Long-Term Outcomes After Autologous Versus Allogeneic Stem Cell Transplantation in Molecularly-Stratified Patients With Intermediate Cytogenetic Risk Acute Myeloid Leukemia: A PETHEMA Study

Rodríguez-Arbolí, Eduardo; Martínez‐Cuadrón, David; Rodríguez‐Veiga, Rebeca; Carrillo‐Cruz, Estrella; Gil-Cortés, Cristina; Serrano-López, Josefina; Bernal, Teresa; Martínez-Sánchez, María del Pilar; Rodríguez-Medina, Carlos; Vidriales, B; Bergua, Juan; Benavente, Celina; García‐Boyero, Raimundo; Herrera-Puente, Pilar; Algarra, Lorenzo; Sayas-Lloris, María José; Fernández, Rosa; Labrador, Jorge; Lavilla, Esperanza; Barrios-García, Manuel; Tormo, Mar; Serrano-Maestro, Alfons; Melo, Claudia Lucía Sossa; García‐Belmonte, Daniel; Vives, Susana; Rodríguez-Gutiérrez, Juan Ignacio; Albo-López, Carmen; Garrastazul-Sánchez, María Paz; Colorado-Araujo, Mercedes; Mariz, José; Sanz, Miguel Á.; Pérez-Simón, Josè Antonio; Montesinos, Pau

doi:10.1016/j.jtct.2020.12.029

Cited by 5 publications

(7 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such prognostic factors historically include the AML-related factors such as FAB-acute promyelocytic leukemia and favorable-risk cytogenetics, response to frontline therapies, but mainly the achievement of MRD negativity and factors related to the graft such as cell dose, and to the recipient. [3][4][5]27,28 demonstrating that patients with low scores do exceedingly well after ACT. 6 In the current study, we added the number of induction courses needed to achieve CR1 as a possible additional prognostic factor for long-term ACT outcome in AML patients demonstrating that achieving a CR1 after the first induction course is an important predictor of transplantation outcome.…”

Section: Discussionmentioning

confidence: 99%

“…One of the key issues in the ACT field is to define prognostic and predictive factors that will help in defining and selecting the AML patients that will benefit most from ACT sparing them the risk of allogeneic transplantation. Such prognostic factors historically include the AML‐related factors such as FAB‐ acute promyelocytic leukemia and favorable‐risk cytogenetics, response to front‐line therapies, but mainly the achievement of MRD negativity and factors related to the graft such as cell dose, and to the recipient 3–5,27,28 . Shouval et al recently added to this list of prognostic factors two frequent AML‐related mutations: FLT3–ITD and NPM1 demonstrating that molecular subtype is a strong predictor of LFS, OS, and relapse and that AML patients with intermediate‐risk cytogenetics expressing the FLT3‐ITD neg /NPM1 mut mutation phenotype experience favorable outcomes when autografted in CR1 with a 5‐year LFS of 62% and OS of 74% indicating that ACT is an attractive option for these patients 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Autologous stem cell transplantation (ACT) is a valid option for post‐remission consolidation for adult patients with favorable and possibly intermediate‐risk acute myeloid leukemia (AML). 1 , 2 , 3 , 4 , 5 Besides the AML cytogenetics and molecular mutations, one of the prognostic factors with the highest significance for outcomes in patients undergoing any type of transplant and especially in those undergoing ACT is disease status at transplantation. 2 , 4 , 5 , 6 , 7 The depth and quality of the remission assessed by both morphology and by the evaluation of measurable residual disease (MRD) are important prognostic factors in ACT for AML.…”

Section: Introductionmentioning

confidence: 99%

“… 1 , 2 , 3 , 4 , 5 Besides the AML cytogenetics and molecular mutations, one of the prognostic factors with the highest significance for outcomes in patients undergoing any type of transplant and especially in those undergoing ACT is disease status at transplantation. 2 , 4 , 5 , 6 , 7 The depth and quality of the remission assessed by both morphology and by the evaluation of measurable residual disease (MRD) are important prognostic factors in ACT for AML. 8 , 9 , 10 , 11 , 12 In addition, the speed required to achieve remission and to clear the leukemic blasts may be important for the outcome and overall survival (OS) in patients with AML.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Autologous stem cell transplantation (ASCT) for acute myeloid leukemia in patients in first complete remission after one versus two induction courses: A study from the ALWP of the EBMT

et al. 2022

View full text Add to dashboard Cite

Background Achieving complete remission (CR) is the main goal in AML treatment and a prerequisite for successful autologous stem cell transplantation (ACT). Methods Comparing results of peripheral blood ACT in patients with AML in CR1 attained following 1 versus 2 chemotherapy courses transplanted in 2000–2019. Results Patients 1532 (84%) with one and 293 (16%) patients with two induction chemotherapies courses (a total of 1825 patients) were included in the study. Follow‐up was 7.9 (95% CI: 7.4–8.4) and 7.7 (95% CI: 7.0–8.6) years (p = 0.8). Time from diagnosis to ACT was 4.7 (range, 3.9–5.8) versus 5.7 (range, 4.7–7.1) months (p < 0.001), respectively. Leukemia free survival (LFS) and overall survival (OS) at 5 years were inferior for patients achieving CR1 with 2 versus 1 course of chemotherapy: 26.6% versus 41.7% (HR = 1.42 [95% CI: 1.22–1.66], p < 0.001) and 36.2% versus 53.3%, (HR = 1.48 [95% CI: 1.25–1.75], p < 0.001), and 5‐year relapse incidence (RI) was higher: 67.2% versus 52.3%, (HR = 1.46 [95% CI: 1.25–1.72], p < 0.001). Five‐year non‐relapse mortality (NRM) was 6.2% versus 6.0% for patients with 2 versus 1 chemotherapy courses, and did not differ significantly (HR = 1.31 [95% CI: 0.81–2.10], p = 0.27). Conclusions LFS and OS were inferior and relapse rate was higher in AML patients who received two inductions chemotherapy courses to reach CR1 before being autografted. AML patients who required 2 induction courses to achieve remission, may be offered allogeneic transplantation rather than an autologous one in an attempt to reduce their high RI and improve outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autologous stem cell transplantation (ASCT) for acute myeloid leukemia in patients in first complete remission after one versus two induction courses: A study from the ALWP of the EBMT

et al. 2022

View full text Add to dashboard Cite

show abstract

“…A total of 2851 patients received any consolidation treatment scheme. A total of 431 patients (16%) were consolidated with an automatic stem cell transplant (auto-HSCT), and 644 (23%) were consolidated with an allogeneic hematopoietic stem cell transplant (allo-HSCT) [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

Ayala

Carreño‐Tarragona

Barragán

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3–ITD-mutated patients, median OS gradually decreased according to FLT3–ITD status and ratio (34.3 months FLT3–ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months ≥ 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3–ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3–ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.

show abstract

Evolving patterns and clinical outcome of genetic studies performed at diagnosis in acute myeloid leukemia patients: Real life data from the PETHEMA Registry

Labrador,

Martínez‐Cuadrón,

Boluda

et al. 2024

Cancer

View full text Add to dashboard Cite

BackgroundThere are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications.MethodsThe REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021.ResultsScreening rates increased for all tests across different time periods (2000–2007, 2008–2016, and 2017–2021) and was the most influential factor for NPM1, FLT3‐ITD, and next‐generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p < .001), whereas FLT3‐ITD testing increased from 38.1% to 74.1% and 95.9% (p < .0001). NGS testing was not performed between 2000–2007 and only reached 3.5% in 2008–2016, but significantly increased to 72% in 2017–2021 (p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702–7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901–2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy.ConclusionsThis unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real‐world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades.

show abstract

Long-Term Outcomes After Autologous Versus Allogeneic Stem Cell Transplantation in Molecularly-Stratified Patients With Intermediate Cytogenetic Risk Acute Myeloid Leukemia: A PETHEMA Study

Cited by 5 publications

References 44 publications

Autologous stem cell transplantation (ASCT) for acute myeloid leukemia in patients in first complete remission after one versus two induction courses: A study from the ALWP of the EBMT

Autologous stem cell transplantation (ASCT) for acute myeloid leukemia in patients in first complete remission after one versus two induction courses: A study from the ALWP of the EBMT

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

Evolving patterns and clinical outcome of genetic studies performed at diagnosis in acute myeloid leukemia patients: Real life data from the PETHEMA Registry

Contact Info

Product

Resources

About