Biomedical subjects

Stefan Faderl

Publications and source records attributed to Stefan Faderl.

At least 73 records · Page 4Linked to original sources

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

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy.

BACKGROUND: The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population. METHODS: Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability. RESULTS: The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups. CONCLUSIONS: ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy.

Adult↗

PubMed2004

The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase.

BACKGROUND: Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression > or = Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown. METHODS: The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response. RESULTS: Neutropenia > or = Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia > or = Grade 3 occurred in 31 patients (22%). Any myelosuppression > or = Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade > or = 3 myelosuppression compared with a rate of 75% without Grade > or =3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response. CONCLUSIONS: Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated.

Aged↗

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

Monitoring of minimal residual disease in chronic myeloid leukemia.

Detection and monitoring of minimal residual disease has become one of the most prevalent topics in chronic myeloid leukemia(CML) therapy. The goal of early detection of residual disease is to allow timely therapeutic intervention before overt relapse of therapy resistant disease occurs. The most powerful tool to serve this purpose is polymerase chain reaction (PCR). Major improvements in assay techniques have advanced PCR from a purely qualitative test with considerable variability of test results to a real-time quantitative assay with far more reproducible results than were possible before. At the same time, treatment of CML has changed dramatically since the introduction of imatinib. Integration of therapy and molecular assays such as PCR, in addition to a profound understanding of the pathophysiology of CML, has assumed even more importance. Quantitative PCR testing has become the standard monitoring strategy for patients undergoing stem cell transplantation. Although correlations have been established between positive test results and probability of relapse, no absolute guidelines for monitoring exist, especially for patients treated with imatinib.

Drug Monitoring↗

PubMed2004

Chronic myeloid leukemia in a patient with acquired immune deficiency syndrome: complete cytogenetic response with imatinib mesylate: report of a case and review of the literature.

We report a patient with acquired immune deficiency syndrome (AIDS) who developed Philadelphia-positive chronic myeloid leukemia (CML) and was successfully treated with imatinib mesylate. He achieved a complete cytogenetic response after 7 months of treatment. It appears that there is no in vivo interaction between imatinib and highly active anti-retroviral therapy (HAART) and these drugs can be concurrently administered with safety to patients with CML and AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Telomerase activity is not a prognostic factor in chronic lymphocytic leukemia.

We measured telomerase activity (TA) in bone marrow samples from 214 patients with CLL and correlated it with patients' characteristics and survival. In >50% of cases (126/214; 59%) no detectable TA was found. There was no difference in TA between previously treated (n = 153) and untreated (n = 61) patients (P = 0.4), or patients with various Rai (0-IV) stages (P = 0.85). TA correlated significantly with white blood cell and lymphocyte count (P = 0.02 and 0.01, respectively) but not with bone marrow cellularity, beta2-microglobulin (beta2M), or other patient characteristics. Patients who had no TA had slightly lower beta2M and lower lymphocyte counts (P = 0.5 and 0.04, respectively) as compared with patients with detectable TA. However, there was no correlation between TA and survival. This data suggests that TA may not play a significant role in the clinical behavior of CLL.

Adult↗

PubMed2004

Extramedullary relapse in a patient with acute promyelocytic leukemia: successful treatment with arsenic trioxide, all-trans retinoic acid and gemtuzumab ozogamicin therapies.

Acute promyelocytic leukemia (APL) is characterized by the presence of the t(15;17) translocation, resulting in the PML-RAR fusion protein. Standard treatment consists of the combination of all-trans retinoic acid (ATRA) with an anthracycline that results in complete remission (CR) rates in excess of 90%. Recently, several new agents have been shown to have clinical activity in APL. These include a liposomal formulation of ATRA (lipo-ATRA), and gemtuzumab ozogamicin (GO). Herein, we report a patient with APL who relapsed with extramedullary disease 2.5 years after lipo-ATRA therapy and was successfully treated with the sequence of A2O3, ATRA, and GO and we summarize our experience with patients with isolated extramedullary relapse in APL.

Aminoglycosides↗

PubMed2004

Hematopoietic recovery following induction therapy of acute leukemias: prognostic implications and a new look at the definition of remission.

Adult patients with acute leukemia may expect relatively high initial response rates with chemotherapy, but most will ultimately relapse and die from their disease. Prognostic models based mostly on pretreatment factors have been established and attempt to identify good- and poor-prognosis patients to assign them to risk-adapted therapies. Although achievement of a complete response (CR) is still the most significant clinical endpoint for survival, criteria for CR are arbitrarily defined. Besides the questionable numerical cut-off points that characterize CR, remission is not an all-or-none phenomenon. The shorter the time to CR, the better is the long-term outcome in chemotherapy-treated patients. Response during therapy can thus supplement pretreatment prognostic information. Shorter time to platelet recovery in patients achieving CR has been demonstrated to be associated with longer overall and disease-free survival in patients with acute lymphoblastic leukemia (ALL), including Philadelphia chromosome-positive ALL. Focusing on hematpoietic recovery may reflect a multitude of biological processes that occur during response to therapy and provide important information about the host's ability to fight and contain residual leukemic cells. It may complement current approaches to measuring minimal residual disease by flow cytometry and polymerase chain reaction (PCR).

Blood Platelets↗

PubMed2004

Management guidelines for use of alemtuzumab in B-cell chronic lymphocytic leukemia.

An expert opinion roundtable held August 8-9, 2002, brought together clinicians with the most extensive experience with the use of alemtuzumab to pool knowledge and develop treatment goals and guidelines for optimal therapy. By sharing our collective experience, we have been able to formulate recommendations for current clinical practice, which are included in this report, and have emphasized results that have implications for future practice. Guidelines for the management of acute "first-dose" events, prophylaxis for infection, detection and treatment of cytomegalovirus reactivation, and hematologic support are presented, with emphasis on allowing patients to proceed smoothly through therapy while maximizing therapeutic benefit. Management of adverse events is facilitated by the predictable timing of their appearance. In general, hematologic adverse events are transient, manageable, and reversible. Clinicians should be cautious of prematurely terminating treatment at 4-6 weeks in patients whose disease responds to treatment. Although resolution of peripheral blood lymphocytosis occurs early in most patients, bone marrow is unlikely to be clear of disease. In particular, grade 4 neutropenia at this time is common and, because it is manageable, it is not an indication to discontinue treatment. The eradication of minimal residual disease from blood and bone marrow observed with alemtuzumab therapy is a major step forward in the treatment of B-cell chronic lymphocytic leukemia. Combination therapies such as alemtuzumab/fludarabine with the potential to maximize eradication at all disease sites should be systematically investigated. Because high response rates and few complications are observed in previously untreated patients, the use of alemtuzumab earlier in therapy may provide optimum benefit to patients.

Aged↗

PubMed2003

High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia.

Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] < 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P =.0005), major molecular response (QPRC < 0.05%; P =.00001), and complete molecular response (undetectable BCR-ABL; P =.001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML.

Adolescent↗

PubMed2003

Imatinib mesylate therapy improves survival in patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in the chronic phase: comparison with historic data.

BACKGROUND: The International Randomized study of Interferon-alpha plus cytarabine (IFN-alpha plus ara-C) versus STI571 (imatinib mesylate) [IRIS trial] in patients with newly diagnosed Philadelphia chromosome (Ph)-positive, chronic-phase chronic myelogenous leukemia (CML) has not shown (to date) a survival advantage for imatinib. This was most likely because approximately 90% of patients receiving IFN-alpha plus ara-C changed to imatinib therapy after a median of 8 months into therapy. METHODS: The authors analyzed the results with imatinib therapy in patients with newly diagnosed Ph-positive CML in chronic phase and compared their outcome with patients who received IFN-alpha regimens. A total of 187 patients with Ph-positive CML in early chronic phase treated with imatinib were compared with a historic group of 650 similar patients treated with IFN-alpha regimens from 1982 until 1997. RESULTS: Patients who received imatinib were significantly older and had significantly more bone marrow basophilia and less leukocytosis. The complete cytogenetic response (Ph 0%) rates were better with imatinib (81% vs. 32%; P < 0.001), as were the survival rates (30-month estimated survival rates 98% vs. 88%; P = 0.01). A multivariate analysis of the total study group of 837 patients identified imatinib therapy to be a significant independent favorable prognostic factor for survival (P = 0.01). CONCLUSIONS: The current study is the first to indicate the survival advantage of imatinib compared with IFN-alpha, the previous standard of care, in patients with early chronic-phase CML.

Administration, Oral↗

PubMed2003

Pharmacokinetics and pharmacodynamics of plasma clofarabine and cellular clofarabine triphosphate in patients with acute leukemias.

PURPOSE: The purpose of our study was to investigate the pharmacology of clofarabine and its triphosphate and the pharmacodynamic actions in circulating blasts obtained from acute leukemia patients who entered a Phase I clinical trial of clofarabine. EXPERIMENTAL DESIGN: Adults with refractory acute leukemias including lymphoblastic (ALL), myelogenous (AML) and chronic myelogenous leukemia in blastic phase (CML-BP) received clofarabine from 4 mg/m(2) to 55 mg/m2/day for 5 days as a 1-h i.v. infusion. A total of 26 of the 32 patients were studied for pharmacological investigations. RESULTS: The maximum tolerated dose was 40 mg/m2/day for 5 days. Plasma pharmacology studies done in 25 patients indicate a linear increase in the plasma clofarabine concentration with increasing doses. At 40 mg/m2 the median plasma clofarabine level was 1.5 micro M (range, 0.42-3.2 micro M; n = 7). Cellular pharmacokinetic studies done at the end of the first clofarabine infusion in 26 patients appeared dose proportional but showed a wide variation in the concentrations of clofarabine triphosphate. At the maximum tolerated dose, the concentration was a median 19 micro M (range, 3-52 micro M). In the majority of cases, more than 50% of the analog triphosphate was present at 24 h after infusion. Compared with clofarabine triphosphate concentration, the endogenous level of dATP was low, resulting in a favorable ratio of analog triphosphate:normal deoxynucleoside triphosphate (dNTP) for incorporation into DNA. In association with the accumulation of triphosphate, there was a decrease in DNA synthesis. At 40- and 55-mg/m2 doses, the inhibition of DNA synthesis was maintained to 24 h. CONCLUSIONS: Clofarabine at the maximum tolerated dose was effective with regard to inhibition of DNA synthesis and decline in circulating leukemia blasts. Given the clinical activity of clofarabine in adult acute leukemias, it is of interest to conduct a detailed characterization of the cellular pharmacology of clofarabine triphosphate and its relationship to clinical responses.

Adenine Nucleotides↗

PubMed2003

Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies.

Decitabine (5-aza-2'-deoxycytidine) inhibits DNA methylation and has dual effects on neoplastic cells, including the reactivation of silenced genes and differentiation at low doses and cytotoxicity at high doses. We evaluated, in a phase 1 study, low-dose prolonged exposure schedules of decitabine in relapsed/refractory leukemias. Patient cohorts received decitabine at 5, 10, 15, or 20 mg/m2 intravenously over one hour daily, 5 days a week for 2 consecutive weeks, doses 5- to approximately 30-fold lower than the maximum tolerated dose (MTD). There were 2 groups that also received 15 mg/m2 daily for 15 or 20 days. A total of 50 patients were treated (44 with acute myelogenous leukemia [AML]/myelodysplasia [MDS], 5 with chronic myelogenous leukemia [CML], and 1 with acute lymphocytic leukemia [ALL]), and the drug was well tolerated at all dose levels, with myelosuppression being the major side effect. Responses were seen at all dose levels. However, the dose of 15 mg/m2 for 10 days appeared to induce the most responses (11 of 17 or 65%), with fewer responses seen when the dose was escalated or prolonged (2 of 19 or 11%). There was no correlation between P15 methylation at baseline or after therapy and response to decitabine. We conclude that decitabine is effective in myeloid malignancies, and low doses are as or more effective than higher doses.

Adolescent↗

PubMed2003

Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate.

Imatinib mesylate, an inhibitor of the Bcr-Abl tyrosine kinase, has modest activity in refractory/relapsed Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia (ALL). Use of concurrent chemotherapy and imatinib mesylate in newly diagnosed Ph-positive ALL was explored. There were 20 patients who received hyper-CVAD (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and imatinib mesylate followed by imatinib mesylate-based consolidation/maintenance therapy. Of these patients, 11 had de novo disease, 4 were primary failures after induction (without imatinib mesylate), and 5 were in complete remission (CR) after induction (without imatinib mesylate). All 15 patients treated for active disease achieved CR. Within a median of 3.5 months in first CR, 10 patients underwent allogeneic stem cell transplantation (SCT). One patient relapsed after matched related SCT. The other 9 patients remained alive in CR with median follow-up of 12 months after SCT (range, 1+ to 17+ months). Among 10 patients ineligible for (no donor or older age) or refusing allogeneic SCT, 1 patient relapsed after one year. There were 5 patients who remained alive in continuous CR for a median of 20 months (range, 4+ to 24+ months), with 2 older patients dying in CR at 15 and 16 months of comorbid conditions. Molecular CRs were achieved in both groups (SCT or no SCT). Outcome with hyper-CVAD and imatinib mesylate appears better than with prior regimens; continued accrual and longer follow-up of the current cohort is needed.

Adolescent↗

PubMed2003

The biology and therapy of adult acute lymphoblastic leukemia.

BACKGROUND: Much progress has been made in understanding the biology of acute lymphoblastic leukemia (ALL). This has translated into the recognition of several subgroups of ALL and the institution of risk-adapted therapies. New therapies are emerging based on the definition of specific cytogenetic-molecular abnormalities. METHODS: A review from the English literature, including original articles and related reviews from Medline (Pubmed) and abstracts based on publication of meeting material, was performed. RESULTS: Changes in the pathologic classification of ALL have led to therapeutic consequences. Adaptation of successful treatment strategies in children with ALL has resulted in similar complete response rates in adults. Prognosis has especially improved in mature-B-cell and T-lineage ALL. The role of tyrosine kinase inhibitors in Philadelphia chromosome-positive ALL was evaluated in the current study. However, regardless of the ALL subgroup, long-term survival of adults is still inferior to that in children. CONCLUSIONS: Intense clinical and laboratory research is attempting to close the gap in outcome between children and adults with ALL. Investigations are focusing on 1) refinement of the basic treatment stratagem of induction, consolidation, and maintenance; 2) expansion of risk-based, subgroup-oriented therapies; 3) assessment of minimal residual disease, its impact on disease recurrence, and its practical implications in clinical practice; 4) salvage strategies; 5) the role of stem cell transplantation in ALL; and 6) the development of new drugs based on a better understanding of disease biology.

Adult↗

PubMed2003

Analysis of the impact of imatinib mesylate therapy on the prognosis of patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha regimens for early chronic phase.

BACKGROUND: The effect on prognosis of adding imatinib mesylate to the treatment of patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) has not been explored fully. The objective of the current study was to evaluate the benefit of adding imatinib to the treatment sequence of patients with early chronic phase Ph-positive CML who received interferon alpha (IFN)-based regimens as frontline therapy. METHODS: A total of 201 patients with early chronic phase Ph-positive CML who were treated on our 3 recent frontline IFN-based programs and were impacted early by the availability of sequential therapy with imatinib were analyzed. Their outcome was compared with that of a historical control group of 293 patients treated from 1982 until 1990 who were treated with IFN programs for early chronic phase CML and who did not have the opportunity of early access to imatinib (because it was not available during that period). Multivariate analysis was used to evaluate the independent effect of imatinib therapy on survival. RESULTS: Of 201 patients who were treated, 159 patients (79%) had their regimen changed sequentially to imatinib after a median duration of 14 months of IFN therapy. Of 139 patients who continued evaluation at our institution, 101 patients (73%; 64% of the total group) achieved a complete cytogenetic response, and 20 of 80 patients analyzed (25%; 10% of the total group) had no disease according to molecular studies (quantitative polymerase chain reaction studies). The estimated 5-year survival rate for the total study group of 201 patients was 86%. Survival of this group was significantly superior to the historic control group of IFN-treated patients who did not have the benefit of imatinib (P = 0.03). The trend also was observed within defined CML risk groups. Imatinib therapy was confirmed as an independent, significant, favorable prognostic factor for survival by multivariate analysis, after accounting for the independent prognostic effect of pretreatment prognostic factors (P = 0.005). CONCLUSIONS: The current analysis is the first to indicate the independent, favorable effect of imatinib on the survival of patients with Ph-positive CML.

Aged↗