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Maher Albitar

Publications and source records attributed to Maher Albitar.

At least 91 records · Page 5Linked to original sources
PubMed2002

Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies.

We investigated the clinical activity of the farnesyl transferase inhibitor R115777 in 22 patients with chronic myelogenous leukemia (CML) in chronic, accelerated, or blastic phase and in 8 patients with myelofibrosis (MF) and 10 patients with multiple myeloma (MM). R115777 was administered at 600 mg orally twice daily for 4 weeks every 6 weeks. Seven patients with CML (6 in chronic phase, 1 in advanced phase) achieved complete or partial hematologic response. Four of them had a minor cytogenetic response. Responses were transient, with a median duration of 9 weeks (range, 3-23 weeks). Two patients discontinued therapy because of toxicity while in complete hematologic response. Two MF patients had a significant decrease in splenomegaly, one had normalization of white blood cell count and differential, and one became transfusion independent. One patient with MM had a reduction in monoclonal protein of 34%. Adverse events included nausea in 22 patients (55%; all grade 2 or lower) and fatigue in 19 (48%; grade 3 or higher in 1). Other grade 3 or 4 toxicities included skin rash (4 patients, 10%), peripheral neuropathy (2 patients, 5%), and liver toxicity (2 patients, 5%). Patients who responded to therapy had significantly higher plasma vascular endothelial growth factor (VEGF) concentrations prior to treatment than nonresponders. Plasma concentrations decreased significantly during therapy among responders. R115777 showed clinical activity in patients with CML and MF. The effect on VEGF needs to be further investigated to determine whether this might be a possible mechanism of action of R115777.

Adult↗
PubMed2002

Characteristics and outcome of patients with Philadelphia chromosome negative, bcr/abl negative chronic myelogenous leukemia.

BACKGROUND: Up to 5% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia (Ph) translocation t(9;22)(q34;q11) or a bcr/abl molecular rearrangement. Although the diagnostic criteria of this entity are still under debate, there is general agreement that patients with Ph negative, bcr/abl negative CML have a severe clinical course that is not affected significantly by current treatment options. METHODS: A population of 76 patients with bcr/abl negative CML who had received minimal or no previous therapy was characterized carefully with the intent of investigating clinical and hematologic variables and their association with survival by univariate, correlation, and multivariate analyses. A group of 73 patients with Ph negative CML who were not tested for the bcr/abl rearrangement (bcr/abl unknown) was analyzed separately and used for extension of the analysis. RESULTS: In the bcr/abl negative patient population, the median overall survival was 24 months. At the time of the analysis, 38 patients (50%) had died, and blastic transformation preceded death in 31%. Chromosomal abnormalities were found in 30% of the 76 patients, with trisomy 8 the most common abnormality. Complex chromosomal abnormalities were rare, and monosomy 7 was not observed. Survival was not affected significantly by treatment. Multivariate analysis identified older age (> 65 years), anemia (hemoglobin < 10 g/dL), and severe leukocytosis (white blood cells > 50 x 10(9)/L) as variables with independent prognostic significance for poor survival. A prognostic scoring system stratified patients into a low-risk group (53%) and a high-risk group (47%), with median survivals of 38 months and 9 months, respectively. CONCLUSIONS: Bcr/abl negative CML is a distinct clinical entity associated with very poor prognosis. Two risk categories are identifiable using a simple scoring system based on age, hemoglobin level, and leukocyte number.

Adult↗
PubMed2002

Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia.

BACKGROUND: Interleukin 6 (IL-6) is a B-cell growth and differentiation factor, which may promote the growth of B-cell neoplasms. In chronic lymphocytic leukemia (CLL) patients, IL-6 plasma levels increased in a stage-dependent manner, suggesting that IL-6 may be a useful prognostic marker. The purpose of this study is to fully assess the prognostic value of IL-6 in CLL patients. METHODS: We measured the plasma levels of IL-6 in 100 CLL patients using an enzyme-linked immunoassay method. RESULTS: Increasing levels of IL-6 significantly correlated with patient age, severity of anemia, Rai stage, white cell count, and beta-2-microglobulin (beta-2M). Although CLL patients did not differ significantly from the normal controls in the median IL-6 plasma level (P = 0.38), patients with advanced diseases (defined by Rai stage III/IV or beta-2M > 3.5) had a significantly higher median IL-6 plasma level than the normal controls (P < 0.05). Furthermore, in patients with advanced diseases, Cox regression hazards model showed that a higher IL-6 level correlated with shorter survival (P = 0.0001). Using IL-6 level of 3 pg/mL as a cutoff, patients with low IL-6 levels had a significantly longer overall survival than those with high IL-6 levels (log rank test, P = 0.002). In patients with CD38-positive CLL, patients with high IL-6 levels (> 3 pg/mL) had significantly shorter survival (P = 0.03). To conclude, IL-6 is a particularly useful predictor for survival in CLL patients with advanced diseases. CONCLUSIONS: Our findings suggest that patients with advanced-stage CLL as well as high IL-6 plasma levels may require aggressive therapeutic approaches and special consideration for experimental therapy.

ADP-ribosyl Cyclase↗
PubMed2002

The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine possessing pleiotropic biological activities, is produced by leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL) and acts as an autocrine and paracrine growth factor in this disease. In this study, TNF-alpha levels were determined in 150 patients with CLL and correlated with disease characteristics, prognostic factors, and survival. The mean TNF-alpha plasma concentration in the patients with CLL was significantly higher than in the healthy control population (16.4 versus 8.7 pg/mL; P <.0001). Patients having an elevated TNF-alpha level had more advanced Rai and Binet stage disease, higher serum beta(2)-microglobulin (beta(2)M) levels, a greater percentage of cells expressing CD38, and lower hemoglobin and platelet levels. Patients having chromosomal abnormalities such as 11q deletion, trisomy 12, and chromosome 17 aberrations had a higher mean TNF-alpha level (27.5 pg/mL) than patients having a diploid karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL; P <.001). The TNF-alpha level was a predictor of survival when the Cox proportional hazards model was used with TNF-alpha entered as a continuous variable (P =.0001). Also, patients having a TNF-alpha level above the mean value of 14 pg/mL had significantly shorter survival duration (P =.00001). The TNF-alpha level remained predictive of survival in Cox multivariate analysis independent of Rai staging and beta(2)M, hemoglobin, prior therapy, white cell count, and platelet level (P =.005). We conclude that the TNF-alpha level serves as a prognostic factor in patients with CLL and that inhibition of TNF-alpha in these patients could have therapeutic importance.

ADP-ribosyl Cyclase↗
PubMed2002

Myelodysplastic syndrome is not merely "preleukemia".

Myelodysplastic syndrome (MDS) is a disease characterized by ineffective hematopoiesis. There are significant biologic and clinical differences between MDS and acute myeloid leukemia (AML). We studied a cohort of 802 patients, 279 (35%) with newly diagnosed MDS and 523 (65%) with newly diagnosed AML, and compared clinical and biologic characteristics of the 2 groups. Complete clinical and cytogenetic data were available on all patients, and a subgroup of patients was studied for apoptosis, angiogenesis, proliferation, and growth factors. Our results demonstrate that MDS is a discrete entity that is different from AML and is characterized primarily by increased apoptosis in early and mature hematopoietic cells. Using cell sorting and loss of heterozygosity, we demonstrate that the leukemic cells from MDS patients are capable of differentiation into mature myeloid cells and monocytes. We also demonstrate that there is a significant overlap between AML and MDS when MDS is defined on the basis of an arbitrary percentage of blasts of 20% or 30%. These data suggest that despite similarities between AML and MDS in their responses to treatment and outcomes, MDS is biologically and clinically different from AML and should not be considered an early phase of AML. The data indicate that MDS must be better defined on the basis of its biology rather than the percentage of blasts; further, the data suggest that there is a need to develop therapeutic approaches that specifically address the biologic abnormalities of MDS.

Acute Disease↗
PubMed2002

Recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein Enbrel in patients with refractory hematologic malignancies.

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is an important effector and regulatory cytokine involved in the pathophysiology of hematologic malignancies, including hairy cell leukemia (HCL), chronic lymphocytic leukemia (CLL), agnogenic myeloid metaplasia (AMM) and Philadelphia-negative myeloproliferative disorders (MPD). We conducted a pilot study to assess the safety of the soluble TNF receptor, etanercept (p75 TNFR:Fc; Enbrel) in patients with refractory hematologic malignancies. METHODS: Patients were eligible if they had refractory HCL, CLL, AMM, or Philadelphia-negative MPD. Enbrel was administered twice weekly at a dose of 25 mg subcutaneously for a minimum of eight doses, and was continued in patients without overt progression. RESULTS: Among the 26 patients enrolled on study, 25 patients were evaluable. Nine patients had AMM, eight CLL, three HCL, and five Philadelphia-negative MPD. Their median age was 60 years (range 30-83 years). A total of 70 courses consisting of 486 doses of Enbrel were administered. Enbrel was well tolerated, without any overt increase in infectious episodes. Stable disease/no objective response was seen in 22 patients (88%) and progression in 3 patients (12%). Three patients with AMM improved (two showed hematologic improvement, and one showed a reduction in liver and spleen size), and two patients (one with CLL and one with Philadelphia-negative MPD) showed improvement in disease-related symptoms. CONCLUSIONS: Enbrel was well tolerated, but no responses were noted in these immunosuppressed patients with refractory hematologic malignancies.

Adult↗
PubMed2002

Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase.

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph(+) below 35%], and 4 minor [Ph(+), 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P =.001), longer median survival (7 versus 4 months, P =.04), and lower 4-week induction mortality (4% versus 15%, P =.07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

Adult↗
PubMed2002

Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study.

This study investigated the efficacy, safety, and clinical benefit of alemtuzumab (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy. Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim to obtain an overall response rate of at least 20%. Dosage was increased gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2 months after treatment. Responses were assessed at weeks 4, 8, and 12, and patients were followed for 34 months. Overall objective response in the intent-to-treat population (n = 93) was 33% (CR 2%, PR 31%). Median time to response was 1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were alive; overall median survival was 16 months (95% CI: 11.8-21.9) and 32 months for responders. Nineteen responders survived more than 21 months. Clinical benefit was observed both in responders and in patients with stable disease. The most common adverse events were related to infusion, generally grade 1 or 2 in severity, occurring mainly in the first week. Grade 3 or 4 infections were reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study. Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group.

Adult↗
PubMed2002

The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease.

BACKGROUND: CD23 antigen is a cell surface protein considered important in the differentiation of chronic lymphocytic leukemia (CLL) from other lymphoid leukemias. METHODS: To better clarify CD23 role as a diagnostic tool, the authors retrospectively evaluated clinical and laboratory features of 372 patients who were referred to M.D. Anderson Cancer Center with a diagnosis of CLL or B-cell chronic lymphoproliferative disease. RESULTS: Most of the patients (91%) were CD19+/CD5+. Only 6% of these CD19+/CD5+ patients were CD23-. Overall, CD23- patients had the worse prognostic features compared with CD23+ cases, including anemia (P = 0.03), massive splenomegaly (P = 0.000), high lactate dehydrogenase (P = 0.007), high beta2-microglobulin (P = 0.006), older age (P = 0.001), and male gender (P = 0.02). Surface immunoglobulin expression was moderate/strong in 19 (82%) patients, and FMC-7 was positive in 22 (96%) patients. None of the 13 patients tested for CD10 expressed the antigen. Based on morphology, of the CD23, 16 (70%) were diagnosed with mantle cell leukemia (MCL) was diagnosed in 16 (70%) CD23- patients, 3 (13%) with splenic marginal-zone leukemia, 3 (13%) with prolymphocytic leukemia (PLL) or PLL/CLL, and 1 (4%) with CLL. No cyclin D1 protein expression was noted by Western blot analysis in the one case that showed typical CLL morphology, and this patient did not require therapy. On the whole, the survival rate of CD23- patients was significantly worse than that of patients with CD23+. In contrast, 15 of 32 (49%) CD19+/CD5- patients were CD23-. CD23 negativity in this group was not associated with distinct clinical features or outcome. Eleven (73%) of these patients were classified as having splenic marginal-zone lymphoma and 4 as having follicular lymphoma. CONCLUSIONS: These data indicate that CD23 negativity is rare in typical B-cell CLL, and CD23 negativity in patients with CD19+/CD5+ is suggestive of mantle cell leukemia a more aggressive disease with poor response to conventional therapy in which newer chemotherapy regimens such as hyper-CVAD may be more effective.

Adult↗
PubMed2002

Prognostic significance of cellular vascular endothelial growth factor expression in chronic phase chronic myeloid leukemia.

The impact of elevated vascular endothelial growth factor (VEGF) expression on the course of chronic myeloid leukemia (CML) is unknown. By radioimmunoassay, we measured pretreatment cellular VEGF protein in bone marrow samples from 184 (148 chronic and 36 accelerated/blastic phases) CML patients and found the levels to be 1.6-fold higher than in 31 normal control bone marrow samples (P =.000 01). No significant differences were found in VEGF levels by different phases of CML (P =.1). VEGF levels correlated with older age (P =.01) and higher platelet count (P =.0003), but also with smaller spleen size (P =.004), lower white blood cell count (P =.0006), and lower percentage of peripheral blasts (P =.04). With the use of Cox proportional hazard model and VEGF levels as a continuous variable, high VEGF levels correlated with shorter survival of patients in chronic CML (P =.008). Multivariate analysis showed that VEGF was not independent of the synthesis stage (P =.09). These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

Aged↗
PubMed2002

Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells.

BACKGROUND: Bone marrow contains stem cells with the potential to differentiate into mature cells of various organs. We determined whether circulating stem cells have a similar potential. METHODS: Biopsy specimens from the liver, gastrointestinal tract, and skin were obtained from 12 patients who had undergone transplantation of hematopoietic stem cells from peripheral blood (11 patients) or bone marrow (1 patient). Six female patients had received transplants from a male donor. Five had received a sex-matched transplant, and one had received an autologous transplant. Hematopoietic stem-cell engraftment was verified by cytogenetic analysis or restriction-fragment--length polymorphism analysis. The biopsies were studied for the presence of donor-derived epithelial cells or hepatocytes with the use of fluorescence in situ hybridization of interphase nuclei and immunohistochemical staining for cytokeratin, CD45 (leukocyte common antigen), and a hepatocyte-specific antigen. RESULTS: All six recipients of sex-mismatched transplants showed evidence of complete hematopoietic donor chimerism. XY-positive epithelial cells or hepatocytes accounted for 0 to 7 percent of the cells in histologic sections of the biopsy specimens. These cells were detected in liver tissue as early as day 13 and in skin tissue as late as day 354 after the transplantation of peripheral-blood stem cells. The presence of donor cells in the biopsy specimens did not seem to depend on the intensity of tissue damage induced by graft-versus-host disease. CONCLUSIONS: Circulating stem cells can differentiate into mature hepatocytes and epithelial cells of the skin and gastrointestinal tract.

Adult↗
PubMed2002

Prognostic significance of Tie-1 protein expression in patients with early chronic phase chronic myeloid leukemia.

BACKGROUND: The Tie-1 tyrosine kinase receptor and its thus far unidentified ligand appear to play a distinct role in the regulatory pathways of early hematopoiesis and angiogenesis. Because vascularity is increased in the bone marrow of patients with chronic myeloid leukemia (CML), the authors evaluated the clinical significance of Tie-1 expression in such patients. METHODS: Using Western blot analysis and solid-phase radioimmunoassay (RIA), the authors quantified Tie-1 protein in bone marrow samples from 128 patients with CML and 31 normal controls. RESULTS: The median Tie-1 RIA value of CML samples was significantly higher than in normal controls (P = 0.01). The authors found no significant differences in Tie-1 levels in patients with early chronic, late chronic, accelerated, and blastic phases (P = 0.2). High Tie-1 levels correlated with short survival in patients with early chronic phase (P = 0.003; Cox proportional hazard model) but not in patients with late chronic (P = 0.2) or accelerated/blastic (P = 0.2) phase CML. Tie-1 protein level was also prognostic when patients were separated into two groups by the median value. High Tie-1 level in early chronic phase was associated with significantly shorter survival than low Tie-1 level (median survival, 116 vs. 61 months; P = 0.03). In patients with early chronic phase CML, Tie-1 levels correlated directly with patient age (P = 0.004) and platelet count (P = 0.003), and inversely with leukocyte count (P = 0.007). Tie-1 as a predictor of survival in early chronic phase CML was independent of risk group, spleen size, age, hemoglobin, and basophil count (P = 0.03; multivariate Cox proportional hazard model). CONCLUSIONS: The authors' findings support the hypothesis that angiogenesis may play a major role in the pathophysiology of chronic phase CML.

Aged↗
PubMed2002

Polymerase chain reaction on blood for the diagnosis of invasive pulmonary aspergillosis in cancer patients.

BACKGROUND: The premortem diagnosis of invasive pulmonary aspergillosis (IPA) is difficult to make and often missed. Several retrospective studies have suggested that Aspergillus polymerase chain reaction (PCR) performed on serum or whole blood is useful in diagnosing IPA. Two prospective studies confirmed this finding but included a small number of IPA cases. METHODS: The current study was performed to determine the diagnostic role of Aspergillus PCR performed on whole blood specimens from 54 patients with cancer and pulmonary infiltrates for which bronchoscopy with fungal stains and cultures were performed. PCR through amplified Aspergillus mitochondrial DNA and alkaline protease genes was performed on whole blood samples. RESULTS: The cohort in the current study was comprised of 4 patients with definite IPA, 7 patients with probable IPA, 7 patients with possible IPA, and 36 control patients with no evidence of IPA. The sensitivity, specificity, and positive and negative predictive values all were 100% for definite IPA cases and 57%, 100%, 100%, and 92%, respectively, for each of the probable and possible IPA cases. CONCLUSIONS: Aspergillus PCR on whole blood samples is highly sensitive for the detection of IPA and is predictive for IPA. The sensitivity appears to be correlated with the certainty of diagnosis as proven by tissue invasion.

Adolescent↗
PubMed2002

Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients.

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by wide heterogeneity of clinical presentation and course. CMML shares myelodysplastic characteristics with features of myeloproliferative disorders. No treatment has proven effective in modifying the natural course of the disease. To improve the prognostic assessment of clinical outcome, the associations of patient and disease characteristics with survival times of 213 patients with CMML was investigated retrospectively. Median survival was 12 months. Univariate analysis identified low hemoglobin level; low platelet count; high white blood cell, monocyte, and lymphocyte counts; presence of circulating immature myeloid cells, high percentage of marrow blasts, low percentage of marrow erythroid cells, abnormal cytogenetics, and high levels of serum lactate dehydrogenase and beta(2)-microglobulin as characteristics associated with shorter survival. Hemoglobin level below 120 g/L (12 g/dL), presence of circulating immature myeloid cells, absolute lymphocyte count above 2.5 x 10(9)/L, and marrow blasts 10% or more were independently associated with shorter survival by multivariate analysis and were used to generate a prognostic score. The model identified 4 subgroups of patients with median survival of 24, 15, 8, and 5 months for low, intermediate-1, intermediate-2, and high risk, respectively. Researchers could not confer objective evidence suggesting that arbitrary divisions of CMML by white blood cell counts into "dysplastic" and "proliferative" categories reflect clinical entities differing in the risk of acute leukemia development, although a trend of shorter survival in patients with leukocytosis was observed. The prognostic model was compared with 6 previously published scoring systems for myelodysplastic syndrome/CMML. The reported results should provide an improved assessment of prognosis in CMML.

Adult↗
PubMed2002

Clinical significance of plasma endostatin in acute myeloid leukemia/myelodysplastic syndrome.

BACKGROUND: Endostatin, a C-terminal fragment of collagen XVIII, is an endogenous angiogenesis inhibitor. While endostatin is being investigated for its usefulness in treating solid tumors, its significance in hematologic malignancies is unknown. METHODS: The authors evaluated plasma endostatin (PE) levels using an enzyme linked immunoassay in 71 patients with acute myeloid leukemia (AML) and 43 patients with myelodysplastic syndrome (MDS), and correlated PE with various clinical parameters. RESULTS: There was no significant difference in the median PE level between AML/MDS patients and the normal controls. Nevertheless, patients who achieved complete remission (CR) had a significantly lower median PE level compared to those who did not. In multivariate analysis, PE was found to be a significant (P = 0.03) predictor of overall survival (OS) with adjustment of the other baseline covariates, including patient age, history of antecedent hematologic disorders, and the use of protective environments. The prognostic value of PE was also evaluated by dividing MDS/AML patients into high and low PE groups using the median PE level of normal controls as the cut-off. The authors found that patients in the high PE group survived for a significantly shorter time than those patients in the low PE group. CONCLUSIONS: PE is a useful prognostic predictor of CR and OS for AML/MDS patients. The mechanism underlying the association between high PE and poor clinical outcome is unclear, although it may be related to the possible PE reflection of tumor burden.

Acute Disease↗
PubMed2002

Comparison between pediatric acute myeloid leukemia (AML) and adult AML in VEGF and KDR (VEGF-R2) protein levels.

We reported previously that high levels of vascular endothelial growth factor (VEGF) were associated with shorter survival in adult acute myeloid leukemia (AML) patients. In this study, cellular VEGF and its receptor, VEGF-R2 (kinase domain receptor (KDR)), were analyzed in 45 pediatric AML patients using Western blot and solid-phase radioimmunoassay (RIA). Cellular VEGF levels were significantly lower in pediatric AML compared to adult AML patients. In contrast, there was no significant difference in VEGF-R2 levels between adult and pediatric AML. Higher VEGF and VEGF-R2 levels in pediatric AML patients correlated with higher white blood cell (WBC). Unlike in adults, VEGF and VEGF-R2 levels in pediatric AML patients did not correlate with survival. This data suggest that the role of VEGF and its receptor VEGF-R2 in pediatrics AML may be different from that in adult AML.

Acute Disease↗
PubMed2002

Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome.

Clonal expansion of leukemic cells is thought to be due to proliferation in excess of apoptosis. To define and compare proliferation and apoptosis between various leukemias and myelodysplastic syndrome (MDS), we measured proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation as surrogate markers for proliferation and caspase 3 activity and annexin V surface binding as surrogate markers for activation of the apoptotic cascade in patients with MDS, chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). We found high proliferation in bone marrow cells from MDS and CMML as measured by PCNA and BrdU incorporation. The lowest level of proliferation was found in CLL. Apoptosis was also highest in MDS and CMML as measured by annexin V and caspase 3 activity. Unexpectedly, we found no significant difference in proliferation in bone marrow CD34+ cells from various leukemias or MDS. Apoptosis was significantly higher in bone marrow CD34+ cells from MDS and CML in chronic phase as compared to CD34+ cells from AML patients. Our results illustrate differences in proliferation and apoptosis between acute and chronic leukemias and MDS. These differences may have diagnostic and therapeutic implications.

Acute Disease↗