Patients with secondary acute myeloid leukemia undergoing allogeneic stem-cell transplant have inferior outcomes than de novo acute myeloid leukemia regardless minimal residual disease level by flow cytometry.

Secondary acute myeloid leukemia (s-AML) patients have a poor prognosis and currently the only curative therapy is allogeneic stem-cell transplant (HSCT). However, we do not yet know whether transplantation is sufficient to reverse the poor prognosis compared to de novo AML patients. We analyzed survival after HSCT comparing a cohort of 58 patients with s-AML versus 52 de novo patients who were transplanted between 2012 and 2020. Patients with s-AML had worse event-free survival (EFS) (p = 0.001) and overall survival (OS) (p < 0.001) compared to de novo AML due to an increased risk of relapse (p = 0.06) and non-relapse mortality (p = 0.03). The main difference in survival was observed in patients who achieved complete remission (CR) before HSCT (EFS p = 0.002 OS and <0.001), regardless minimal residual disease (MRD) by |multiparametric flow cytometry cohorts. In patients transplanted with active disease (AD), the prognosis was adverse in both s-AML and de novo AML groups (EFS p = 0.869 and OS p = 0.930). After excluding patients with AD, we stratified the cohort according to conditioning intensity, noticing that s-AML who received MAC had comparable outcomes to de novo AML, but the survival differences remained among reduce intensity conditioning group. In conclusion, transplanted s-AML patients have worse survival among patients in CR before HSCT, regardless of MRD level by flow cytometry compared to de novo AML. MAC patients had similar outcomes irrespective of leukemia ontogeny.

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia.

Background: The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified. Objective: The aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD-) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD. Study design: We retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD- before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD. Results: Patients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD- patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD- before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status. Conclusions: Patients with MRD+ before HSCT have worse outcomes than MRD- patients. In patients who received MAC, MRD- patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.

Real-life experience of venetoclax and hypomethylating agents in acute myeloid leukemia patients not candidates for intensive chemotherapy or who are refractory/relapsed: A single-centre experience.

We report our experience with venetoclax/hypomethylating agents (Ven/HMA) in 8 AML patients not candidates for intensive CT or refractory/relapsed with limited treatment options. The response rate was 50%. Venetoclax was well-tolerated in 62.5% of the patients. Ven/HMA provides a benefit particularly when used in patients without prior HMA exposure.

Evaluation of adherence and clinical outcomes in patients undergoing allogeneic haematopoietic stem cell transplantation.

OBJECTIVE: To measure adherence to cyclosporine, tacrolimus and  sirolimus prophylaxis against secondary graft failure; cyclosporine,  tacrolimus, sirolimus and mycophenolate prophylaxis against graft- versus-host disease; and posaconazole, voriconazole, valganciclovir  prophylaxis against infection in patients undergo to transplantation of  haematopoietic stem cells; and to analise the incidence of acute  complications based on adherence. METHOD: Retrospective observational study of patients who underwent  allogeneic haematopoietic stem cell transplantation between May 2017  and May 2018. Analyses were carried out between 0 and +100 days  post-engraftment. Whenever possible, adherence to mycophenolate,  tacrolimus, sirolimus, posaconazole, voriconazole and valganciclovir was  evaluated by means of the dispensation records of the Pharmacy  Department of our hospital. To be considered adherent, patients should  have proved an adherence rate equal to or higher than 95%. Adherence  to cyclosporine was determined based on serum levels.  Patients were considered to be non-adherent if their cyclosporine serum  concentrations dropped below 100 ng/mL at any time between days 0  and +100, in the absence of any specific justifying circumstances. The  association between adherence and the inci dence of acute  complications (secondary graft failure, acute graft-versushost disease  and infection) was determined by means of the odds ratio (confidence  interval: 95%). RESULTS: The study sample was made up by 46 patients, all of whom were started on immunosuppressive cyclosporine prophylaxis; 8.7%   needed to be switched to tacrolimus or sirolimus due to toxicity issues.   All the patients received cyclosporine as prophylaxis against graft-  versus-host disease. Mycophenolate was also administered in 41.3% of  cases. A total of 82.6% patients were found to be adherent to their  prophylaxis treatment against graft failure and 80.4% were found to be  adherent to prophylaxis against graft-versus-host disease. All patients  were adherent to anti-infection prophylaxis. The incidence of acute  graft-versus-host disease in prophylaxisadherent patients was 45.9%,  compared with 55.6% for non-adherent patients (odds ratio 0.68;  confidence interval: 95% 0.157-2.943; p = 0.718). CONCLUSIONS: Patients undergoing allogeneic haematopoietic stem cell transplantation demonstrated acceptable adherence to prophylaxis  against acute complications, although a considerable percentage of  patients was found not to take their medication as prescribed. Correct  adherence to immunosuppressants seems to reduce the risk of  developing acute graftversus- host disease.

Objetivo: Medir la adherencia a la profilaxis del fallo secundario del implante (ciclosporina, tacrolimus, sirolimus), de la enfermedad  injerto contra receptor (ciclosporina, tacrolimus, sirolimus,  micofenolato) y de las infecciones (posaconazol, voriconazol,  valganciclovir) en el paciente sometido a trasplante alogénico de  progenitores hematopoyéticos. Comparar la incidencia de  complicaciones agudas en función de la adherencia.Método: Estudio observacional retrospectivo en pacientes sometidos a trasplante alogénico de progenitores hematopoyéticos desde mayo de 2017 hasta mayo de 2018, entre el día 0 y +100 postrasplante. La adherencia a micofenolato, tacrolimus, sirolimus, posaconazol,  voriconazol y valganciclovir se evaluó mediante los registros de  dispensación del servicio de farmacia, siempre que fuera posible. Se  definió como paciente adherente aquel con un porcentaje de adherencia  igual o superior al 95%. La evaluación de la adherencia a ciclosporina se  realizó mediante medida de los niveles plasmáticos. Se definió como  paciente no adherente aquel cuyos niveles plasmáticos de ciclosporina  fueran inferiores a 100 ng/ml en alguna medida entre los días 0 y +100,  en ausencia de factores asociados que lo justificaran. La  asociación entre adherencia e incidencia de complicaciones agudas (fallo  secundario del implante, enfermedad injerto contra receptor  aguda e infección) se estimó mediante la odds ratio y su intervalo de  confianza del 95%.Resultados: Se incluyó a 46 pacientes. Todos comenzaron rofilaxis inmunosupresora con ciclosporina; en el 8,7% se cambió a  tacrolimus o sirolimus por toxicidad. Todos los pacientes recibieron  ciclosporina para la profilaxis de la enfermedad injerto contra receptor.  En el 41,3% de los casos también se administró micofenolato. El 82,6%  fueron adherentes a la profilaxis del fallo de injerto. En cuanto a la  profilaxis de enfermedad injerto contra receptor, resultó adherente el  80,4%. Todos los pacientes resultaron adherentes a la profilaxis  infecciosa. La incidencia de enfermedad injerto contra receptor aguda de  los pacientes adherentes a la profilaxis fue del 45,9% frente al  55,6% en los no adherentes (odds ratio 0,68; intervalo de confianza del  95% 0,157-2,943; p = 0,718). Conclusiones: Los pacientes sometidos a trasplante alogénico de  progenitores hematopoyéticos presentan una aceptable adherencia a la  profilaxis de complicaciones agudas, pero existe un considerable  porcentaje de pacientes que no toman su tratamiento adecuadamente.  La correcta adherencia a los inmunosupresores parece disminuir el  riesgo de sufrir enfermedad injerto contra receptor aguda.