post induction
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2022 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jan Philipp Bewersdorf ◽  
Thomas Prebet ◽  
Lohith Gowda
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2021 ◽  
Vol 9 (11) ◽  
pp. 1231-1247
Author(s):  
Bhavini Shah ◽  
Shweta Bhimashankar Birajdar

Introduction: Laryngoscopy and subsequent tracheal intubation cause a fugitive tachycardia and hypertension as a result of sympathoadrenal stimulation. Careful selection of anestheshetic is thus required, as cardiovascular reserve is decreased in certain patients, so as to avoid undue depressions of cardiac and circulatory function Aims And Objectives: This randomized double blind prospective study had been designed for comparative evaluation of inj propofol 2.5 mg/kg, inj Etomidate 0.3 mg/kg an induction agent on haemodynamic changes such as HR, SBP, DBP, MAP and oxygen saturation during induction and tracheal intubation and also to study the adverse effects the two drugs under study Material And Methods: After approval from medical ethics committee, Dr D Y Patil Medical College and Hospital, Pune, the study was carried out on sixty (60) patients undergoing elective surgeries under standard general anesthesia. ? All patients were premedicated with Ondansetron 0.1mg/kg i.v., inj midazolam 0.02mg/kg and inj fentanyl 2 mcg/kg i.v. ? All patients pre-oxygenated with 100% oxygen for 3 min, all vital parameters recorded (T1) ? Group P received inj. propofol 2.5 mg/kg i.v. and group E received Etomidate 0.3mg/kg i.v. over 30 sec and vital parameters recorded as (T2) ? Inj succinylcholine as muscle relaxant given after administering induction agent, laryngoscopy and tracheal intubation attempted with appropriate sized endotracheal tube. All vital parameters recorded during laryngoscopy(T3), periodic monitoring of vital parameters carried out at 1,2,3,5 and 10 minutes intervals post intubation ? Further the patient was maintained on O2 /N2O / Isoflurane and Vecuronium i.v. top-ups as and when required ? At the end of surgery, patient reversed with inj. Glycopyrrolate 0.008mg/kg i.v. along with inj. Neostigmine 0.05mg/kg intravenously and extubated after gaining consciousness and adequate power ? Patient shifted to recovery room observed for any side effects such as nausea, vomiting, Result: The demographic profile was comparable. There was no statistically considerable difference between the two study groups with respect to baseline parameters of HR, SBP, DBP, MAP and SpO2. There was decrease in mean heart rate seen in group P compared to group E at post induction (T2), after intubation 1 min, 2min, the values were statistically significant with P value <0.05,.and decrease in mean SBP, mean DBP AND MAP in group P compared to group E at post induction (T2), after intubation 1,2 3, 5 min values were statistically significant with p value <0.05 Pain on injection was more in group P 26 out of 30(86.7%) than group E, which was statistically significant with p value <0.05 Incidence of myoclonus was more in group E 23 patients out of 30(76.7%) compared to group P which was statistically significant with p value <0.05. In group P 2 out of 30 patients (6.7%) had vomiting and in group E 3 out of 30 patients (10%) had vomiting, difference was statistically insignificant with p value >0.05 Conclusion: A• Both, Propofol and etomidate are safe induction agents A• Etomidate maintains better haemodynamic stability than propofol as induction agent A• Pain on injection was more with propofol. However, myoclonus was more with etomidate A• Both drugs were associated with no significant side effects/complication.


Author(s):  
Dhimitri A Nikolla ◽  
Jestin N Carlson ◽  
Paul M Jimenez Stuart ◽  
Irtaza Asar ◽  
Michael D April ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2308-2308
Author(s):  
Leiah Brigitha ◽  
Marta Fiocco ◽  
Rob Pieters ◽  
Birgitte Klug Albertsen ◽  
Gabriele Escherich ◽  
...  

Abstract PURPOSE Asparaginase is a key component of acute lymphoblastic leukemia (ALL) therapy. Hypersensitivity reactions challenge its use and occur frequently (30-75%) after native Escherichia. Coli (E.coli) asparaginase (Appel et al., 2008; Muller et al., 2001; Panosyan et al., 2004; Silverman et al., 2001). The international ALL Ponte di Legno Toxicity Work Group (PTWG) classifies hypersensitivity to asparaginase as (i) allergy in case of symptoms of allergy (always associated with undetectable asparaginase activity levels), (ii) allergic-like reactions in case of symptoms without inactivation, and (iii) silent inactivation (SI) with inactivation of asparaginase activity, but without hypersensitivity symptoms (Schmiegelow et al., 2016). Allergic-like reactions and SI can only be diagnosed with monitoring of asparaginase activity levels. A meta-analysis was performed based on data from the PTWG to estimate the incidence of hypersensitivity and risk factors for hypersensitivity to asparaginase in ALL protocols using pegylated E.coli asparaginase (PEGasparaginase) as first line of treatment. PATIENTS AND METHODS Questionnaires were sent to all members of the PTWG. Information on protocol level regarding PEGasparaginase dose, dosing regimen (e.g. dosing frequency, total number of doses, PEGasparaginase-free intervals(s)), administration route, total induction and post-induction hypersensitivity rates per protocol and per risk group and use of therapeutic drug monitoring (TDM). To facilitate comparison between protocols with and without TDM, we defined allergic reactions as the sum of allergies and allergic-like reactions. Silent inactivation was analyzed separately. RESULTS A total of 5880 patients with newly diagnosed ALL, aged 1 to 24 years old, were enrolled in seven different upfront ALL protocols using PEGasparaginase as first-line treatment. The overall incidence of allergic reactions along with 95% confidence interval (CI) were 9% [6%; 13%], 2% [1%; 3%] and 8% [5%; 11%] in the overall protocol, induction and post-induction, respectively (Figure 1). Severity of allergic reactions were described, according to the CTCAE version 3.0 or 4.03, per protocol. 47% of the reactions were classified as grade 3/4. Univariate meta-regression analysis showed a positive association between the incidence of allergic reactions and number of PEGasparaginase-free intervals (P=0.005). High risk group stratification (P&lt;0.001), post-induction treatment phase (P&lt;0.001) and start of PEGasparaginase treatment in post-induction (P=0.006) were also associated with a higher incidence of allergic reactions. Route of administration (IV (8.9%, range 8.6-10.5%) versus IM (6.5%, range 5.5-14.8%)) did not significantly influence risk of hypersensitivity. Number of doses, duration of first PEGasparaginase-free interval and dosage did not significantly influence risk of hypersensitivity. Multivariate meta-regression analysis showed a positive association between the incidence of allergic reactions and the number of PEGasparaginase-free intervals (P=0.006) and start of PEGasparaginase in the post-induction treatment phase (P=0.02). Two out of seven study groups reported an incidence of allergic reactions of 1.6-2.0%, which was 9-16% of all hypersensitivity. Three out of seven study groups reported an incidence of SI of 3.7-4.1%, which was 23-29% of all hypersensitivity reactions. All protocols prescribed a switch to Erwinia asparaginase in case of clinical hypersensitivity and/or SI. 308 out of 348 (89%) of the patients with hypersensitivity to PEGasparaginase received Erwinia asparaginase. 19 out of these 308 (6%) exposed patients had an allergic reaction to Erwinia asparaginase, of which 7 out of 19 (37%) were grade 3/4. CONCLUSION The incidence of allergic reactions is lower in protocols using PEGasparaginase as first-line treatment compared to that reported for native E.coli asparaginase or PEGasparaginase after native E.coli asparaginase. Post-induction phase, a higher number of PEGasparaginase-free intervals, and initiation of PEGasparaginase in post-induction phase are risk factors for allergic reactions. These results are important for planning of PEGasparaginase administrations in future frontline therapy. Figure 1 Figure 1. Disclosures Albertsen: Erytech: Honoraria, Speakers Bureau; Servier: Speakers Bureau; BKA: Other: Sponsor of the investigator-initiated trial NOR-GRASPALL2016.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2909-2909
Author(s):  
Guldane Cengiz Seval ◽  
Klara Dalva ◽  
Dilek Oz ◽  
Sule Mine Bakanay ◽  
Ender Soydan ◽  
...  

Abstract Introduction: Post-induction minimal residual disease (MRD) within but not outside (peripheral blood/stem cell graft) of marrow among transplant eligible patients with multiple myeloma (MM) is currently recognized as poor-prognostic. Emerging number of studies are evaluating MRD within the context of cytogenetic risk. In this study we aimed to quantify circulating plasma cells (PCs) by flow in apheresis products (graft=gMRD) and compare with marrow MRD(mMRD) and outcome according to cytogenetics. Patients & Methods: Four hundred eleven subsequent newly diagnosed multiple myeloma (NDMM) patients transplanted (AHCT) between September 2006 - June 2021 were included prospectively. Standard-risk cytogenetics(SR) is defined as t(11;14), t(6;14), or a normal karyotype , whereas del(17p13), t(4;14), t(14;16), t(14;20), + 1q21 and complex findings are high-risk cytogenetics (HR). In the sample drawn for HPSC quantification of the graft and bone marrow, the number of clonal PCs were quantified by Flow. CD27 PC7 orCD27 A750, CD56 A700, CD19 ECD, CD38 FITC orCD38 A750, CD138 APC, CD45 KO, CD81 PE, CD117 PC7, polyclonal Rabbit Anti-Human Kappa or Lambda Chains /FITC antibodies and acquisition of at least 10 5 cells per tube Analysis was performed using the Navios Flow Cytometer (3L10C, Beckman Coulter) using the Kaluza software (Beckman Coulter, USA) according to the criteria defined by Montero et al and also abnormal distribution of kappa vs. Lambda expression. Undetectable MRD was defined as absence of clonal PCs at a sensitivity of 10 -4 prior to 2017(n=217) and 10 -5 after 2017(n=131). MRD assessment is similar in the graft and marrow. Impact of postinduction MRD analysis was performed in 131 patients with MRD data of 10 -5 sensitivity level. Results were reported in the intention-to-treat (ITT) population for mMRD. Results: Median follow-up after AHCT was 61.5 months (range:3.2-168) (prior to 2017) and 17.7 months (range: 3-47.4) (after 2017). Induction regimen consisted of bortezomib without or with immunomodulatory drug (IMID) 78.8%, 2.8% (prior to 2017) and 74.1%, 22.9% (after 2017). Consolidation 18% (n=39/217), 22.1% (n=29/131) (prior and after 2017) and maintenance 21.2% (n=46/217), 35.1% (n=46/131) (prior and after 2017) were administered based on the response to AHCT. Cytogenetically HR was observed 14.1% (n=47) (among total cohort) and 15.8% (n=19) (after 2017 cohort). Post-induction biochemical response distribution among patients with undetectable MRD are shown in Table-1. MRD assessments were performed at a sensitivity of 10 -4 and 10 -5 in graft (n=147 and 76), marrow (n=18 and 4) or both (n=52 and 51). A statistically significant correlation was detected between marrow and graft MRD only at sensitivity level 10 -5 (SE: 0.638, p&lt;0.001). Additionally, correlations between CR and gMRD (Kappa coefficient (SE): -0.284, p=0.03); CR and mMRD (SE: -0.452, p:0.001) were found. Since marrow and graft MRD results are correlated, all graft and marrow results were merged for the multivariate analysis (MVA) (Table-2). Having undetectable vs detectable MRD in either graft or marrow estimates a 2 years-PFS of 83.6% vs 46.5% (p=0.007). Among 42 MRD(-) patients, only four (two with HR)have relapsed. There is a tendency for better two year probability of PFS with undetectable mMRD vs gMRD at 10-5 ( not reached vs 84.7% ; ns)(Figure 1). The patients (after 2017) are divided into four groups according to MRD status and cytogenetic risk stratification: MRD(-)SR (n=35; 29.2%), MRD(-)HR (n=7; 5.8%), MRD(+)SR (n=66; 55%), MRD(+)HR (n=12; 10%). Kaplan-Meier curves revealed significant differences in PFS among these groups (p=0.03) (Figure-2). Conclusion: Our real-world triplet drug induction-based experience shows for the first-time post-induction mMRD and MRD to be correlated with each other and with PFS. PFS with MRD(-) at 10 -5 results have displayed a better outcome compared to 10 -4. MVA showed MRD and age to determine PFS, independent from post-induction CR, ISS and cytogenetic risk. Although observed less frequently, achieving post-induction MRD(-) either in graft or marrow may ameliorate the poor prognosis of HR. With improvement in induction it may be possible to achieve more frequent MRD(-) and thus analyze the impact of each cytogenetics risk group ie 1q amplification separately. Furthermore, MRD in graft may be a non-invasive therapeutic efficacy tool which is subject to less sampling variation. Figure 1 Figure 1. Disclosures Beksac: Amgen,Celgene,Janssen,Takeda,Oncopeptides,Sanofi: Consultancy, Speakers Bureau.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1585-1585
Author(s):  
David M Foureau ◽  
Manisha Bhutani ◽  
Fei Guo ◽  
Kateryna Fesenkova ◽  
Shebli Atrash ◽  
...  

Abstract Introduction: The addition of elotuzumab (Elo), an anti SLAMF7 immunostimulatory antibody, to carfilzomib, lenalidomide and dexamethasone (KRd) can lead to synergistic anti-myeloma immune effects. Pre-clinical data showed that both Elo and KRd promote innate NK cell response and adaptive cytotoxic T cell response. Here we report longitudinal NK and T cell profiling data in relation to clinical response and MRD status in the context of an Elo-KRd Phase II study (NCT03361306). Methods: Patients with relapsed refractory multiple myeloma (RRMM) after first-line therapy who enrolled in this phase II study received treatment with 4 cycles of Elo-KRd induction followed by Elo-Rd maintenance. Peripheral blood (PB) specimens were collected pre-induction (n=15), after induction (n=14), and every other month during maintenance (n=10). Bone marrow (BM) aspirates were collected pre- and post-induction and at the time of CR confirmation. Minimal residual disease (MRD) was assessed by next-generation flow cytometry (MRD NGF, 10 -5 sensitivity) post-induction for patients achieving very good partial response or better (≥VGPR). PB and BM NK, CD4 and CD8 T cell subset distribution, activation and anergy status were assessed by flow cytometry. Longitudinal Elo-KRd immune modulatory effect was modelled by polynomial regression analyses. Wilcoxon signed rank tests were used for timepoints comparisons. Mann-Whitney U tests were used for response groups comparisons between. Population frequency data, among mononuclear cells, are presented as mean±SD unless otherwise noted. Results: We first investigated Elo-KRd immune modulatory activity during induction treatment. Immature / mature NK cell distribution in PB remained unaltered pre- and post-induction (iNK: 8.9±6.4 vs 8.6±3.5, p=0.808; mNK: 14.9±6.8 vs 13.1±6.1, p=0.463). No significant change in PB NK activation markers KIR2DS4, KIR3DL1, NKG2A, NKG2D or NKp46 was observed throughout Elo-KRd induction. A lack of NK cell maturation was also observed in the BM despite a rise of iNK NKG2D expression (iNK NKG2D+: 22.5±7.7 vs 30.1±8.8, p=0.0.039). The number of both PB effector T helper (CD4+ Th) and cytotoxic T cell (CD8+ CTL) significantly decreased post-induction (PB ThEff: 28.5±16.4 vs 14.4±10.6, p&lt;0.001; PB CTLEff: 58.6±19.7 vs 39.0±13.9, p=0.005), whereas CTL central memory cell counts increased (PB CTLCM 11.7±11.2 vs, 15.9±11.4 p=0.058). A similar effector to central memory T cell conversion was observed in BM and was more pronounced among CTL (BM CTLEff/CM ratio: 21.6±54.8 vs 2.1±1.6, p= 0.002). Overall response rate on study was 80%, with 53.5% (8/15) achieving ≥VGPR. MRD negativity rate (at 10-5 sensitivity) post-induction was 20% (3/15). The subset of patients who achieved ≥VGPR had higher rates of Th and CTL CM cell differentiation at baseline [≥VGPR vs &lt;VGPR; PB ThEff/CM ratio: median 1.0 (range 0.1 - 1.5) vs 3.1 (0.8 - 212.1); p=0.018; PB CTLEff/CM ratio: median 4.1 (range 0.7 - 16.3) vs 13.2 (4.3 - 10607.1); p=0.056]. Among the MRD negative group, one patient remained in sustained CR at 38 months follow up and retained a high Th/CTL CM conversion rate throughout. At the time of relapse, PB (n=6) and BM (n=2) specimens were collected. While no significant alterations in PB NK cell maturation or activation were observed, circulating CTL Eff / CM distribution reverted to baseline levels (baseline vs relapse; PB CTLEff/CM ratio: 743.6±2755.1 vs 282.7±672.0; p=0.156). BM CTL cell effector / central memory distribution also tends to return to pre-induction levels. Conclusions: Unlike preclinical data where Elo has shown to enhance NK cell activity, longitudinal immune profiling analysis in patients with RRMM treated with Elo-KRd revealed limited activation of NK cell and no effect on NK cell maturation. Instead, we noted several changes within T cell compartment, notably activation and subsequent loss of Th and CTL effector cells, along with gain of central memory phenotype. This observation was most apparent for patients achieving ≥VGPR who exhibited significant higher rate of Effector to CM T cell conversion. On relapse, CM CTL cell frequency in both PB and BM compartments decreased to baseline level. Taken together, our results suggest that higher CM conversion rate, typically associated with sustained antigen stimulation, was associated with response to study treatment. Disclosures Foureau: Cytognos: Honoraria; TeneoBio, Celgene: Research Funding. Bhutani: Amgen, BMS, Takeda: Speakers Bureau; Sanofi: Consultancy; Janssen, MedImmune, Takeda, Celgene, BMS, Cerecor, Celularity: Research Funding. Atrash: GSK: Research Funding; AMGEN: Research Funding; Jansen: Research Funding, Speakers Bureau. Paul: Regeneron: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Speakers Bureau; Bristol Myers Squibb: Divested equity in a private or publicly-traded company in the past 24 months. Symanowski: Eli Lilly: Consultancy, Other: DSMB Member; Immatics: Consultancy, Other: DSMB Member; Carsgen: Consultancy. Voorhees: Bristol-Myers Squibb Company.: Other: Data Safety & Monitoring; AbbVie Inc, Bristol-Myers Squibb Company; Consulting Agreement: GlaxoSmithKline, Novartis, Oncopeptides: Other: Advisory Committee. Usmani: EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Array BioPharma: Consultancy, Research Funding; Abbvie: Consultancy; GSK: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; SkylineDX: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3396-3396
Author(s):  
Jonathan D. Paolino ◽  
Yael Flamand ◽  
Kristen E. Stevenson ◽  
Victoria Koch ◽  
Uma H. Athale ◽  
...  

Abstract Introduction: Increased toxicity with pegaspargase (PEG) in older and higher body mass index (BMI) patients (pts) with acute lymphoblastic leukemia (ALL) has recently led to dose capping practices. We assessed the influence of age, body surface area (BSA), and BMI on PEG-related toxicity and pharmacokinetics from two consecutive DFCI ALL Consortium trials without dose capping. Methods: Patient (pts) aged 1 to &lt;19 years (DFCI 05-001) or 1 to &lt;22 years (DFCI 11-001) with newly diagnosed ALL were eligible for enrollment. Those who received PEG (2500 IU/m 2) were included in this analysis. Pts received 1 dose of IV PEG on day 7 of Induction and every 2 weeks for 15 doses post-induction. Serum asparaginase activity (SAA), considered therapeutic at &gt;0.1 IU/mL, was assessed 4, 11, 18, and 25 days after the Induction dose and nadir SAA was assessed before each Post-Induction dose. Asparaginase-related toxicities were prospectively assessed and graded by CTCAE version 3.0 (DFCI 05-001) or 4.0 (DFCI 11-001). Asparaginase toxicity for this analysis was defined as ≥1 of the following: pancreatitis, thrombosis, ≥grade 4 hyperbilirubinemia, ≥grade 4 hypertriglyceridemia. Allergy was analyzed separately (due to presumed dose independence). Height and weight at diagnosis were used for analyses. BMI categories were assigned using standard percentile ranges based on gender specific 2000 CDC growth charts. BSA was calculated using the Mosteller formula. Univariate analyses evaluated the relationship of age, BMI, and BSA with asparaginase toxicity. Comparisons of toxicity across BMI and BSA categories were performed using a Jonckheere-Terpstra test. Categorical comparisons for dichotomized BMI and BSA utilized a Fisher's exact test or chi square test. The relationships between BMI and BSA with toxicity were explored using multivariable models. Results: Between 4/2005-12/2011 802 pts enrolled on DFCI 05-001 and between 6/2012-6/2015 240 pts enrolled on DFCI 11-001. Both trials included random assignment of asparaginase formulation. In total 911 patients received pegaspargase during Induction and 351 during Post-Induction. During Induction, pts ≥15 years of age had higher asparaginase toxicity rates (17.1% vs 6.2%, p=0.0003) (Figure 1a). Toxicity differed significantly across BSA categories (&lt;1.5 m 2, 1.5 to &lt;2.0 m 2, ≥2.0 m 2, p= 0.007) with increased toxicity in those with BSA ≥2.0m 2 (22.7% vs. 6.8% for those &lt;2.0 m 2, p = 0.016) (Figure 1b). Age was highly correlated with BSA (Pearson r = 0.93, p &lt;0.0001). There was numerically higher toxicity in the BMI category of overweight vs. those underweight or normal weight (11.3% vs 6.5%) however this did not extend to the obese category, and overall, increasing BMI was not associated with statistically higher toxicity (p= 0.13, Figure 1c). Post-Induction, age ≥15 years was associated with increased asparaginase toxicity (57.1% vs 21%, p&lt;0.0001) (Figure 1d). Toxicity differed significantly across BSA categories (p&lt;0.0001) but was similar between BMI categories (p=0.19, Figure 1e-f). The impact of BSA was observed when dichotomized at thresholds of 1.5m 2 (54% vs. 19%, p&lt;0.0001) and 2.0m 2 (70% vs. 23%, p=0.003) (Figure 1e). Considering only those ≥10 years of age, trends for BSA/BMI and toxicity were similar. There was no significant association between BMI or BSA and allergy. In multivariable analysis, BSA was a significant predictor of Post-Induction toxicity (OR 4.21, p&lt;0.0001). Age was significant in the univariate setting (OR 1.14, p&lt;0.0001) however due to high correlation with BSA, was not included with BSA in the multivariable model. Post-Induction, median nadir SAA levels were ≥0.1IU/mL for all BSA and age categories. Median SAA was similar or lower at all time-points for those ≥15 years of age compared with younger children. Median SAA for pts with BSA ≥1.5m 2 were similar or lower compared to those with BSA &lt;1.5m 2 (Figure 2a-d). Conclusion: Age ≥15 years and BSA ≥2m 2 were each associated with significantly increased asparaginase toxicity. Older patients and those with higher BSA had similar or lower median SAA levels at all time-points. These results suggest that the differential toxicity seen in older patients and those with higher BSA is not explained by these patients having higher SAA levels. Prospective exploration of interventions to decrease toxicity in older patients and those with high BSA are needed. Figure 1 Figure 1. Disclosures Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Silverman: Takeda, Servier, Syndax, Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1287-1287
Author(s):  
Reyes María Martín-Rojas ◽  
Jon Badiola ◽  
Pablo Silva De Tena ◽  
Ana Pérez-Corral ◽  
Ignacio Gómez-Centurión ◽  
...  

Abstract INTRODUCTION Several studies have shown that morphological remission at day 14 is a predictor of post-induction response in patients with acute myeloid leukemia (AML) undergoing an intensive treatment. However, the role of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) at day 14 remains unknown. The aim of our study is to explore the role of MRD at day 14 and its association with outcomes of patients with AML undergoing an intensive treatment. METHODS We conducted a retrospective study in adult patients with newly a diagnosed AML in our center between 2007 and 2020. Adult patients who received intensive chemotherapy, excluding those with an acute promyelocytic leukemia, were included. Bone marrow aspiration was performed at day 14 after induction to assess morphological response and MRD by MFC. Early blast clearance (EBC) was defined as &lt;5% of blasts and negative MRD was defined as &lt;0.1% abnormal cells within mononucleated cells by MFC. Day 14 aspiration findings were compared with clinical data. This study was approved by our Institutional Ethics Committee. Data were analyzed using IBM SPSS Statistics version 24. RESULTS A total of 131 patients were analyzed. Median age was 55.6 years (IQR 42.3-64.2). The most frequent AML subtype was AML with myelodysplasia-related changes (34.4%), followed by NPM1-mutated AML (32.1%). The most commonly used induction regimen was "7+3" (96.2%) (Table 1). On day 14 bone marrow aspiration, median cellularity was 0.5/5 (IQR 0.5-1). 107 patients (81.7%) showed a blast reduction &gt;50% compared to diagnosis and 87 patients (66.4%) had less than 5% of blasts. In this latter group, 28.6% of patients had a positive MRD and 71.4% had a negative MRD. NPM1-mutated AML showed the highest EBC rates while AML with myelodysplasia-related changes had the lowest rates (83.3% versus 55.5%; p=0.04). Furthermore, there were statistically significant differences in EBC rates based on the 2017 European Leukemia Net risk stratification, with 80% of EBC in low risk, 66.6% in intermediate risk and 53.4% in high risk AML (p=0.038). No differences were observed in MRD at day 14 based on AML subtypes or risk stratification. We subsequently analyzed the negative (NPV) and positive predictive values (PPV) of day 14 bone marrow aspiration results by morphology and MFC to predict post-induction results. As a predictor of post-induction CR, day 14 EBC had a NPV of 82% and a PPV of 69%, while day 14 MRD had a NPV of 86% and a PPV of 49%. However, for predicting post-induction MRD, day 14 EBC had a NPV of 49% and a PPV of 15%, while day 14 MRD had a NPV of 71% and PPV of 74%. The correlation between day 14 and post-induction bone marrow aspiration is shown in Table 2. Bivariate analysis showed that achieving CR with negative MRD in post-induction bone marrow aspiration was associated with EBC (p&lt;0.001) and negative MRD (p=0.04) at day 14 bone marrow aspiration. No statistically significances were observed based on marrow cellularity. A multivariate analysis using logistic regression showed that negative MRD by MFC at day 14 was the only independent predictor variable to achieve post-induction CR with negative MRD (OR 4.95% CI 1.0-15.9; p=0.04). CONCLUSION Patients showing EBC with negative MRD on day 14 bone marrow aspiration are more likely to achieve post-induction CR with negative MRD, with day 14 MRD by MFC being the only independent factor able to predict post-induction CR with negative MRD in our cohort. However, further prospective studies are needed to confirm our findings. Figure 1 Figure 1. Disclosures Martín-Rojas: Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria.


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