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Maher Albitar

Publications and source records attributed to Maher Albitar.

100 records · Page 6Linked to original sources
PubMed2002

Less apoptosis in patients with 5q-syndrome than in patients with refractory anemia.

The WHO classification of hematological malignancies includes 5q-syndrome as a separate category within myelodysplastic syndromes (MDS). Clinically, patients with 5q-syndrome have a milder disease than patients with other MDS. The basis for this difference is not known. Identifying 5q-syndrome can be difficult because some of its morphologic and cytogenetic features are similar to those of other MDS. We compared apoptosis between 5q-syndrome and other refractory anemias. We found lower levels of apoptosis in 5q-syndrome as detected by less disruption of mitochondrial potential (P=0.008) and decreased annexin V positivity (P=0.01). Our results suggest that lower apoptosis in 5q-syndrome may explain the milder clinical course of the disease and distinguish 5q-syndrome from other MDS.

Anemia, Refractory↗
PubMed2002

Clinical relevance of vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukaemia and myelodysplastic syndrome.

We have previously reported that high levels of cellular vascular endothelial growth factor (VEGF) protein correlated with short survival of patients with acute myeloid leukaemia (AML). As VEGF exerts its effects via two receptors, VEGF receptor 1 (VEGFR-1) and VEGFR-2, we evaluated the significance of VEGFR-1 and VEGFR-2 protein levels in AML and myelodysplastic syndrome (MDS), and their relationship to VEGF protein levels. Western blot analysis and radioimmunoassay confirmed and quantified specific protein levels in bone marrow samples from 41 MDS and 66 AML previously untreated patients. VEGFR-1 levels were significantly higher in AML than in MDS (P = 0.0004), but no significant difference was found in the VEGFR-2 levels (P = 0.5). No significant correlation between VEGFRs levels and duration of survival was found. VEGF protein levels were significantly higher in MDS than in AML (P < 0.0001). A Cox proportional-hazard regression model showed increasing VEGF levels to significantly correlate with shorter survival of patients with MDS (P = 0.008), a finding similar to our previous report of the inverse relationship between VEGF levels and survival of AML patients. We found a significant correlation between VEGF and VEGFR-2 levels in both AML and MDS (P < 0.0000001 andP < 0.0002 respectively) but not between VEGF and VEGFR-1 levels. These data suggest that VEGF expression, rather than the expression of its receptors, is the determining factor in the biological behaviour of AML and MDS, and that VEGFRs are differentially expressed in AML and MDS.

Acute Disease↗
PubMed2002

Bone marrow cyclooxygenase-2 levels are elevated in chronic-phase chronic myeloid leukaemia and are associated with reduced survival.

Increased angiogenesis is important in the pathophysiology of haematological malignancies. Cyclooxygenase-2 (Cox-2) converts arachidonic acid to prostaglandins, which induce expression of angiogenic factors, including vascular endothelial growth factor (VEGF), basic-fibroblast growth factor, transforming growth factor-beta and interleukin 6. Cox-2 may also reduce apoptosis and reduce cellular attachment to the extracellular matrix (ECM). Increased bone marrow (BM) vascularity, increased BM cellular and plasma VEGF levels, and decreased progenitor adherence to BM ECM have all been observed in chronic myeloid leukaemia (CML). We investigated the prognostic significance of levels of Cox-2 in BM cells from patients with CML. Western blot and solid-phase radioimmunoassay (RIA) were used to measure Cox-2 BM levels in 149 patients with chronic phase CML (CP CML). Results were compared with those of normal controls. Expression of Cox-2 was significantly higher in CML than in normal controls (P < 0.0001). Increasing levels of Cox-2 were significantly associated with shorter survival (P = 0.0002, Cox proportional hazard model). A multivariate model based on Cox-2 and degree of splenomegaly was developed for survival in patients with early CP CML. Agents that inhibit Cox-2 activity merit investigation in patients with CP CML.

Adolescent↗
PubMed2002

Epidemiology, molecular mycology, and environmental sources of Fusarium infection in patients with cancer.

OBJECTIVE: To investigate the epidemiology and environmental sources of Fusarium infections in patients with cancer. DESIGN: Retrospective case-control study conducted following surveillance environmental cultures and DNA analysis of isolated organisms. SETTING: A tertiary-care, university cancer center. METHODS: In 1996 and 1997, environmental cultures were performed on air samples and water systems. A retrospective chart review was performed for 70 patients with cancer identified with fusariosis between 1987 and 1997. Patients with fusariosis were compared with 49 uninfected control patients who occupied hospital rooms with positive environmental cultures for Fusarium. With the use of random amplification of polymorphic DNA, organisms isolated from infected patients were compared with environmental organisms. RESULTS: Most of the patients with Fusarium (40, 57%) were infected on or within 3 days of admission, indicating community rather than nosocomial acquisition. Patients were comparable in terms of underlying immunocompromised status to 49 uninfected control patients. However, the duration from admission to infection in the patients with fusariosis tended to be shorter than the duration from admission to discharge in the exposed control patients (P = .06). Water cultured from the hospital tanks and from sinks and water fountains was negative for Fusarium. With the use of polymerase chain reaction, environmental isolates did not match clinical ones. Quantitative air sampling showed that the quantitative outdoor Fusarium levels were eightfold higher than the indoor levels. During the rainy summer season, outdoor air concentrations of Fusarium were at their highest, coinciding with the peak incidence of fusariosis at our center. CONCLUSION: The most likely source of fusariosis was the external environment rather than nosocomial sources, such as water.

Adolescent↗
PubMed2002

Differences in CD33 intensity between various myeloid neoplasms.

We measured the concentration of CD33 antigen on the surface of cells in 315 bone marrow (BM) samples and 114 corresponding peripheral blood (PB) samples from patients with various leukemias (acute myeloid leukemia [AML], chronic myelogenous leukemia [CML], myeloproliferative disorder [MPD] other than CML, myelodysplastic syndrome [MDS]) and from control subjects. Overall CD33 intensity in total CD33+ cells was significantly higher in BM than in PB. CD33 intensity in total BM CD33+ cells differed significantly with the type of disease. The median number of CD33 molecules per cell was highest in AML, followed by MDS, CML, and control subjects and lowest in MPD. When only CD34+/CD33+ cells were examined, CD33 molecules per cell were highest in CD34+ cells in AML and lowest in MPD (P = .027). Patients with AML or MDS younger than 60 years had significantly higher intensity of CD33 expression on CD34+ cells than patients 60 years or older. Levels of CD33 intensity did not correlate with cytogenetics in patients with AML or MDS. There was no correlation between CD33 intensity and response to therapy or overall survival in 35 patients treated with protocols including Mylotarg. These data demonstrate variation in CD33 intensity between various leukemias.

Aminoglycosides↗
PubMed2002

Diagnosis of invasive pulmonary aspergillosis using polymerase chain reaction-based detection of aspergillus in BAL.

STUDY OBJECTIVE: To assess the value of Aspergillus polymerase chain reaction (PCR) test performed on the BAL in diagnosing invasive pulmonary aspergillosis (IPA). DESIGN: Between January 1996 and 1997, we prospectively followed up 249 cancer patients with pulmonary infiltrates suggestive of pneumonia. Bronchoscopy with fungal stains, cultures, and PCR was performed on all patients. PCR was used for the detection of Aspergillus mitochondrial and alkaline protease gene DNA. The PCR products were visualized either directly on polyacrylamide gel or after Southern transfer and probing with specific probes for mitochondrial and alkaline protease DNA. RESULTS: The 249 patients consisted of 10 patients with proven IPA (tissue invasion), 22 patients with probable IPA (microbiologic culture), 18 patients with possible IPA (consistent clinical and radiologic findings), and 199 control patients with no evidence of IPA. PCR positivity was strongly associated with all forms of IPA (p < 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value of PCR were 80%, 93%, 38%, and 99%, respectively, for proven IPA, and 64%, 93%, 52%, and 96%, respectively, for probable IPA. Southern blotting analysis did not improve the diagnostic yield of the PCR test. CONCLUSION: PCR performed on BAL is associated with high specificity and negative predictive value for IPA. The low positive predictive value could be related to the transient colonizing presence of aspergilli in the respiratory tract. The sensitivity correlates with the certainty of the diagnosis based on tissue invasion.

Adolescent↗
PubMed2002

Chronic lymphocytic leukemia with t(14;18) and trisomy 12.

The chromosomal abnormality t(14;18) is most commonly associated with neoplasms of follicular center cell origin. However, t(14;18) also has been reported in rare cases of chronic lymphocytic leukemia (CLL). In 2215 cases of CLL studied by conventional cytogenetics in our institution, we identified 2 cases of CLL carrying t(14;18). Both patients were men, aged 52 and 71 years at the time of diagnosis. One patient presented with leukemia and the other primarily with nodal disease. In addition to t(14;18), trisomy 12 (+12) was identified in the same clone in both cases. Atypical morphologic features were identified: case 1 contained more than 15% lymphoid cells with cleaved nuclei, whereas case 2 contained more than 15% plasmacytoid lymphoid cells. The immunophenotype of case 2 was also unusual for CLL, showing weak CD23 expression and FMC7 positivity. We identified 6 other t(14;18)-carrying CLL cases in the literature; 2 had t(14;18) as the sole abnormality and 2 contained +12 as the additional abnormality. To conclude, cases of CLL carrying t(14;18) are exceedingly rare, and +12 appears to be the most common cytogenetic abnormality coexisting with t(14;18) in CLL.

Aged↗
PubMed2002

Emerging information on the use of rituximab in chronic lymphocytic leukemia.

Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) is a chimeric monoclonal antibody that targets mature B cells in most lymphoid B-cell malignancies. While rituximab was approved by the US Food and Drug Administration for the treatment of recurrent B-cell lymphoma, initial studies suggested that it had less activity in small lymphocytic lymphoma, the nodal counterpart of chronic lymphocytic leukemia (CLL). Two studies have now investigated the activity of higher-dose and more intensive therapy with rituximab in CLL. They have shown a dose-response relationship and a higher response rate than previously seen in the lower-dose studies. This is presumably caused by the overcoming of lower antigen density on CLL cells compared with lymphoma cells, and the shorter half-life of rituximab in small lymphocytic lymphoma. There is now evidence that CD20 is shed into the plasma in patients with CLL, which may explain the shorter half-life of the antibody in small lymphocytic lymphoma/CLL. The higher dose may then be effective in overcoming this so-called "antigen sink." Toxicity was uncommon except in previously untreated patients and those with atypical forms of CLL such as mantle cell lymphoma and prolymphocytic leukemia. There is now evidence in vitro of additive or synergistic activity of rituximab with a variety of chemotherapeutic agents including fludarabine and cyclophosphamide. Combinations of fludarabine with rituximab or these two drugs combined with cyclophosphamide have given very high complete response rates in series of patients with both previously untreated and treated CLL. It is apparent that rituximab is playing a significant role in the management of patients with CLL as salvage therapy and is a potential potentiating agent for combined chemoimmunotherapy strategies for front-line or relapsed patients with CLL.

Antibodies, Monoclonal↗
PubMed2002

Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results.

We treated 261 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) in chronic phase after failure of IFN-alpha with the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (400 mg/day given p.o.) and analyzed hematological and cytogenetic responses, long-term prognosis, factors associated with achievement of major cytogenetic response and survival, and comparative survival in similar patients treated with other regimens. Median patient age was 55 years; 34% were 60 years or older, and median chronic-phase duration was 33 months. Overall, 94% achieved a complete hematological response, and 71% had a cytogenetic response [major (Ph+ cells <35%) in 62% and complete in 45%]. At a median follow-up of 17 months, 241 patients (92%) were still taking imatinib mesylate; estimated 18-month freedom from progression and survival rates were 93 and 96%. Multivariate analysis of factors associated with major cytogenetic response identified long chronic phase, marrow basophilia, high percentage of Ph+ cells before therapy, and prior hematological resistance to IFN-alpha as being adverse factors. This model was used to generate good-, intermediate- and poor-risk subgroups who had estimated major cytogenetic response rates of 93, 53, and 34%, respectively. Univariate analysis in terms of survival identified leukocytosis, high percentages of peripheral and marrow blasts, marrow basophilia, and the presence of cytogenetic clonal evolution as being adverse factors. Achieving a cytogenetic response at 3 or 6 months of therapy was associated with prolonged survival. In a subset analysis, survival rates among 161 patients with Ph-positive CML after hematological or cytogenetic failure after IFN-alpha who had been treated with imatinib mesylate were better than those for similar patients treated previously with other regimens. In summary, imatinib mesylate is highly effective in chronic-phase CML after IFN-alpha failure. We identified pretreatment and treatment-associated factors that were associated with higher major cytogenetic response rates and with improved survival.

Benzamides↗