 45 no data) harbored IDH2 mutation, 1/16 (6.25%) IDH2 mutation, 2/33 FLT3 mutation (6.06%, 29 no data), 1/24 (4.17%, 38 no data), 2/15 (13.33%, 47 no data) TP53 mutation. According to ELN 2017, 3/62 patients (4.83%) had low risk, 34/62 (54.84%) intermediate risk and 23/62 (37.10%) high risk AML. According to AML-CM score, 13/62 patients (20.97%) were in group A, 20/62 (32.36%) in group B, 21/62 (33.87%) in group C, 6/62 (9.68%) in group D, 2/62 (3.23%) were not allocated for incomplete AML-CM score. There was no difference in term of age, ELN risk, secondary AML prevalence, HMA administered, or response to HMA according to ELN criteria between group 1, 2, 3, 4 or between macro-group A and B. Cardiovascular comorbidity, diabetes mellitus, obesity, previous tumor, hypoalbuminemia, elevated LDH were prevalent in higher risk AML-CM groups (3-4) and in macro-group B. Median OS was 658 days (95% C.I. 316-1000) in group 1, 556 days (95% C.I. 463-649 in group 2, 243 days (95% C.I. 153-353) in group 3, 107 days (95% C.I. 47-167) in group 4 (p=.021, figure 1A). Furthermore, we observed a median OS of 589 days (95% C.I. 328-850) in macro-group A and 219 days (95% C.I. 96-342) in macro-group B (p=.003, figure 1B). Reduced survival was correlated with a non-statistical trend toward augmented incidence of infections and adverse events in higher risk AML-CM groups (3-4). Conclusions AML-CM is a useful indicator of prognosis in old patients that receive HMAs. Prognosis in our set is influenced by comorbidity (measured with AML-CM, a quantitative score) more than by disease biology. We identified a group of patients (macro-group A) that has median OS after HMAs outlying OS reported in literature. This brilliant result can be due to lower comorbidity. AML-CM could help in defining candidate patients for therapy intensification and care utilization or for team comorbidity management. GM and RDN equally contributed Figure 1 Disclosures Martinelli: Roche: Consultancy; Novartis: Consultancy; ARIAD: Consultancy; BMS: Consultancy; Pfizer: Consultancy. Baccarani:Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Takeda: Consultancy. Papayannidis:Pfizer: Honoraria; Teva: Honoraria; Shire: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Incyte: Honoraria. Cavo:janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Download Full-text

Acute Myeloid Leukemia with Myelodisplasia-Related Changes (AML-MRC) Defined Only By Morphological Findings May Not Represent a Poor Prognosis AML

Blood ◽

10.1182/blood-2019-129153 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2612-2612

Author(s):

Ana Pérez ◽

Olga Salamero ◽

Helena Pomares ◽

Maria Julia Montoro ◽

Montserrat Arnan Sangerman ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Poor Prognosis ◽

Advisory Committees ◽

Group 3 ◽

Group 2 ◽

Acute Myeloid ◽

Group 1

According to the 2016 WHO classification, AML-MRC encompasses an heterogeneous group of acute myeloid leukemias (AML) comprising: AML emerged from a previous myelodysplastic syndrome (MDS) or myeloproliferative /myelodysplastic disease (group 1), AML with MDS-defining cytogenetic abnormalities (group 2), or acute myeloid leukemia (AML) with dysplasia in at least 2 cell lineages without the above mentioned (group 3). In spite that AML-MRC has been considered a high-risk entity with poor prognosis, little is known on the relationship of clinical and biological characteristics with outcomes in these three groups. The aim of this study was to describe the clinical and biological characteristics of patients with AML-MRC and analyze their prognostic variables and outcomes. We retrospectively analyzed AML-MRC cases diagnosed between January-2009 and December- 2018 in two institutions. Descriptive variables were studied to compare the three AML-MRC groups. AML cytogenetic risk and response were defined according to the European Leukemia Net recommendations. Overall survival (OS) was considered as the time from the diagnosis to the last visit. Survival analysis were performed with Kaplan Meier method and comparisons with the log-rank test. Among 575 cases of AML identified, 186 (32.3%) met AML-MRC criteria and were included in the study. The main patient characteristics are shown in Table1. Median age was 72 (range, 22-88) years and 32% were female. Adverse karyotype was present in 29% of patients, being more prevalent in the AML-MRC group 2. Sixty one patients (33%) received an intensive chemotherapy approach and 36 (19%) an allogeneic stem cell transplantation. Patients in group 3 exhibit a higher probability of achieving a complete response than groups 1 and 2 (Table 2). After a median follow-up for survivors of 28.5 months (range, 5-130), 149 (80%) died in this period. Three years Overall Survival (OS) for patients in groups 1, 2 and 3 was 3 (0-117), 5 (0-93) and 10 (0-130) months, respectively (p=0.012) (Figure 1). Type of treatment (intensive, non intensive or best supportive care) and cytogenetic risk also showed impact on OS. Multivariant analysis adjusting these factors showed that patients in group 3 also presented better OS than patients in group 1 (HR=0,42 [IC95% 0,18-0,84], p=0,02), both with around a 30% of patients with adverse cytogenetics. To conclude the present study suggests that group 3 of AML-MRC, for which the diagnosis is based solely on morphologic findings, showed better prognosis than the other groups. A more detailed molecular characterization might contribute to improve prognostic stratification of this heterogeneous AML entity, particularly in patients with non-high risk cytogenetics. Disclosures Salamero: Pfizer: Honoraria; Daichii Sankyo: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Valcárcel:Jazz Pharmaceuticals: Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: spouse is an employee in the company, Speakers Bureau; Pfizer: Honoraria. Bosch:AstraZeneca: Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Download Full-text

Do MYC Alterations Matter in HIV-Associated Large B Cell Lymphomas? the "Euromyc" Study (a European retrospective study)

Blood ◽

10.1182/blood-2021-151149 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2506-2506

Author(s):

Chiara Pagani ◽

Chiara Rusconi ◽

Alessia Dalla Pria ◽

Emanuele Ravano ◽

Philipp Schommers ◽

...

Keyword(s):

B Cell ◽

Board Of Directors ◽

Clinical Characteristics ◽

Prognostic Impact ◽

Advisory Committees ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Large B Cell ◽

Group 1

Abstract Introduction: In the general HIV negative population, patients (pts) with diffuse large B cell lymphoma (DLBCL) or high grade B cell lymphoma (HGBCL) carrying MYC rearrangements and BCL2 and/or BCL-6 translocations [double hit (DHL) or triple hit lymphomas (THL)] have shown a dismal prognosis when treated with standard R-CHOP and are frequently candidates to intensive therapeutic regimens, without having a standard of care. Moreover, several authors have demonstrated a negative prognostic impact of isolated MYC rearrangements [single hit lymphomas (SHL)] and the best therapeutic approach for SHL are even less clear. In HIV-associated "non Burkitt" large B cell lymphomas (Ly), scanty data are available on the prevalence and the clinical and prognostic impact of MYC rearrangements, with or without BCL2 and BCL6 concomitant translocations. Due to the peculiar biology and pathogenesis of HIV-associated Ly, data from HIV negative population cannot be simply translated to the HIV positive pts. Aim: To evaluate the impact of MYC rearrangements or translocations (isolated or with BCL2 and/or BCL6 translocations) on clinical features and outcome of HIV-associated large B cell Ly. Methods: Retrospective analysis of clinical characteristics, treatment received and outcome of all HIV-associated large B cell Ly [including DLBCL, B cell Ly unclassifiable, with features intermediate between DLBCL and Burkitt (BCLU), and HGBL] with MYC rearrangements or translocations, evaluated by FISH analysis, in 11 European centers, and comparison with pts who do not have the MYC alterations. Results: One hundred-sixty-one pts were enrolled, 49 (30%) had MYC translocation or other MYC rearrangements (MYC+ pts), and 112 (70%) were negative for MYC mutation (7 pts had MYC increased copy number) (MYC- pts). Table 1 shows the clinical characteristics of the two groups, and the treatment received. MYC+ pts had higher involvement of central nervous system at presentation (17% vs 3%, p 0,023), higher Ki67% (median 91% vs 85%, p 0,005), histology other than DLBCL (32% vs 9%, p 0,0001), concomitant translocation of BCL2 (14% vs 3%, p 0,022), germinal center B phenotype (according to Hans algorithm) (85% vs 49%, p 0,0001). No differences in CD4 count or HIV viral load at Ly diagnosis were found, while a previous diagnosis of AIDS was more frequent in the MYC- group (27% vs 10%, p 0,023). MYC+ pts received more frequently intensive treatment (iCT) (41% vs 12%, p 0,0001) and less frequently the standard CHOP regimen (41% vs 74%, p 0,001). Ten pts (9%) had a DHL/THL and had similar clinical characteristics compared to SHL. With a median follow-up of 62 months, there were no significant differences in overall survival (OS) and progression-free survival (PFS) between MYC+ and MYC- pts (5 years-OS and PFS were respectively 55% and 47% in MYC+ and 59% and 53% in MYC- pts). In univariate analysis for the whole population, IPI≥3, ECOG≥ 2 and increased LDH were related to a worse OS and PFS while BCL2 translocation correlated with shorter PFS alone. In multivariate analysis ECOG and IPI mainteined their negative prognostic impact on OS and PFS. In the MYC+ group, 41% pts received R-CHOP or CHOP-like treatment (group 1), 16% infusional therapy (group 2), 41% iCT (group 3), 2% palliative therapy (PT) (group 4); 5-years OS and PFS were 47% and 32% for group 1, 47% and 37% for group 2, 67% and 68% for group 3 and both 0% for group 4. Median OS and PFS were respectively 18 and 2 months for group 1, 29 and 7 months for group 2, both not reached for group 3, both 2 months for group 4. A significant difference between group 3 and group 1 both in therm of OS (p 0,054) and PFS (p 0,005) was observed (Figure 1). Pts with DHL/THL received R-CHOP (40%), infusional schedule (30%), iCT (20%) and PT (10%). No significant difference in term of PFS and OS were observed for each treatment group with DHL/THL respect to those with SHL. In DHL/THL, 5 years OS and PFS were 50% and 30%, respectively; in SHL 56% and 51%, respectively. Of note, no pts treated with iCT died from toxicity in the MYC+ group. Conclusion: In this retrospective analysis, MYC+ pts had not different clinical characteristics compared to MYC- pts other than higher proliferative index and and more CNS involvement at diagnosis. MYC+ pts were frequently treated with iCT, this aggressive approach seemed feasible and could allow to obtain better outcome compared to standard R-CHOP treatment but further prospective studies are needed. Figure 1 Figure 1. Disclosures Bastos-Oreiro: F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Arcaini: Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Gilead Sciences: Research Funding; Celgene: Speakers Bureau. Rossi: Novartis: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

A Comparison of Droplet Digital PCR and RT-qPCR for BCR-ABL1 Monitoring in Chronic Myeloid Leukemia

Blood ◽

10.1182/blood-2019-125614 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2092-2092

Author(s):

Carmen Fava ◽

Paola Berchialla ◽

Jessica Petiti ◽

Maria Teresa Bochicchio ◽

Barbara Izzo ◽

...

Keyword(s):

Board Of Directors ◽

Digital Pcr ◽

Advisory Committees ◽

Coefficients Of Variation ◽

One Step ◽

Group 3 ◽

Group 5 ◽

Group 2 ◽

The One ◽

Group 1

Background: Monitoring of BCR-ABL1 molecular levels is essential for the management of Chronic Myeloid Leukemia (CML) patients treated with Tyrosine Kinases Inhibitors (TKIs). Real Time Quantitative PCR (RT-qPCR) is currently the standard method for assessing molecular remission (MR) in patients with CML. Recently, droplet digital PCR (ddPCR) has emerged to provide a more accurate detection of minimal residual disease (MRD). In order to hypothesize the use of this new technology in the clinical practice, in the era of TKI discontinuation, we designed a multi-centric study to evaluate the potential value of ddPCR in diagnostic routine. Aims of the study were:1) the evaluation of the agreement between the measures obtained by ddPCR and RT-qPCR and 2) the assessment of the repeatability of the two methods. Methods: Total RNA was extracted from 37 CML patients using Maxwell 16 LEV simplyRNA Blood kit (Promega), following the manufacturer's instructions. Samples were divided in 5 groups based on molecular response (MR) as follow: group 1, MR<3, n=5; group 2, MR 3, n=5; group 3, MR 4, n=9; group 4, MR 4.5, n=9 and group 5, MR 5, n=9. BCR-ABL1 p210 was quantified by RT-qPCR and ddPCR in 3 different Italian laboratories namely Lab A, Lab B and Lab C. Lab B and C performed 1 amplification session each, while Lab A performed 3 independent sessions. All ddPCR experiments were performed using Kit QXDxTM BCR-ABL%IS (Bio-Rad) on the QX200 system (Bio-Rad), according to the manufacturer's instructions. For RT-qPCR experiments, BCR-ABL1 p210 was quantified with three different methods: by using the One-Step BCR-ABL P210 ELITe MGB Kit (ELITech Group), according to manufacturer's protocol (Lab A); by using the One-Step Philadelphia SensiQuant Kit (Bioclarma), according to the manufacturer's instructions (Lab B) and as described in Gabert et al (Lab C). The results obtained were corrected for the laboratory-specific conversion factor, as recommended by Standard Operating Procedures of Labnet CML network (GIMEMA group). The target quantification for each sample was expressed as BCR-ABL1/ABL1 %IS for both RT-qPCR and ddPCR. Statistical analysis: Bland-Altman analysis was performed. For the measurement of the agreement we reported the bias, which is the mean of the difference between the methods, the 95% limits of agreement and the coefficient of variation. Residual variance and coefficients of repeatability (i.e. the upper limits of a prediction interval for the absolute difference between two measurements by the same method on the same item) were computed to achieve the second endpoint. An analysis of sensitivity on the labs was also carried out. All analyses were stratified by the level of disease. Results: A total of 370 measures were included in the analysis, 185 for ddPCR and 185 for RT-qPCR divided as follow: 50 for group 1 and for group 2, 90 for group 3, 4 and 5. In Table 1 we reported the median and interquartile range (IQR) for all levels of disease. Results of the Bland-Altman analysis are shown in Table 2. The coefficients of variation, which expresses the standard deviation as a percentage of the mean, were 2.35, 2.31, 1.10, 1.34, 39.12 in group 1, 2, 3, 4 and 5 respectively. The repeatability coefficients of ddPCR were smaller than qRT-PCR across all the levels of disease, showing a slightly better precision of ddPCR (Table 2). Conclusions: Higher coefficients of variation in group 1 and 2 were probably due to a greater heterogeneity of the patients. In fact, BCR-ABL1/ABL1 levels by RT-qPCR ranged between 1.43 and 6.94 and between 0.10 and 0.25 in group 1 and in group 2 respectively (Table 1). Sensitivity analysis showed that the high coefficient of variation in group 5 can be explained almost all by the variability observed in Lab B. Coefficient of repeatability of ddPCR was always smaller than RT-qPCR for all level of disease showing a slightly better precision. Our results showed that ddPCR has a good agreement with RT-qPCR and it is more precise to quantify BCR-ABL1 transcript levels, particularly for MR 4 and MR 4.5. Thus, ddPCR may be valuable in diagnostic routine. Disclosures Fava: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria. Martino:Bio-Rad: Employment. Saglio:Ariad: Consultancy; Incyte: Consultancy; Pfizer: Consultancy; Jansen: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy. Martinelli:Roche: Consultancy; BMS: Consultancy; Novartis: Consultancy; ARIAD: Consultancy; Pfizer: Consultancy. Pane:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: research founding; Janssen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Cilloni:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Preliminary Results Of A Mass Spectrometry Based Bottom Up Proteomic Approach On Bone Marrow Plasma Cells From Patients With Multiple Myeloma (MM)

Blood ◽

10.1182/blood.v122.21.1887.1887 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1887-1887

Author(s):

Beycan Ayhan ◽

Duygu Ozer Demiralp ◽

Klara Dalva ◽

Meral Beksac

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Plasma Cell ◽

Plasma Cells ◽

B Cell Lymphoma ◽

Ionization Mass ◽

Advisory Committees ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Aim The molecular mechanisms responsible from evolution to malignant monoclonal plasmacytosis is still under investigation. The aim of this prospective study was to analyze the proteomics profile of plasma cells obtained from MGUS, SMM and symptomatic myeloma patients to be able to investigate the differences at protein level between patients with low vs high plasma cell content (PCC). Material and Methods Marrow samples were collected from 30 patients newly diagnosed with Multiple Myeloma (n: 28 symptomatic and n: 1 smoldering (SMM)) and n:1 MGUS) at Ankara University Department of Hematology. Plasma cells were isolated by CD138+ selection before protein extraction. The patients were classified mainly in to three groups according to marrow PCC by flow cytometry: group1: 0-9, group 2: 10-20 and group 3: >20 %. The protein profiles of these three groups were constructed and compared via 2D gel electrophoresis by using PDQuest 8.01 analysis. Up/down regulated protein spots were identified with Matrix-assisted laser desorption/ionization mass spectroscopy(MALDI) by Peptide Mass Fingerprinting (PMF) analysis Results All protein spots that were detected according to PCC with PDQuest analysis are as follows: 135 spots in group 1 142 spots in group 2 and 145 spots in group 3 Among these spots, 27 spots with significant expression density difference (at least 2-fold) were detected between group 1 and 2, 36 spots between group 1 and group 3 and 28 spots between group 2 and group 3. 36 of these protein spots were were used in peptide isolation by using trypsin. PMF analyses were carried out in MALDI-TOF mass spectrometer. From these spots, eight proteins were identified by using Mascot: Endoplasmin (ERp99), Calreticulin(ERp60), MZB1(Marginal zone B and B1 cell specific protein/pERp1), Actin cytoplasmic1(ACTB), Myeloblastin (Leukocyte proteinase 3), Thioredoxin domain-containing protein 5 (TXNDC5/ERp46), Apoptosis regulator B-cell lymphoma 2 (Bcl-2) and Peroxiredoxin-4 ( Table 1, Figure 1). The remaining 28 spots are under investigation. In group 3 the density of protein spots which contain Calreticulin, MZB1, Myeloblastin and TXCDN5 increased, and which contain Actin and Endoplasmin decreased significantly (Table 1). There was a negative corelation between the Peroxiredoxin expression level and the PCC which resulted in disappearance as the percentage of PCC increased. Moreover, not only Peroxiredoxin, but also BCL-2 protein was detected only in the group with PCC >20 %. To avoid the changes that can be attributable to PC counts equal amounts of protein were analyzed from each group. Conclusion Until now there is only one published study utilizing proteomics in MM and reports 268 proteins (Chun Hua Lu et al, J Proteomics Informatics 2010). Ours is the first proteomics study comparing plasma cell proteins with PCC. The functional properties of these proteins are summarized (Table 2). High protein production and folding plus Ca changes in MM support our findings on chaperons and Ca binding protein changes. Out of these eight proteins only bcl-2, MZB1 and calreticulin were previously reported to be involved in the biology of MM. Disclosures: Beksac: Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Download Full-text

Postoperative Morphine Use and Hyperalgesia Are Reduced by Preoperative but Not Intraoperative Epidural Analgesia

Anesthesiology ◽

10.1097/00000542-200306000-00023 ◽

2003 ◽

Vol 98 (6) ◽

pp. 1449-1460 ◽

Cited By ~ 78

Author(s):

Joel Katz ◽

Lorenzo Cohen ◽

Roger Schmid ◽

Vincent W.S. Chan ◽

Adarose Wowk

Keyword(s):

Morphine Consumption ◽

Gynecologic Surgery ◽

Control Group ◽

Epidural Administration ◽

Blinded Manner ◽

Group 3 ◽

Group 2 ◽

Double Blinded ◽

Postoperative Morphine ◽

Group 1

Background The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control. Methods Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia. Results One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg). Conclusions Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.

Download Full-text

Antioxidant Effect of MnTE-2-PyP on Lung in Asthma Mice Model

The Scientific World JOURNAL ◽

10.1100/2012/379360 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Lyudmil Terziev ◽

Violeta Dancheva ◽

Veneta Shopova ◽

Galya Stavreva

Keyword(s):

Superoxide Dismutase ◽

Glutathione Peroxidase ◽

Control Group ◽

Mice Model ◽

Antioxidant Defence ◽

Group 4 ◽

Antioxidant Defence System ◽

Group 3 ◽

Group 2 ◽

Group 1

Aim. To investigate the effects of MnTE-2-PyP on some markers of antioxidant defence system in asthma mice model.Material and Methods. The animals were divided into four groups: group 1, controls; group 2, injected with ovalbumin, group 3, treated with MnTE-2-PyP, and group 4, treated with ovalbumin and MnTE-2-PyP. The activities of superoxide dismutase, catalase, glutathione peroxidase and nonprotein sulfhydryl groups content (NPSH) were determined in lung homogenate.Results. The activities of superoxide dismutase and catalase in group 2 decreased significantly as compared to control group. The decrease of the same enzymes in group 4 was lower and significant as compared to group 2. Changes in the glutathione peroxidase activity showed a similar dynamics. The NPSH groups content decreased in group 2. In group 4 this decrease was relatively lower as compared to group 2.Conclusions. The application of MnTE-2-PyP mitigated the effects of oxidative stress in asthma mice model.

Download Full-text

Pengaruh Monoklonal Antibodi Bovine Zona Pelusida 3 (bZP3) terhadap Diameter dan Atresia Folikel Ovarium Mencit (Mus musculus)

Majalah Obstetri & Ginekologi ◽

10.20473/mog.v24i12016.37-42 ◽

2018 ◽

Vol 24 (1) ◽

pp. 37

Author(s):

Annisa Trissatharra ◽

Sri Ratna Dwiningsih ◽

Ratna Sofaria Munir

Keyword(s):

Mus Musculus ◽

Ovarian Follicles ◽

Observation Time ◽

Control Group ◽

Control Group Design ◽

Treatment Groups ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Group 1

Objectives: To identify the effect of monoclonal antibody bZP3 at ovarian follicles that undergo atresia and diameter of various ovarian follicles.Materials and Methods: This is a true experimental research with post only control group design. Samples were 36 female mices (Mus musculus) which is divided into 6 groups, there are 3 control groups (group 1, 2, and 3) injected by Phospatase Buffer Saline (PBS) 50µl and 3 treatment groups (group 4, 5, and 6) injected by Mab bZP3 50µl. Group 1 and 4 terminated at 5th day, group 2 and 5 terminated at 10th day, and group 3 and 6 terminated at 20th day. Evaluation of atretic ovarian follicles and diameter of ovarian follicles performed by hematoxylin eosin (HE) and the data processed by parametric statistic.Results: There are no significant in different among groups in the aspect of atretic follicles and diameter of folicles (p>0.05), but descriptively, number of follicles undergo atresia of the follicle primary, secondary, and tertiary treatment group was higher than the control group, except on the 20th day of observation time.Conclusion: administration of Mab bZP3 had no effect to amount of atretic follicles and diameter of folicles during observation time.

Download Full-text

Zingerone Ameliorates Hepatotoxicity

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1817 ◽

2020 ◽

Vol 11 (1) ◽

pp. 280-284 ◽

Cited By ~ 1

Author(s):

Julietpoornamathy J ◽

Parameswari C.S.

Keyword(s):

The Body ◽

Control Group ◽

Medical Sciences ◽

Toxic Compounds ◽

Group 4 ◽

Group 3 ◽

Group 5 ◽

Group 2 ◽

Insight Into ◽

Group 1

In medical sciences, toxicity is an area wherein extensive studies have been carried to improve the diseases as well as to prevent. So, there is a high requirement for novel and improved alternative therapeutic strategies to manage diseases. The liver is the largest gland in the body, which executes several important mechanisms; it stores minerals and vitamins and releases them in periods of need. The main aim of this study was to give a closer insight into potent non- toxic compounds that is capable of modifying the responses. Animals were divided into five equal groups viz control (Group 1), administered with food and water ad libitum, (Group 2) administered with olive oil, (Group 3) administered with zingerone, (Group 4) administered with concanavalin A, (Group 5) administered with cyclosporine A followed by zingerone. Our results revealed significant changes in liver marker enzymes and liver histology of zingerone treated rats when compared to control rats. A corollary, zingerone has no toxic effect on hepatocytes and was found to be safe at a dose of 10mg/kg b wt and also ameliorates hepatotoxicity.

Download Full-text

Comparative parasitological and electron microscopic studies on the effects of Nitazoxanide and Praziquantel in Schistosoma mansoni-infected mice

International Journal of Pharmacology and Toxicology ◽

10.14419/ijpt.v4i2.6822 ◽

2016 ◽

Vol 4 (2) ◽

pp. 228

Author(s):

Hend A. El-Taweel ◽

Mona H. El-Sayad ◽

Sahar A. Abu Helw ◽

Mohammad A. Al-Kazzaz

Keyword(s):

Schistosoma Mansoni ◽

Control Group ◽

Electron Microscopic ◽

Male And Female ◽

Scanning Electron Microscopic ◽

Antischistosomal Activity ◽

Microscopic Studies ◽

Group 3 ◽

Group 2 ◽

Group 1

This study was designed to evaluate antischistosomal activity of Nitazoxanide (NTZ) in Schistosoma mansoni-infected mice compared to Praziquantel (PZQ). Fifty four infected mice were recruited into 3 groups, each of 18 mice. Group 1 was infected non-treated control. Group 2 was infected and then treated with PZQ 500 mg for two days, and group 3 was infected and treated with NTZ 100 mg/kg for seven days. Efficacy of drugs was assessed by Parasitological, and scanning electron microscopic studies. PZQ reduced (4.9%, 22.5% and 50.7%) of faecal eggs, (22%, 22.6% and 55.1%) of intestinal eggs, (20.4%, 44.3% and 46.7%) of hepatic egg counts and (27%, 45.1% and 64.9%) of total worm load whereas, NTZ reduced (4.9%, 22.5% and 50.7%),of faecal eggs, (22%, 22.6% and 55.1%) of intestinal eggs ,(20.4%, 44.3% and 46.7%) of hepatic egg counts and (27%, 45.1% and 64.9%) of total worm load at 1, 2 and 4 WPT, respectively. The percentages of dead eggs were more than 80% after PZQ treatment and only 30% after NTZ at 4 WPT. PZQ showed extensive tegumental damages in male and female worms more than NTZ at 2 WPT. Our findings concluded that Nitazoxanide showed weaker antischistosomal activity in animal models than praziquantel.

Download Full-text