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BACKGROUND: Acute promyelocytic leukemia (APL) is uncommon among subjects aged ≥ 70 years and the better therapeutic strategy represents an unmet clinical need. MATERIALS AND METHODS: This prompted us to explore our real-life data on a retrospective cohort of 45 older APL patients (≥ 70 years) consecutively diagnosed at eight different hematologic institutions in Latium, Italy, from July 1991 to May 2019. RESULTS: Two patients (4.4%) died from early hemorrhagic complications before treatment could begin. Twenty-two patients (51.1%) (Group A) were enrolled or treated according to standard clinical protocols, while 21 (48.8%) (Group B) received an ATRA-based personalized approach due to poor performance status. Morphologic complete remission (CR) after induction therapy was achieved in 33 patients (76.7%) with 100% of patients in Group A and 52.3% in Group B (p < 0.001). Molecular CR was documented in 30 patients (69.7%) [20/22 (90.9%) in Group A and 10/21 (47.6%) in Group B (p = 0.002)]. Ten patients (23.2%) died during induction therapy, all in Group B. Five-year overall survival (OS) of the entire cohort was 46.1% (95% CI 28.2-64.0), with 72.6% (95% CI 42.9-100) in Group A vs. 27.2% (95% CI 7.5-46.9) in the Group B (p = 0.001). CONCLUSIONS: The present analysis highlights that almost half of the patients received sub-optimal induction treatments and registered dismal outcomes demonstrating the importance of adopting standard therapies instead of modified or reduced personalized approaches also in the setting of frail older patients.
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Leucemia Promielocítica Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trióxido de Arsénico/uso terapéutico , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Tretinoina/uso terapéuticoRESUMEN
Pneumococcal (PC) vaccination is recommended for patients with chronic lymphocytic leukemia (CLL). However, response to vaccines has been investigated in a small series of CLL patients. We analyzed the antibody response and outcomes of 112 CLL patients who received the 13-valent pneumococcal conjugate vaccine (PCV13). An immune response was defined by a twofold increase in the PC-IgG levels assessed by ELISA. The median age of patients was 68 years, 23.2% showed IgG levels ≤ 400 mg/L, 6.3% progressive disease, 52% unmutated IGHV. Twenty-two (19.6%) patients were treatment-naïve and 90 (80.4%) previously treated (40.2% front-line chemoimmunotherapy; ibrutinib first/advanced-line, 9.8%/21.4%; idelalisib advanced-line, 8.9%). Nine (8%) patients developed an immune response, eight treatment-naive, and one on front-line ibrutinib. No responses were observed in patients previously treated with chemoimmunotherapy. Age ≥ 60 years (p = 0.007), IgG levels < 400 mg/L (p < 0.0001), prior treatment (p < 0.0001), and signs of disease progression (p = 0.04) were associated with a lower response rate. Pneumonia-free survival was significantly shorter in patients with clinical signs of progressive disease (HR, 8.39), prior pneumonia (HR, 7.03), and TP53 disruption (HR, 2.91). In conclusion, our results suggest that vaccination should be offered at diagnosis to CLL patients with early stage and stable disease who have better resources for an effective immune response.
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Leucemia Linfocítica Crónica de Células B/mortalidad , Vacunas Neumococicas/uso terapéutico , Vacunación/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Vacunación/métodosRESUMEN
BACKGROUND: According to 2008/2016 classification of the World Health Organization (WHO), a platelet (PLT) count ≥ 450 × 109/L, reduced from the previously published WHO 2001 indicated level ≥ 600 × 109/L, was considered the new PLT threshold for the diagnosis of essential thrombocythemia (ET). PATIENTS AND METHODS: To validate this important diagnostic change in a setting of current clinical practice, we retrospectively analyzed clinical and hematologic features at diagnosis and during follow-up of 162 patients with ET, diagnosed in our center from January 2008 to December 2017. We subdivided patients according to PLT value at baseline into Group A (PLT ≥ 600 × 109/L) (124 patients; 76.5%) and Group B (PLT ≥ 450 × 109/L < 600 × 109/L) (38 patients; 23.5%). RESULTS: Among clinical features, only the median value of leukocytes (P < .001) was significantly higher in Group A. Cytostatic treatment was administered in 103 patients, with a significantly higher rate in patients of group A (P < .001). After a median follow-up of 42.4 months (interquartile range, 22.1-70.6 months), 8 thrombotic events were recorded in the entire cohort, without differences between the 2 groups (P = .336). The 5-year overall survival (OS) of the entire cohort was 96.9% (95% confidence interval, 92.6%-100%), without differences between the 2 groups (P = .255). CONCLUSIONS: Our data indicate a substantial homogeneity among patients with ET regardless of the PLT count at diagnosis, thus confirming the usefulness of the 2008/2016 WHO diagnostic criteria.
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Citostáticos/administración & dosificación , Recuento de Plaquetas/normas , Trombocitemia Esencial/diagnóstico , Trombosis/epidemiología , Anciano , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Factores de Riesgo , Trombocitemia Esencial/sangre , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/tratamiento farmacológico , Trombosis/sangre , Trombosis/etiología , Trombosis/prevención & control , Organización Mundial de la SaludRESUMEN
Previous studies investigated the efficacy and the safety of bendamustine (B) vs. chlorambucil (Chl) associated with rituximab (R) in fludarabine-ineligible patients with treated and untreated chronic lymphocytic leukemia (CLL). We conducted a retrospective multicenter study in the Lazio region to further evaluate and compare the efficacy and the toxicity of Chl-R and B-R regimen in CLL patients over the age of 65. We enrolled 192 untreated CLL patients: 111 treated with B-R and 81 with Chl-R. The overall response rates (ORR; 93.6% in B-R and 86.5% in Chl-R) were not statistically different between the two groups, such as progression-free survival (PFS), time to retreatment (TTR), and overall survival (OS). The B-R group showed a higher hematological (p = 0.007) and extra-hematological (p = 0.008) toxicity. When comparing the toxicities according to age, we noted that the extra-hematological toxicity was higher in patients over the age of 75 who were treated with B-R than those treated with Chl-R (p = 0.03). This retrospective study confirms the feasibility of B-R and Chl-R in elderly untreated CLL patients. Currently, patients who are over 75 and unfit are usually treated with Chl-R. This scheme allows achieving the same ORR, PFS, TTR, and OS when compared with B-R because of hematological and extra-hematological toxicities due to B, in which a greater dose reduction has been shown in comparison to Chl.
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Prognostic role of chromosomal translocations (CT) in myelodysplasia (MDS) was retrospectively analyzed in 77 patients from GROM-L registry. Forty (51.9%) balanced, 28 (36.4%) unbalanced and 9 (11.7%) concomitant balanced and unbalanced CT were identified. Five-year overall survival (OS) of the entire cohort was 34.5% (CI 95% 22.5-46.5). Five-year OS of patients with unbalanced CT was significantly shorter than that of patients carrying balanced CT [22.3% (CI 95% 4.0-40.6) vs 44.0% (CI 95% 26.7-61.3) (p = 0.042)]. Five-year OS of patients with CT included in complex karyotype (CK) was significantly shorter than that of patients with isolated CT or CT with another abnormality [5.5% (CI 95% 0-15.7) vs 42.9% (CI 95% 21.3-64.5) and vs 4% (CI 95% 31.6-79.2) (p < 0.001)]. Presence of CT in MDS characterizes a more aggressive outcome only when associated with CK.
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Síndromes Mielodisplásicos , Translocación Genética , Aberraciones Cromosómicas , Humanos , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: In recent years, innovative mechanism-based drugs have enriched the therapeutic armamentarium for patients with chronic lymphocytic leukemia (CLL) and are widely used in the clinical practice. These small molecules targeting the B-cell receptor signaling pathway and the BCL-2 anti-apoptotic protein offer new chemo-free options to both unfit patients and high-risk patients who show a poor response to chemoimmunotherapy. Nonetheless, treatment with ibrutinib, idelalisib and venetoclax is associated with unique side effects. Awareness, prevention and the appropriate management of these specific toxicities are of crucial importance for a successful treatment. Areas covered: The purpose of this review is to discuss the most relevant studies on small molecules in CLL, with particular attention to the emerging toxicity profile of these agents and to the factors that should be considered to address the most appropriate treatment approach for each patient. Expert opinion: The increased knowledge on the biology of CLL has translated into the development of targeted agents that are highly effective and produce deep responses. Toxicities potentially associated with these agents should be known for an optimal management of CLL patients.