Clofarabine As a Bridge to Allogeneic Stem Cell Transplant at New York-Presbyterian Hospital

Outcomes in patients with relapsed/refractory acute myeloid leukemia or advanced myelodysplastic syndrome with active disease at the time of allogeneic hematopoietic stem cell transplant (HSCT) are generally poor. Published data indicate the purine analog clofarabine can be used for cytoreduction in patients with active disease as a “bridge” to HSCT when followed by a standard conditioning regimen.

At Weill Cornell Medical Center (WC) clofarabine has been used in refractory patients as a bridge to HSCT since 2011. While published studies transplanted patients at cytopenic nadir following clofarabine therapy, WC transplanted patients without regard to cytoreductive response.  

The purpose of this study was to retrospectively examine survival following clofarabine therapy and to determine if cytoreduction affects outcomes. Secondary outcomes included cytoreduction (defined as post-treatment cellularity <20% and blasts <10%), relapse after transplant, and non-hematologic toxicity.

The study included adult patients who received clofarabine 30 mg/m²/day IV x 5 days prior to HSCT between November 2011 and June 2013. Twenty-one patients received a clofarabine bridge; 18 (86%) proceeded to HCST. The three who did not were septic at the scheduled time of transplant. Two patients refused a day 14 bone marrow and were not evaluated for response. Both died post-transplant.

Of the evaluable 16 patients, 8 (50%) are alive and in remission at a median of 3 months (range 2-10). One is alive, but relapsed. Overall, 5 patients (31%) relapsed. Of the 7 patients who died after transplant, median overall survival was 94 days (range 5-188). Causes of death included relapse, sepsis, and engraftment failure.

Eight (50%) patients achieved the pre-defined cytoreductive response. Five are alive and in remission at a median of 5 months (range 3-10). See table 1.

Based on preliminary analysis, cytoreduction with a clofarabine bridge appears to positively affect outcomes of refractory patients who proceed to HSCT. 

Table 1

	Cytoreductive Response n (%)	No Cytoreductive Response n (%)
n=16	8 (50)	8 (50)
Alive at Day 100	5 (31)	6 (38)
Alive, Day 100 Not Reached	1 (25)	1 (25)
Alive, in remission	5 (31)	3 (19)
Alive, relapsed	0 (0)	1 (6)