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Jorge Cortes

Publications and source records attributed to Jorge Cortes.

159 records · Page 9Linked to original sources
PubMed2002

Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course.

BACKGROUND: Neutrophilic-chronic myeloid leukemia (CML-N) has been described as a CML variant associated both with a distinctive molecular defect of the Philadelphia chromosome and with a more benign clinical course than classic CML. The translocation (9;22) in CML-N results in the transcription of an e19/a2 type BCR/ABL mRNA that codes for a 230-kD BCR/ABL protein (p230). The indolence of the clinical course of patients with CML-N has been disputed. METHODS: The objectives of this study were to quantify and correlate with clinical outcome the p230 mRNA and protein in patients with CML-N, to describe six new patients and the follow-up (with molecular analysis) of five previously reported patients with CML-N, and to review characteristics of all patients with CML-N and p230 BCR/ABL reported to date in the literature. RESULTS: Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML-N revealed minimal numbers of molecules of p230 BCR/ABL transcripts per total RNA. This also was associated with a lack of detectable p230 BCR/ABL protein in patient specimens, even in one patient who was followed for 16 years after diagnosis. This may explain the milder leukemic phenotype in most patients with CML-N. A review of all 23 patients who had an e19/a2 type BCR/ABL translocation suggested that the low level of p230 BCR/ABL mRNA and the lack of detectable p230 BCR/ABL protein in patients with no additional cytogenetic abnormalities may predict their indolent clinical course. CONCLUSIONS: Patients with p230 positive CML-N have indolent course, probably as a result of low p230 mRNA and protein levels. This supports the need to conduct additional molecular studies, even if cytogenetic studies have revealed t(9;22), because of the prognostic importance of the molecular findings.

Adult↗
PubMed2002

Simultaneous homoharringtonine and interferon-alpha in the treatment of patients with chronic-phase chronic myelogenous leukemia.

BACKGROUND: Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon-alpha (IFN-alpha), and cytarabine (ara-C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN-alpha therapy in patients with chronic-phase CML who were not exposed previously to either agent. METHODS: Forty-seven patients were treated: 37 patients with early chronic-phase CML (2 patients with clonal evolution) and 10 patients with late chronic-phase CML. Their median age was 62 years (range, 23-73 years). HHT was given at a dose of 2.5 mg/m(2) by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN-alpha was given daily at a target dose of 5 x 10(6) units/m(2) subcutaneously. Response, survival, and treatment toxicity were analyzed. RESULTS: Overall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronic-phase CML. Among the 10 patients with late chronic-phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6-24 courses, the median daily IFN-alpha dose was 1 MU/m(2), and the median number of days on HHT per month was 2 days. With a median follow-up of 26 months, the estimated 2-year survival rate was 90% (95% confidence interval, 79-100%). CONCLUSIONS: The simultaneous combination of HHT and IFN-alpha is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal-transduction inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN-alpha chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored.

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

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

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia.

BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma/leukemia have a poor prognosis and are frequently treated with low-intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a dose-intensive chemotherapy regimen, in patients with AIDS-associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients. METHODS: Thirteen patients with AIDS-associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper-CVAD alternating with high-dose methotrexate and ara-C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32-55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18-137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/microL (range, 9-544); only one patient had a count > 200/microL. RESULTS: Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7-45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7-45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non-HIV patients with Burkitt lymphoma/leukemia treated with the same regimen. CONCLUSIONS: Hyper-CVAD is an effective regimen for patients with AIDS-associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper-CVAD and HAART is associated with long-term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically.

Acquired Immunodeficiency Syndrome↗
PubMed2002

CD56 expression predicts occurrence of CNS disease in acute lymphoblastic leukemia.

We examined the pre-treatment bone marrow samples from 200 consecutive adult patients with acute lymphoblastic leukemia (ALL) treated on various protocols at the University of Texas, M.D. Anderson Cancer Center between 1986 and 1998. Standard MFC techniques were used to determine CD56 expression on the leukemia blasts cells. The expression of CD56 was correlated with clinical characteristics at diagnosis, response to therapy, survival and disease-free survival. Blast expression of CD56 (> or = 20% of leukemic blasts) was seen in 16 (8%) of patients, with a median expression of 67% (range 20-99%). CD56 expression was associated with a higher incidence of central nervous system (CNS) disease at diagnosis (19% versus 4%; P=0.016). Incidence of CNS disease at any time was higher in patients with CD56+ disease (31% versus 14%; P=0.057). Among the 109 patients uniformly treated with the hyperCVAD regimen, CD56 expression was associated with a statistically significant higher incidence of CNS disease (33% versus 9%; P=0.026). CD56 expression in ALL is uncommon but may predict a higher risk for CNS disease. If these results are confirmed, CD56 expression could be used in combination with other high-risk features (e.g. lactate dehydrogenase (LDH), S-phase fraction, mature B-cell phenotype) to design a risk-oriented approach to CNS prophylaxis.

Adolescent↗
PubMed2002

Response of idiopathic hypereosinophilic syndrome to treatment with imatinib mesylate.

Idiopathic hypereosinophilic syndrome (HES) is a rare hematologic disorder characterized by persistent eosinophilia with organ involvement. Patients with HES have a poor prognosis, but the disease course can be heterogeneous. Treatment of HES has included corticosteroids, chemotherapeutic agents such as cyclophosphamide, vincristine, hydroxyrea, and most recently interferon-alpha (IFN-alpha) which has shown long-term beneficial effects. We herein report on a patient with HES who had disease resistant to steroids, and chemotherapy with 2-chlorodeoxyadenosine and cytarabine, but who had a significant response after only 8 days of treatment with imatinib mesylate 100mg daily. The possible mechanism of response is discussed. This observation may lead to a better understanding of the pathophysiology of HES, and may provide a new form of effective therapy for the disease.

Alkylating Agents↗
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

New agents in the treatment of acute lymphocytic leukaemia.

The overall prognosis of adult patients with acute lymphocytic leukaemia (ALL) has improved significantly over the past few decades. Combined modality strategies (e.g. chemotherapy used with targeted therapies such as monoclonal antibodies or tyrosine kinase inhibitors) may improve long-term disease-free survival. Still, most patients succumb to complications of disease progression, with current long-term disease-free survival rates of 30-45% overall. Thus, either new strategies or refinements of old ones are needed to improve the long-term prognosis. An increasing number of unique active new chemotherapeutic and biological agents are available for study. This chapter reviews new agents with the potential to be incorporated into therapeutic strategies for the treatment of ALL.

Angiogenesis Inhibitors↗
PubMed2002

Clinical development of farnesyltransferase inhibitors in leukemias and myelodysplastic syndrome.

Farnesyltransferase inhibitors (FTIs) target multiple pathways including the Ras pathway implicated in the pathogenesis of some hematologic malignancies. R115777 and BMS-214662, selective FTIs in clinical development, exhibit preclinical activity against cell lines and tumor xenografts with or without ras mutations. Phase I dose-escalating trials at M.D. Anderson Cancer Center have explored the potential of these agents as monotherapy for leukemias and myelodysplastic syndrome (MDS). In 20 patients with MDS, two cycles of oral R115777 for 3 consecutive weeks followed by a 1-week rest produced an overall response rate of 30%, consistent with 29% reported in poor-prognosis acute leukemia or blast-phase chronic myelogenous leukemia (CML). Administration of BMS-214662 as a weekly intravenous infusion produced a decrease in bone marrow blasts of greater than 50% in 23% of patients with acute leukemia or MDS; 18% achieved normalization of blast counts to less than 5%. In both studies, most responding patients did not have ras mutations. The most common side effects at maximum tolerated doses of R115777 (400 mg twice daily) and BMS-214662 (118 mg/m(2) weekly) were myelosuppression and nausea, respectively. Further evaluation of FTIs for hematologic malignancies clearly is warranted. Future research should address whether molecular techniques can identify patients most likely to respond to an FTI, optimal administration schedules for these agents, and the value of incorporating an FTI into combination regimens for difficult-to-treat hematologic malignancies.

Alkyl and Aryl Transferases↗
PubMed2002

Chronic myelogenous leukemia.

The treatment options for chronic myelogenous leukemia (CML) continue to evolve rapidly. Imatinib mesylate (Gleevec, Glivec, formerly STI571) has continued to show remarkable clinical benefits and the updated results with this agent are reviewed. As relapses using single agent imatinib have occurred, particularly in advanced phase patients, the issue of whether combinations of other antileukemic agents with imatinib may yield improved results is addressed. In addition, data on new agents that have potential in the treatment of CML are reviewed. These agents are presented in the context of their molecular mechanism of action. The most recent data for stem cell transplantation, along with advances in nonmyeloablative transplants, are also reviewed. In Section I, Drs. Stephen O'Brien and Brian Druker update the current status of clinical trials with imatinib and review ongoing investigations into mechanisms of resistance and combinations of imatinib with other agents. They also present their views on integration of imatinib with other therapies. In Section II, Dr. Jorge Cortes describes the most recent data on novel therapies for CML, including farnesyl transferase inhibitors, arsenic trioxide, decitabine, and troxatyl, among others. These agents are discussed in the context of their molecular mechanism of action and rationale for use. In Section III, Dr. Jerald Radich updates the results of stem cell transplants for CML, including emerging data on nonmyeloablative transplants. He also presents data on using microarrays to stratify patients into molecularly defined risk groups.

Antineoplastic Agents↗
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

A phase I study of idarubicin dose escalation with amisfostine and high-dose cytarabine in patients with relapsed acute myelogenous leukemia and myelodysplastic syndromes.

BACKGROUND AND OBJECTIVES: Early studies have suggested that increasing doses of anthracycline improve outcome in younger patients with acute myelogenous leukemia (AML), but dose escalation has been precluded by the acute and chronic toxicities of these agents. Amifostine is a cytoprotective compound that has been shown to protect against the acute cytotoxicities of anthracyclines in animal models. We report the results of a phase I study of dose escalation of idarubicin with amifostine and high-dose ara-C in patients with relapsed or refractory AML or myelodysplastic syndrome (MDS). DESIGN AND METHODS: The continuous reassessment method was used to predict the probability of toxicity. RESULTS: Five patients were treated at an idarubicin dose of 18 mg/m2/day x 3, three of whom developed grade 3 diarrhea or mucositis. Subsequently, three additional patients were treated at a dose of 15 mg/m2 x 3 days, all of whom experienced grade 3 diarrhea or mucositis. One patient achieved complete remission (CR rate 12.5%, 95% CI 0-0.52%). INTERPRETATION AND CONCLUSIONS: The addition of amifostine does not allow dose escalation of idarubicin when combined with high-dose ara-C.

Adult↗
PubMedDate not supplied

Seagull wing graft: a technique for the replacement of lower lateral cartilages.

OBJECTIVES: To present and evaluate outcomes with the seagull wing technique, which was designed to replace the lower lateral cartilages and to reconstruct the nasal tip. METHODS: The seagull wing technique is illustrated and described in detail. Sixty patients who underwent surgery 1981 and 2002 were retrospectively evaluated. A preoperative diagnosis of tip deformities was made based on photographs, which were compared with the postoperative results. Patient satisfaction was subjectively evaluated. RESULTS: The postoperative results showed a significant statistical improvement in the following tip deformities: underprojected tip (P<.001), poorly defined tip (P<.001), alar retraction (P<.001), alar pinch (P<.001), overrotated tip (P<.001), and tip ptosis (P<.01). The average follow-up period was 14.6 months. Fifty-five patients (92%) stated that they were very satisfied with the surgical results; they required no additional revision surgery. CONCLUSIONS: The seagull wing technique is a safe and efficient reconstructive treatment for the aesthetic and functional problems that were caused by the overresection of the nasal tip cartilaginous framework. The outcomes were pleasing, and the results were stable during the follow-up period. Patient satisfaction was high.

Adolescent↗