Article

Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL)

University Hospital Essen, Essen, North Rhine-Westphalia, Germany
Cancer (Impact Factor: 4.89). 05/2007; 109(10):2068-76. DOI: 10.1002/cncr.22631
Source: PubMed

ABSTRACT

Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known.
Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (Ind(IM)) or multiagent, age-adapted chemotherapy (Ind(chemo)). Imatinib was subsequently coadministered with consolidation chemotherapy.
In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to Ind(IM) and 50% in patients allocated to Ind(chemo) (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Ind(chemo); none failed imatinib induction. Severe adverse events were significantly more frequent during Ind(chemo) (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% +/- 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002).
In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction.

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Available from: Matthias Stelljes, Nov 20, 2014
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    • "These genetic alterations are linked to distinct clinical profiles and show specific interaction with other mutation types [8]. Following the success of the tyrosine kinase inhibitor (TKI) imatinib in chronic myeloid leukemia (CML), research focused on targeted therapy strategies for Ph-positive ALL and other ALL subtypes [9] [10] [11] [12] [13]. Imatinib has since become part of preand posttransplant treatment for patients with Ph-positive ALL [13] [14]. "
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    • "These genetic alterations are linked to distinct clinical profiles and show specific interaction with other mutation types [8]. Following the success of the tyrosine kinase inhibitor (TKI) imatinib in chronic myeloid leukemia (CML), research focused on targeted therapy strategies for Ph-positive ALL and other ALL subtypes [9] [10] [11] [12] [13]. Imatinib has since become part of preand posttransplant treatment for patients with Ph-positive ALL [13] [14]. "

    Full-text · Article · Jan 2011 · Advances in Hematology
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    • "In particular, CD20 antibody treatment has been successfully introduced in B-ALL [1]. In addition, signal transduction inhibitors such as the tyrosine kinase inhibitor Imatinib have been used in BCR-ABL positive ALL patients leading to improved response rates [2,3]. Investigation of further targeted therapy approaches e.g. "
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