Approximately half of respondents would treat this patient with a tyrosine kinase inhibitor.  Treatment with imatinib mesylate has been associated with 62% complete molecular response in patients treated for molecular or cytogenetic relapse of CML after transplant¹ with lower rates for patients with hematological relapse.²  Treatment with alpha interferon has been reported to result in 65% complete cytogenetic response (CCR) with complete molecular remission also achieved in some patients.^3,4   However, both interferon and imatinib responses are usually dependent on continued drug administration.  Only 10-25% of patients attaining molecular remissions with imatinib are able to discontinue therapy after 6-24 months and retain their molecular remissions.¹  Thus, these approaches do not augment immunologic control of CML and true disease eradication is unlikely.

While second transplantation from the other HLA-matched sibling could be considered, the patient has full donor chimerism, did experience acute GVHD, and had disease control for 10 years.  I would defer serious consideration of transplantation from a second donor until it was clear there was no immunologic benefit to using the first donor.

Forty-four percent of respondents would treat this patient with donor lymphocyte infusion (DLI).  DLI represents an effective approach for management of recurrent CML after HCT with the highest durable responses reported in this setting.  An 85% molecular response rate is seen in patients treated for cytogenetic or molecular relapses alone.  However, DLI is associated with several serious risks, including graft-versus-host disease (6% - 33%), myelosuppression (6% - 33%), and treatment-related mortality (4% - 20%).  Low dose DLI minimizes some of these risks.

I would recommend treating this patient with low dose of DLI at 1 x 10⁶ CD3/kg because of the high durable responses and low toxicity reported with this approach.^5-7  I would monitor her blood for bcr/abl by PCR and FISH at monthly intervals, repeating a bone marrow at three month intervals for 6-12 months and monitoring her CBC at weekly intervals.  I would also monitor her closely for any evidence of GVHD including liver function tests and physical examinations at 2-4 week intervals.  If no response is observed after 6 months following DLI, a 4-8 week course of interferon (1 x 10⁶ units daily) is reasonable to try to optimize the graft-versus-leukemia effect of DLI.  If there is still no response, a second dose of DLI (1 x 10⁷ CD3/kg) could be considered if there are no contraindications such as active GVHD.  Concurrent treatment with interferon-a or tyrosine kinase inhibitors plus DLI is an option and, if initiated, I would recommend indefinite administration, although this may not be necessary in the context of DLI.