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Bone Marrow Transplant for Children with CML Presenting in Blast Crisis in the Era of TKIs
Although management of CML has changed dramatically in the era of tyrosine kinase inhibitors (TKIs), there is still a dichotomy in outcome for patients who present in Chronic Phase (CP) versus Accelerated Phase (AP) or with acute leukemic blast crisis (BC) CML. For patients with CP-CML prognosis is excellent when treated with TKIs alone while for patients with AP- or BC-CML, the goal of therapy is to get back into chronic phase CML and then proceed to an allogeneic bone marrow transplant (allo-BMT). Even with this intensified approach, patients with advanced CML historically have had a poor prognosis with an OS of ~65% one year after allo-BMT. In the pre-TKI era roughly 20% of patients with CML would progress to blast crisis. This has declined to ~1% in the TKI era, but the overall survival of these patients has not changed.
METHODS
After obtaining IRB approval, we reviewed the medical records of all patients evaluated for allo-BMT for CML at our institution between January 1, 2010 and June 30, 2013. There were five children who presented with CML in accelerated phase or blast crisis.
RESULTS
Five patients developed advanced stage CML during the observed period. Ages ranged from 12-18 years old at the time of transplant (median age 13). The male:female ratio was 4:1. 4/5 presented in lymphoid blast crisis and 1/5 in accelerated phase. All patients were started on imatinib though two required a second or third line TKI to achieve stable phase prior to transplant. Prior to transplant, all patients were in at least a morphologic and cytogenetic remission; 3/5 also were in a molecular remission. 4/5 patients received a matched unrelated donor transplant; the other underwent a matched sibling transplant. Conditioning was TBI (1440 cGy) and Cyclophosphamide. GVHD prophylaxis was Cyclosporine and Methotrexate with Prednisone added for unrelated donors per our institutional standard. Median day of engraftment was + 24. 1/5 patients developed stage 2-4 aGVHD and none developed grade 3-4 aGVHD. TKI’s were restarted in all patients (median day 114) with a goal of continuing until 2 years post transplant. One patient developed joint pain and night sweats which resolved with dose reduction, another myelosuppression which resolved with TKI holiday and dose reduction. All patients are alive and remain in molecular remission with undetectable BCR-ABL transcript with an average duration of remission of 435 days [190-1347].
DISCUSSION
The outcomes of children with CML presenting in blast crisis in the era of TKIs has not been previously documented. The use of TKI’s pre- and post-transplant may lead to improved disease free survival for this group. Disease control prior to SCT and close monitoring remain essential for optimal outcome.