Hematology and cell therapy最新文献

Many clinical trials have been engaged to prove the benefits of new drugs in the treatment of hematological tumours. However, no real progress have occurred in diseases such as multiple myeloma, the association of melphalan and prednisone is still the mainstay of the treatment. During all these years, the family of glucocorticoids have not been totally studied. Their efficiency in the cure of lymphoid malignancies has been early recognised, but still to be based on their anti-inflammatory potency for the dosages. Only few works reported the comparison between members of this family. We demonstrate in this work, in vitro, with a cell line of medium sensibility and a B cell of tumoral origin grew up in our laboratory, that exists some differences in the anti-neoplastic potency of the more commonly used corticoids. If the order in which we can class these drugs is not surprising and empirically known, the importance of the differences observed need a special attention. We also found that these drugs might have stimulatory effects, at various degree in function of their concentrations, on the proliferation of the B cell lines. Theses side effects coupled to the efficiency variations of each corticoid present the need of paying more attention to the choice of the molecule implied in the chemotherapy.

The occurrence of leukemic pleural effusion is a rare complication in chronic lymphocytic leukemia and has not been reported in B-cell prolymphocytic leukemia (B-PLL). We report a case of pleural effusion revealing a B-PLL. The diagnosis was made on the cytological and immunological characteristics of cells in the blood and pleural effusion. This patient was treated with fludarabine and was in complete remission after three courses. This observation may have clinical implications for the use of new adenoside nucleotide analogues in symptomatic B-PLL.

The objective of this study was to define the type, the incidence and the outcome of early infectious complications (mean interval between day 1 post-BMT and the onset of fever was 9+/-3 days) occurring in granulocytopenic bone marrow transplant recipients, requiring medical intensive care unit admission. Over a five-years period, forty-one patients with microbiologically confirmed infection were enrolled, with a statistically significant higher frequency of allogeneic marrow transplant recipients (51%, p < 0.02). Infectious pneumonia occurred in 24 patients (59%), septicemia with septic shock in ten patients (24%), catheter-related infection in 5 patients (12%) and meningitis in 2 patients (5%) (p < 0.001). Twenty-six patients died (63%). Among the patients with confirmed infectious pneumonitis, which occurred most frequently in allogeneic marrow recipients (p < 0.02), 16 died (67%). This poor outcome was related to the requirement of mechanical ventilation. Eight patients (80%) with septicemia and septic shock and the two patients with meningitis died. Bacteria (Pseudomonas aeruginosa and Staphylococcal species) were the most common isolated in bronchoalveolar lavage fluid and blood cultures. We found a lower incidence of fungal or viral infections compared to previous studies. Empiric antimicrobial therapy in the cases of patients admitted in ICU may be included antibiotics anti-Pseudomonas and anti-Staphylococcus, as the ecology of hematology unit. The requirement of mechanical ventilation is the main adverse prognostic factor in transplanted patients. At ICU admission, patients with hepatic failure combined with respiratory failure represented a subgroup with a dismal prognosis.

Autoimmune neutropenia (AIN) is a rare hematological disorder for which no standard treatment has been established so far. A brief review of the literature is presented herein concerning the use of G-CSF in this indication. The good results in terms of neutrophils increment and infection prophylaxis render G-CSF attractive for treating AIN. Hypotheses explaining its mechanisms of action are also discussed.

We propose a simple and fast method of detecting apoptosis using an automated hematology analyzer. Detection is based on cellular optical light scatter properties and demonstration of the membrane fragility which characterizes cells undergoing the process of apoptosis. As part of it's routine leucocyte differential analysis, the Abbott Cell-Dyn 4000 collects multi-angle cellular light scatter data. In addition red fluorescence (FL3) emitted by cells following propidium iodide labeling is collected. This provides quantitation of both the erythroblast count and a leukocyte viability index (WVF). Fresh or cryopreserved peripheral blood cells from 17 B-chronic lymphocytic leukemia (B-CLL) patients were incubated in presence of theophylline, fludarabine or in medium alone. After 36-hrs of culture the percentage of apoptotic cells of the sample was determined from the parameters of the CD 4000 described above and thereafter this was compared with reference methods for estimation of apoptosis. The reference methods used were in situ detection of cell death on slides (TUNEL test) and also flow cytometry (Annexin V). Results showed an excellent correlation between the 3 techniques. This rapid, easy and reliable method of quantifying apoptosis may be very useful means of routinely predicting the response to chemotherapy.

The principle aim of residual disease analysis in patients with chronic myeloid leukaemia (CML) is to gauge patient response to treatment and, in patients after allogeneic BMT, to enable early diagnosis of relapse. RT-PCR is by far the most sensitive assay to detect residual disease in CML and can enable a single leukaemia cell to be detected in a background of 10(5)-10(6) normal cells. This is approximately 1000 x greater than the routine detection limit of the other methods. After allogeneic BMT, many CML patients are BCR-ABL positive for prolonged periods of time without subsequently relapsing. Thus the simple presence or absence of residual BCR-ABL transcripts in patients' leukocytes is of little value in the management of individual cases. Quantitative PCR techniques can distinguish between those PCR positive patients who have low or falling BCR-ABL levels on sequential analysis from those who have levels that are increasing. Provided assays are performed frequently enough, rising or persistently high numbers of BCR-ABL transcripts can be detected prior to frank relapse and this information may be used for early therapeutic intervention. Most patients who respond to treatment for relapse by donor lymphocyte infusion (DLI) achieve durable molecular remission. Quantitative PCR is also useful to gauge the response of CML patients to IFN-alpha. We have found that the great majority of patients in complete cytogenetic remission after treatment with IFN-alpha remain PCR positive and harbour a minority population of BCR-ABL positive myeloid precursor cells. It is unlikely therefore this treatment modality completely eliminates the disease in any patient.

In patients with Chronic Myeloid Leukemia (CML), the neoplastic (Bcr-Abl+) progenitors are characterised by an increased proliferative activity. These cells appear to become resistant to apoptosis following growth factor withdraw. We demonstrate that despite this property, Bcr-Abl transformed cells (primitive hematopoietic progenitors or cell lines) remains sensitive to apoptosis induced by Ceramides analogues. This effect is dose dependent and occurs faster in transformed cells as compared to their normal counterparts. In addition to the classical features of apoptosis, we observed that Ceramide-treated CML cells display a rapid and sequential activation of the Bcr-Abl and PI3 kinases. We then demonstrated the role of the Bcr-Abl kinase activity in the accelerated response observed in CML cells treated by Ceramide. The PI3 kinase seems to be partly involved in the accelerated Phosphatidyl-Serine exposure observed in Bcr-Abl transformed cells. Finally, we observed that Ceramide-induced apoptosis does not seem to implicate a Bcl2 protein modulation. Taken together these results support the hypothesis of at least two independent signaling pathways initiating programmed cell death: one will be involved in apoptosis mediated by signals such as cytokine-starving is blocked by the Bcr-Abl fusion protein while the other one initiated by Ceramide is accelerated by the Bcr-Abl protein.