RESUMO
The limited effects of current treatments of primary myelofibrosis (PM) led us to prospectively evaluate recombinant interferon-α (rIFNα) in "early" PM patients with residual hematopoiesis and only grade 1 or 2 myelofibrosis. Seventeen patients meeting World Health Organization PM diagnostic criteria received either rIFNα-2b 500 000 to 3 million units 3 times weekly, or pegylated rIFNα-2a 45 or 90 µg weekly. International Working Group for Myelofibrosis Research and Treatment criteria for prognosis and response were used. Eleven patients were women and 6 were men. Their median age at diagnosis was 57 years. Eleven patients were low risk and 6 were intermediate-1 risk. Two achieved complete remission, 7 partial, 1 clinical improvement, 4 stable disease, and 3 had progressive disease. Thus, more than 80% derived clinical benefit or stability. Improvement in marrow morphology occurred in 4. Toxicity was acceptable. These results, with documented marrow reversion because of interferon treatment, warrant expanded evaluation.
Assuntos
Interferon Tipo I/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Adulto , Idoso , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Interferon Tipo I/administração & dosagem , Interferon Tipo I/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/patologia , Prognóstico , Proteínas Recombinantes , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Although reduction in the JAK2(V617F) allele burden (%V617F) has been suggested as a criterion for defining disease response to cytoreductive therapy in polycythemia vera, its value as a response monitor is unclear. The purpose of this study is to determine whether a reduction in %V617F in polycythemia vera is a prerequisite to achieving hematologic remission in response to cytoreductive therapy. DESIGN AND METHODS: We compared the clinical and hematologic responses to change in %V617F (molecular response) in 73 patients with polycythemia vera treated with either interferon (rIFNα-2b: 28, Peg-rIFNα-2a: 18) or non-interferon drugs (n=27), which included hydroxyurea (n=8), imatinib (n=12), dasatinib (n=5), busulfan (n=1), and radioactive phosphorus (n=1). Hematologic response evaluation employed Polycythemia Vera Study Group criteria, and molecular response evaluation, European Leukemia Net criteria. RESULTS: Of the 46 treated with interferon, 41 (89.1%) had a hematologic response, whereas only 7 (15.2%) had a partial molecular response. Of the 27 who received non-interferon treatments, 16 (59.3%) had a hematologic response, but only 2 (7.4%) had a molecular response. Median duration of follow up was 2.8 years. Statistical agreement between hematologic response and molecular response was poor in all treatment groups. CONCLUSIONS: Generally, hematologic response was not accompanied by molecular response. Therefore, a quantitative change in %V617F is not required for clinical response in patients with polycythemia vera.
Assuntos
Alelos , Janus Quinase 2/genética , Mutação , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Adulto , Idoso , Seguimentos , Humanos , Interferon-alfa/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I-II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3-15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0-50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1-5) in cohort SLND and 18 (range 7-36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent long-term cure rates while avoiding morbidities associated with ALND or addition of axillary RT field.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Mama/patologia , Estudos de Coortes , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Radioterapia/métodos , Radioterapia Adjuvante/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
We treated 37 patients with polycythemia vera with imatinib mesylate (IM). The overall response rate was 49%. Thirty percent had a complete response, and 19%, a partial response. Thirty-one patients were treated for >120 days. Frequent side effects included nausea, diarrhea, edema, and skin rash. Whereas IM was effective in controlling erythropoiesis and reducing spleen size it was ineffective in controlling thrombocytosis. Normocellular marrow developed in 4 patients who had a complete response. Progression to overt myelofibrosis occurred in 3. Nevertheless, 6 patients have had a sustained complete response while on IM for >6 years. These patients were young, had high phlebotomy requirements, and only slightly elevated platelet counts. Therefore, we believe there may be a role for IM in patients with these characteristics whose disease cannot be controlled by, or as an alternative to, other myelosuppressive treatments.
Assuntos
Antineoplásicos/uso terapêutico , Piperazinas/uso terapêutico , Policitemia Vera/tratamento farmacológico , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Relação Dose-Resposta a Droga , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Policitemia/tratamento farmacológico , Prognóstico , Trombocitose/tratamento farmacológicoRESUMO
In a series of 105 patients with polycythemia vera, we retrospectively determined whether the JAK2(V617F) mutation correlated with severity of disease phenotype. Higher JAK2(V617F) allele burden correlated with more advanced myelofibrosis, greater splenomegaly, and higher white blood cell count, but not with age, gender, hematocrit level, or frequency of phlebotomy prior to cytoreductive therapy. Although a subgroup at increased risk for thrombosis was not clearly defined, there was a suggestion that frequency of thrombosis increased as the JAK2(V617F) allele burden increased. The JAK2(V617F) allele burden did not change significantly in treated patients with serial JAK2 analyses.