Treatment of Chronic Myeloid Leukemia Following Imatinib Resistance

Abstract

The introduction of the BCR-ABL inhibitor imatinib revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, resistance to imatinib has become a clinically significant issue, limiting its long-term efficacy. Numerous mechanisms have been associated with imatinib resistance, including mutations to the BCR-ABL gene, increased production of BCR-ABL, and activation of BCR-ABL-independent pathways (e.g., SRC-family kinases [SFKs]). Resistance to imatinib has driven the development of second-line therapies, such as dasatinib, a dual BCR-ABL/SFK inhibitor more potent than imatinib at targeting BCR-ABL. Dasatinib is approved for the treatment of patients with imatinib-resistant and -intolerant CML and Philadelphia chromosome-positive acute lymphoblastic leukemia. Nilotinib, an analog of imatinib, more potent than its parent compound, is another approved agent for patients with imatinib-resistant or -intolerant CML in the chronic or accelerated phase. Nurses must be aware of what constitutes a requirement for treatment change and the mechanisms of resistance that inform the choice of second-line agents. Oncology nurses also must ensure that patients have been educated appropriately to understand imatinib resistance and second-line treatment options. This article explores the mechanisms and identification of resistance and treatment options for when resistance occurs, as well as nursing implications.

Reversal of Human Multi‐Drug Resistance Leukaemic Cells by Stemofoline Derivatives via Inhibition of P‐Glycoprotein Function

“…VER and CSA have been reported as MDR modulators , but they have limited clinical use due to their side effects, such as hypertension and immunosuppression . Tyrosine kinase inhibitors (TKI) are a class of commercial, adjuvant agents used against MDR cancers, for example imatinib, which has shown adverse effects in the thyroid gland and the heart and also can lead to TKI resistance cancers . Our recent studies aimed to discover and develop high potential MDR modulators that have no toxicity or adverse drug effects.…”

Clinical Significance as It Relates to Evidence‐Based Practice

“…The recommendations varied in their level of specificity, from general admonishments for nurses to become more involved in policy making to prescriptive advice with specific recommendations for practical application. Examples of recommendations to guide nursing interventions included recommendations for medication prescribing (Schaffer et al., 2009), treating postsurgical pain (Kokki et al., 2003; Wilson & Helgadottir, 2006), managing medication responses (Bauer & Romvari, 2009; Marrs & Zubal, 2009), and interpreting or implementing protocols, policies, or procedures (Doughty et al., 2006; Farnell et al., 2005; Gilbert et al., 2002; Harrington, 2005; Hogan, 2009; Kurlowicz, 2001; Ruchala et al., 2002; Swanson & Koch, 2010; Zengin & Enc, 2008).…”

“…Outpatient settings were represented by individuals in rehabilitation (Baird et al., 2008; Riegel et al., 2006) or nursing homes (Dowling, Graf, Hubbard, & Luxenberg, 2007; Fjelltun, Henriksen, Norberg, Gilje, & Normann, 2009), and those receiving postsurgical care (Wilson & Helgadottir, 2006) or psychotherapeutic treatment (England, Tripp‐Reimer, & Rubenstein, 2005) in their homes or in outpatient clinics. Inpatient settings were represented by individuals receiving treatment for cancer (Bauer & Romvari, 2009; Cella et al., 2003; Swanson & Koch, 2010) and psychiatric conditions (Bowers, Brennan, Flood, Lipang, & Oladapo, 2006), as well as obstetrical care (Callahan & Hynan, 2002; Simpson, Parsons, Greenwood, & Wade, 2001; Waltman, Brewer, Rogers, & May, 2004), pre‐ and postsurgical care (Gallagher & McKinley, 2009; Kurlowicz, 2001), and intensive care (Happ, Tuite, Dobbin, DiVirgilio‐Thomas, & Kitutu, 2004).…”

Successful Nilotinib Treatment in a Child with Chronic Myeloid Leukemia

“…Moreover, the BCR-ABL protein inhibits DNA repair, causing genomic instability and making the cell more susceptible to developing further genetic abnormalities [ 6 ]. The identification of this protein has made it an ideal target for therapeutic intervention [ 7 ]. Most patients (60%) are diagnosed in the initial chronic phase (CP) of the disease, in which patients experience night sweats, general malaise, diminished appetite, fatigue, and breathlessness.…”