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1.
Hematol Oncol ; 39(3): 409-418, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33590502

RESUMO

In 816 patients with 2016 World Health Organization-defined polycythemia vera (PV) enrolled in a multicenter retrospective study, we investigated the predictive value of Charlson comorbidity index (CCI) and body mass index (BMI) on thrombosis, progression to post-PV myelofibrosis (PPV-MF) and survival. Patients were subgrouped according to CCI = 0 (58.1%, no comorbidities) or CCI ≥ 1 (41.9%) and according to normal/underweight (BMI < 25, 54.5%) or overweight/obesity (BMI ≥ 25, 45.5%) at PV diagnosis. BMI was available for 529 patients. Patients with CCI ≥ 1 were older and more frequently presented cardiovascular risk factors compared to patients with CCI = 0 (p < 0.001), while overweight/obese patients were more frequently males (p < 0.001). Cumulative incidence of thromboses with death as competing risk was 13.3% at 10 years. Multivariable analysis with death as competing risk showed that previous thromboses (subdistribution hazard ratio [SHR]: 2.1, p = 0.01) and hypertension (SHR: 1.77, p = 0.04) were significantly associated with a higher thrombotic risk, while BMI ≥ 25 lost statistical significance (SHR: 1.69, p = 0.05) and CCI ≥ 1 was excluded after evaluation of goodness of fit. After a median follow-up of 6.1 years, progression to PPV-MF occurred in 44 patients, and 75 patients died. BMI ≥ 25 was associated with a lower probability of progression to PPV-MF (SHR: 0.38, CI95%: 0.15-0.94, p = 0.04) and better survival (hazard ratio [HR]: 0.42, CI95%: 0.18-0.97, p = 0.04). CCI ≥ 1 did not affect progression to PPV-MF (p = 0.44) or survival (p = 0.71).  The evaluation of CCI and BMI may improve the prognostic definition of PV. In patients with hypertension an accurate evaluation of thrombotic risk is warranted.


Assuntos
Índice de Massa Corporal , Policitemia Vera/mortalidade , Mielofibrose Primária/mortalidade , Trombose/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Policitemia Vera/terapia , Mielofibrose Primária/terapia , Estudos Retrospectivos , Fatores de Risco , Trombose/terapia
2.
Blood ; 118(12): 3273-9, 2011 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-21791425

RESUMO

Thirteen patients with acute myeloid leukemia, 5 with active disease, 2 in molecular relapse, and 6 in morphologic complete remission (CR; median age, 62 years; range, 53-73 years) received highly purified CD56(+)CD3(-) natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor-ligand mismatched donors after fludarabine/cyclophosphamide immunosuppressive chemotherapy, followed by IL-2. The median number of infused NK cells was 2.74 × 10(6)/Kg. T cells were < 10(5)/Kg. No NK cell-related toxicity, including GVHD, was observed. One of the 5 patients with active disease achieved transient CR, whereas 4 of 5 patients had no clinical benefit. Both patients in molecular relapse achieved CR that lasted for 9 and 4 months, respectively. Three of 6 patients in CR are disease free after 34, 32, and 18 months. After infusion, donor NK cells were found in the peripheral blood of all evaluable patients (peak value on day 10). They were also detected in BM in some cases. Donor-versus-recipient alloreactive NK cells were shown in vivo by the detection of donor-derived NK clones that killed recipient's targets. Adoptively transferred NK cells were alloreactive against recipient's cells, including leukemia. In conclusion, infusion of purified NK cells is feasible in elderly patients with high-risk acute myeloid leukemia. This trial was registered at www.clinicaltrial.gov as NCT00799799.


Assuntos
Efeito Enxerto vs Leucemia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/administração & dosagem , Imunoterapia Adotiva/métodos , Células Matadoras Naturais , Leucemia Mieloide Aguda , Receptores KIR/análise , Antígenos CD/análise , Antígenos CD/biossíntese , Separação Celular , Ciclofosfamida/administração & dosagem , Citometria de Fluxo , Teste de Histocompatibilidade , Humanos , Imunofenotipagem , Interleucina-2/biossíntese , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Leucaférese , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Fatores de Risco , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
3.
Cancers (Basel) ; 15(14)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37509367

RESUMO

In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.

6.
J Clin Oncol ; 26(9): 1519-25, 2008 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-18268357

RESUMO

PURPOSE: The Prospective Oral Mucositis Audit assessed the incidence, duration, and determinants of severe oral mucositis (OM; WHO oral toxicity scale grades 3 to 4) in patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) receiving high-dose conditioning chemotherapy before autologous stem-cell transplantation. PATIENTS AND METHODS: Patients with MM (n = 109; mean age, 57 +/- 8 years) or NHL (n = 88; mean age, 50 +/- 13 years) were treated with high-dose melphalan (200 mg/m(2)) or carmustine 300 mg/m(2), etoposide 800 mg/m(2), cytarabine 800 to 1,600 mg/m(2), and melphalan 140 mg/m(2) chemotherapy, respectively, in 25 European centers. OM assessments were made daily until 30 days after transplantation or hospital discharge. High quality of OM assessment was ensured by an intensive training program. RESULTS: Severe OM occurred in 46% (95% CI, 36% to 56%) of patients with MM and 42% (95% CI, 32% to 53%) of patients with NHL, with a mean duration of 5.3 days (95% CI, 4.4 to 6.1 days) and 5.5 days (95% CI, 4.5 to 6.7 days), respectively. Time from start of conditioning to peak OM score was 12.1 +/- 2.6 and 14.6 +/- 2.4 days. Severe OM risk and/or duration was significantly associated with higher chemotherapy dose per kilogram of body weight and poor performance status, but in contrast with some previous reports, this was not related to age. CONCLUSION: Severe OM is more common in the transplantation setting than previously reported, justifying effective preventative and therapeutic measures.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Estomatite/induzido quimicamente , Estomatite/epidemiologia , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Masculino , Auditoria Médica , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Estudos Prospectivos , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Condicionamento Pré-Transplante/métodos , Transplante Autólogo
7.
Br J Haematol ; 139(3): 415-24, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17910631

RESUMO

Fifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti-idiotype (Id) vaccination with dendritic cells (DCs). CD14(+)-derived DCs were loaded with the autologous Id as whole protein (=6) or Id-derived class I-restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T-cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id-specific T-cell proliferative response, 8/15 increased interferon-gamma-secreting T cells and 4/15 showed an Id-positive delayed-type hypersensitivity test. Anti-Id cytotoxic T-lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T-cell response was observed after sc DC injections and increased Id-specific T-cell proliferation was found up to 1 year after vaccination. VDJ-derived peptides were as effective as the whole protein in stimulating T-cell responses. Clinically, 7/15 patients have stable disease after a median follow-up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id-pulsed DCs were safe and, in contrast with intravenous administrations, induced anti-MM T-cell responses.


Assuntos
Vacinas Anticâncer/uso terapêutico , Células Dendríticas/transplante , Idiótipos de Imunoglobulinas/imunologia , Mieloma Múltiplo/terapia , Adulto , Idoso , Anticorpos Antineoplásicos/biossíntese , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/administração & dosagem , Feminino , Hemocianinas/imunologia , Humanos , Imunidade Celular , Região de Junção de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/imunologia , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Fragmentos de Peptídeos/imunologia , Resultado do Tratamento , Vacinação/efeitos adversos , Vacinação/métodos
8.
Biol Blood Marrow Transplant ; 13(10): 1224-32, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17889360

RESUMO

We assessed the capacity of positively selected autologous CD133(+) hematopoietic stem cells (HSCs) to reconstitute lymphomyelopoiesis in chronic lymphocytic leukemia (CLL) patients receiving myeloablative chemotherapy. Ten resistant/relapsed CLL patients underwent HSC mobilization with chemotherapy and granulocyte-colony stimulating factor (G-CSF). Positive selection of circulating CD133(+) HSCs was performed by immunomagnetic technique. Highly purified HSCs were reinfused after busulphan/melphalan myeloablative treatment. A median number of 4.2 x 10(6) CD34(+) cells/kg and of 3.14 x 10(6) CD133(+) cells/kg were collected. Immunomagnetic selection resulted in the reinfusion of a median number of 2.45 x 10(6) CD133(+) cells/kg (median purity: 94.8%; median recovery: 84%) and 2.4 x 10(6) CD34(+) cells/kg (median purity: 93%; median recovery: 71%). HSC selection resulted in a median T cell and CD19(+)/CD5(+) cell depletion of 3.85 log and 2.8 log, respectively. At the molecular level, however, 7 of 8 valuable purified HSC fractions were contaminated by leukemic cells. All CLL patients showed rapid and sustained myeloid engraftment after reinfusion of purified CD133(+) cells. Immunologic reconstitution was comparable to that routinely observed in patients reinfused with unmanipulated leukapheresis products and no late infectious complications were observed. With a median follow-up of 28 months for transplanted patients, 5 patients are in clinical complete remission, 3 are in partial remission, and 1 is in progression. In conclusion, the reinfusion of highly purified CD133(+) HSCs allowed the rapid and sustained recovery of hematopoiesis after myeloablative treatment in resistant/relapsed CLL patients. However, the purging potential of positive selection of CD133(+) cells is not adequate to achieve tumor-free autografts.


Assuntos
Antígenos CD/sangue , Glicoproteínas/sangue , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Linfocítica Crônica de Células B/terapia , Recidiva Local de Neoplasia/terapia , Peptídeos/sangue , Células-Tronco Pluripotentes/transplante , Transplante Autólogo/métodos , Antígeno AC133 , Purging da Medula Óssea , Separação Celular , Doença Crônica , Feminino , Sobrevivência de Enxerto , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Terapia de Salvação/métodos , Condicionamento Pré-Transplante/métodos
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