Case Report: Allogeneic Stem Cell Transplantation Following Induction With CPX-351 in Patients With Acute Myeloid Leukemia Is Feasible.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and treatment-related acute myeloid leukemia (tAML) after chemotherapy or radiation therapy for other neoplasms are associated with poor outcomes. CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, has been shown to improve outcomes in AML-MRC and tAML compared with standard 7+3 regimens. Here we report the cases of four consecutive patients with AML-MRC or tAML who received CPX-351 as outpatient induction therapy immediately followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two patients received allo-HSCT in remission (one in complete remission and one in partial remission) and two patients received allo-HSCT in aplasia (one at 11 days and one at 52 days after the start of induction therapy with CPX-351). With a median follow-up of 188 days after allo-HSCT, all but one patient are alive and two are in remission. Further studies will help define and expand the role of CPX-351 in the treatment of AML-MRC and tAML, especially in patients expected to undergo allo-HSCT.

High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy.

Mutations in the kinase domain (KD) of BCR-ABL are the leading cause of acquired imatinib resistance. In some cases, identical mutations were detected at relapse and in pretherapeutic specimens, consistent with selection of resistant clones in the presence of drug. However, the incidence of KD mutations in imatinibnaive patients, irrespective of response to therapy, is unknown. We studied mutation frequency in 66 patients with chronic myelogenous leukemia (CML), using cDNA sequencing and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) assays for 8 common mutations. Thirteen patients were positive by ASO-PCR only, 1 by ASO-PCR and sequencing, and 1 by sequencing only (overall frequency, 22.7%). T315I was most frequent (12% of patients). Eleven of the 14 patients with positive ASO-PCR had follow-up samples available for sequencing. Wild-type sequence was detected in 6 of 11, 2 different mutations in 1 of 11, and identical mutations in 4 of 11 patients, 2 of whom had achieved major cytogenetic response. In multivariate analysis mutation detection was associated with clonal cytogenetic evolution, exposure to 6-Thioguanine, and a low platelet count, but not with response to imatinib, event-free survival, and overall survival. KD mutants present at low levels do not invariably lead to relapse, and additional factors are required to induce a fully drug-resistant phenotype.

Quantitative reverse transcription polymerase chain reaction should not replace conventional cytogenetics for monitoring patients with chronic myeloid leukemia during early phase of imatinib therapy.

BACKGROUND AND OBJECTIVES: Imatinib is the new standard drug treatment for patients with chronic myelogenous leukemia (CML). Quantitative reverse transcription-polymerase chain reaction (qPCR) for detection of BCR-ABL transcripts is frequently used for monitoring patients in addition to or instead of conventional cytogenetics, although its place in the overall diagnostic framework is not yet clear. In this study, we compared qPCR and conventional cytogenetics for monitoring of patients during the early phases of imatinib therapy. DESIGN AND METHODS: One hundred and seventeen patients treated with imatinib for CML in chronic or accelerated phase were prospectively followed with qPCR and karyotyping. Comparisons were made between both methods and between qPCR results from bone marrow and peripheral blood. To determine the prognostic impact of qPCR and cytogenetics during the early phase of imatinib treatment on subsequent cytogenetic response and progression-free survival (PFS), a multivariate model was generated that included established prognostic baseline variables. RESULTS: We found a significant correlation between the proportion of Philadelphia (Ph) chromosome-positive metaphases and qPCR in the bone marrow and peripheral blood. Low qPCR values after 3 months of therapy were correlated with major cytogenetic response (MCyR) at 6 months and PFS at 2 years. However, in multivariate analysis, the cytogenetic response at 3 months emerged as the only independent parameter predictive of MCyR at 6 months and PFS at 2 years. INTERPRETATION AND CONCLUSIONS: Our data suggest that conventional karyotyping should remain the standard method for following patients on imatinib during the early phases of therapy.

Pseudomonas aeruginosa, como indicador de contaminaçäo hídrica / Pseudomonas aeruginosa as an indicator of water contamination

Procura mostrar a importância da Pseudomonas aeruginosa como indicador de contaminaçäo hídrica, levando-se em conta ser este microorganismo muito resistente e capaz de inibir as bactérias do grupo coliforme, que säo as que atuam na legislaçäo brasileira como parâmetro para reprovar ou liberar uma água para consumo humano. Aborda a avaliaçäo da qualidade microbiológica de 571 amostras de água, utilizando a técnica do Número Mais Provável (N.M.P) com tubos múltiplos, metodologia recomendada pelo "Standard Methods for Examination of Water and Wastwater", onde 333 amostras eram tratadas, 134 näo tratadas, 44 minerais naturais e 60 para hemodiálise. Na comparaçäo dos resultados numéricos e percentuais, chegou-se à conclusäo que muitas destas amostras foram consideradas satisfatórias e liberadas para consumo, de acordo com a legislaçäo vigente no país, embora tenha sido detectada a presença em muitas delas, de P.aeruginosa.