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

BACKGROUND: There 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. METHODS: The 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. RESULTS: Screening 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. CONCLUSIONS: This 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.

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant / Impacto de las puntaciones del riesgo en los resultados de los pacientes con neoplasias mieloides tras el trasplante alogénico de células madre

Background:The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity.Methods:Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed.Results:175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32–17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%–44%), 28% (21%–35%), 38% (30%–46%) and 24% (17%–31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0–1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0–1 and HCT-CI 0–2 showed OS probabilities of 45% vs. 26% for those with DRI 0–1 and HCT-CI ≥3; p=0.041.Conclusions:In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS. (AU)

Antecedentes:Las principales causas de fallo del trasplante alogénico de células madre hematopoyéticas (alotrasplante) en pacientes con leucemia mieloide aguda (LMA) y síndromes mielodisplásicos (SMD) son las recaídas y la mortalidad debida al trasplante. Se han diseñado diferentes puntuaciones para predecir el pronóstico de dichos pacientes. El objetivo de este estudio fue evaluar qué puntuación o combinación tiene la mejor capacidad predictiva del resultado.Métodos:Análisis retrospectivo de pacientes con LMA y SMD que recibieron un primer alotrasplante de sangre periférica en un único centro, entre diciembre de 2001 y octubre de 2019. Se calcularon las puntuaciones del Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), del European Group for Blood and Marrow Transplantation (EBMT) y del Disease Risk Index (DRI). Para cada puntuación y para las combinaciones HCT-CI/DRI y HCT-CI/EBMT se analizaron la supervivencia global (SG), la incidencia acumulada de recaídas (CIR), la mortalidad no relativa a las recaídas (NRM) y la supervivencia libre de recaídas y libre de enfermedad de injerto versus huésped (GRFS).Resultados:Se evaluaron 175 pacientes. Con un seguimiento medio (rango) de 3,96 (0,32-17,22) años, las probabilidades a 5años (IC95%) de SG, CIR, NRM y GRFS fueron del 36% (28-44), del 28% (21-35), del 38% (30-46) y del 24% (17-31), respectivamente. Para la SG, solo la puntuación DRI seleccionó dos grupos con diferencias estadísticamente significativas (DRI 0-1: 41% vs. DRI≥2: 24%; p=0,011). La combinación de DRI 0-1 y HCT-CI 0-2 reflejó probabilidades de SG del 45% vs. 26% para los pacientes con DRI 0-1 y HCT-CI≥3 (p=0,041).Conclusiones:En los pacientes con LMA y SMD sometidos a alotrasplante la combinación de las puntuaciones HCT-CI y DRI proporcionó la mejor estratificación para la SG. (AU)

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant.

BACKGROUND: The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity. METHODS: Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed. RESULTS: 175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32-17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%-44%), 28% (21%-35%), 38% (30%-46%) and 24% (17%-31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0-1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0-1 and HCT-CI 0-2 showed OS probabilities of 45% vs. 26% for those with DRI 0-1 and HCT-CI ≥3; p=0.041. CONCLUSIONS: In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS.

Gemtuzumab ozogamicina a bajas dosis en adultos con leucemia mieloide aguda / Low doses of gemtuzumab ozogamicin in adults diagnosed with acute myeloid leukaemia

Introducción: Gemtuzumab ozogamicina (GO) es un anticuerpo monoclonal activo frente la leucemia mieloide aguda (LMA) CD33+. A dosis de 9mg/m2, su beneficio se vio limitado por la hepatotoxicidad y el síndrome de oclusión sinusoidal (SOS). Dosis fraccionadas (3mg/m2) mejoraron la toxicidad sin comprometer la eficacia. En este estudio se evaluó la eficacia y la toxicidad de GO administrado a dosis bajas.MétodosSe incluyeron 24 pacientes con LMA tratados con GO a dosis de 3mg/m2 durante el tratamiento de inducción o reinducción.ResultadosCatorce pacientes con LMA de novo y 10 con LMA en recaída o refractaria (R/R) recibieron GO como parte del tratamiento de inducción o reinducción. Se observó hepatotoxicidad grado 3-4 en 3 y ningún paciente, respectivamente. Trece pacientes recibieron posteriormente un trasplante de progenitores hematopoyéticos (TPH) observándose en ellos 2 casos de hepatotoxicidad y ningún caso de SOS.ConclusionesLa administración de GO a dosis de 3mg/m2 es segura y no compromete la realización de un ulterior TPH. Aunque la hepatotoxicidad fue frecuente, no se observó SOS antes o después del TPH. (AU)

Background: Gemtuzumab ozogamicin (GO) is a monoclonal antibody with significant activity in CD33+acute myeloid leukaemia (AML). At doses of 9mg/m2, its benefit was limited by hepatotoxicity and sinusoidal obstruction syndrome (SOS). Fractionated doses improved toxicity without compromising efficacy. We evaluated the efficacy and the toxicity of low doses of GO.MethodsTwenty-four patients with AML received 3mg/m2 of GO as a part of the induction or reinduction therapy.ResultsFourteen patients diagnosed with de novo AML and 10 patients with relapsed or refractory (R/R) AML received GO as a part of the induction or reinduction therapy. Three and no cases of hepatotoxicity were observed, respectively. Thirteen patients received a subsequent haematopoietic stem cell transplantation (HSCT) after GO therapy. Hepatotoxicity was observed in 2 patients and no SOS was observed in any patient.ConclusionsThe administration of low dose GO is feasible and does not have impact on subsequent HSCT outcome. Although some degree of hepatotoxicity was observed, there were no cases of SOS, either before or after HSCT. (AU)

Low doses of gemtuzumab ozogamicin in adults diagnosed with acute myeloid leukaemia. / Gemtuzumab ozogamicina a bajas dosis en adultos con leucemia mieloide aguda.

BACKGROUND: Gemtuzumab ozogamicin (GO) is a monoclonal antibody with significant activity in CD33+acute myeloid leukaemia (AML). At doses of 9mg/m2, its benefit was limited by hepatotoxicity and sinusoidal obstruction syndrome (SOS). Fractionated doses improved toxicity without compromising efficacy. We evaluated the efficacy and the toxicity of low doses of GO. METHODS: Twenty-four patients with AML received 3mg/m2 of GO as a part of the induction or reinduction therapy. RESULTS: Fourteen patients diagnosed with de novo AML and 10 patients with relapsed or refractory (R/R) AML received GO as a part of the induction or reinduction therapy. Three and no cases of hepatotoxicity were observed, respectively. Thirteen patients received a subsequent haematopoietic stem cell transplantation (HSCT) after GO therapy. Hepatotoxicity was observed in 2 patients and no SOS was observed in any patient. CONCLUSIONS: The administration of low dose GO is feasible and does not have impact on subsequent HSCT outcome. Although some degree of hepatotoxicity was observed, there were no cases of SOS, either before or after HSCT.

Estudio comparativo sobre la utilidad de la profilaxis antibacteriana con levofloxacino en pacientes receptores de un trasplante de progenitores hematopoyéticos / Comparative study on the usefulness of antibacterial prophylaxis with levofloxacin in patients submitted to hematopoietic stem cell transplantation

Fundamento: La infección bacteriana continúa siendo una complicación frecuente en pacientes receptores de un trasplante de progenitores hematopoyéticos (TPH). No obstante, el impacto de la profilaxis antibacteriana en la mortalidad de estos pacientes es controvertido. Pacientes y métodos: Comparación retrospectiva de 2 grupos consecutivos de receptores de TPH según recibieran (n = 132) o no (n = 107) profilaxis antibacteriana con levofloxacino. Resultados: En el 41% de los procedimientos de TPH en los que se administró profilaxis con levofloxacino se constató infección microbiológicamente documentada (IMD) con bacteriemia, frente a un 40% de los que no recibieron levofloxacino. La frecuencia de bacteriemia por bacilos gramnegativos fue del 11 y del 38%, la resistencia a levofloxacino fue del 39 y del 14%, y hubo un 8 y 7% de muertes, respectivamente. Conclusiones: En nuestra experiencia, el uso de levofloxacino se asoció a una menor frecuencia de bacteriemia por microorganismos gramnegativos, pero no se asoció a disminución en la tasa de IMD ni influyó en su evolución. En cambio, hubo un aumento de la resistencia a quinolonas en los pacientes tratados con levofloxacino (AU)

Background: Bacterial infection remains a frequent complication in patients receiving a hematopoietic stem cell transplantation (HSCT). However, the impact of the antibacterial prophylaxis mortality in these patients is controversial. Patients and methods: Retrospective comparison of 2 consecutive groups of patients undergoing HSCT receiving (n = 132) or not (n = 107) antibacterial prophylaxis with levofloxacin. Results: 41% of patients receiving prophylaxis with levofloxacin had microbiologically documented infection (MDI) with bacteremia, compared with 40% of those not receiving levofloxacin. The frequency of gram-negative bacteremia was 11 and 38%, the resistance to levofloxacin was 39 and 14%, and the mortality was 8 and 7%, respectively. Conclusions; In our experience, the use of levofloxacin as prophylaxis in HSCT was associated with a lower frequency of gram-negative bacteremia but was not associated with a decreased rate of MDI and did not influence their outcome. In contrast, there was an increase in quinolone resistance in patients treated with levofloxacin (AU

[Comparative study on the usefulness of antibacterial prophylaxis with levofloxacin in patients submitted to hematopoietic stem cell transplantation]. / Estudio comparativo sobre la utilidad de la profilaxis antibacteriana con levofloxacino en pacientes receptores de un trasplante de progenitores hematopoyéticos.

BACKGROUND: Bacterial infection remains a frequent complication in patients receiving a hematopoietic stem cell transplantation (HSCT). However, the impact of the antibacterial prophylaxis mortality in these patients is controversial. PATIENTS AND METHODS: Retrospective comparison of 2 consecutive groups of patients undergoing HSCT receiving (n=132) or not (n=107) antibacterial prophylaxis with levofloxacin. RESULTS: 41% of patients receiving prophylaxis with levofloxacin had microbiologically documented infection (MDI) with bacteremia, compared with 40% of those not receiving levofloxacin. The frequency of gram-negative bacteremia was 11 and 38%, the resistance to levofloxacin was 39 and 14%, and the mortality was 8 and 7%, respectively. CONCLUSIONS: In our experience, the use of levofloxacin as prophylaxis in HSCT was associated with a lower frequency of gram-negative bacteremia but was not associated with a decreased rate of MDI and did not influence their outcome. In contrast, there was an increase in quinolone resistance in patients treated with levofloxacin.