Molecular Monitoring in ASCT

Notwithstanding the recent excitement regarding imatinib mesylate, ASCT is the only proven curative therapy for CML, with cure rates of 70% to 80% in young (age <40 years), chronic-phase patients that have HLA-matched donors and undergo transplantation within 1 year of diag-

Table 35-2. Responses to Treatment for Early Chronic-Phase CML

Therapeutic Response (% patients)

Cytogenetic

Molecular

Standard Therapies

Hematologic (complete)

Major

Complete

Major

Complete

ASCT

Chemotherapy Interferon-a Imatinib mesylate

Cure

Data summarized and averaged from a variety of studies.13,14-18,19

With regard to molecular testing, only in ASCT is the endpoint complete molecular remission, while for interferon-a and imatinib mesylate, the goal is a response, with complete molecular remission rarely attained. However, reports of molecular responses vary widely with different definitions and test methods, with some studies16 reporting a complete molecular response rate of up to 28%. Major molecular response is currently best defined as a >3log reduction in % BCR-ABL/ABL.

nosis.13'20 Despite the curative success of ASCT, the associated morbidity and mortality are significant; furthermore, the majority (~65%) of young patients do not have a suitably matched donor, while older patients are often suboptimal candidates for transplantation.

After transplantation, molecular testing serves two functions, first to document remission and then to monitor for disease relapse. Molecular monitoring for relapse permits early disease detection (prior to hematologic or cytoge-netic manifestations), when the tumor burden is low and presumably more amenable to treatment. At molecular relapse, therapeutic options include the withdrawal of immunosuppressive agents, the administration of donor lymphocyte infusions (DLI), or both, with an increased likelihood of response achieved when DLI are administered prior to overt hematologic relapse.21

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