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In: Leukemia & Lymphoma, Informa UK Limited, Vol. 62, No. 12 ( 2021-10-15), p. 2928-2938

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.1080/10428194.2021.1948031

Language: English

Publisher: Informa UK Limited

Publication Date: 2021

detail.hit.zdb_id: 2030637-4

In: Experimental Hematology, Elsevier BV, Vol. 101-102 ( 2021-09), p. 49-57

Type of Medium: Online Resource

ISSN: 0301-472X

URL: Article

DOI: 10.1016/j.exphem.2021.08.003

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2005403-8

In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-04-21)

Abstract: Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287] , followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40–2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98–1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes. Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-023-32265-5

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2615211-3

In: Leukemia Research, Elsevier BV, Vol. 115 ( 2022-04), p. 106821-

Type of Medium: Online Resource

ISSN: 0145-2126

URL: Article

DOI: 10.1016/j.leukres.2022.106821

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2008028-1

In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2866-2866

Abstract: Background: Preliminary results with the combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (G-CSF) (FLAG-IDA), reported complete response (CR) rates of 47–95% in patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with acceptable toxicity. These results lead to a generalized use of FLAG-IDA regimen in this set of patients. However, these studies have been made in small series and the long-term outcome of patients have not been described. Objectives: Analyze the results of FLAG-IDA regimen, in terms of CR rate and long-term outcome, in a large series of patients with high-risk AML and MDS treated in a single institution. Methods: From 1997 to 2007, 158 adult patients (median age 60 years, range 16–79) received FLAG-IDA regimen (Fludarabine, 30 mg/m2 intravenous (iv) for 4 days, cytarabine 2 g/m2 iv for 4 days, idarubicin 10 mg/m2 iv for 3 days and glycosylated G-CSF at a daily dose of 300 mcg/m2, from day -1 until day 5). Post-remission therapy consisted of allogeneic transplantation (Allo-HSCT) in eligible patients, or consolidation (idarubicin, 10 mg/m2 iv for 3 days and cytarabine, 200 mg/m2 iv for 5 days), followed by intensification with Auto-HSCT or one cycle of carboplatin (300 mg/m2 for 4 days, as a 24 h continuous infusion). Patients were diagnosed with high-risk MDS (11%), treatment related AML (10%), AML secondary to MDS (29%), primary refractory AML (17%), AML in first relapse (27%), and AML in second or subsequent relapse (6%). Median follow-up of the cohort was 40 months (range 2–104). We calculated the Kaplan-Meier estimates curves for overall survival (OS), disease-free (DFS) and relapse-free survival (RFS). Results: CR and partial remission (PR) was achieved in 84 patients (53%) and in 19 patients (12%), respectively. Twenty-three patients (15%) died during induction, mostly due to infection (19 patients). The CR rates according to the disease status were the following: high-risk MDS 61%, treatment related AML 73%, AML secondary to MDS 52%, primary refractory AML 54%, AML in first relapse 49%, and AML in second or subsequent relapse 30%. Post-remission therapy consisted of Allo-HSCT in 16 patients (8 related and 8 unrelated), Auto-HSCT in 15 patients, and chemotherapy alone in 53 patients. The 1 and 5 year OS, DFS and RFS of the entire cohort were 36% and 11%, 40% and 11%, and 51% and 23%, respectively. The 1 and 5 year OS in patients achieving CR, PR and resistance were 64% and 22%, 26% and 7%, and 4% and 0%, respectively (p 〈 0.0001). The 5 year RFS of patients treated with chemotherapy alone, Auto-HSCT and Allo-HSCT were 13%, 16% and 64%, respectively (p=0.09). The 5 year RFS of patients aged 〉 55 years and ≤55 years were 4% and 53%, respectively (p=0.0005). The 5 year DFS of patients treated with chemotherapy alone, Auto-HSCT and Allo-HSCT were 7%, 13% and 35%, respectively (p=0.22). Conclusion: Our results confirm the acceptable toxicity and high response rate observed with FLAG-IDA regimen in this very high-risk subgroup of patients. This regimen can be a bridge towards Allo-HSCT, that appear to be the most curative therapy in this setting.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V110.11.2866.2866

Language: English

Publisher: American Society of Hematology

Publication Date: 2007

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4579-4579

Abstract: Introduction: There is scarce information concerning incidence and risk factors for central nervous system (CNS) relapse in adult patients with acute myeloid leukemia (AML). In acute lymphoblastic leukemia CNS relapse occurs in up to 30% of patients without prophylactic intrathecal chemotherapy (ITC). This has lead to establish its prophylactic use during induction and post-remission phase. Due to the lack of information about incidence of CNS relapse in adult patients with AML, the usefulness of ITC prophylaxis is not clear. Objectives: Analyze incidence and risk factors for CNS relapse in a large cohort of adult patients with newly diagnosed AML. Material y methods: Between 1976 y 2005, 747 adult patients (median 54 years, range 16–81) were diagnosed of de novo AML in our institution. All of them received induction with intensive chemotherapy. Prophylactic ITC was not administered, and cerebrospinal fluid was analyzed only if CNS infiltration was suspected. We analyzed the incidence and risk factors for CNS relapse in patients who reached a complete remission. To calculate the Kaplan-Meier estimates of event-free survival (EFS) we considered as an event the first relapse in CNS, censoring patients at the moment of death or at first relapse in a site different than CNS. Results: 432 patients (58%) obtained complete remission. Between 1976 and 1989 (period 1) 12 of 136 patients (9%) were submitted to autologous or allogeneic stem-cell transplantation (SCT), whereas 129 of 296 (44%) received SCT between 1990 and 2005 (period 2). Overall, 8 of 432 patients (2%) had a CNS relapse, 3 isolated in CNS and 5 in bone marrow plus CNS. Of them, only 1 presented CNS infiltration at diagnosis. In univariate analysis, CNS relapse was associated with high LDH (3% vs 0%, p=0.06), lisozyme 〉 30 (8% vs 1%, p=0.06), FAB M4–M5 (5% vs 1%, p=0.04) and period 1 (5% vs 0.3%, p 〈 0.01). The median follow-up of the cohort was 85 months. CNS relapses occurred at a median of 10 months after complete remission (range, 3 to 84 months). The EFS at 10 years was 95%, and it was lower in patients with elevated LDH (91% vs 100%, p=0.02), FAB M4–M5 (88% vs 97%, p 〈 0.01), leukocytes 〉 10 ×109/L (92% vs 98%, p=0.07), no SCT (92% vs 100%, p 〈 0.01), and period 1 (80% vs 99%, p 〈 0.01). In multivariate analysis, AML M4–M5 remained as the only independent prognostic factor for EFS (HR 6.4, p=0.01). Only 1 of 8 patients with CNS relapse is alive (AML M3, 11 years after a second complete remission). Median survival after CNS relapse was 168 days (range, 16 to 3821 days). Conclusion: In adults with de novo AML CNS relapse is an infrequent event. Intensification of post-remission therapy, especially with SCT, during the last decades may have contributed to reduce its incidence. Therefore, administration of prophylactic intrathecal chemotherapy should not be recommended, even in patients with high risk of CNS relapse, such as monocytic AML.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V108.11.4579.4579

Language: English

Publisher: American Society of Hematology

Publication Date: 2006

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4462-4462

Abstract: Introduction: It has been suggested that acute myeloid leukemia (AML) showing mature phenotype is associated with favourable outcome. In a study recently published by JALSG, myeloperoxidase (MPO) positivity in over 50% of blasts had favourable prognostic impact, independent from karyotype, on achieving complete remission (CR), overall survival (OS) and disease free survival (DFS). No other studies have established the independent prognostic value of MPO expression. Objectives: Analyze the clinico-biological characteristics of AML with high percentage of MPO+ blasts and its impact on CR, OS and DFS. Material and methods: Between 1986 and 2005, 418 adult patients (median 53 years, range 15–80) were diagnosed with de novo non-APL AML and evaluated for percentage of MPO+ blasts. All patients received intensive chemotherapy. Diagnosis was made by optic microscopy of bone marrow (BM) aspirates stained with May-Grumwald giemsa, MPO, butyrate esterase and or non specific esterase. Cytogenetic and immunophenotype analysis was evaluated in 66% and in 76% of the cases respectively. Results: 118 patients (28%) showed a percentage of MPO+ blasts 〉 75%. AML with MPO+ blasts 〉 75% was associated with M1-M2-M4 subtypes, leucocytes 〉 50×109/L, blasts in BM 〉 70% and HLA-DR negativity (p 〈 0.01). It was also significantly associated with favourable karyotype (11% vs 3% favourable, 52% vs 48% intermediate and 3% vs 15% unfavourable). Patients with AML and MPO+ blasts 〉 75% obtained higher CR rate (71% vs 55%), due to less resistant disease (9% vs 22%, p 〈 0.01). In multivariate analysis favourable karyotype, leukocytes 〈 50×109/L and age 〈 60 were favourable prognostic factors for CR. Median OS and DFS was higher in patients with AML and MPO+ blasts 〉 75% (15 vs 7 months, p 〈 0.001, y 41 vs 12 months, p 〈 0.001, respectively). ). In multivariate analysis, favourable karyotype, leukocytes 〈 50×109/L, age 〈 60 years and MPO+ 〉 50% were favourable prognostic factors for OS; and age 〈 60 and MPO+ 〉 75% were the only independent factors for DFS. Median DFS was higher in patients with AML and MPO+ blasts 〉 75% in the intermediate cytogenetic risk group (59 vs 13 months, p=0.015), age 〈 60 (109 vs 15 months, p=0.003), age 〉 60 (13 vs 7 months, p=0.03), autologous stem cell transplantation (100 vs 9 months, p=0.04) and chemotherapy alone (16 vs 8 months, p=0.003). Conclusion: In our series, patients with AML and MPO+ blasts 〉 75% show less chemoresistant disease and a longer remission duration, the latter independently from the karyotype. This biological characteristic could be useful in designing therapeutic strategies in patients that lack other prognostic markers.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V108.11.4462.4462

Language: English

Publisher: American Society of Hematology

Publication Date: 2006

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4301-4301

Abstract: Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by specific morphological and clinical features. However, its relative incidence among patients with AML is not yet established. Objectives: To define the relative incidence of APL in a large series of patients diagnosed with AML in a single institution and to identify the clinical-biological features characterizing the APL patients within the target population of AML. Methods: From 1976 to 2007, 1205 patients (median age 56 years, range 15–98) were consecutively diagnosed with AML in our institution. One hundred patients (8%) were considered AML secondary to solid neoplasia or chemotherapy, while 143 (12%) were secondary to myelodysplastic or myeloprolypherative syndromes (MDS/MPCS). The APL diagnosis was achieved through cytological studies supported by cytogenetics, and since 1995 by molecular techniques. Inmunophenotype analysis, using flow cytometry or inmunohistochemistry, was available in 808 (67%) patients. Positivity was defined as more than 20% blasts expressing a specific antigen. Results: Overall, 170 patients (14%) were diagnosed of APL. Of them, 43 (25%) were classified as M3 variant. The relative incidence of APL within AML secondary to solid neoplasia or chemotherapy and de novo AML was 13% y 16%, respectively (p=ns). In contrast, the relative incidence of APL within AML secondary to MDS/MPCS was 0.7% (p 〈 0.0001) (only 1 case of APL secondary to MDS/MPCS was registered). The median age of APL patients was 44 years, and its relative incidence decreased with older age: 26% between 15 and 50 years, 12% between 51 and 60, 8% between 61 and 70, and 5% in older than 70 (p 〈 0,0001). The percentage of APL patients receiving induction was higher compared with the rest of AML (93% vs 79%, p 〈 0,0001). The complete remission rate was higher in APL (72% vs 53%), due to a lower resistance (3% vs 22%, p 〈 0,0001), whereas the induction mortality was similar (25% vs 25%). The frequency of causes of death were different in APL compared with the rest of AML: hemorrhage (59% vs 22%), infection (27% vs 56%), hemorrhage and infection (8% vs 6%) and other (6% vs 16%). APL was associated with the following clinical-biological features: presence of Auer rods (80% vs 27%, p 〈 0,0001), peroxidase positive blasts 〉 75% (94% vs 27%, p 〈 0,0001), bone marrow blasts 〉 70% (92% vs 49%, p 〈 0,0001), WBC 〈 10x109/L (70% vs 48%, p 〈 0,0001), LDH 〈 600 U/L (68% vs 58%, p=0,003), uric acid 〈 7,5 mg/dL (96% vs 87%, p=0,002), fibrinogen 〈 170 mg/dL (53% vs 3%, p 〈 0,0001), hemorrhagic syndrome at diagnosis (84% vs 32%, p 〈 0,0001), lack of hepatosplenomegaly (12% vs 24%, p=0,001). APL was significantly associated with the following surface or cytoplasmatic antigens: CD34 negative (−), CD36(−), HLA-DR(−), CD14(−), CD4(−), CD56(−), TdT(−), CD11b(−), CD7(−), CD2 positive (+), CD9(+), CD33(+), CD71(+), CD117(+) and myeloperoxidase(+). Conclusion: In this large series of patients diagnosed with de novo or secondary AML, the relative incidence of APL was 14%, being exceptional the APL secondary to MDS/MPCS. To our knowledge, this is the larger hospital registry establishing the relative incidence of APL in a target AML population.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V110.11.4301.4301

Language: English

Publisher: American Society of Hematology

Publication Date: 2007

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4036-4036

Abstract: Introduction: Current recommendations for the treatment of AML in newly diagnosed elderly patients (≥ 65 years) include different therapeutic options (intensive or semi-intensive chemotherapy, low-dose chemotherapy, hypomethylating agents, and supportive care). Regardless of the selected treatment, the results are disappointing because of low overall survival (OS) rates and significant toxicity. Objectives: The primary objective of FLUGAZA trial is to compare the 1-year-OS in 350 patients aged ≥ 65 years diagnosed with AML assigned to azacytidine (n=175) or FLUGA (n=175) arms. Here we present the results of a pre-planned interim safety analysis for both outpatient treatment regimens. Methods Inclusion criteria: Patients diagnosed with de novo or secondary AML according to WHO classification (except for APL), previously untreated, age ≥ 65 years, ECOG 〈 4. Randomization arms (1:1): azacytidine (AZA) (75 mg/m2 SC days 1-7) and FLUGA (fludarabine 40 mg/m2 PO days 2-6, cytarabine 75 mg/m2 SC days 2-6, filgrastim 5 µg/Kg SC days 1-3), cycles of 28 days. The treatment schedule consisted of 3 induction cycles (C1, C2, C3), 6 consolidation cycles and a maintenance treatment until relapse or progression. FLUGA was reduced in patients older than 75 years and filgrastim in the FLUGA arm was omitted when white blood cells (WBC) were 〉 25 x109/L. Concomitant use of hydroxyurea was allowed in the AZA arm if WBC was between 15 and 50 x109/L. In patients with more than 50 x109/L WBC assigned to the AZA arm, the first induction cycle was FLUGA. An interim analysis to assess myelotoxicity, early mortality and response rate was planned in the trial when the last of the first 100 randomized patients completed the first 3 induction cycles. Results: From October 2014 to April 2016, 162 patients were enrolled in 26 Spanish centers from the PETHEMA group. Of them, 22 patients were screen failure and 16 patients did not receive the assigned treatment. The first 100 patients treated were analyzed (58 patients were assigned to AZA arm and 42 to FLUGA arm). Baseline characteristics are shown in Table 1. Median age was 75 [65;90] years in AZA arm vs. 77 [65;88] years in FLUGA arm; 36 (62%) vs. 19 (45%) males. Five patients from AZA arm (n=58) received the first cycle of FLUGA because of WBC 〉 50 x109/L. Outcomes: overall response rate (CR+CRu+PR) based on the best response accumulated with 3 cycles of treatment was 62% in the AZA arm and 57% in the FLUGA arm. CR+CRu was achieved in 14 patients (24%) from AZA arm and 15 (36%) from FLUGA arm. Early mortality rate (8 weeks) was 14% in AZA and 22% in FLUGA arm. Toxicities: there were no differences in hospitalization and non-hematological ≥ G3 serious adverse events (SAEs) between both arms. Overall, 71 patients (71%), 61 out of 79 (77%) vs. 41 out of 64 (64%) patients, developed neutropenia ( 〈 0.5 x x109/L) after C1, C2 and C3, respectively. Median duration of neutropenia in the AZA arm was 14 days (6;40), 21 days (4;95) and 18 days (1;45) after in C1, C2 and C3, respectively, vs. 15 days (4;33), 15 days (3;36) and 20 days (7;41) after C1, C2 and C3, respectively, in the FLUGA arm (no statistically significant differences). Eighty-one (81%), 55 out of 79 (70%) vs. 40 out of 64 (62%) patients, developed thrombocytopenia ( 〈 50 x109/L) after C1, C2 and C3, respectively. Median duration of thrombocytopenia was 14 days (5;29) after C1, 18 days (4;88) after C2 and 14 days (7;25) after C3 in the AZA arm; vs. 16 (3;63), 20 (6;42) and 13 days (7;56) after C1, C2 and C3, respectively, in the FLUGA arm (NS). Conclusions: Outpatient treatment with AZA or FLUGA was feasible. Both treatment arms showed a similar rate of early mortality and relatively low CR/CRu rates. The study is currently enrolling patients until the planned accrual goal (350 patients) to assess the primary end-point (1-year OS). The study is registered at www.ClinicalTrials.gov as NCT02319135. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.4036.4036

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 32-32

Abstract: Background: AML is the most common acute leukemia in adults and its prevalence significantly increases in the elderly. The 5-year survival rate for adults younger than 60 is around 40% and decreases to 10% in patients above this age. Even those patients who tolerate intensive induction chemotherapy and achieve complete remission (CR) have poor outcome. Detection of MRD in younger AML refines outcome prediction of patients in CR after intensive chemotherapy. However the value of MRD in elderly patients is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. Aim: Define the role of MRD assessment by multidimensional flow cytometry (MFC) for therapeutic decision making in elderly AML patients treated with semi-intensive chemotherapy vs hypomethylating agents (HMA). Methods: Two-hundred eighty-three elderly AML patients were included in the PETHEMA phase III FLUGAZA clinical trial and randomized to receive three induction cycles with fludarabine and cytarabine (FLUGA) followed by six consolidation cycles with reduced intensity FLUGA, or three induction cycles with 5-azacitidine (AZA) followed by 6 consolidation cycles with AZA. After consolidation, patients continued with the same treatment if MRD ≥0.01% or stopped if MRD & lt;0.01%. MRD was prospectively assessed using MFC after induction and consolidation. Patient-specific aberrant phenotypes were used for highly-purified FACSorting of leukemic cells at diagnosis and after treatment in MRD positive patients, or CD34 progenitors in MRD negative cases. Results: Patients in CR/CRi with undetectable MRD (N = 13/72) had significantly improved 1-year cumulative incidence of relapse (CIR, 38% vs 81%; HR: 0.43, P =.030) and relapse free survival (RFS, median of 13 vs 5 months; HR: 0.40, P = .012) as compared to cases with persistent MRD (N = 59/72), though not overall survival (median of 19 vs 11 months; HR: 0.56, P =.097). Achieving undetectable MRD significantly improved RFS of patients with adverse genetics (HR: 0.32, P =.013). On multivariate analysis including genetic risk and treatment arm, MRD status in patients achieving CR was the only independent prognostic factor for CIR (HR: 2.95; P =.002) and RFS (HR: 3.45; P =.002). Eleven of the 13 patients with detectable MRD did relapse or died after the last update of the follow-up, notwithstanding these patients showed a trend for longer overall survival. To better understand the limitations of MFC-based MRD assessment in identifying patients with long-term survival and driven by the paucity of data about immunophenotyping in elderly AML, we investigated the level of phenotypic divergence/overlap between leukemic cells vs their normal maturation-stage counterpart in healthy adults (N=10). Using an unbiased scoring approach based on principal component analysis of merged data, we found that only 7/265 (3%) patients harbored leukemic cells showing phenotypic profiles fully overlapping with their normal maturation-stage counterpart. We thus hypothesized that in patients with undetectable MRD, phenotypically normal CD34 progenitors would contain cells with leukemic-initiating-potential that could be identified on genetic grounds. Using whole exome sequencing, we systematically identified mutations and copy-number abnormalities (CNA) consistent with genetic MRD (gMRD). These findings were similar to that observed when the genomic landscape of leukemic cells at diagnosis were compared to persistent MRD cells, underpinning the extent of gMRD in patients achieving CRMRD by MFC. Interestingly, there was a significant increase in the number of genetic alterations from diagnosis to MRD stages in patients treated with FLUGA vs AZA (1.9-fold vs 1.1-fold, P =.002), which could be related to the mutagenic potential of antimetabolites. Conclusions: Our results show that older AML patients achieving undetectable MRD after semi-intensive therapy or HMA have lower risk of relapse and a trend for longer survival. However, this study unveiled that phenotypically normal CD34 progenitors possess substantial genetic abnormalities in cases with negative MRD. Thus, improved sensitivity of MRD testing by MFC and possibly the combined use of this method with NGS, might be warranted to identify elderly AML patients in CRMRD that may experience long-term survival and could benefit from treatment individualization based on MRD status. Disclosures Paiva: SkylineDx: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Adaptive: Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Kite: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding. Tormo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Ramos:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel and research grants; Novartis: Consultancy, Other: travel grant; Amgen: Consultancy, Other: travel grant; Abbvie: Consultancy, Other: travel grant; Jannsen: Other: travel grant; Roche: Other: travel grant; Rovi: Other: travel grant; Merck-Sahrp & Dohme: Other: travel grant; Daiichi-Sankyo: Other: travel grant; Takeda: Consultancy, Other: travel grant . Vidriales:Janssen, BMS, Novartis, Roche, Astellas Pharma, and Jazz Pharmaceuticals.: Honoraria, Other: Advisory boards. Martinez-Lopez:Novartis: Consultancy; Janssen-cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Incyte: Consultancy, Research Funding. San-Miguel:Bristol-Myers Squibb, Celgene, Novartis, Takeda, Amgen, MSD, Janssen, and Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche, AbbVie, GlaxoSmithKline, and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sanz:Teva, Daiichi-Sankyo, Orsenix, AbbVie, Novartis, and Pfizer: Other: Consulting or Advisory Role.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-134651

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7