RESUMO
Donor lymphocyte infusions (DLI) are an effective treatment for patients with chronic myeloid leukemia (CML) in relapse after allografting but the optimal cell dose has yet to be identified. To address this question, we investigated the factors affecting the dose required to achieve remission (effective cell dose, (ECD)) in 81 patients treated with an escalating dose regimen. The overall proportion of patients who achieved a molecular remission was 88%. The cumulative proportion of remitters increased significantly at each dose level. With a CD3(+) cell dose < or =10(7)/kg, 56% of patients in molecular/cytogenetic relapse obtained molecular remission, whereas only 20% of those in hematologic relapse did so. At the same cell dose, 58% of patients who received lymphocytes from volunteer unrelated donors achieved remission, as compared to 29% of those who received DLI from sibling donors. We conclude that the response to DLI is dose-dependent and that the ECD is influenced by the quantity and phase of CML at relapse and degree of donor/recipient histocompatibility.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos , Doença Aguda , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , RecidivaRESUMO
Urastoma cyprinae is a turbellarian parasite infecting the gills of several marine bivalves. We observed the presence of virus-like particles (24 to 30 nm in diameter; icosahedral symmetry) arranged in paracrystalline arrays in the cytoplasm of subepidermal dorsal cells. These particles appear to be RNA viruses, possibly related to the Picornaviridae. This is the first report of viral particles in the parasite U. cyprinae.
Assuntos
Mytilus/parasitologia , Turbelários/virologia , Vírus/isolamento & purificação , Animais , Brânquias/parasitologia , Vírus/ultraestruturaRESUMO
We monitored BCR-ABL transcript levels by quantitative real-time PCR in 103 patients treated with imatinib for chronic myeloid leukaemia in chronic phase for a median of 30.3 months (range 5.5-49.9) after they achieved complete cytogenetic remission (CCyR). The patients could be divided into three groups: (1) in 32 patients transcript levels continued to decline during the period of observation (nadir BCR-ABL/ABL ratio 0.015%); in five of these patients BCR-ABL transcripts became undetectable on repeated testing, (2) in 42 patients the transcript levels reached a plateau and (3) in 26 patients transcript numbers increased and the initial CCyR was lost. Three patients were not evaluable. Patients who remained in CCyR for at least 24 months appeared to have a low risk of subsequent cytogenetic relapse. We conclude that the pattern of 'residual' disease after achieving CCyR on imatinib is variable: some patients in CCyR show a progressive reduction in the level of residual disease, some reach a plateau where transcript numbers are relatively stable and others relapse with Ph-positive metaphases.
Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Benzamidas , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Incidência , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/epidemiologia , Neoplasia Residual/genética , Reação em Cadeia da Polimerase , Prognóstico , Recidiva , Indução de Remissão , Fatores de RiscoRESUMO
We assessed clinical results in 145 patients with chronic myeloid leukaemia in chronic phase who satisfied criteria for interferon-alpha failure and were thus eligible for treatment with imatinib at the Hammersmith Hospital. We used univariate and multivariate analyses to develop a risk score based on features defined after treatment for 3 months. We identified a low neutrophil count and poor cytogenetic response (<35% Ph-negative marrow metaphases) at 3 months as principal independent predictive factors and incorporated them into a three-tier prognostic scoring system for individual patients. For patients in the low-, intermediate- and high-risk groups, the probabilities of survival at 24 months were 100, 82 and 40% (P<0.0001) and progression-free survival 100, 66 and 15% (P<0.0001), respectively. This Hammersmith prognostic scoring system was validated with an independent cohort of patients treated at another UK centre.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Terapia de Salvação/métodos , Adolescente , Adulto , Idoso , Benzamidas , Análise Citogenética , Avaliação de Medicamentos , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Prognóstico , Pirimidinas/administração & dosagem , Medição de Risco , Terapia de Salvação/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida , Falha de TratamentoRESUMO
Ten parasite species were identified after a study carried out on 125 swordfish from the Gulf of Guinea waters. The samples were taken between August and November 1997; 3 of the parasite species, Caligus coryphaenae. Pelichnibothrium speciossum, and Sphyriocephalus viridis were recorded for the first time on this host.
Assuntos
Crustáceos , Doenças dos Peixes/parasitologia , Helmintos/isolamento & purificação , Doenças Parasitárias em Animais/parasitologia , Perciformes/parasitologia , Animais , Oceano Atlântico , Helmintíase Animal/parasitologia , EspanhaRESUMO
Natural killer (NK) cells are expanded in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitors (TKI) and exert cytotoxicity. The inherited repertoire of killer immunoglobulin-like receptors (KIR) may influence response to TKI. We investigated the impact of KIR-genotype on outcome in 166 chronic phase CML patients on first-line imatinib treatment. We validated our findings in an independent patient group. On multivariate analysis, KIR2DS1 genotype (RR=1.51, P=0.03) and Sokal risk score (low-risk RR=1, intermediate-risk RR=1.53, P=0.04, high-risk RR=1.69, P=0.034) were the only independent predictors for failure to achieve complete cytogenetic response (CCyR). Furthermore, KIR2DS1 was the only factor predicting shorter progression-free (PFS) (RR=3.1, P=0.03) and overall survival (OS) (RR=2.6, P=0.04). The association between KIR2DS1 and CCyR, PFS and OS was validated by KIR genotyping in 174 CML patients on first-line imatinib in the UK multi-center SPIRIT-1 trial; in this cohort, KIR2DS1(+) patients had significantly lower 2-year probabilities of achieving CCyR (76.9 vs 87.9%, P=0.003), PFS (85.3 vs 98.1%, P=0.007) and OS (94.4 vs 100%, P=0.015) than KIR2DS1(-) patients. The impact of KIR2DS1 on CCyR was greatest when the ligand for the corresponding inhibitory receptor, KIR2DL1, was absent (P=0.00006). Our data suggest a novel role for KIR-HLA immunogenetics in CML patients on TKI.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Receptores KIR/genética , Adolescente , Adulto , Idoso , Benzamidas , Feminino , Genótipo , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de SobrevidaRESUMO
Novel agents are increasingly used during induction therapy for multiple myeloma (MM), but there is concern about their potential impact on stem cell mobilization. Regimens containing either thalidomide or cyclophosphamide have little or no impact on stem cell collection. In this retrospective review of 136 patients with newly diagnosed MM, we show that the combination of thalidomide and oral CY with dexamethasone (CTD) during induction therapy impaired stem cell mobilization substantially. Compared with VAD (vincristine, doxorubicin, dexamethasone) and a VAD-like induction regimen, the stem cell collection yield after CTD was decreased by 49% (median 5.0 vs 9.8 × 10(6) CD34+cells/kg, P<0.001). Following CTD, more patients failed to mobilize enough stem cells for one (25.4 vs 5.8%, P=0.002) or two (39.4 vs 15.9%, P=0.002) transplants. These results demonstrate that the combination of thalidomide and oral CY impairs stem cell mobilization and indicate that drugs with no previously reported relevant effect on stem cell mobilization can have a substantial impact when given in combination.