RESUMEN
BACKGROUND: This monocentric retrospective study describes the treatment patterns and outcomes of chronic lymphocytic leukemia (CLL) patients. METHODS: Adult CLL patients treated between 1992 and 2022 were included. The time to next treatment (TTNT) was defined as the time from the treatment's start to the start of a subsequent therapy or death. The time to next treatment failure or death (TTNTF) was defined as the time from treatment discontinuation to the discontinuation of a subsequent therapy or death. RESULTS: Of 637 registered patients, 318 (49.9%) received treatment. We evaluated 157 cBTKi-exposed, 34 BCL2i-exposed cBTKi-naïve, and 26 double-exposed patients. The five-year TTNT values in the cBTKi-exposed patients were 80% (median NR), 40% (median 40 months), and 21% (median 24 months) months in the first line (1L), second line (2L), and beyond the second line (>2L), respectively (p < 0.0001). The five-year TTNT values in the BCL2i-exposed patients were 83% (median NR), 72% (median NR), 12% (median 28 months) in the 1L, 2L, and >2L, respectively (p = 0.185). The median TTNTF was 9 months (range 1-87) after cBTKi and 17 months (range 8-49) after both a cBTKi and BCL2i. CONCLUSIONS: This study suggests that, in CLL patients, the earlier we used targeted therapies, the better was the outcome obtained. Nonetheless, the poor outcomes in the advanced lines of therapy highlight the need for more effective treatments.
RESUMEN
An interventional pilot study to assess the tolerability and activity of the intralesional injection of rituximab, a chimeric mAb that targets the CD20 antigen, in patients with orbital B-cell lymphoma. Five patients received four intralesional injections (one injection a week) of rituximab together with ropivicaine 2%. Side-effects and tumor response were assessed after each injection and during the follow-up (20 months). Two patients obtained complete remission of the intraorbital lesion. Two patients showed incomplete response after induction therapy and received planned escalating rituximab doses, obtaining regression of subjective symptoms. One patient did not achieve tumor regression after the first injection and underwent systemic treatment. This small exploratory study suggests that intralesional rituximab is a well-tolerated treatment for patients with primary ocular adnexal lymphoma. These preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in anterior intraorbital lesion localization of lymphoma.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antineoplásicos/administración & dosificación , Linfoma no Hodgkin/tratamiento farmacológico , Neoplasias Orbitales/tratamiento farmacológico , Anciano , Femenino , Humanos , Infusiones Intralesiones , Aparato Lagrimal/patología , Linfoma , Masculino , Persona de Mediana Edad , Proyectos Piloto , RituximabRESUMEN
The fludarabine plus cyclophosphamide (FC) regimen was reported to be superior to chlorambucil or fludarabine alone in terms of complete response (CR), overall response (OR) and progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukaemia (CLL). In the present study, we compared the efficacy and toxicity of FC administered through oral and intravenous route in 65 untreated patients affected by advanced CLL. No statistical differences were noticed between the two routes of administration in terms of OR, PFS, time to re-treatment (TTR) and overall survival (OS) of analysed patients. We also assessed the influence on the clinical outcome of the mutation status of the immunoglobulin variable region heavy chain (IgVH) gene, of the cytogenetic abnormalities and of the expression of ZAP70 and CD38 in patients' primary samples. Among the 58 evaluable patients, 31 (53%) achieved a CR and 18 (31%) a partial response. The median PFS was 35 months, median TTR was 42 months and median OS was not reached after 45 months (range, 1-161). A significantly lower OR rate was noticed in patients with high-risk cytogenetic abnormalities (del 17p, del 11q). In this study, high-risk cytogenetic abnormalities and unmutated IgVH genes were independent predictors of TTR. These results underline the importance of biological stratifications in front-line treatment of CLL patients. We confirm that FC is an effective regimen with mild toxicities; it could be recommended for patients with low-risk biological parameters who represent, in our experience, about 30% of the total.
Asunto(s)
Ciclofosfamida/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Vidarabina/análogos & derivados , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores/sangre , Biomarcadores/metabolismo , Ciclofosfamida/efectos adversos , Femenino , Humanos , Inyecciones Intravenosas , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversosRESUMEN
INTRODUCTION: There are no standard therapies for chronic lymphocytic leukemia (CLL)-associated immune thrombocytopenia (IT) so far. PATIENTS AND METHODS: We report the results of therapy with single agent rituximab in 21 patients with CLL-associated IT. The mean age at CLL and IT diagnosis was 64 and 68 yr, respectively. IT developed at a mean time of 44 months from the diagnosis of CLL. In four cases, IT was diagnosed at the same time as CLL. For three patients, IT was considered fludarabine-related and two patients showed autoimmune hemolysis also. All patients but one received steroids as first-line treatment for IT. Some patients received intravenous high-dose Ig, vincristine, and Cytoxan also, without beneficial effect. After a mean time of 43 d from the diagnosis of IT, all patients were scheduled to receive rituximab at a dosage of 375 mg/mq/weekly. RESULTS: Eighteen (86%) patients completed the scheduled four cycles of rituximab. Irrelevant first infusion side effects were seen only in one patient. Twelve (57%) patients showed a complete response (CR), six (29%) patients a partial response (PR), and three (14%) patients did not respond. In responding patients, the mean duration of response was 21 months (4-49 months). At a mean follow-up of 28 months, 14 (66%) patients were still alive, 10 (48%) of them in CR and three (14%) in PR. CONCLUSIONS: This retrospective analysis prove that rituximab is an effective and well-tolerated alternative treatment for CLL-associated IT.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Factores Inmunológicos/administración & dosificación , Leucemia Linfocítica Crónica de Células B/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/etiología , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Factores Inmunológicos/efectos adversos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/mortalidad , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Tasa de SupervivenciaRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anciano , Ciclofosfamida/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
We tested the efficacy and safety of oral fludarabine and cyclophosphamide as front-line therapy in chronic lymphocytic leukemia (CLL) and assessed the influence of immunoglobulin variable region heavy chain (IgVH) gene mutation status, interphase cytogenetic abnormalities, and expression of ZAP-70 and CD38 on clinical outcome. Thirty-seven patients with previously untreated CLL received oral fludarabine (30 mg m(2)) and oral cyclophosphamide (250 mg m(2)) for three consecutive days every 4 weeks for six cycles. Eighteen patients had unmutated and 15 had mutated IgVH genes. Nine patients had the 'high risk' cytogenetic abnormality del(11q22.3) or del(17p13.1). Fifteen patients were ZAP-70-positive and eight patients were CD38-positive. Among the 35 valuable patients, 14 patients (40%) obtained a complete response and 13 (37%) a partial response. The median progression-free survival (PFS) was 23 months and median time to re-treatment (TTR) was 38 months. A significantly lower overall response rate (43% vs. 85%, p = 0.011), a shorter PFS (22 vs. 27 months, p = 0.015), and a shorter TTR (22 vs. 40 months, p = 0.031) were noticed in the 'high risk' cytogenetic abnormalities group; TTR was also shorter in IgVH-unmutated than in IgVH-mutated patients (26 vs. 41 months, p = 0.035). Hematologic toxicity included grade IV neutropenia (ten patients) and grade III/IV anemia (three patients). Gastrointestinal toxicity was mild and no patient required hospitalization. The oral combination of fludarabine and cyclophosphamide is an effective, safe, and well-tolerated regimen that, if confirmed with larger series, will be appropriate especially in patients with low risk biological parameters.
Asunto(s)
Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Neutropenia/inducido químicamente , Administración Oral , Anciano , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mutación , Inducción de Remisión , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
Elevated levels of TNF-alpha have been associated with progressive disease in patients with chronic lymphocytic leukemia (CLL). Thalidomide has been shown to inhibit production of TNF-alpha. We investigated the effects of thalidomide on clinical outcome and TNF-alpha serum levels in five pre-treated CLL patients. The schedule consisted on daily thalidomide (Thal), oral fludarabine (Flu) and oral cyclophosphamide (CTX). Median duration of treatment was 60 days; four patients stopped treatment for disease progression and one patient for neurological toxicity. Serum TNF-alpha levels did not show any decrease during treatment. Low-dose thalidomide is not effective in CLL patients with refractory disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Talidomida/administración & dosificación , Vidarabina/análogos & derivados , Administración Oral , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Talidomida/efectos adversos , Insuficiencia del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangre , Vidarabina/administración & dosificación , Vidarabina/efectos adversosRESUMEN
B-cell lymphomas constitute the most frequent malignant neoplasm of the ocular adnexal, often presenting with localized disease. Five patients with primary localized CD20 positive B cell non Hodgkin ocular adnexal lymphomas received intralesional rituximab at the dose of 5mg once a week for one month, followed by 10mg weekly in case of incomplete response. Four of five patients obtained regression of symptoms and 2 of them showed complete response. No patients experienced side effects besides pain on the site of the injection. Local treatment with Rituximab for OAL is a safe and useful first-line therapeutic option.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anciano , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Antígenos CD20/inmunología , Antígenos CD20/metabolismo , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Femenino , Humanos , Inyecciones Intralesiones , Linfoma , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/tratamiento farmacológico , Proyectos Piloto , Radiografía , Inducción de Remisión , Rituximab , Resultado del TratamientoRESUMEN
Regulatory T-cells (Treg) actively maintain immunological self-tolerance and play a significant role in the progression of cancer. Treg cell numbers have been evaluated in 80 patients with previously untreated chronic lymphocytic leukemia (CLL) and in 40 normal healthy volunteers. Treg cells are higher in CLL patients than in controls and correlate with disease status (more advanced clinical stage, peripheral blood B-cell lymphocytosis, absolute CD38+ B-cell number, and more elevated LDH levels). No correlation was found with ZAP-70 expression, IgVH mutational status and cytogenetic abnormalities. This data shows that Treg cell number is abnormal in CLL patients.