Article

Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia

Department of Pediatrics, University of Washington Seattle, Seattle, Washington, United States
Blood (Impact Factor: 10.43). 05/2007; 109(7):2791-3. DOI: 10.1182/blood-2006-04-019836
Source: PubMed

ABSTRACT Relapse occurs frequently after allogeneic hematopoietic cell transplantation (HCT) for treatment of high-risk Philadelphia chromosome-positive (Ph+) leukemia. Administration of imatinib early after HCT might provide an effective approach for preventing recurrent Ph+ leukemia, but the feasibility of this approach has not been systematically tested. Twenty-two patients, 15 with Ph+ acute lymphoblastic leukemia and 7 with high-risk chronic myelogenous leukemia, were enrolled in a prospective study and given imatinib from the time of engraftment until 365 days after HCT. Before day 90, adults (n = 19) tolerated a median average daily imatinib dose of 400 mg/d (range, 200-500 mg/d), and children (n = 3) tolerated 265 mg/m2/d (range, 200-290 mg/m2/ d). The most common adverse events related to imatinib administration were grade 1-3 nausea, emesis, and serum transaminase elevations. We conclude that imatinib can be safely administered early after myeloablative allogeneic HCT at a dose intensity comparable to that used in primary therapy.

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    • "An excellent response measured by MRD detection may identify a subgroup with a good survival following transplantation (Cazzaniga et al, 2002; Lee et al, 2009). Additional post-transplant tyrosine kinase inhibitor therapy is well tolerated and may be an important factor in maintaining remission (Carpenter et al, 2007). "
    British Journal of Haematology 02/2011; 152(3):347-9. DOI:10.1111/j.1365-2141.2010.08465.x · 4.96 Impact Factor
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    • "Promising novel therapeutics for lymphoma, including immunotherapeutic and radioimmunotherapeutic agents might be incorporated into novel conditioning regimens targeting specific diseases, and post-transplant maintenance therapy may further improve outcomes. Similarly, for Philadelphia chromosome positive acute leukaemias, tyrosine kinase inhibitors have already shown promise in post-transplant maintenance after conventional transplantations (Carpenter et al, 2007) and require examination in the cord blood setting. As additional molecular aberrations are identified in specific acute leukaemias, the potential benefit of targeted therapies (i.e. "
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    British Journal of Haematology 10/2009; 147(2):207-16. DOI:10.1111/j.1365-2141.2009.07782.x · 4.96 Impact Factor
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    • "In a separate prospective study, 15 patients with Ph+ ALL were treated with imatinib for 1 year after allo-HSCT, with dosing initiated at 400 mg/d in adults and 260 mg/m 2 in children. Following imatinib treatment, 87% remained in CHR and the molecular remission rate increased from 46% prior to transplant to 80% at last followup (Carpenter et al, 2007). These studies indicate that imatinib treatment post allo-HSCT may prolong remission duration. "
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    ABSTRACT: Acute lymphoblastic leukaemia (ALL) is a heterogeneous disease that is often associated with several chromosomal and molecular abnormalities. Patients who have the Philadelphia (Ph) chromosome and associated BCR-ABL1 oncogene have a particularly poor prognosis. Currently, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only known curative treatment for Ph+ ALL and facilitating allo-HSCT in eligible patients is a key treatment goal. However, many patients relapse after allo-HSCT, particularly those with measurable residual disease prior to transplantation, and a significant percentage of patients are ineligible for allo-HSCT, particularly older patients. Hence, many patients require additional/alternative therapies to prolong survival. Studies are ongoing to determine the most effective first-line drug regimens for patients who subsequently undergo allo-HSCT and ineligible patients. Tyrosine kinase inhibitors targeted to Bcr-Abl are important novel therapies for Ph+ ALL. Although imatinib administered in combination with chemotherapy is established as the current first-line strategy, relapse is common, even among allo-HSCT recipients. Emerging data indicate that more potent multi-targeted kinase inhibitors (including dasatinib, nilotinib, and bosutinib) have promising efficacy in the first- or second-line setting. Here, the evidence base for existing drug treatments for Ph+ ALL is discussed and emerging therapeutic strategies are explored.
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