Biomedical subjects

Jorge Cortes

Publications and source records attributed to Jorge Cortes.

At least 145 records · Page 8Linked to original sources

PubMed2003

Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies.

We explored the safety and efficacy of rituximab plus alemtuzumab in patients with relapsed or refractory lymphoid malignancies. Forty-eight patients were treated and were assessable for response (32 with chronic lymphocytic leukemia [CLL], 9 with CLL/prolymphocytic leukemia [PLL], 1 with PLL, 4 with mantle cell leukemia/lymphoma, 2 with Richter transformation). The overall response rate was 52% (complete remission, 8%; nodular partial response, 4%; partial response, 40%). With a median follow-up of 6.5 months (range, 1-20 months), the median time to progression was 6 months (range, 1-20 months); median survival, 11 months (11+ months for responders vs 6 months for nonresponders). Most toxicities were grade 2 or lower and infusion-related. Infections occurred in 52% of the patients. Cytomegalovirus (CMV) antigenemia assays were positive in 27% of the patients, but only 15% were symptomatic and required therapy. The combination of rituximab and alemtuzumab is feasible, has an acceptable safety profile, and has clinical activity with a short course in a group of patients with poor prognoses.

Adult↗

PubMed2003

Mitoxantrone and prolonged infusion gemcitabine as salvage therapy in patients with acute myelogenous leukemia.

In a recent phase I study, a combination of gemcitabine at 10 mg/(m(2)min) for 12 h and mitoxantrone 12 mg/m(2) daily for 3 days, achieved a complete remission (CR) in 3 of 12 (25%) patients with refractory leukemia. A pilot assessment of this regimen was conducted to determine its tolerability in patients with refractory acute myeloid leukemia (AML). In a cohort of 18 patients with very refractory disease (6 primary refractory, 12 relapsed, mean initial CR duration 3.5 months), one patient achieved a CR, a second CR with incomplete platelet recovery (CRp). Sepsis and mucositis were significant extramedullary toxicities. The gemcitabine and mitoxantrone regimen was feasible to administer even in heavily pre-treated patients. It was not active in patients who had failed a prior salvage regimen. It may warrant further study in patients with primary resistant AML.

Adolescent↗

PubMed2003

Clinical relevance of VEGF receptors 1 and 2 in patients with chronic myelogenous leukemia.

Vascularity is increased in the bone marrow of patients with chronic myeloid leukemia (CML) and high vascular endothelial growth factor (VEGF) levels correlate with worse survival. We analyzed the significance of VEGF-receptor 1 (VEGF-R1) and VEGF-R2 levels in bone marrow samples from 170 CML patients (137 chronic, 24 accelerated, and 9 blastic phase). Median VEGF-R1 and VEGF-R2 levels were 4.66 and 2-fold, respectively, that in normal control samples. Receptor levels did not correlate with disease phase or other host and disease features examined. Chronic phase CML patients with increased VEGF-R2 levels had significantly inferior survival than patients without receptor up-regulation (P=0.009). Patients in accelerated/blastic phase CML with elevated VEGF-R2 expression had marginally worse survival (P=0.05). In contrast, high VEGF-R1 levels did not correlate with a specific CML phase, characteristic, or outcome. Our findings support VEGF-R2 over-expression as an independent prognostic indicator for shortened survival in patients with CML.

Adolescent↗

PubMed2003

Pilot study of gemtuzumab ozogamicin, liposomal daunorubicin, cytarabine and cyclosporine regimen in patients with refractory acute myelogenous leukemia.

Multi-drug resistance (MDR) protein expression is associated with reduced gemtuzumab ozogamicin (Mylotarg) activity. Both cyclosporine-A (CSA) and liposome-encapsulated daunorubicin, DaunoXome (DNX) may reduce the negative impact of MDR. A gemtuzumab ozogamicin, DNX, cytarabine (ara-C) and CSA (MDAC) regimen was piloted in patients with refractory acute myelogenous leukemia (AML) (relapsed 10, primary refractory 1) (median age 37 years (16-67)). One (9%) patient achieved a transient CR, one CRp. Grade 3/4 toxicities included sepsis (seven patients; 63%); hyperbilirubinemia (six patients; 54%), with transaminitis in one patient; mucositis (three patients; 27%). The inclusion of CSA in a gemtuzumab ozogamicin-containing regimen is feasible. The MDAC regimen was associated with significant toxicity in a cohort of patients with very advanced AML.

Adolescent↗

PubMed2003

Gemtuzumab ozogamicin, fludarabine, cytarabine and cyclosporine combination regimen in patients with CD33+ primary resistant or relapsed acute myeloid leukemia.

Clinical resistance to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia (AML) is associated with blast multidrug resistance (MDR) phenotype. A Phase II study of Mylotarg, fludarabine, ara-C and the MDR-modifier, cyclosporine (CSA) (MFAC) was conducted in 32 patients with primary resistant (11, 34%) or relapsed (21, 66%) AML. Nine (28%) patients obtained complete remission (CR), two (6%) CR with incomplete platelet recovery. Overall median survival was 5.3 months, 12-month survival rate 19%. Fourteen patients (44%) developed grade 3/4 hyperbilirubinemia; six (18%) grade 3/4 hepatic transaminitis; three (9%) hepatic veno-occlusive disease (VOD). CSA inclusion in gemtuzumab ozogamicin-based regimens is feasible. MFAC is an effective regimen for refractory AML.

Acute Disease↗

PubMed2003

Empirical examination of the neutrophil criterion (>1500 microl(-1)) currently needed to declare CR in AML.

Currently, NCI guidelines require that the neutrophil count exceed 1500 before complete remission (CR) may be declared in acute myeloid leukemia (AML). We tested the empirical validity of this formulation by comparing event-free survival (EFS) in CR in (a). 305 patients who met the NCI criteria for CR and (b). 36 patients who met all the criteria for CR except that the neutrophil count at what we considered CR was 1000-1499 (lower neutrophil group) at which time they began post-remission therapy. EFS was statistically identical in both groups. We extended these findings to 752 patients, who met the NCI criteria for CR except that some may have had circulating blasts at "CR"; 82 of the 752 were in the lower neutrophil group. These data suggest that the minimum needed to declare CR in AML be changed from 1500 to 1000.

Acute Disease↗

PubMed2003

Single agent thalidomide in patients with relapsed or refractory acute myeloid leukaemia.

Thalidomide is a putative anti-angiogenesis agent that has significant anti-tumour activity in haematological malignancies with increased bone marrow angiogenesis, including multiple myeloma (MM) and myelodysplastic syndromes (MDS). Increased levels of the mitogen for angiogenesis, vascular endothelial growth factor (VEGF), correlate with worse survival in acute myeloid leukaemia (AML). A phase II trial of thalidomide was conducted in patients with relapsed- or refractory-AML previously treated with cytarabine-containing regimens. A total of 16 patients with refractory- or relapsed-AML were treated with thalidomide 200-800 mg orally daily (median dose 400 mg daily) for a median of 27 d (range, 3-94 d). Overall, one patient (6%) achieved complete remission (CR) lasting for 36 months, and two patients had a transient reduction in marrow blasts from 8% and 7% to less than 5% in both cases. There was no correlation between reduction in levels of angiogenesis markers and response. Toxicities related to thalidomide were significant, and precluded dose escalation beyond 400 mg orally daily in most patients. Although there appears to be some evidence of biological activity, single agent thalidomide is not an optimal choice of therapy for salvaging patients with relapsed- or refractory-AML. Thalidomide analogues with more potent immunomodulatory activities and more favourable toxicity profiles may offer more promise as anti-AML therapy.

Acute Disease↗

PubMed2003

Advanced-phase chronic myeloid leukemia.

Chronic myeloid leukemia (CML) typically runs a biphasic or triphasic course, with diagnoses usually made in the chronic phase (CP). Without effective treatment, patients eventually progress to a blastic phase (BP), frequently through an intermediate or accelerated phase (AP). Because the definition of AP varies among studies, comparisons of outcome and prognosis are difficult. The management of patients in these advanced phases of the disease has been much less satisfactory than that of patients in CP. Treatment with interferon-alfa (IFNalpha)-based therapy is ineffective for most patients in AP and for all of those in BP. Imatinib mesylate has demonstrated significant activity AP and BP disease, although the results are inferior compared to treatment in CP. In AP, 82% of patients achieve a hematologic response, with 24% achieving a major cytogenetic remission (MCR). Early MCR (within 3 months of diagnosis) provides a survival advantage over patients who do not achieve this response or achieve it later. In BP, 21% of previously treated patients and 36% of previously untreated patients have responded to imatinib, and up to 17% of patients may achieve a major cytogenetic response. However, responses are frequently short-lived. Several agents are being investigated for treatment of advanced-phase CML, including decitabine (DAC), homoharringtonine (HHT), troxacitabine, clofarabine, farnesyl transferase (FTase) inhibitors (FTI), and others. Many have also proven to be synergistic with imatinib in vitro and combination studies are ongoing. Continued investigation of these approaches is needed to improve the long-term prognosis of advanced-phase CML.

Antineoplastic Agents↗

PubMed2003

Farnesyltransferase inhibitors in acute myeloid leukemia and myelodysplastic syndromes.

Farnesyltransferase inhibitors were initially developed as Ras inhibitors as they inhibit the prenylation necessary for Ras activation. It is clear now that their mechanism of action is more complex and probably involves other proteins unrelated to Ras. At least 3 drugs within this family have been investigated in acute myeloid leukemia, myelodysplastic syndromes, and other leukemias. These are tipifarnib (R115777, Zarnestra), lonafarnib (SCH66336, Sarasar), and BMS-214662. The first 2 are administered orally, whereas BMS-214662 is given intravenously. These drugs are at different stages of development, and design of treatment schedules and methodology of the available studies are very different. Although most of the information is still preliminary, these agents have demonstrated clear evidence of clinical activity in these diseases and very favorable toxicity profiles. Several studies are still ongoing to better define the efficacy of these agents in the treatment of leukemias, as well as to determine the best schedules, the role of combination with other agents, and the role of these agents in different settings, such as the management of minimal residual disease. It is very possible that these agents will soon find their way to the ranks of established agents for the management of myeloid malignancies

Alkyl and Aryl Transferases↗

PubMed2003

Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; gleevec) in chronic-phase chronic myelogenous leukemia.

PURPOSE: The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate. EXPERIMENTAL DESIGN: One hundred eighty patients with Philadelphia chromosome (Ph)-positive chronic-phase CML after IFN-alpha failure, treated with imatinib mesylate, had 543 simultaneous cytogenetic and QC-PCR analyses at different times during their therapy. RESULTS: The median QC-PCR values [ratio-percentage of (BCR-ABL/ABL transcripts) x 100] for cytogenetic response categories were: no response (Ph, >90%), 36%; minor response (Ph, 35-90%), 22%; partial response (Ph, 1-34%), 7.3%; complete response (Ph, 0%), 0.89%. There was good correlation between cytogenetic and QC-PCR studies (P < 0.001; r = 0.92) and good concordance between QC-PCR values (>10%, 2-10%, and <2%) and cytogenetic response categories (none, minor, partial, complete) with a concordance rate of 66%, and major discordance of only 10%. Of 170 samples in complete cytogenetic response, 21% still had QC-PCR values of >10%, and 53% had QC-PCR values of <1%. There was excellent concordance between blood and marrow QC-PCR values (r = 0.965; P < 0.01; concordance rate, 88%; major discordance, 0%). No patient in complete cytogenetic response regardless of QC-PCR value has yet relapsed. At a median follow-up time of 26 months, higher QC-PCR values within each cytogenetic category at 3, 6, and 9 months have not been associated with a higher occurrence cytogenetic relapse or disease progression. However, the significance of this may become different with longer follow-up. CONCLUSION: QC-PCR studies provide a useful tool to monitor patients with CML on imatinib mesylate therapy.

Antineoplastic Agents↗

PubMed2003

CMML: a biologically distinct myeloproliferative disease.

Chronic myelomonocytic leukemia (CMML) is a myeloproliferative disorder with unique characteristics. Dysplasia is usually present in the bone marrow, thus CMML has usually been classified as a myelodysplastic syndrome. The recent World Health Organization classification of myeloid malignancies proposes to classify CMML into a new category of myelodysplastic syndromes and myeloproliferative disorders. A new prognostic score has also been developed exclusively for patients with CMML that recognizes four groups with distinct prognoses. Significant biologic findings in the recent months include the recognition of the importance of angiogenesis in CMML with a possible autocrine role for vascular endothelial growth factor, and the further understanding of the role of tyrosine kinase fusion genes and activation in some patients with CMML Therapeutic discoveries have been hampered by the paucity of studies looking specifically at CMML Among agents with potential significant activity are imatinib mesylate (for patients with platelet-derived growth factor beta receptor-associated fusion genes), hypomethylating agents, antiangiogenic agents, farnesyltransferase inhibitors, and topoisomerase I inhibitors. Future studies should consider CMML as a separate entity to promote a better understanding and identify more effective therapy for patients with this disease.

Humans↗

PubMed2002

Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia.

PURPOSE: Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce platelet counts, and reduce the bone marrow megakaryocyte mass in patients with essential thrombocythemia (ET). A semisynthetic protein-polymer conjugate of IFN-alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducted a pilot study of Peg-IFN2b in patients with ET. PATIENTS AND METHODS: Patients with a history of persistent (greater than 2 months) platelet counts >600 x 10(9)/l, with hyperplasia of bone marrow megakaryocytes in the absence of an alternate identifiable cause of thrombocytosis were eligible. Patients were required to have either thrombohemorrhagic signs and/or symptoms if previously untreated; persistence of thrombohemorrhagic signs and/or symptoms if receiving anagrelide, IFN-alpha, or hydroxyurea; or intolerance to anagrelide, IFN-alpha, or hydroxyurea. The initial PEG-IFN2b dose was from 1.5 to 4.5 micro g/kg per week subcutaneously with subsequent dose adjustments as indicated by response and adverse events. RESULTS: Eleven patients (nine female, median age 54 years, range 26-69 years) were treated. PEG-IFN2b rapidly controlled platelet counts and resolved symptoms in all patients. The median duration of PEG-IFN2b therapy on-study was 9 months (range 4-17 months). No patient had signs or symptoms of thrombosis or hemorrhage while on study. After 2 months of therapy, 10 patients (91%) were in complete remission, and 11 (100%) after 4 months. One patient discontinued therapy at 4 months because of persistent grade 3 fatigue and a second at 5 months because of anxiety and depression. CONCLUSION: PEG-IFN2b has significant activity in patients with ET. Long-term follow-up of a larger cohort of patients is needed to define its role in this disease.

Adult↗

PubMed2002

Pilot study of Mylotarg, idarubicin and cytarabine combination regimen in patients with primary resistant or relapsed acute myeloid leukemia.

PURPOSE: Mylotarg has moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myelogenous leukemia (AML). A combination of an anthracycline and cytarabine (ara-C) is the core of most AML induction regimens. We conducted a pilot study of Mylotarg combined with idarubicin and ara-C in patients with refractory or relapsed AML. METHODS: Mylotarg was administered at 6 mg/m(2) intravenously on days 1 and 15, idarubicin 12 mg/m(2) daily on days 2 through 4, and ara-C at 1.5 g/m(2) daily on days 2 through 5 (MIA) RESULTS: Of 14 patients were treated, 4 (29%) had primary resistant AML, and 10 (71%) relapsed AML. The median age of the patients was 61 years (range 34-74 years). MIA induced complete remission (CR) in three patients (21%) and CR with incomplete platelet recovery (CRp) in three patients (21%). The median survival was 8 weeks (range 2-64 weeks), and the median failure-free survival of CR patients was 27 weeks (range 11-64 weeks). All patients developed grade 3/4 myelosuppression - severe sepsis occurred in ten patients (71%). Other grade 3/4 nonhematologic toxicities included hepatic transaminitis, oral mucositis, and diarrhea. Two patients (14%) developed hepatic venoocclusive disease (VOD). CONCLUSIONS: The addition of Mylotarg to idarubicin and ara-C is feasible. MIA has significant activity in patients with refractory AML. Hepatotoxicity and VOD are significant toxicities of Mylotarg-based combinations.

Adult↗

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

Mylotarg combined with topotecan and cytarabine in patients with refractory acute myelogenous leukemia.

PURPOSE: Mylotarg, a humanized anti-CD33 antibody linked to an antitumor antibiotic, is approved for the treatment of patients with relapsed acute myeloid leukemia (AML). Topotecan and cytarabine (ara-C) is an effective anti-AML regimen. A pilot study of Mylotarg combined with topotecan and ara-C (MTA) was conducted in patients with refractory AML. METHODS: MTA consisted of Mylotarg 9 mg/m(2) intravenously (i.v.) over 2 h on day 1, ara-C 1 g/m(2) over 2 h i.v. on days 1 through 5, and topotecan 1.25 mg/m(2) by continuous infusion i.v. on days 1 through 5. RESULTS: A group of 17 patients (9 primary resistant, 8 relapsed) with AML or advanced myelodysplastic syndrome (MDS) received 20 courses of MTA. The median age of the patients was 55 years (20-70 years). Two patients (12%) achieved complete remission. The median overall survival was 8.2 weeks. Five patients (29%) developed grade 3/4 hepatic transaminitis, including one patient (6%) who died with hepatic venoocclusive disease. CONCLUSIONS: MTA was moderately effective and associated with significant toxicity in patients with refractory AML.

Acute Disease↗

PubMed2002

Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia.

We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance in patients with Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia (CML) whose disease manifests relapse or refractoriness to therapy. Fifty-four patients with Ph(+) CML in chronic phase and with hematologic or cytogenetic resistance or relapse on imatinib mesylate therapy at 400 mg orally daily were treated with a higher dose of 400 mg orally twice daily (800 mg daily, 47 patients; or 600 mg daily increased from 300 mg daily, 7 patients). Among 20 patients treated for hematologic resistance or relapse, 13 (65%) achieved a complete (n = 9) or partial (n = 4) hematologic response, but only 1 had a cytogenetic partial response (Ph reduction from 100% to 10%) and 1 had a minor response (Ph reduction from 100% to 50%). Among 34 patients treated for cytogenetic resistance or relapse, 19 (56%) achieved a complete (n = 6) or partial (n = 7) cytogenetic response. We conclude that higher doses of imatinib mesylate may overcome disease-poor response to conventional doses and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.

Adult↗

PubMed2002

The role of local radiation therapy for mediastinal disease in adults with T-cell lymphoblastic lymphoma.

BACKGROUND: Mediastinal recurrence remains the most common cause of failure in patients with mediastinal T-cell lymphoblastic lymphoma (LBL). The role of mediastinal radiation therapy in improving local disease control and overall prognosis is not well-known with modern intensive chemotherapy. The objective of this study was to investigate the role of mediastinal radiation therapy in patients who achieve a complete response (CR) to chemotherapy. METHODS: The authors reviewed 47 patients with mediastinal T-cell LBL with or without bone marrow (BM) involvement who presented between 1980 and 1998. The median patient age was 25 years, and 33 patients (70%) were males. BM involvement was present in 16 patients (34%), 5 patients (11%) were in leukemic phase, lymph node involvement in was present 23 patients (49%), hepatosplenomegaly was present in 4 patients (9%), and pleural effusions were present in 22 patients (45%). The initial chemotherapy regimens were fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) in 23 patients; cyclophosphamide, vincristine, doxorubicin, and dexamethasone in 9 patients; vincristine, doxorubicin, and dexamethasone in 4 patients; cyclophosphamide, doxorubicin, vincristine, and prednisone in 4 patients; and other in 7 patients. Forty-three patients achieved a CR to chemotherapy and were the subject of this analysis. Nineteen of those patients received adjuvant mediastinal radiation therapy at a dose ranging from 26 grays (Gy) to 39 Gy. RESULTS: There was no difference in patient characteristics between the 19 patients who were treated with mediastinal radiation therapy and the 24 patients who did not receive mediastinal radiation therapy. The median follow-up for all 43 patients was 43 months. The 5-year overall survival (OS) rate was 66%, and the freedom from progression (FFP) rate was 64%. None of 19 patients who received radiation therapy experienced a mediastinal recurrence compared with 8 of 24 patients who did not receive radiation therapy and experienced a mediastinal recurrence. Patients who were treated with mediastinal radiation therapy had a significantly better mediastinal FFP rate (P = 0.01), but the differences in overall FFP and OS rates were not significant (P = 0.14 and P = 0.25, respectively). The effectiveness of the hyper-CVAD regimen seemed to underscore the role of mediastinal radiation therapy; only 2 patients experienced a recurrence among 16 patients who received mediastinal radiation therapy, both outside the mediastinum. This compared with two patients who experienced a recurrence among six patients who did not receive mediastinal radiation therapy, both in the mediastinum. CONCLUSIONS: Local radiation therapy significantly decreased the risk of mediastinal recurrence in adult patients with mediastinal T-cell lymphoblastic lymphoma. The benefit of adjuvant radiation therapy was particularly evident in patients treated with more intensive chemotherapy regimens.

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↗