RESUMO
Both Dasision and ENESTnd trials had many exclusion criteria, with a possible selection bias compared with the real-life. To address the impact of this bias on the first-line treatment in the current clinical practice, we revised 207 unselected newly diagnosed chronic phase chronic myeloid leukaemia (CML) patients [M/F 108/99, median age 58.8 years, interquartile range 42.3-70.2] treated with front-line imatinib from June 2002 to June 2013 at our Institution, and evaluated how many of them would have been excluded from enrolment in the two trials. Twenty-eight patients (13.5%) should have been excluded by both trials because of polycomorbidities (12), severe cardiomyopathy (five), age > 80 with frailty (three), drug abuse (two) or other severe concomitant diseases (six). In addition, eight patients should have been excluded by Dasision due to isolated chronic obstructive broncopulmonar disease, and 19 patients should have been excluded by ENESTnd due to isolated diabetes (10), arrhythmia (four), acute myocardial infarction > 6 months before CML diagnosis (two), chronic pancreatic disease (two) and peripheral arterial obstructive disease (one). On the whole, 36 patients (17.4%) would have been excluded by Dasision trial and 47 (22.7%) by ENESTnd trial. The patients potentially not eligible for both trials were significantly older and with imatinib had a worse outcome compared with patients potentially eligible. Our data highlight that an automatic transposition of results available in clinical controlled trials into the frontline real-life management of CML patients should be regarded with caution. Copyright © 2015 John Wiley & Sons, Ltd.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adulto , Idoso , Ensaios Clínicos Controlados como Assunto , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To report our experience concerning sustained response (SR) after TPO-RA discontinuation in adult pITP patients and to identify possible predictive factors for outcome. METHODS: Thirty-nine pITP patients who received a TPO-RA were evaluated. Response (R) was defined as a platelet count ≥30 × 109 /L and at least a twofold increase in the baseline count and complete response (CR) as a platelet count ≥100 × 109 /L, in the absence of bleeding. Durable response (DR) was defined as a R/CR persisting ≥4 wk with a stable dose of TPO-RA, and SR as the first assessed platelet count ≥30 × 109 /L, available at more than 4 wk after discontinuation of TPO-RA, in the absence of other concomitant or rescue therapies. RESULTS: Twenty-nine/39 (74%) were responders: 18 (46%) reached a CR and 11 (28%) a R. A DR was observed in 16/29 (55%) responders. Seven SR (18%) were reached: five of seven patients achieved a SR from a prior DR. CR was statistically associated with the achievement of a subsequent DR: 13/18 (72%) CR patients obtained a DR, while only three of 11 (27%) R ones did (P = 0.027). CONCLUSIONS: CR was a significant prognostic factor for the achievement of a DR. Moreover, we observed a trend for DR patients to obtain a subsequent SR.
Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/mortalidade , Trombopoetina/uso terapêutico , Adolescente , Adulto , Idoso , Benzoatos/uso terapêutico , Criança , Terapia Combinada , Feminino , Humanos , Hidrazinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/cirurgia , Pirazóis/uso terapêutico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/farmacologia , Resultado do Tratamento , Adulto JovemRESUMO
Lenalidomide induces in patients with myelodysplastic syndrome (MDS) and del(5q) erythroid and cytogenetic response rates as high as 75% and 50%, respectively. It is still unclear, however, how long lenalidomide treatment should be continued and whether or not the drug could be interrupted. To assess the feasibility of lenalidomide discontinuation, we revised a cohort of 16 low-risk MDS patients with del(5q) treated at our institute in a phase II multicentric Italian study. Among the 12 responding patients, four discontinued lenalidomide while in complete response. All four patients needed during treatment a permanent lenalidomide reduction from 10 to 5 mg/day because of haematological toxicity (three patients) or grade 3 muscular and bone pain (one patient). At lenalidomide discontinuation after 16, 20, 27 and 20 months from the start, respectively, all four patients were in complete hematologic response and three forth in complete cytogenetic response. Three patients are still in response after 36, 30 and 20 months from lenalidomide discontinuation, respectively: The remaining patient relapsed after 20 months, and she is now receiving a new course of lenalidomide. In conclusion, long-lasting remissions are achievable in MDS patients with del(5q) in complete response after lenalidomide discontinuation.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Talidomida/análogos & derivados , Idoso , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Lenalidomida , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Dor/induzido quimicamente , Indução de Remissão , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
All-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a very curable disease also in patients aged >60 years; however, there are only few case reports in very elderly APL patients. To address this issue, we reviewed treatment results in 13 patients aged >70 years with newly diagnosed APL followed at our institution from January 1991 to December 2008. According to Sanz score, seven patients were at low risk, five at intermediate risk, and one at high risk. Induction therapy consisted of ATRA + idarubicin in nine patients (3/9 with reduced idarubicin dosage) and ATRA alone in four patients; in this latter group, however, 2/4 needed to add chemotherapy (CHT) due to hyperleukocytosis during ATRA treatment. All patients achieved both morphological and molecular complete remission (CR) after a median time of 51 [interquartile range (IR) 43-55] and 114 (IR 74-155) days, respectively. Infective complications were observed in 10/13 patients, APL differentiation syndrome in 3/13 patients. Twelve patients received consolidation therapy, followed by maintenance treatment in nine patients. Five patients relapsed after 7, 8, 11, 35, and 56 months. At present, seven patients are still alive, five died due to disease progression (four) or senectus while in CR (one), and one was lost to follow-up while in CR. The 5-year event-free survival was 56.1 % (95 % CI, 26.0-86.2); the 5-year overall survival (OS) was 64.5 % (95 % CI, 35.6-93.4). ATRA-based treatment of APL is safe and effective also in very elderly patients, with long-lasting disease-free OS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Idarubicina/administração & dosagem , Interferon-alfa/administração & dosagem , Masculino , Mercaptopurina/administração & dosagem , Mitoxantrona/administração & dosagem , Indução de Remissão , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Tretinoína/administração & dosagemRESUMO
In patients with chronic myeloid leukemia (CML) responsive to imatinib, it is still unknown whether the long-lasting treatment could induce the appearance of a persistent/late chronic anemia. To highlight this issue, we revised 128 patients with CML (M/F 64/64, median age at diagnosis 56.9 years, interquartile range 43.0-69.3) treated at our Institution with 1st line imatinib for at least 36 months and in stable complete cytogenetic response. At the 36th month of imatinib, a chronic anemia (Hb < 12 g/dl for > 6 months) was present in 38/128 patients (29.6%): the anemia was moderate (Hb > 8 ≤ 10 g/dl) in 12 patients (9.3%) and mild (Hb > 10 < 12 g/dl) in 26 patients (20.3%). All patients with persistent/late chronic anemia had a low reticulocyte count and 8/38 a condition of iron deficiency without clinical and instrumental signs of chronic blood loss. Four out of 38 patients (10.5%) needed red cell transfusions during the follow-up. At a landmark analysis from the 36th month of imatinib treatment, cumulative 4-year overall survival (OS) for patients with chronic anemia was 94.4% (CI 95% 83.8-100) compared to 93.5% (CI 95% 87.2-99.8) for patients without chronic anemia (P = 0.617). In conclusion, the occurrence of a late chronic anemia during long-lasting treatment with imatinib has been observed in about 30% of our responsive patients: its occurrence does not seem to affect OS, but its real impact should be evaluated on a larger cohort of patients.
Assuntos
Anemia/tratamento farmacológico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Anemia/complicações , Anemia/patologia , Doença Crônica , Esquema de Medicação , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Reticulócitos/patologia , Índice de Gravidade de Doença , Fatores Sexuais , Análise de SobrevidaRESUMO
AIM: To address the incidence and the prognostic role of a very early standard complete cytogenetic response (CCyR) or all Ph- metaphases (MET-, when <20 cells were evaluable). METHODS: We revised 182 chronic phase chronic myelogenous leukemia patients treated with frontline imatinib (IM) at two institutions from June 2002 to June 2011. RESULTS: After 3 months of treatment, 138 patients (75.8%) achieved CCyR/MET- while 44 patients (24.2%) still presented Ph+ metaphases (MET+) (<33%, 24 patients; ≥33%, 20 patients). On univariate analysis, palpable spleen enlargement (p < 0.001), WBC count >100.0 × 10(9)/l at onset (p < 0.001), and male gender (p = 0.019) had a negative impact on achievement of CCyR/MET- at 3 months. Among patients with CCyR/MET- after 3 months, there were 15 failures (10.8%) compared to 21 (47.7%) among patients with MET+ (p < 0.001). The 5-year overall survival was 97.0% in patients CCyR/MET- at 3 months and 91.8% in patients MET+ at 3 months (p = 0.277); the 5-year progression-free survival was 88.2% in patients CCyR/MET- at 3 months and 48.4% in patients MET+ at 3 months (p < 0.001). CONCLUSIONS: The achievement of CCyR/MET- at 3 months seems to have prognostic relevance and could be a very early and useful indicator of an excellent response to IM beyond European LeukemiaNet guidelines.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia/efeitos dos fármacos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Idoso , Benzamidas , Intervalo Livre de Doença , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Metáfase/efeitos dos fármacos , Pessoa de Meia-Idade , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidoresAssuntos
Anemia/induzido quimicamente , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Talidomida/análogos & derivados , Idoso , Feminino , Humanos , Lenalidomida , Talidomida/efeitos adversos , Talidomida/uso terapêuticoRESUMO
Thrombopoietin receptor agonists (TPO-RAs) are used as effective alternative treatments in ITP patients unresponsive to first-/second-line therapies. TPO-RAs can also be used to normalize platelet count to safely perform invasive procedures and chemotherapy, in case of malignancies. In few responsive patients, TPO-RAs can be suspended maintaining a sustained response.
RESUMO
Selective splenic artery embolization (SSAE) is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP) and warm auto-immune hemolytic anemia (AIHA) both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy.
RESUMO
To evaluate follow-up after α-interferon (IFN) discontinuation, 23 patients with chronic myeloid leukemia (CML) in stable complete molecular response (CMolR) with IFN were revisited. After a median IFN treatment of 105.8 months (IR 56.1 - 127.3), all patients discontinued IFN for prolonged CMolR (12), intolerance (8) or planned ABMT (3). After 12.5 months, one patient developed an extramedullar blast crisis. Four patients needed to start imatinib, all achieving again molecular response. Eighteen patients are still off-therapy (median time from IFN discontinuation 125.5 months, IR 86.9-205.3); among these, five are BCR-ABL negative, six present with a sporadic positivity (BCR-ABL ratio < 0.1) and seven show a stable and long-lasting mild positivity (BCR-ABL ratio < 0.5). Patients in prolonged CMolR with IFN have low risk of recurrence after discontinuation; the reappearance of a BCR-ABL positivity < 0.5 did not always precede a relapse, suggesting mechanisms of immunological control induced by IFN.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adulto , Biomarcadores , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: The aim of the present study was to assess the role of a concomitant type 2 diabetes as a potentially negative factor in the management of low-risk myelodysplastic syndrome (MDS) patients treated with high-dose (40,000 UI s.c. 2 times/week) recombinant human erythropoietin (EPO) alpha (rHuEPO alpha). METHODS: One hundred and forty patients (M/F 69/71, median age 76, interquartile range [IR] 68-81) were included in the analysis: 27/140 (19.2%) had a concomitant type 2 diabetes. RESULTS: No difference was reported between patients with and without diabetes as to the grade of anemia, the EPO endogenous levels and the need for transfusional requirement at baseline. Erythroid response was achieved in 79/140 patients (56.4%): factors associated with response were lower EPO levels (P < 0.0001), higher baseline Hb levels (P < 0.0001) and transfusion independence (P < 0.0001). Diabetes was not predictive of response: 17/27 (62.9%) patients with diabetes were responsive to high-dose EPO compared with 62/113 (54.8%) patients without diabetes (P = 0.446). This was confirmed in multivariate analysis, controlling for the effects of Hb levels, transfusion-dependence and serum EPO levels. No difference was observed in relapse rate, response duration and OS between patients with and without diabetes. CONCLUSIONS: Concomitant type 2 diabetes was not a major concern in the management of MDS patients.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Eritropoetina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Síndromes Mielodisplásicas/complicaçõesRESUMO
Fewer than 10% of patients with myelodysplastic syndromes (MDS) are younger than 50 years. A series of 91 younger patients (median age 44 years with female prevalence) are reported and compared with elderly patients. Frequent karyotypic changes were trisomy 8 (9.8%) and monosomy 7 (5%). Twenty-three patients had occupational exposure to potential mutagens (benzene and solvents), with a male predominance, higher frequency of refractory cytopenia with multilineage dysplasia (RCMD) (52%) and higher frequency of monosomy 7 (21.7%). At a median follow-up of 72 months, 22 patients (24%) evolved to acute leukemia, with higher frequency being observed among the exposed cohort (39% vs. 19% non-exposed). Unfavorable factors for overall survival were: age > 40 years, > 5% of blasts, trilinear bone marrow involvement and intermediate-high World Health Organization Prognostic Scoring System (WPSS) risk. The present results suggest that younger MDS could be identified as a distinct subset. For patients belonging to the low/intermediate-I risk group, due to a low transformation rate, aggressive approaches should rarely be recommended.
Assuntos
Aberrações Cromossômicas , Síndromes Mielodisplásicas/genética , Doenças Profissionais/genética , Exposição Ocupacional , Doença Aguda , Adulto , Idoso , Análise de Variância , Benzeno/intoxicação , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 8/genética , Progressão da Doença , Feminino , Humanos , Leucemia/genética , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Monossomia , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/patologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/patologia , Prognóstico , Solventes/intoxicação , Análise de Sobrevida , Trissomia , Adulto JovemRESUMO
The age role was evaluated in 117 consecutive patients with newly diagnosed CML at our Institution treated with front-line Imatinib from 9/02 to 3/08. Forty patients (34.1%) aged ≥ 65 years and 77 (65.9%) <65 years. Thirty-four older patients (85%) had at least 1 comorbidity versus 39 younger patients (50.6%) (p<0.001). Complete cytogenetic response (CCyR) was achieved in 34/40 older patients (85%) as compared to 69/77 younger patients (89.6%), without statistically significant differences. Severe (grades 3-4 WHO) hematological and extra-hematological toxicities were more common in older patients (p=0.02 and p=0.017, respectively). Rates of permanent Imatinib discontinuation and dose reduction to 300 mg or less were significantly higher in older patients (p=0.009 and p=0.001, respectively). In conclusion, Imatinib in older patients with newly diagnosed CML seems to have the same efficacy as in younger patients, but tends to be more toxic, leading to higher rates of discontinuation and dose reduction. To overcome this problem, future trials concerning best dosage in this subset of patients could be useful.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Fatores Etários , Idoso , Benzamidas , Comorbidade , Relação Dose-Resposta a Droga , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Piperazinas/toxicidade , Pirimidinas/toxicidade , Indução de Remissão , Resultado do TratamentoRESUMO
We prospectively tested, at diagnosis in essential thrombocythemia (ET) patients with no clear indication to platelet (PLT)-lowering treatment, a scoring system based on age, PLT level, cardiovascular diseases, previous thrombotic events, smoking and dysmetabolic diseases. From 04/92 to 03/98, 168 consecutive patients were enrolled. Hydroxyurea (HU) was started at diagnosis in 32 "symptomatic" patients and in 33 patients aged >70 years. The remaining 103 patients ("asymptomatic" and aged <70 years) were classified according to our scoring system. Thirty-two patients with score > or = 4 started HU early after diagnosis. The remaining 71 patients with score <4 at diagnosis received anti-aggregating agents only; of them, 24 (33.8%) started HU during follow-up after a median time from diagnosis of 28 months, while 47 (66.2%) did not start any PLT-lowering treatment. Thrombotic complications occurred in 9/103 patients (8.7%); in particular, they occurred in 4/32 patients (12.5%) with score > or = 4 receiving HU since diagnosis and in 5/71 (7%) with score <4 under anti-aggregating agents only. This scoring system appears effective to discriminate a different risk of thrombotic events, and could be useful to decide when a PLT-lowering therapy needs to be started.