Patients (pts) undergoing allogeneic stem cell transplantation for AML or high-risk MDS usually receive standard induction chemotherapy first, with the goal of achieving a complete remission (CR) or at least best response to conventional chemotherapy. This disease control is often necessary to bridge the time needed for identifying an unrelated donor in case no sibling donor is available, although CR is no absolute prerequisite for successful allografting following RIC (

Bertz et al., J Clin Onc 21:1480, 2003
). Recently, non-intensive treatment with low-dose azanucleosides has been developed for older pts with high-risk MDS. Low-dose Decitabine (DAC) shows a particularly interesting activity in inducing cytogenetic remissions (38%) in MDS pts with poor-risk cytogenetics. The role of DAC prior to allografting has not yet been determined. Here we report our single-center experience of 10 consecutive pts treated with low-dose DAC for MDS (n=5), CMML (n=2) or AML (n=3). The median number of DAC courses given was 3 (range 1–13), with CR and PR as best response in 4 and 1 pt respectively, stable or persistent disease in 4 and 1 pt, resp. Allografting was either done as consolidation at time of best response (n=4) or as salvage for relapsed/refractory disease (n=6). Median age at time of allografting was 65 years (range 63–71). After conditioning with either FBM (n=8) or Flu/2 Gy (n=2), pts were transplanted from either matched sibling (n=3) or unrelated donor (n=7). One pt died before engraftment on day +13 due to infection. The other 9 pts engrafted, and no unexpected toxicities were noted. 6/9 pts have died either due to relapse (n=3) or infection in CR (n=3). Three pts are alive in CR at the time of this report (+1, +10, +26 months following transplant). Prior to transplantation two of them were in PR and CR following 2 and 8 courses of DAC, respectively, one had progression of CMML after 5 courses. In conclusion, we show that RIC and allografting in older pts with myeloid neoplasia following DAC treatment is feasible, and no unexpected toxicities have occurred. DAC pretreatment can induce improvement or even remission with negligible nonhematopoietic toxicity, thus bridging the time period of donor search prior to allografting. The allogeneic option in these pts should be explored more often and response to DAC and transplant risk-assessment (comorbidities, performance status etc.) will likely be major determinants of optimal timing of allografting in this setting.

Topics:
conditioning (psychology), decitabine, hematopoietic stem cell transplantation, older adult, brachial plexus neuritis, allografting, toxic effect, transplantation, disease remission, infections

Disclosures: Consultant for MGI Pharma.

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2006, The American Society of Hematology
2006
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