Ana Garrido

Hospital das Clínicas da Universidade Federal de Pernambuco

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Jorge Sierra

Hospital de Sant Pau

Mar Tormo

INCLIVA Health Research Institute

Olga Salamero

Universitat Autònoma de Barcelona

Jordi Esteve

Hospital Clínic de Barcelona

Salut Brunet

Hospital de Sant Pau

Josep Nomdedéu

Hospital de Sant Pau

Marta Pratcorona

Hospital de Sant Pau

Susana Vives

Institut Català d'Oncologia

Joan Bargay

Hospital Son Llatzer

Rodrigo Martino

Hospital de Sant Pau

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Universitat Autònoma de Barcelona

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Hospital de Sant Pau

Josep Carreras Leukaemia Research Institute

Institut Català d'Oncologia

Universitat de Barcelona

Centro de Investigación Biomédica en Red de Cáncer

Instituto de Salud Carlos III

Fundación Josep Carreras Contra la Leucemia

Hospital Clínic de Barcelona

Hospital Universitario de La Princesa

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Azacitidine As Front-Line Therapy in AML: Results From Spanish National Registry. Alma Study Investigators

Blood (2012)

Fernando Ramos Violeta Martínez‐Robles Joan Bargay Guillermo Debén Ana Garrido

Azacitidine

10.1182/blood.v120.21.3593.3593

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Citations (3)

Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort

Blood Cancer Journal (2023)

Guadalupe Oñate Marta Pratcorona Ana Garrido Alícia Artigas-Baleri Àlex Bataller

Abstract Midostaurin added to intensive chemotherapy is the standard of care for acute myeloid leukemia (AML) with FLT3 mutations ( FLT3 mut). We analyzed the impact of midostaurin in 227 FLT3 mut-AML patients included in the AML-12 prospective trial for fit patients ≤70 years (#NCT04687098). Patients were divided into an early (2012–2015) and late (2016–2020) cohorts. They were uniformly treated except for the addition of midostaurin in 71% of late group patients. No differences were observed in response rates or the number of allotransplants between groups. Outcome was improved in the late period: 2-year relapse incidence decreased from 42% vs 29% in early vs late group ( p = 0.024) and 2-year overall survival (OS) improved from 47% vs 61% ( p = 0.042), respectively. The effect of midostaurin was evident in NPM1 mut patients ( n = 151), with 2-yr OS of 72% (exposed) vs 50% (naive) patients ( p = 0.011) and mitigated FLT3 -ITD allelic ratio prognostic value: 2-yr OS with midostaurin was 85% and 58% in low and high ratio patients ( p = 0.049) vs 67% and 39% in naive patients ( p = 0.005). In the wild-type NPM1 subset ( n = 75), we did not observe significant differences between both study periods. In conclusion, this study highlights the improved outcome of FLT3 mut AML fit patients with the incorporation of midostaurin.

Hematology

Hematologic Neoplasms

10.1038/s41408-023-00839-1

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Citations (8)

Rapid progression of midventricular obstruction in adults with double-chambered right ventricle

Journal of Thoracic and Cardiovascular Surgery (2003)

José M. Oliver Ana Garrido Ana González Fernando Benito Marta Mateos

10.1016/s0022-5223(03)00044-8

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Citations (79)

Low Rate of Invasive Fungal Infections During Induction and Consolidation Chemotherapy for Adults with De Novo Acute Myeloid Leukemia Without Anti-mold Prophylaxis: Single-Center 2002–2018 Empirical/Pre-emptive Approach

Mycopathologia (2020)

Rodrigo Martino Ana Garrido Marta Santaliestra Irene García‐Cadenas Silvana Novelli

Induction chemotherapy

10.1007/s11046-020-00461-w

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Citations (2)

Improved Response to 5-Azacitidine in Patients with Primary Compared to Secondary AML, Particularly If NPM1 Mutations Are Present,

Blood (2011)

Ana Garrido Miguel Ortín Montserrat Hoyos Rodrigo Martino Anna Aventı́n

NPM1

Azacitidine

Clofarabine

10.1182/blood.v118.21.3562.3562

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Azacitidine in older patients with acute myeloid leukemia (AML). Results from the ALMA study according to the MRC risk index score.

Journal of Clinical Oncology (2015)

José Falantes Violeta Martinez Robles Joan Bargay Guillermo Debén Ana Garrido

7061 Background: Treatment of patients (pts) >60y with AML remains challenging. The MRC and LRF validated a 1y survival risk index score in 2843 older AML pts treated with intensive (IC) and non-intensive (NI) chemotherapy, identifying 3 groups with different risk estimates1. Azacitidine (AZA) prolonged OS in older AML pts vs. conventional care (AZA-AML-001 trial)2. Nevertheless, comparison between AZA and IC was jeopardized by the low number of subjects randomized to AZA or IC. Aim: To assess the impact of AZA in a retrospective cohort of older AML pts, unfit for IC, stratified by the MRC/LRF risk score. Methods: The ALMA cohort accrued 110 unfit AML pts who received compassionate front-line AZA before 2011 in 22 Spanish sites (Ramos F et al, Leuk Res. 2014). Cytogenetic, age, white blood count (WBC), PS and AML type categorized pts as good, standard and poor-risk, as stated by Wheatley’s score. Results: Characteristics of the ALMA cohort and distribution across MRC/LRF risk categories are shown in Table 1. After accounting for the above 5 parameters, the ALMA cohort included more poor-risk pts than the MRC/LRF series (63% vs. 31%/37% in the AML11/AML14 trials, respectively). After 28 months median follow-up, 1y survival of ALMA cohort was 66%, 40% and 31%, respectively, for the good, standard and poor-risk groups. Comparison of these estimates with those of MRC/LRF trials are also shown in Table 1. Potentially relevant clinical differences are apparent in the poor-risk group when comparing AZA to either approach. Conclusions: Although retrospective and non-matched, AML pts unfit for IC seemed to benefit from AZA to a similar extent to IC. Moreover, in the poor-risk subset (n=70), 1y survival with AZA was equivalent and likely superior to previous AML/MRC strategies. ALMA cohort. Parameter N (%) Age (median) 75 (56-89) PS 0-1: 77 2: 27 >2: 6 WCB (<109/L) 79 (72) Therapy-related AML & AHD 16 (14%) & 27 (24.5%) MRC cytogenetics Fav: 1 (0.9) Inter: 64 (58.2) Adv: 30 (27.3) NA: 15 (13.6) Risk categories (AML11 risk) Good: 7 (6.4) Standard: 33 (30) Poor: 70 (63.6) 1y survival estimates (%) MRC/LRF Risk group AML11 AML14I AML14NI AML14NIA AML14 (all) ALMA Good 53 60 25 36 59 66 Standard 43 48 33 42 45 40 Poor 16 30 10 14 24 31

Azacitidine

10.1200/jco.2015.33.15_suppl.7061

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PS995 IMPACT OF DNMT3A MUTATIONAL STATUS IN MOLECULAR MEASURABLE RESIDUAL DISEASE CLEARANCE IN ACUTE MYELOID LEUKEMIA WITH MUTATED NPM1

HemaSphere (2019)

Guadalupe Oñate Àlex Bataller Ana Garrido Jordi Esteve M. Arnan

Background: Acute myeloid leukemia (AML) with mutated NPM1 ( NPM1mut ) is a separated category in the latest WHO classification. Persistent detection of NPM1 mutations after therapy is a strong predictor of relapse and measurable residual disease (MRD) monitoring of NPM1 is recommended in the latest European LeukemiaNet (ELN) MRD assessment guidelines. DNMT3A is the third most frequent mutated gene in AML and has been associated with mutations in NPM1 and FLT3. Prognostic significance of mutated DNMT3A (DNMT3Amut) in AML has been controversial. Aims: To explore the differences in molecular MRD clearance in AML with mutated NPM1 according to DNMT3A mutational status. Methods: A total of 67 patients with de novo AML and NPM1 mut were analysed from CETLAM database (median age 53 years (19–72); male:female 31:36 (0.86), median WBC 20.5x10 9 /L (1.3–384), median bone marrow blasts 69%). All patients were included in the AML‐2003 (n = 9) and AML‐2012 (n = 54) CETLAM intensive treatment protocols, 63 patients achieved complete remission (CR) with 1 or 2 cycles of induction intensive chemotherapy (n = 55 vs 8) and followed 1 to 3 consolidation cycles. Notably, since 2012 patients with NPM1mut and FLT3 ‐ITD low ratio are not considered for transplant in first CR. Bone marrow (BM) samples from diagnosis were studied for DNMT3A mutations as previously described and NPM1 molecular MRD monitoring was performed at BM by quantitative RT‐PCR (sensitivity 10 –4 to 10 –6 ) at specific timepoints (diagnose, after induction and following each cycle of consolidation (C1, C2, C3)). The relationship between DNMT3A mutations and various patient characteristics was determined by the Fisher exact test for the categorical variables. Kaplan‐Meier method was used to estimate the distribution of OS. Results: DNMT3A mutations were detected in 31 patients, the majority were found in codon #R882 or corresponded to DNA insertion/deletions. FLT3 ‐ITD was observed in 28 patients (17 low wt/ITD ratio (<0.5) vs 11 high ratio). No association was found between DNMT3Amut and FLT3 ‐ITD mutational status (p = 0,133). In the whole series, bone marrow NPM1 quantitative MRD clearance was found significant when considering MRD log reduction (defined as the log10 reduction between BM NPM1 baseline level and NPM1 after each cycle of intensive chemotherapy), as well as NPM1 total transcripts (> or ≤ than median BM NPM1 transcripts after each cycle). Thus, after C1 patients with ≥3log reduction presented a significantly better outcome than those with <3log (5yr OS 82 ± 6,6% vs 54 ± 15% p = 0,013). In this setting, we contrasted DNMT3A mutational status to the log reduction after C1, and we observed a significant association between the presence of DNMT3Amut and a worse NPM1 clearance (p = 0,001) (Figure 1B). Similar findings of the association between DNMT3A and NPM1 MRD clearance were shown with log reduction after induction (p = 0,011) and NPM1 absolute transcript reduction after induction ( p < 0,001) and C1 (p = 0,011). Summary/Conclusion: In this study, bone marrow NPM1 MRD log and absolute transcript reduction quantified at specific time points associates to a survival benefit. Mutations in DNMT3A are significantly related to a worse clearance of NPM1 MRD. Future studies with larger cohorts are needed to clarify prognoses of AML patients that harbour NPM1, FLT3‐ITD and mutated DNMT3A. image

NPM1

Minimal Residual Disease

Induction chemotherapy

10.1097/01.hs9.0000562276.87064.96

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Acute myeloid leukemia with inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2): Study of 61 patients treated with intensive protocols

European Journal Of Haematology (2020)

Marta Sitges Blanca Boluda Ana Garrido Mireia Morgades Isabel Granada

Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.The aim of this study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.Sixty-one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One- and 4-year CIR were 52% and 56%. One- and 4-year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.

Cumulative incidence

Induction chemotherapy

10.1111/ejh.13417

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Citations (18)

Final Results of the AML12 Trial of the Spanish Cetlam Group in Adults with Acute Myeloid Leukemia (AML) up to the Age of 70 Years: Risk Adapted Post-Remission Allocation Based on Genetic Data and Minimal Residual Disease

Blood (2019)

Jorge Sierra Ana Garrido Marina Díaz Beyà Montserrat Hoyos Marisa Calabuig

Idarubicin

CEBPA

Minimal Residual Disease

Induction chemotherapy

Chemotherapy regimen

10.1182/blood-2019-128682

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Citations (3)

Serotonin Syndrome after Sertraline Overdose in a Child: A Case Report

Case Reports in Pediatrics (2013)

Joana Grenha Ana Garrido Hernâni Brito Maria José Oliveira Fátima Santos

Serotonin syndrome is a potentially life-threatening drug effect. It may be misdiagnosed because it has mostly been reported in adults. Case Report. An 8-year-old girl with behavioral problems and medicated with risperidone and sertraline was admitted in the emergency department after she had taken voluntarily 1500 mg of sertraline (50 mg/kg). At admission, she had marked agitation, visual hallucinations, diaphoresis, flushing, and tremor. She had fever and periods of hypertension. She also showed generalized rigidity and involuntary movements. She was treated with fluids and iv diazepam, midazolam, clemastine, and biperiden. As the patient presented a severe insomnia and a progressive rhabdomyolysis, she was transferred to pediatric intensive care unit (ICU), where she was under treatment with cyproheptadine, mechanical ventilation, and muscular paralysis for 11 days. She was discharged from hospital a few days later with no neurological sequelae. Conclusions. Serotonin syndrome is still not well recognized by physicians. In our patient, the diagnosis was made early due to the history of overdose with serotonin reuptake inhibitors and the triad of mental, neurological, and autonomic signs. Parents must be educated to prevent children from having free access to drugs, avoiding self-medication or overdose.

Serotonin Syndrome

Sertraline

Drug overdose

Trazodone

Midazolam

10.1155/2013/897902

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Citations (15)