RESUMEN
OBJECTIVES: Aim of the study was to evaluate the role of a Domiciliary Hematologic Care Unit (DHCU) compared to standard DH setting in the active frontline treatment with hypomethylating agents (HMAs) +/- venetoclax of frail patients with acute myelogenous leukemia/high-risk myelodysplastic syndromes (AML/HR-MDS). METHODS: All patients with newly diagnosed AML/HR-MDS unfit for intensive care and treated frontline with HMAs from January 2010 to April 2021 were retrospectively included. RESULTS: Among 112 patients (62 AML/50 HR-MDS), 69 (61.6%) were treated in a standard DH setting and 43 (38.4%) were followed by DHCU, allocated to DH or DHCU by responsible physician. Overall response rate was 29/69 (42.0%) in DH versus 19/43 (44.1%) in DHCU (p = .797). Median response duration was 8.7 months (95%CI 7.0-10.3) in DH versus 13.0 months (95%CI 8.3-17.6) in DHCU (p = .460). Infections were also equally reported. Median overall survival of patients treated in DH was 13.7 months (95%CI 9.9-17.4) compared to 13.0 months (95%CI 6.7-19.3) of patients managed by DHCU (p = .753). CONCLUSIONS: Home care management of HMA is feasible and effective, with results similar to standard DH setting: this approach is thus adequate to offer active therapies in frail patients with AML/HR-MDS considered up to now ineligible.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/tratamiento farmacológico , Resultado del Tratamiento , Estudios Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Hospitales , Azacitidina/uso terapéuticoRESUMEN
Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The 'RUX-IOL' study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX-DFX therapy was administered for a median time of 12.4 months (interquartile range 3.1-71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX- or DFX-related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion-independent. Median time to ICR and ER was 6.2 and 2 months respectively. Patients achieving an ER were more likely to obtain an ICR also (p = 0.04). In multivariable analysis, the absence of leukocytosis at baseline (p = 0.02) and achievement of an ICR at any time (p = 0.02) predicted improved survival. In many MF patients, the RUX-DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.
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Sobrecarga de Hierro , Mielofibrosis Primaria , Benzoatos/efectos adversos , Deferasirox/uso terapéutico , Humanos , Quelantes del Hierro/efectos adversos , Sobrecarga de Hierro/inducido químicamente , Sobrecarga de Hierro/etiología , Nitrilos , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles , Pirimidinas , Estudios RetrospectivosRESUMEN
Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n = 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P = .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P = .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P = .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma. This study was registered at www.clinicaltrials.gov as NCT03745378.
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Arterias/patología , Trastornos Mieloproliferativos/patología , Neoplasias Primarias Secundarias/patología , Cromosoma Filadelfia , Trombosis/patología , Estudios de Casos y Controles , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Análisis MultivarianteRESUMEN
Ruxolitinib is approved for polycythemia vera (PV) patients after failure to previous cytoreductive therapy, based on durable results observed in phase 3 trials. We report a multicenter retrospective study demonstrating the efficacy and safety of ruxolitinib in real-life setting. Eighty-three patients were evaluated. Median follow-up was 24.5 months (IQR 14.0-29.3). At a 3-month response assessment, ruxolitinib provided significant benefit in reducing hematocrit (HCT) level (p < 0.001), phlebotomy requirement (p < 0.001), leucocytes (p = 0.044), and disease-related symptoms (p < 0.001). The exposure-adjusted rates (per 100 patient-years) of infectious complications, thromboembolic events, and secondary malignancies were 6.9, 3, and 3.7, respectively. Non-melanoma skin cancers (NMSC) were the most frequent (40%) SM type. Lymphoproliferative disorders were not detected. Five (6%) patients permanently discontinued ruxolitinib treatment and four (5%) evolved in myelofibrosis (MF), but none in acute leukemia. The rate of MF evolution per 100 patient-years of exposure was 2.8. In our experience, ruxolitinib confirmed its efficacy and safety outside of clinical trials.
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Policitemia Vera , Mielofibrosis Primaria , Humanos , Concentración de Iones de Hidrógeno , Nitrilos/uso terapéutico , Policitemia Vera/complicaciones , Mielofibrosis Primaria/diagnóstico , Pirazoles/efectos adversos , Pirimidinas , Estudios RetrospectivosRESUMEN
To evaluate the role of bosutinib in elderly patients aged >65 years with chronic myeloid leukemia (CML), a real-life cohort of 101 chronic-phase CML patients followed up in 23 Italian centers and treated with bosutinib in second or a subsequent line was retrospectively evaluated. Starting dose of bosutinib was 500 mg/day in 25 patients (24.8%), 400 mg/day in 7 patients (6.9%), 300 mg/day in 33 patients (32.7%), 200 mg/day in 34 patients (33.6%), and 100 mg/day in 2 patients (2.0%). Grade 3/4 hematological toxicity occurred in 7/101 patients (6.9%) and grade 3/4 extra-hematological toxicity in 19/101 patients (18.8%). Permanent bosutinib discontinuation due to toxicity was needed in 12 patients (11.9%). Among the 96 patients evaluable for response, 74 (77.0%) achieved a complete cytogenetic response (CCyR), while 64 of these 74 patients in CCyR (66.6% of all 96 evaluable patients) also achieved a molecular response (MR) (major MR [MR 3.0] in 21 [21.8%], deep MR [MR 4.0/4.5] in 43 [44.8%]). The 3-year event-free survival and overall survival of the whole patients' cohort from bosutinib start were 60.9% (CI 95% 49.3-72.5) and 86.4% (CI 95% 77.2-95.6), respectively. Our real-life data show that bosutinib is effective, with a favorable safety profile, also in elderly patients with important comorbidities and resistance and/or intolerance to previous tyrosine-kinase inhibitor treatments. As a consequence, it could play a significant role in current clinical practice for frail patients.
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Compuestos de Anilina/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Nitrilos/administración & dosificación , Quinolinas/administración & dosificación , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/administración & dosificación , Tasa de SupervivenciaRESUMEN
BACKGROUND AND AIMS: Anagrelide is a drug effective in reducing platelet counts in essential thrombocythemia (ET) and Ph1-negative myeloproliferative neoplasms. The aim of this study was to evaluate the real-life use of anagrelide in patients with ET followed over 25 years at the Haematological Institutes belonging to "Ph1-negative Myeloproliferative Neoplasms Latium Group." PATIENTS AND METHODS: Eligibility criteria were diagnosis of ET and treatment with anagrelide. Data were collected through an ad hoc case report form. RESULTS: One hundred and fifty patients received anagrelide for a median time of 7.4 years (0.1-23.2). Anagrelide was administered as first-line therapy in 34.7% of patients, as second-line in 52% and as third-line in 13.3%: 85.4% responded to therapy. Sixty-eight/136 evaluable patients reported side effects: palpitations, peripheral vasodilation, anaemia, diarrhoea and gastric distress. Fourteen thrombotic (arterial 10, venous 4) and 51 bleeding events (minor 48, major 3) occurred. Sixteen/150 (10.6%) patients developed secondary myelofibrosis and 3/150 (2%) an acute myeloid leukaemia. CONCLUSIONS: In our experience, anagrelide is an effective drug in reducing platelet levels in a high percentage of patients with ET. It is especially addressed to younger people. A careful assessment of the thrombotic risk and monitoring of cardiac function, at diagnosis and during follow-up, is mandatory.
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Quinazolinas/uso terapéutico , Trombocitemia Esencial/tratamiento farmacológico , Trombocitemia Esencial/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anemia/diagnóstico , Anemia/etiología , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Sustitución de Medicamentos , Femenino , Estudios de Seguimiento , Encuestas de Atención de la Salud , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones Hematológicas del Embarazo , Pronóstico , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Retratamiento , Estudios Retrospectivos , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/etiología , Trombosis , Resultado del Tratamiento , Adulto JovenRESUMEN
One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A "poor prognosis" SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a "non-poor prognosis" SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.
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Neoplasias Hematológicas/mortalidad , Trastornos Mieloproliferativos/mortalidad , Neoplasias Primarias Secundarias/mortalidad , Factores de Edad , Anciano , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
There have been some reports on a possible role of azacytidine (AZA) in the treatment of accelerated/blastic phase evolved from Philadelphia-negative myeloproliferative neoplasms (MPN-AP/BP), but results are conflicting. In this study, we analyzed a cohort of 39 patients with MPN-AP/BP treated frontline with AZA at the standard dosage (75 mg/m2 ). Median time from diagnosis to AP/BP evolution was 92.3 months (IR 29.9-180.1). All patients were evaluable for hematologic response: two patients (5.2%) died early after AZA initiation, 13 patients (33.3%) had a progressive or stable disease, nine (23.1%) had a hematologic improvement (HI), seven (17.9%) achieved a partial response (PR), and eight (20.5%) a complete response (CR). Overall, 24 patients achieved a clinical hematologic response (HI + PR + CR), with an overall response rate of 61.5%. Median overall survival (OS) from AZA start of the whole cohort was 13.5 months (95% CI, 8.2-18.7). There was no difference in median OS among patients with HI, PR, or CR (P = .908). These three subgroups as "responders" having been considered, a significantly better OS was observed in responder compared with nonresponder patients, with a median OS of 17.6 months (95% CI, 10.1-25.0) versus 4.1 months (95% CI, 0.4-10.0) (P = .001) Only female gender was significant for both achievement of response (.010) and OS duration (P = .002). In conclusion, AZA is useful for the management of MPN-AP/BP, with an overall response rate (HI + PR + CR) of 61.5% and a longer OS in responders.
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Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Crisis Blástica/tratamiento farmacológico , Trastornos Mieloproliferativos/tratamiento farmacológico , Anciano , Crisis Blástica/diagnóstico , Femenino , Humanos , Hidroxiurea/uso terapéutico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/tratamiento farmacológico , Masculino , Melfalán/uso terapéutico , Persona de Mediana Edad , Mutación , Trastornos Mieloproliferativos/diagnóstico , Pipobromán/uso terapéutico , Policitemia Vera/diagnóstico , Policitemia Vera/tratamiento farmacológico , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/tratamiento farmacológico , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials and collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.There were 45 males and 53 females; median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as secondary MF. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline, and out of 94 patients tested, 66 (70%) were JAK2V617F mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. Fifty-eight patients (59%) required a dose reduction during the first 3 months due to hematological toxicity in the majority of cases. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI, and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug. The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms.
Asunto(s)
Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Concentración de Iones de Hidrógeno , Italia/epidemiología , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/epidemiología , Nitrilos , Mielofibrosis Primaria/epidemiología , Pirimidinas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients.
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Benzoatos/uso terapéutico , Eritropoyesis/efectos de los fármacos , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/patología , Triazoles/uso terapéutico , Anciano , Benzoatos/administración & dosificación , Benzoatos/efectos adversos , Terapia por Quelación , Deferasirox , Índices de Eritrocitos , Femenino , Fibrosis , Estudios de Seguimiento , Humanos , Quelantes del Hierro/administración & dosificación , Quelantes del Hierro/efectos adversos , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/diagnóstico , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/mortalidad , Trastornos Mieloproliferativos/terapia , Estudios Retrospectivos , Reacción a la Transfusión , Resultado del Tratamiento , Triazoles/administración & dosificación , Triazoles/efectos adversosRESUMEN
Spleen enlargement, present in 10-20% of Essential Thrombocythemia (ET) patients at diagnosis, is a feature clinically easy to assess, confirmable by echography with a very low chance of misinterpretation. Nonetheless, the clinical and prognostic role of splenomegaly has been seldom evaluated. From 1979 to 2013, 1297 ET patients retrospectively collected in the database of the Lazio Cooperative Group and Bologna University Hospital were evaluable for spleen enlargement at diagnosis and included in the analysis. On the whole, spleen was enlarged in 172/1297 (13.0%) patients; in most cases (94.8%) splenomegaly was mild (≤5 cm). Patients with splenomegaly were younger, predominantly male, presented higher platelet count and JAK2V617F allele burden and had a lower incidence of concomitant cardiovascular risk factors. At least one thrombotic event during follow-up occurred in 97/1,125 (8.6%) patients without spleen enlargement compared to 27/172 (15.7%) patients with spleen enlargement (P = 0.003). Despite comparable use of cytoreductive/antiplatelet therapies in the two groups, the cumulative risk of thrombosis at 5 years was significantly higher in patients with baseline splenomegaly (9.8% versus 4.4% in patients without splenomegaly, P = 0.012). In multivariate analysis exploring risk factors for thrombosis, splenomegaly retained its negative prognostic role, together with previous thrombosis, leucocyte count and male gender. Baseline splenomegaly seems to be an independent additional risk factor for thrombosis in nonstrictly WHO-defined ET patients. This data could be useful in the real-life clinical management of these patients.
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Esplenomegalia/complicaciones , Trombocitemia Esencial/complicaciones , Trombosis/etiología , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Mutación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Esplenomegalia/diagnóstico por imagen , Esplenomegalia/epidemiología , Trombocitemia Esencial/diagnóstico por imagen , Trombocitemia Esencial/epidemiología , Trombosis/epidemiología , Trombosis/prevención & control , UltrasonografíaRESUMEN
We assessed by flow cytometry minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) given standard-dose (SDAC) and high-dose ARA-C (HDAC) regimens. Of 163 patients enrolled, 130 (median age, 45 years; range, 18-59 years) qualified for analysis, all achieving complete remission after treatment with SDAC (n = 78) or HDAC (n = 52) plus etoposide and daunorubicin. Consolidation consisted of intermediate-dose ARA-C and daunorubicin. MRD negativity was significantly more frequent in the SDAC vs. HDAC arm after both induction (37% vs. 15%, P = 0.007) and consolidation (44% vs. 18%, P = 0.002). Respective median residual leukemic cell counts with SDAC and HDAC use were 1.5 × 10(-3) and 4 × 10(-3) (P = 0.033) after induction and 5.7 × 10(-4) and 2.9 × 10(-3) (P = 0.008) after consolidation. Based on ARA-C schedule and post-consolidation MRD status, the four patient groups (SDAC-MRD(-) , HDAC-MRD(-) , SDAC-MRD(+) , and HDAC-MRD(+) ) displayed 5-year overall survival rates of 60%, 33%, 24%, and 42% (P = 0.007), respectively, with 24%, 35%, 74%, and 48% (P < 0.0001) respective cumulative incidence of relapse estimates. MRD may serve as a biomarker for optimal biologic dosing of ARA-C, and SDAC regimen appears to yield more frequent MRD negativity.
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Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Farmacológicos/análisis , Biomarcadores de Tumor/análisis , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasia Residual/tratamiento farmacológico , Adolescente , Adulto , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Neoplasia Residual/mortalidad , Neoplasia Residual/patología , Recurrencia , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
Pulmonary infections (PIs) are a major complication of Acute Myeloid Leukemia (AML) treated with hypomethylating agents (HMA). We retrospectively evaluated 147 AML patients treated frontline with HMA in 2 Centers. Total number of HMA cycles was 1397. There were 88 episodes of PI in 64 patients (43.5%). Thirty-five/147 patients at risk (23.8%) developed at least 1 episode of early PI (during cycles 1-2). Median OS in patients who developed early PI was 3.3 months (95% CI 0.8 - 5.8) versus 10.5 months (95% CI 8.4 - 12.7) in patients without PI or with PI beyond the 2nd cycle (p < .001). Early PIs were an independent factor predicting lower survival (OR 1.94, 95% CI 1.28 - 2.93; p = .002). In conclusion, early PIs are common in AML patients receiving HMA and are associated with an unfavorable outcome. The results of our study raise the issue of a tailored infection prevention strategy.
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Azacitidina , Leucemia Mieloide Aguda , Humanos , Azacitidina/efectos adversos , Estudios Retrospectivos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Inducción de RemisiónRESUMEN
The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed.
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Antineoplásicos/administración & dosificación , Arsenicales/administración & dosificación , Leucemia Promielocítica Aguda/mortalidad , Leucemia Promielocítica Aguda/terapia , Óxidos/administración & dosificación , Trasplante de Células Madre , Tretinoina/administración & dosificación , Adolescente , Adulto , Trióxido de Arsénico , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
Elderly patients represent the most challenging and hard-to-treat patient population due to dismal characteristics of the disease, such as secondary-acute myeloid leukemia (AML), enrichment of unfavorable molecular genes (TP53) and comorbidities. We conducted a multicentric retrospective study to evaluate activity and safety in a real-life setting of hypomethylating drugs (HMAs) in patients older than 75 years with AML. Between September 2010 and December 2021, 220 patients were treated, 164 (74.5%) received AZAcitidine and 56 DECitabine; most patients (57.8%), received more than four cycles of HMAs. The best response obtained was CR in 51 patients (23.2%), PR in 23 (10.5%) and SD in 45 (20.5%); overall transfusion independence was obtained in 47 patients (34%), after a median of 3.5 months. The median OS (mOs) was 8 months (95% CI 5.9-10.2), with 1- and 2-years OS of 39.4% (95% CI 32.7-46) and 17.4% (95% CI 11.7-23.1), respectively; similar mOS was observed according to HMA treatment (AZA 8.3 vs. DEC 7.8 months, p = 0.810). A subset of 57 long survivors (44 in AZA group and 13 in DEC group) received at least 12 cycles of HMAs, their mOS was 24.3 months. In multivariate analysis, age (≥80), Charlson comorbidity index (≥3), creatinine clearance and the type of best response (≥PR) during treatment maintained independent significance in predicting survival. Infectious complications, most frequently pneumonia (35) and septic shock (12), were lethal in 49 patients (22.2%). Our data show that HMAs have similar efficacy compared to pivotal trials and are well tolerated in a setting of very elderly patients with several co-comorbidities.
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Aims: To define the peculiar features of patients with the deletion of the chromosome 20 long arm (del20q), data from 69 patients with myelodysplastic syndromes (MDSs) and isolated del20q, followed by the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L) and Ospedale Torrette of Ancona, were collected and compared with those of 502 MDS patients with normal karyotype (NK-MDS). Results: Compared to the NK-MDS group, patients with del20q at diagnosis were older (p = 0.020) and mainly male (p = 0.006). They also had a higher rate of bone marrow blast < 5% (p = 0.004), a higher proportion of low and int-1 risk according to IPSS score (p = 0.023), and lower median platelet (PLT) count (p < 0.001). To date, in the del20q cohort, 21 patients (30.4%) received no treatment, 42 (61.0%) were treated with erythropoiesis-stimulating agents (ESA), 3 (4.3%) with hypomethylating agents, and 3 (4.3%) with other treatments. Among 34 patients evaluable for response to ESA, 21 (61.7%) achieved stable erythroid response according to IWG 2006 criteria and 13 (38.2%) were resistant. Nine patients (13.0%) progressed to acute myeloid leukaemia (AML) after a median time from diagnosis of 28 months (IR 4.1−51.7). The median overall survival (OS) of the entire cohort was 60.6 months (95% CI 54.7−66.4). the 5-year cumulative OS was 55.9% (95% CI 40.6−71.2). Conclusion: According to our results, we hypothesize that MDSs with isolated del 20q may represent a distinct biological entity, with peculiar clinical and prognostic features. The physio-pathological mechanisms underlying the deletion of the chromosome 20 long arm are still unclear and warrant future molecular analysis.
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BACKGROUND: Platelet (PLT) gel has been successfully used in tissue regeneration of diabetic/surgical wounds through the releasing of growth factors such as basic fibroblast growth factor and PLT-derived growth factor. Therefore, the PLT gel could represent a therapeutic tool in treating the deep and painful wounds sometimes occurring during graft-versus-host disease (GVHD). STUDY DESIGN AND METHODS: The aim of this study was to verify the efficacy and safety of PLT gel for treating GVHD ulcers. Allogeneic hemocomponents were used to obtain PLT gel with an automated system for the on-site preparation and application of patient (autologous) or healthy blood donor (allogeneic)-derived fibrin sealant or PLT-rich fibrin (Vivostat system, Vivostat A/S). Six patients with multiple lesions involving dermis (Grade I, n = 2), subcutaneous (Grade II, n = 4), or oral mucosa and related to GVHD underwent PLT gel as local therapy. RESULTS: After the second PLT gel application, the pain disappeared in all cases and the granulation tissue was observed in the four patients with Grade II lesions. After a median of eight PLT gel applications (range, 4-10), five of six patients showed a complete response, while one patient with a partial response died early from multiorgan failure. No side effects were documented. CONCLUSION: These preliminary data show that the PLT gel may be used as a safe and effective tool in the management of mucosal skin lesions related to the GVHD.