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Jorge Cortes

Publications and source records attributed to Jorge Cortes.

At least 91 records · Page 5Linked to original sources
PubMed2004

Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia.

Deletions of derivative chromosome 9 [der(9)] can be identified by fluorescence in situ hybridization (FISH) in 10% to 15% of patients with chronic myeloid leukemia (CML). Patients with der(9) deletions have been reported to have an adverse outcome when treated with chemotherapy, interferon, and possibly imatinib mesylate. We investigated the frequency and prognostic significance of der(9) deletions among 352 patients with CML treated with imatinib mesylate at our institution, in whom a deletion status of der(9) was determined. Thirty-three patients (9%; 95% CI 0.07, 0.13) (30 in chronic phase, 3 in accelerated phase) had der(9) deletions. The rates of major (82% vs 79%, P = 0.82) and complete cytogenetic response (76% vs 66%, P = .33) with imatinib mesylate therapy were similar in patients with and without der(9) deletions, respectively. After a median follow-up of 28 months, there was no difference in overall survival (P = .30) or response duration (P = .49) in patients with and without deletions. In a multivariate analysis, der(9) deletions had no significant impact on response, survival, or response duration. We conclude that treatment with imatinib mesylate overcomes the adverse prognostic significance of der(9) deletions in patients with CML.

Adolescent↗
PubMed2004

Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias.

Clofarabine (2-chloro-2'-fluoro-deoxy-9-beta-D-arabinofuranosyladenine) is a second-generation nucleoside analog with activity in acute leukemias. As clofarabine is a potent inhibitor of ribonucleotide reductase (RnR), we hypothesized that clofarabine will modulate ara-c triphosphate accumulation and increase the antileukemic activity of cytarabine (ara-C). We conducted a phase 1-2 study of clofarabine plus ara-C in 32 patients with relapsed acute leukemia (25 acute myeloid leukemia [AML], 2 acute lymphoblastic leukemia [ALL]), 4 high-risk myelodysplastic syndrome (MDS), and 1 blast-phase chronic myeloid leukemia (CML).(1) Clofarabine was given as a 1-hour intravenous infusion for 5 days (days 2 through 6) followed 4 hours later by ara-C at 1 g/m(2) per day as a 2-hour intravenous infusion for 5 days (days 1 through 5). The phase 2 dose of clofarabine was 40 mg/m(2) per day for 5 days. Among all patients, 7 (22%) achieved complete remission (CR), and 5 (16%) achieved CR with incomplete platelet recovery (CRp), for an overall response rate of 38%. No responses occurred in 3 patients with ALL and CML. One patient (3%) died during induction. Adverse events were mainly less than or equal to grade 2, including transient liver test abnormalities, nausea/vomiting, diarrhea, skin rashes, mucositis, and palmoplantar erythrodysesthesias. Plasma clofarabine levels generated clofarabine triphosphate accumulation, which resulted in an increase in ara-CTP in the leukemic blasts. The combination of clofarabine with ara-C is safe and active. Cellular pharmacology data support the biochemical modulation strategy.

Acute Disease↗
PubMed2004

Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies.

BACKGROUND: The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAMPATH-1H; anti-CD52) is currently approved for the treatment of patients with refractory chronic lymphocytic leukemia (CLL). The authors investigated the possibility that CD52 may be shed from cells and, once soluble, may bind to injected alemtuzumab, forming immune complexes. METHODS: The authors used Western blot analysis, immunoprecipitation, and enzyme-linked immunoadsorbent assay to investigate the presence of soluble CD52 (sCD52) in the plasma specimens of 117 patients with CLL. They also used in vitro mixing experiments to examine the ability of sCD52 to compete with cells and sequester therapeutic alemtuzumab. RESULTS: The authors detected high levels of sCD52 in the plasma specimens of patients with CLL. sCD52 can compete with cells in vitro for binding to alemtuzumab, and can form complexes in patients receiving alemtuzumab. Plasma levels of sCD52 were found to be correlated (r)with Rai stage (P = 0.0001), beta-2-microglobulin (beta-2M) levels (P = 0.00002), soluble CD23 levels (r = 0.42, P < 0.001), and immunoglobulin mutation status (P = 0.003). In the multivariate analysis adjusted for beta-2M level, patients with sCD52 levels > 2336 nM/L had a nearly 4-fold increase in risk of death. Higher levels of plasma alemtuzumab were achieved when levels of sCD52 were lower. CONCLUSIONS: These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy.

Adult↗
PubMed2004

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia.

BACKGROUND: Reticulin-stained bone marrow fibrosis is associated with a poor prognosis in patients with chronic myelogenous leukemia (CML). Resolution of fibrosis with therapy may improve patient outcome. METHODS: The effect of imatinib therapy on bone marrow fibrosis was evaluated in 40 patients with chronic-phase CML who were treated after interferon-alpha failure. RESULTS: Thirty-one patients (78%) had severe (Grade 3 or 4) reticulin fibrosis prior to therapy. After imatinib therapy was administered for 3 to > 24 months, fibrosis was reduced by at least 2 grades in 19 of the 31 patients (61%) and by at least 1 grade in 34 patients (85%). There was no correlation noted between reduction of fibrosis and cytogenetic response. However, a reduction in fibrosis was found to correlate with a reduction in bone marrow megakaryocytosis (P = 0.002). CONCLUSIONS: Treatment with imatinib mesylate appears to reduce CML-associated bone marrow fibrosis in most patients who are treated during the chronic phase of disease. This effect may be independent of the degree of suppression of Philadelphia chromosome-positive cells, and may improve prognosis in patients with CML.

Adult↗
PubMed2004

Granulocyte-colony-stimulating factor (filgrastim) may overcome imatinib-induced neutropenia in patients with chronic-phase chronic myelogenous leukemia.

BACKGROUND: Imatinib mesylate administration has become standard treatment for patients with chronic myelogenous leukemia (CML). Although the safety profile of imatinib is favorable, Grade > or = 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria) occurs in 35-45% of patients with CML in chronic phase who receive standard-dose imatinib. Myelosuppression results in treatment interruptions, which may compromise responses to imatinib. The authors investigated the ability of granulocyte-colony-stimulating factor (filgrastim) to reverse imatinib-associated neutropenia, thereby allowing for more continuous imatinib administration. METHODS: Thirteen patients with chronic-phase CML and Grade > or = 3, imatinib-induced neutropenia were treated with filgrastim. Treatment with filgrastim was initiated after a median of 22 months from the start of imatinib. Eleven patients received filgrastim 5 microg/kg 1-3 times weekly, and 2 patients received filgrastim 5 microg/kg daily; doses were titrated to maintain an absolute neutrophil count (ANC) > or = 10(9)/L. RESULTS: Seven of 11 patients (64%) who began treatment with an ANC < 1.5 x 10(9)/L had responses (i.e., their ANC improved to > or = 2 x 10(9)/L within 21 days); the other 4 patients experienced slower recovery but were able to continue receiving imatinib uninterrupted. Before filgrastim administration was initiated, patients did not receive imatinib (due to neutropenia-related treatment interruptions) for an average of 21% of the total time since the start of imatinib. This figure decreased to 6% after the start of filgrastim treatment (P = 0.0008). Before filgrastim treatment was initiated, only one patient had achieved a major (partial) cytogenetic response. After the start of filgrastim treatment, five patients had major cytogenetic responses (including two complete responses). CONCLUSIONS: The authors concluded that filgrastim may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Some patients may experience improvements in their responses to therapy as a result.

Adult↗
PubMed2004

Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma.

Therapy of lymphoblastic lymphoma (LL) has evolved with use of chemotherapy regimens modeled after those for acute lymphocytic leukemia (ALL). We treated 33 patients with LL with the intensive chemotherapy regimens hyper-CVAD (fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone) or modified hyper-CVAD used for ALL at our institution. Induction consolidation was administered with 8 or 9 alternating cycles of chemotherapy over 5 to 6 months with intrathecal chemotherapy prophylaxis, followed by maintenance therapy. Consolidative radiation therapy was given to patients with mediastinal disease at presentation. No consolidation with autologous or allogeneic stem cell transplantation was performed. At diagnosis, 80% were T-cell immunophenotype, 70% were stages III to IV, 70% had mediastinal involvement, and 9% had central nervous system (CNS) disease. Of the patients, 30 (91%) achieved complete remission, and 3 (9%) achieved partial response. Within a median of 13 months, 10 patients (30%) relapsed or progressed. Estimates for 3-year progression-free and overall survival for the 33 patients were 66% and 70%, respectively. Estimates for the patients with known T-cell immunophenotype were 62% and 67%, respectively. No parameters (eg, age, stage, serum lactate dehydrogenase [LDH], beta(2) microglobulin) appeared to influence outcome except for CNS disease at presentation. Modification of the hyper-CVAD regimen with anthracycline intensification did not improve outcome. Other modifications of the program could include incorporation of monoclonal antibodies and/or nucleoside analogs, particularly for slow responders or those with residual mediastinal disease.

Adolescent↗
PubMed2004

Erythropoietin is effective in improving the anemia induced by imatinib mesylate therapy in patients with chronic myeloid leukemia in chronic phase.

BACKGROUND: Myelosuppression occurs in up to 50% of patients with chronic myeloid leukemia (CML) who are treated with imatinib and > or = Grade 3 myelosuppression is reported in approximately 10% of patients. METHODS: The authors investigated the prognostic significance of anemia occurring during therapy with imatinib in patients with CML in chronic phase. RESULTS: Of 338 patients treated with imatinib (150 patients after interferon failure and 188 patients with newly diagnosed CML), 230 (68%) developed anemia. In a multivariate analysis, factors associated with an increased probability of developing anemia were a starting hemoglobin level < 12 g/dL, age > or = 60 years, female gender, higher imatinib dose, and intermediate or high Sokal risk group. Of these 230 patients, 102 patients received treatment with 40,000 U of recombinant human erythropoietin administered subcutaneously once weekly. An increase in the hemoglobin level of > or = 2 g/dL was achieved in 69 patients (68%) and 22 patients (22%) had an increase of 1-1.9 g/dL. Patients who developed anemia had a trend toward a lower probability of complete cytogenetic remission compared with patients without anemia (68% vs. 77%; P = 0.14), as well as a trend for inferior survival. Patients with anemia and other manifestations of myelosuppression were found to have a significantly worse outcome than those with isolated anemia. CONCLUSIONS: The authors concluded that erythropoietin is safe and effective in patients in chronic-phase CML who develop anemia with imatinib therapy.

Anemia↗
PubMed2004

Beyond chronic myelogenous leukemia: potential role for imatinib in Philadelphia-negative myeloproliferative disorders.

The myeloproliferative disorders (MPDs) are chronic malignant conditions originating from the clonal expansion of a multipotential hematopoietic stem cell. These diseases include polycythemia vera (PV), essential thrombocythenia, atypical chronic myeloid leukemia, idiopathic hypereosinophilic syndrome (HES), agnogenic myeloid metaplasia with myelofibrosis, and others. Receptor tyrosine kinases-the platelet-derived growth factor receptors (PDGFRs) and c-Kit-and their respective ligands have been implicated in the pathogenesis of MPDs. For example, a constitutively activated PDGFR fusion tyrosine kinase (FIP1L1-PDGFRA) was identified in some patients with HES, a disease characterized by sustained overproduction of eosinophils that has been classified by the World Health Organization as a chronic subtype of the MPDs. Imatinib is a selective inhibitor of PDGFRs, c-Kit, Abl and Arg protein-tyrosine kinases, as well as Bcr-Abl, the oncogenic tyrosine kinase that causes chronic myeloid leukemia. The efficacy of imatinib in treating HES, systemic mast cell disease, chronic myelomonocytic leukemia associated with PDGFRbeta fusion genes, and (to a lesser extent) PV and idiopathic myelofibrosis was reviewed from institutional experience and a review of the literature. In 3 studies that involved 11 patients with PV, 10 patients had reductions in phlebotomy with imatinib. Eight studies of 42 patients with HES indicated that 70% achieved complete hematologic remissions with imatinib. Four studies of 6 patients with MPD indicated responses with imatinib in 5 patients. Insight into the molecular pathogenesis of MPDs will improve the definitions of different disease categories and suggests that signal transduction inhibition is likely to be an increasingly important treatment option in the future.

Antineoplastic Agents↗
PubMed2004

Phase I study of bortezomib in refractory or relapsed acute leukemias.

Bortezomib (Velcade, formerly PS-341) is proteasome inhibitor with documented antitumor activity in multiple myeloma and other lymphoid malignancies. We performed a Phase I study to investigate the maximum tolerated dose and dose-limiting toxicity of bortezomib in patients with acute leukemias refractory to or relapsing after prior therapy. Fifteen patients were treated with 0.75 (n = 3), 1.25 (n = 7), or 1.5 (n = 5) mg/m(2) bortezomib administered twice weekly for 4 weeks every 6 weeks. Dose-limiting toxicity included orthostatic hypotension (n = 2), nausea (n = 2), diarrhea (n = 1), and fluid retention (n = 1), all at 1.5 mg/m(2) bortezomib. Proteasome inhibition was dose dependent and reached 68% at 1.5 mg/m(2) bortezomib. Peak inhibition was observed 1 h after treatment and returned to near baseline levels by 72 h after treatment. Incubation of blast cells with bortezomib in vitro showed induction of apoptosis in three of five patients investigated. We conclude that the maximum tolerated dose of bortezomib in patients with acute leukemia is 1.25 mg/m(2), using a twice-weekly for 4 weeks every 6 weeks schedule. The in vitro evidence of antileukemia and transient hematological improvements observed in some patients warrants further investigation of bortezomib in acute leukemias, probably in combination with other agents.

Adolescent↗
PubMed2004

A Phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia.

PURPOSE: VNP40101M is a novel sulfonylhydrazine alkylating agent with broad antitumor activity in animal models. As alkylating agents are important antileukemia drugs, a Phase I and pharmacokinetic study of VNP40101M was conducted in patients with refractory or relapsed leukemias or poor-risk myelodysplastic syndromes (MDS). EXPERIMENTAL DESIGN: VNP40101M was given as a single i.v. infusion over 15-70 min on day 1. Courses were repeated every 4 weeks according to antileukemic activity. The starting dose of 220 mg/m(2) was escalated by approximately 33% in cohorts of 3-6 patients until a maximum-tolerated dose was established. One additional cohort was treated with the maximum-tolerated dose divided over days 1 and 8. RESULTS: Thirty-eight patients, including 28 with acute myeloid leukemia and 5 with MDS, received 52 courses of treatment. Nondose-limiting, reversible infusion-related toxicities were the most frequent adverse event, occurring in 24 (63%) patients on the first course. Dose escalation was terminated at 708 mg/m(2) for prolonged myelosuppression in 1 of 7 patients, and 600 mg/m(2) was selected as the recommended Phase II dose, with no significant extramedullary toxicity at this dose level. Two patients, 1 with MDS treated with 300 mg/m(2) and 1 with acute myeloid leukemia treated with 600 mg/m(2), achieved complete remission. CONCLUSIONS: VNP40101M had significant antileukemic activity and minimal extramedullary toxicity in patients with relapsed or refractory disease.

Acute Disease↗
PubMed2004

Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation.

Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P =.006), patients in first CR (28% versus 3%, P =.008), and HLA-matched sibling donors (81% versus 40%, P =.001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P =.036), and lower cumulative incidence of relapse-related mortality (P =.029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.

Adult↗
PubMed2004

Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome undergoing induction chemotherapy.

BACKGROUND: Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (i.v. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I). METHODS: Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily. RESULTS: One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with i.v. ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of i.v. ITRA was NCI Grade 3-4 hyperbilirubinemia (6%). CONCLUSIONS: Despite its theoretic advantages, the authors found no evidence that i.v. ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole.

Adult↗
PubMed2004

New agents in acute myeloid leukemia and other myeloid disorders.

Over the past several decades, improvements in chemotherapeutic agents and supportive care have resulted in significant progress in treating patients with acute myeloid leukemia (AML). More recently, advances in understanding the biology of AML have resulted in the identification of new therapeutic targets. The success of all-trans-retinoic acid in acute promyelocytic leukemia and of imatinib mesylate in chronic myeloid leukemia have demonstrated that targeted therapy may be more effective and less toxic when well defined targets are available. At the same time, understanding mechanisms of drug resistance and means to overcome them has led to modification of some of the existing cytotoxic agents. Rational design and conduct of clinical trials is necessary to ensure that the full potential of these new agents is realized.

Antineoplastic Agents↗
PubMed2004

Survival advantage with imatinib mesylate therapy in chronic-phase chronic myelogenous ;eukemia (CML-CP) after IFN-alpha failure and in late CML-CP, comparison with historical controls.

PURPOSE: The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-alpha failure treated with imatinib to historical experiences with standards of care or other therapies. EXPERIMENTAL DESIGN: The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival. RESULTS: In the first analysis involving 261 patients on imatinib plus 204 historical patients, the complete cytogenetic response rates were 62% and 19%, respectively (P < 0.001). A multivariate analysis identified pretreatment peripheral blasts and thrombocytosis to be independent poor prognostic factors for survival. Imatinib therapy (versus others) was a significant independent favorable prognostic factor for survival (hazard ratio, 0.17; P < 0.0001). In the second analysis involving the subset of 147 patients receiving imatinib plus 95 historical patients treated with IFN regimens, the complete cytogenetic response rates were 41% and 7%, respectively (P < 0.001). A multivariate analysis selected pretreatment anemia and peripheral blasts to be significant independent poor prognostic factors for survival. Imatinib therapy (versus IFN) was an independent favorable prognostic factor for survival (hazard ratio, 0.20; P < 0.0001). Three-month and 6-month landmark analyses showed that patients in all cytogenetic response categories (major, minor, and none) after imatinib therapy had survival outcomes better than the historical control population. Within each cytogenetic response category, survival was also better with imatinib than with other therapies. CONCLUSIONS: This analysis provides evidence for a survival advantage with imatinib versus other therapies in chronic-phase CML post-IFN failure, and for a survival advantage with imatinib versus IFN in late chronic-phase CML.

Antineoplastic Agents↗
PubMed2004

Management of patients with systemic mastocytosis: review of M. D. Anderson Cancer Center experience.

Mastocytosis is characterized by mast cell proliferation that may be limited to the skin (cutaneous mastocytosis) or may involve one or more extracutaneous organs, e.g., the bone marrow (systemic mastocytosis; SM). This study objective is to evaluate the features and outcome of patients referred to M. D. Anderson Cancer Center (MDACC) with SM. A search of the MDACC database from 1944 to 2002 was conducted for patients with SM and review of their clinical charts. Eighteen patients with mastocytosis were identified in the MDACC database; 15 (11 males and 4 females) had SM and available information. Two had associated myelodysplastic syndrome (MDS), and one had acute myeloid leukemia (AML). The median age was 58 years (range 31-80). Nine patients were treated with subcutaneous interferon-alpha, and only 1 experienced temporary control of the disease. Three of these patients were then treated with imatinib mesylate: transient improvement was noted in two patients. One patient underwent stem cell transplantation as first therapy and achieved complete remission; this patient had associated MDS and is now in complete remission for 8 years. The patient with associated AML was treated with high-dose cytarabine and idarubicin; he has been in complete remission for 16 months. One patient was treated with induction chemotherapy consisting of high-dose cytarabine and 2CDA but expired due to sepsis. Three patients received symptomatic therapy only; these were the only 3 patients who presented with normal blood counts. SM is rare and has no effective standard of care. Collaboration among academic centers to accrue enough patients to evaluate novel therapeutic strategies is needed.

Adult↗
PubMed2004

Natural history and staging of chronic myelogenous leukemia.

The natural history of chronic myelogenous leukemia (CML) has changed in recent years, partly due to earlier diagnosis but mostly as a consequence of the availability of effective therapies that have the potential to eradicate the Philadelphia chromosome-positive clone. Highly effective therapy with imatinib has changed the prognostic significance of clinical features traditionally associated with poor outcome. Achieving a complete cytogenetic response and a major molecular response early during the course of therapy with imatinib may be the most important factor in determining longterm outcome. Therefore, treatment modalities that increase the probability of achieving this goal should be pursued. This article describes the natural history of CML and its prognostic factors,with emphasis on changes due to the emergence of imatinib.

Benzamides↗
PubMed2004

Clonal evolution in chronic myelogenous leukemia.

Clonal evolution (CE) may be a marker of disease progression in chronic myelogenous leukemia (CML) and is thought to reflect the genetic instability of the highly proliferative CML progenitors. The frequency of CE increases with advancing stage, rising from 30%in accelerated phase and up to 80% in blast crisis. Given its association with disease progression, CE is considered a feature that defines accelerated-phase CML; however, not all studies have demonstrated a uniformly poor outcome for patients with CE. Chromosomal abnormalities in Ph chromosome negative metaphases increasingly have been recognized in patients treated with imatinib. The true incidence of this phenomenon is not clear but appears to occur in 2% to 17% of imatinib-treated patients. Regardless of the precise mechanism and the long-term clinical implications, the findings described in this article underscore the importance of routine cytogenetic analysis for patients treated with imatinib. The continued study of these phenomena will help us to understand better the pathogenesis of CML and improve the long-term treatment of patients with CML.

Antineoplastic Agents↗