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1.
Transplant Direct ; 9(3): e1451, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36845852

RESUMO

The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome.

2.
Eur J Haematol ; 109(1): 83-89, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35389543

RESUMO

OBJECTIVES: Early chimerism analysis is important to assess engraftment in allogeneic hematopoietic stem cell transplantations. METHODS: We retrospectively investigated the impact of T-cell chimerism at day 30 in bone marrow on acute graft-versus-host disease (aGVHD), relapse, and overall survival in 142 adult allo-transplanted patients. RESULTS: The majority of patients (89%) received myeloablative conditioning and 90% have undergone T-cell replete donor graft. At day 30, 103 patients showed T-complete chimerism with prevalence in haploidentical transplants, whereas 39 cases had CD3+ mixed chimerism, including 30 patients transplanted with HLA identical donors, and 21 with T-cell donors<90%. T-cell chimerism at day 30 was weakly inversely related to aGVHD grades II-IV (p = .078) with no cases of grades III-IV aGVHD in patients with CD3+ <95%. Mixed T-cell chimerism did not impact on relapse (p = .448) and five of the seven patients who relapsed had T-cell chimerism ≤90%. Older age and active disease at transplant had a statistically significant negative effect on overall survival (p = .01 and p = .0001, respectively), whereas mixed CD3+ chimerism did not. CONCLUSIONS: T lymphocyte chimerism analysis at day +30 in bone marrow could identify allo-transplanted patients at major risk of aGVHD grades III-IV (CD3+ donors >95%) mainly post-myeloablative conditioning regimen.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Medula Óssea , Quimerismo , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Linfócitos T , Condicionamento Pré-Transplante/efeitos adversos
3.
Transplant Cell Ther ; 28(2): 96.e1-96.e11, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34818581

RESUMO

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Idoso , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Sistema de Registros , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos
4.
Blood Transfus ; 13(3): 478-83, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25761321

RESUMO

BACKGROUND: Filgrastim biosimilars have recently been introduced into clinical practice. To date biosimilars have demonstrated comparable efficacy and safety as the originator in chemotherapy-induced neutropenia. Published experience in engraftment after autologous stem cell transplantation (ASCT) is limited and concerns relatively few patients. MATERIALS AND METHODS: With the aim of assessing the efficacy and the safety of filgrastim biosimilars in post-ASCT bone marrow recovery, we conducted a single institution, retrospective study in 56 lymphoma and myeloma patients who received filgrastim biosimilars (Tevagrastim(®) and Zarzio(®)) at standard doses from day 5. We compared our results with recently published data on the originator. A cost analysis of each biosimilar was performed. RESULTS: Neutrophil counts recovered in 55 patients. The median number of filgrastim biosimilar vials injected was seven per patient. The median time to neutrophil and platelet recovery was 10 and 12 days, respectively. Twenty-six patients had febrile neutropenia, in half of whom the agent involved was identified. In the cost analysis, the use of Tevagrastim(®) and Zarzio(®) was associated with cost reductions of 56% and of 86%, respectively. DISCUSSION: Despite differences in CD34+ cell counts and time of starting filgrastim, our results in terms of time to engraftment and median number of vials injected are similar to published data. Comparing our results by single conditioning regimen to recent literature data, the time to engraftment and duration of hospitalisation were equivalent. Significant differences were observed in the incidence of febrile neutropenia, perhaps due to different preventive and prophylactic protocols for infections. Although prospective studies should be performed to confirm our results, filgrastim biosimilars were found to be effective and safe in engraftment after ASCT.


Assuntos
Medicamentos Biossimilares/administração & dosagem , Filgrastim/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Autoenxertos , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/economia , Custos e Análise de Custo , Feminino , Filgrastim/efeitos adversos , Filgrastim/economia , Humanos , Linfoma/economia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/economia , Estudos Retrospectivos
6.
Transfus Apher Sci ; 43(3): 321-326, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21036667

RESUMO

Pegfilgrastim has equivalent efficacy to daily G-CSF in enhancing neutrophil recovery after chemotherapy, but conclusive data concerning its use for peripheral blood stem cell (PBSC) mobilization are lacking. From 2003 to 2008 we used high-dose chemotherapy in 64 lymphoma patients. At mobilization chemotherapy (ESHAP) the first 26 patients used unconjugated G-CSF, while the remaining 38 patients received Pegfilgrastim. At the time of harvest 25 patients collected stem cells after the use of G-CSF and 36 in the Peg group. No statistical by significant differences were observed in median peripheral CD34+ cells mobilized (77 µL versus 71 µL) and in collected PBSC (12.3 × 10(6)/kg versus 9.4 × 10(6)/kg p = 0.76). In the PEG group all patients collected the target PBSC with a single apheresis with a greater proportion of "optimal" mobilizers (83% versus 64%; p = 0.05). In conclusion a single dose of Pegfilgrastim could be a valid alternative to unconjugated G-CSF to mobilize PBSC in lymphoma patients.


Assuntos
Sobrevivência de Enxerto , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Filgrastim , Humanos , Polietilenoglicóis , Proteínas Recombinantes , Transplante Autólogo
7.
J Clin Oncol ; 28(29): 4480-4, 2010 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-20697092

RESUMO

PURPOSE: We report the long-term results of a randomized clinical trial comparing induction therapy with once per week for 4 weeks single-agent rituximab alone versus induction followed by 4 cycles of maintenance therapy every 2 months in patients with follicular lymphoma. PATIENTS AND METHODS: Patients (prior chemotherapy 138; chemotherapy-naive 64) received single-agent rituximab and if nonprogressive, were randomly assigned to no further treatment (observation) or four additional doses of rituximab given at 2-month intervals (prolonged exposure). RESULTS: At a median follow-up of 9.5 years and with all living patients having been observed for at least 5 years, the median event-free survival (EFS) was 13 months for the observation and 24 months for the prolonged exposure arm (P < .001). In the observation arm, patients without events at 8 years were 5%, while in the prolonged exposure arm they were 27%. Of previously untreated patients receiving prolonged treatment after responding to rituximab induction, at 8 years 45% were still without event. The only favorable prognostic factor for EFS in a multivariate Cox regression was the prolonged rituximab schedule (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P = .009), whereas being chemotherapy naive, presenting with stage lower than IV, and showing a VV phenotype at position 158 of the Fc-gamma RIIIA receptor were not of independent prognostic value. No long-term toxicity potentially due to rituximab was observed. CONCLUSION: An important proportion of patients experienced long-term remission after prolonged exposure to rituximab, particularly if they had no prior treatment and responded to rituximab induction.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Seguimentos , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Indução de Remissão , Rituximab , Fatores de Tempo , Resultado do Tratamento
8.
Leuk Lymphoma ; 51(8): 1485-93, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20578816

RESUMO

The aim of this study was to investigate the efficacy of combined treatment with rituximab and subcutaneous cladribine in patients with newly diagnosed and relapsed chronic lymphocytic leukemia (CLL). Forty-three patients with active CLL or small lymphocytic lymphoma received rituximab 375 mg/m(2) on day 1 and cladribine 0.1 mg/kg subcutaneously on days 2-6. The treatment was repeated every 4 weeks for a total of four cycles. Sixteen patients were pretreated. The overall response rate was 88% (50% complete remission and 38% partial remission). The median time to treatment failure was 37.9 months. Grade 4 neutropenia developed in 5% of patients. The data indicate that combination therapy with rituximab and cladribine is a valuable and safe treatment for patients with CLL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Estudos de Casos e Controles , Cladribina/administração & dosagem , Transportador Equilibrativo 1 de Nucleosídeo/genética , Feminino , Citometria de Fluxo , Humanos , Hibridização in Situ Fluorescente , Infusões Subcutâneas , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rituximab , Taxa de Sobrevida , Resultado do Tratamento
9.
Oncology ; 76(1): 26-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19033694

RESUMO

BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) differs in biology and clinical behaviour from classic Hodgkin disease. Almost 100% of LPHD neoplastic cells express CD20 and thus rituximab could be effective; yet limited data are available. PATIENTS AND METHODS: We performed a retrospective analysis on patients with LPHD who were treated with rituximab at our institution to determine the magnitude of benefit offered by this drug. RESULTS: Seven patients were identified; 4 received the drug as single agent while the rest received it in combination with chemotherapy. All except 2 received the drug in the salvage setting. Response rate was 100% with 6 of 7 patients achieving complete remission. At a median follow-up of 2 years, 4 patients are still disease free while the rest relapsed at a median time of 27 months. CONCLUSION: Rituximab is effective in LPHD and should be considered; however, the optimal schedule remains to be determined.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Linfócitos/patologia , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Progressão da Doença , Feminino , Seguimentos , Doença de Hodgkin/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Rituximab , Resultado do Tratamento
10.
Haematologica ; 93(12): 1792-6, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18838477

RESUMO

BACKGROUND: Imatinib mesylate is the first line treatment for chronic myeloid leukemia. In patients with advanced phase of the disease, the advent of imatinib significantly increased survival. However, few long-term data, based on large, prospective and controlled trials are available on the outcome of these patients. DESIGN AND METHODS: We conducted a phase II trial of imatinib 600 mg daily in patients with chronic myeloid leukemia in blast crisis. The return to chronic phase was defined as <15% blasts and <30% blasts plus promyelocytes in blood or bone marrow and <20% peripheral basophils. A complete hematologic response required the normalization of platelet and white cell differential counts and absence of extramedullary involvement. Cytogenetic response was assessed by the standard banding technique and rated as usual. RESULTS: Ninety-two patients were enrolled (20 with lymphoid blast crisis and 72 with myeloid blast crisis). Forty-six patients (50%) returned to chronic phase, and 24 patients (26%) achieved also a complete hematologic response. Sixteen patients (17%) had a cytogenetic response (9 complete, 1 partial, and 6 minor or minimal). The complete cytogenetic response was subsequently lost by all but two patients between 2 and 12 months after first having achieved it: the median duration of complete cytogenetic response was 7 months. All responses were sustained for a minimum of 4 weeks. The median survival of all the patients was 7 months. After a median observation time of 66 months, seven (8%) patients are alive. Three of these patients are on imatinib treatment (1 in complete hematologic remission, 1 in partial cytogenetic response and 1 in complete cytogenetic remission). Three patients are in complete remission after allogeneic stem cell transplantation. One patient is alive in blast crisis, on therapy with a second-generation tyrosine kinase inhibitor. CONCLUSIONS: Imatinib was effective and safe in the short-term treatment of chronic myeloid leukemia in blast crisis, but longer-term outcome was not significantly influenced (ClinicalTrials.gov identifier: NCT00514969).


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Crise Blástica , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
11.
Haematologica ; 92(1): 101-5, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17229641

RESUMO

To assess the effect of age on response and compliance to treatment in patients with chronic myeloid leukemia (CML) we performed a sub-analysis within a phase II trial of the GIMEMA CML Working Party (CML/002/STI571). Since the WHO cut-off age to define an older patient is 65 years, among the 284 patients considered, we identified 226 (80%) younger patients (below 65 years) and 58 (20%) older patients (above 65 years) before starting imatinib. Response rates (hematologic and cytogenetic) were lower in the older age group but the probabilities of progression-free survival and overall survival (median observation time 3 years) were the same. Moreover, among complete cytogenetic responders, no differences were found in the level of molecular response between the two age groups. As might be expected, older patients experienced more adverse events, both hematologic and non-hematologic: this worsened compliance did not, however, prevent a long-term outcome similar to that of younger patients.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Benzamidas , Intervalo Livre de Doença , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Clin Cancer Res ; 12(10): 3037-42, 2006 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-16707599

RESUMO

PURPOSE: Most patients with chronic-phase chronic myeloid leukemia (CML) who receive imatinib achieve a complete cytogenetic remission (CCgR) and low levels of BCR-ABL transcripts. CCgR is durable in the majority of patients but relapse occurs in a subset. EXPERIMENTAL DESIGN: To determine the potential of quantitative reverse transcription-PCR of BCR-ABL to predict cytogenetic relapse, we serially monitored residual disease in 97 CML patients with an imatinib-induced CCgR. Patients with late chronic phase CML after IFN-alpha failure were treated with imatinib (400 mg daily). RESULTS: During the imatinib median follow-up time of 36 months (range, 12-54 months), disease monitoring occurred by cytogenetics and quantitative PCR. Twenty percent of patients experienced cytogenetic relapse at a median of 18 months after CCgR and a median of 24 months after starting imatinib. None of the possible prognostic factors studied in univariate and multivariate analyses seemed to predict for loss of cytogenetic response but the reduction of BCR-ABL transcript levels at the time of CCgR is an important prognostic factor. CONCLUSIONS: In our study, we showed not only that achieving a major molecular remission at 12 months is predictive of a durable cytogenetic remission but also that patients who achieved a major molecular remission (expressed both as the BCR-ABL/beta2 microglobulin ratio % <0.0005 and as a 3-log reduction from median baseline value) already at the time of first achieving a CCgR have significantly longer cytogenetic remission durations than those without this magnitude of molecular response (P < 0.05).


Assuntos
Antineoplásicos/uso terapêutico , Genes abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Benzamidas , Determinação de Ponto Final , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Resultado do Tratamento , Microglobulina beta-2
13.
J Clin Oncol ; 23(18): 4100-9, 2005 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-15867198

RESUMO

PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.


Assuntos
Antineoplásicos/uso terapêutico , Análise Citogenética/métodos , Resistencia a Medicamentos Antineoplásicos/genética , Genes abl/genética , Leucemia Mieloide de Fase Crônica/genética , Piperazinas/uso terapêutico , Mutação Puntual , Pirimidinas/uso terapêutico , Adulto , Idoso , Benzamidas , Crise Blástica , Distribuição de Qui-Quadrado , Cromatografia Líquida de Alta Pressão , Análise Mutacional de DNA , Progressão da Doença , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Análise de Sobrevida
14.
Blood ; 104(13): 4245-51, 2004 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-15319292

RESUMO

Since interferon-alpha and imatinib (IM; STI571, Glivec, Gleevec) are effective for the treatment of chronic myeloid leukemia (CML), and their mechanisms of action are different, we designed an exploratory study investigating the effects of a standard IM dose (400 mg/d) and a variable pegylated interferon-alpha (PegIFN) dose (50 microg/wk, 100 microg/wk, and 150 microg/wk). The criteria for dose adjustment were designed so as to ensure the delivery of the IM dose and to protect life quality. There were 76 patients with previously untreated Philadelphia (Ph)-positive CML enrolled in the study. There were 3 patients who discontinued IM and 45 patients who discontinued PegIFN. The severity of adverse events increased with increasing PegIFN dose. The IM dose could be administered to the patients who were assigned to receive 50 microg/wk or 100 microg/wk PegIFN but not to those who were assigned to receive 150 microg/wk. The median administered dose of PegIFN ranged between 32 microg/wk and 36 microg/wk. The cytogenetic response was 70% complete (Ph-neg 100%) and 83% major (Ph-neg > 65%). The BCR/ABL transcript was reduced by at least 3 logs in 68% of complete cytogenetic responders. These data of toxicity, compliance, and efficacy may assist in the design and preparation of prospective studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Benzamidas , Relação Dose-Resposta a Droga , Feminino , Humanos , Mesilato de Imatinib , Interferon alfa-2 , Interferon-alfa/toxicidade , Masculino , Pessoa de Meia-Idade , Piperazinas/toxicidade , Pirimidinas/toxicidade , Proteínas Recombinantes
15.
Leuk Lymphoma ; 45(2): 321-6, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15101718

RESUMO

Patients with aggressive non-Hodgkin's lymphoma (NHL) who relapse after initial therapy have a poor prognosis and with standard dose salvage therapy the outlook remains poor. In this work we examine the patient characteristics and outcome of patients with aggressive NHL treated with HDT and autologous transplantation at our Institute from 1982 to 1999. A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for hematopietic recovery, complications of transplantation, response rates, overall survival (OS) and relapse-free survival (RFS). One hundred and thirty-four patients with aggressive NHL were treated with estimated 10-year OS and RFS rates of 50% and 66%, respectively. Disease status (sensitive vs. refractory) pre-HDT was the most powerful predictive parameter for OS and RFS, at both univariate and multivariate analysis. For the entire cohort, transplant-related mortality was only 3.5% without evidence of second malignancies. Our results confirm that HDT with autologous transplantation is associated with a durable RFS in a remarkable proportion of aggressive NHL patients with very low global early and late toxicity. Improved patient selection, transplant timing, ongoing improvements in supportive care, and selected phase III trials should increase outcomes further.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Transplante Autólogo/métodos , Adolescente , Adulto , Ensaios Clínicos como Assunto , Terapia Combinada , Meios de Cultivo Condicionados/farmacologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
16.
Blood ; 103(6): 2284-90, 2004 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-14645009

RESUMO

Imatinib is a tyrosine-kinase inhibitor that binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia (CML). In these patients measuring response by molecular techniques is clearly required. We determined the cytogenetic and molecular response (CgR, MR) to imatinib in 191 patients with late chronic-phase Philadelphia-positive (Ph+) CML, previously treated with interferon alpha. MR was assessed with real-time quantitative (TaqMan) reverse transcription-polymerase chain reaction and was expressed as the ratio between BCR/ABL and beta 2-microglobulin x 100, the lowest level of detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in 85 (44%) of 191 patients and was maintained for 2 years in 67 (79%) of 85 patients. A reduction of the transcript level of more than 2 logs was achieved in all but 9 patients with CCgR versus none of 23 with partial CgR. In the CCgRs the median value of the MR was 0.0008 after 12 months and 0.0001 after 24 months, with the transcript level undetectable in 22 cases. We conclude that in CCgRs the degree of MR may vary from 2 to more than 4 logs, and that there is a progressive decrease of transcript level by time. Only 1 of 22 negative cases has had a relapse as yet.


Assuntos
Antineoplásicos/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Antineoplásicos/efeitos adversos , Benzamidas , Células da Medula Óssea/fisiologia , Seguimentos , Genes abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Recidiva , Resultado do Tratamento , Microglobulina beta-2/genética
17.
Haematologica ; 88(5): 522-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12745271

RESUMO

BACKGROUND AND OBJECTIVES: In this work we examine the characteristics and outcome of patients with Hodgkin's disease (HD) treated with high-dose therapy (HDT) and autologous transplantation at our Institute between 1982 to 2000. DESIGN AND METHODS: A retrospective analysis was performed examining patients' characteristics, prior chemotherapy regimens, pre-transplant disease status, HDT regimen, source of stem cells, time for hematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and relapse-free survival (RFS). RESULTS: Ninety-seven patients with HD were treated and had estimated 10-year OS and RFS rates of 32% and 60%, respectively. Disease status (sensitive vs. refractory) before HDT was the most powerful predictive parameter for OS and RFS in both univariate and multivariate analyses. The rate of transplant-related mortality in the whole cohort was only 1% whereas the rate of second malignancies was 3%. INTERPRETATION AND CONCLUSIONS: Our results confirm that HDT with autologous transplantation is associated with a durable RFS in a remarkable proportion of HD patients and that the procedure has a very low global early and late toxicity.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/radioterapia , Doença de Hodgkin/terapia , Adolescente , Adulto , Transplante de Medula Óssea , Criança , Terapia Combinada , Feminino , Doença de Hodgkin/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Recidiva , Estudos Retrospectivos , Espanha , Análise de Sobrevida , Resultado do Tratamento
18.
Haematologica ; 88(3): 256-9, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12651262

RESUMO

BACKGROUND AND OBJECTIVES: We compared the early cytogenetic response (CgR) to a combination of imatinib mesylate (Glivec, Novartis Pharma, Basel, Switzerland) and a pegylated form of human recombinant interferon-alpha2b (pegIFN-alpha2b, PegIntron, Schering Plough, Kenilworth, New Jersey, USA) with the relative risk, either according to Sokal's or Euro scoring systems. DESIGN AND METHODS: Seventy-seven patients with early chronic phase, previously untreated, Ph-positive chronic myeloid leukemia (CML) received a combination of imatinib mesylate (400 mg/day) and pegIFN-alpha2b (3 consecutive cohorts treated with 50, 100 or 150 mg/weekly). Fifty-seven patients have completed the first 6 months of treatment and are evaluable for CgR. RESULTS: After 6 months of treatment, the overall major CgR rate was 89% and 90% in low risk patients (Sokal's and Euro, respectively), 76 and 59% in intermediate risk and 23% and 17% in high risk patients. These differences were significant (p=0.0001 for Sokal and 0.001 for e). INTERPRETATION AND CONCLUSIONS: For the first time, these data suggest that the early CgR rate to a imatinib mesylate-based regimen is significantly risk-related.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon-alfa , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Polietilenoglicóis , Adolescente , Adulto , Idoso , Benzamidas , Análise Citogenética , Humanos , Mesilato de Imatinib , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Proteínas Recombinantes , Medição de Risco , Resultado do Tratamento
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