Clofarabine Salvage in Refractory Acute Myeloid Leukemia Before Allogeneic Stem Cell Tranplant

Introduction: Refractory acute myeloid leukemia (AML) is incurable unless allogeneic stem cell transplant (HCT) is performed. Remission or bone marrow aplasia is not attainable in many and thus they do not proceed to HCT. Clofarabine has been used in these patients but may be associated with increased risk of fungal infection and veno occlusive disease (VOD) and is expensive. In refractory AML patients who fail at least one prior salvage therapy, we administer clofarabine with plan for HCT in bone marrow aplasia. This study reviews outcome in these patients. The ability of clofarabine to achieve aplasia (with or without residual AML) , assess how many patients were able to proceed to HCT and describe the incidence of fungal infection, VOD incidence and relapse free survival after HCT was evaluated.

Patients/Methods: 15 patients with refractory AML received clofarabine between January 1, 2011 and June 30, 2012. Retrospective chart review was performed for demographic data, disease characteristics, pathology results and outcomes data. Specific data on fungal disease, ability to achieve aplastic bone marrow (defined as <10% cellularity approximately 14 days after treatment), subsequent treatment with HCT and mortality data after treatment were collected.

Results: See Table 1. Clofarabine was given alone (8 patients), or in combination with other agents: clofarabine plus cytarabine (5 patients) and clofarabine, cytarabine and filgrastim (2  patients). 2 (13%) patients developed new fungal infection after clofarabine and there was no incidence of VOD.

Conclusion: Patients with refractory AML have a dismal prognosis and better treatment options are needed. This study confirms prior reports that clofarabine is active in refractory AML and can be used as a cytoreductive bridge to HCT in aplasia. 40% of patients with refractory AML treated with clofarabine in this study are alive (range, day 100 to 365) without evidence of disease after HCT.  No increase in fungal infections was noted after clofarabine and no post HCT VOD observed. These results show favorable outcomes for patients with refractory AML given clofarabine salvage with subsequent HCT in aplasia. Future studies comparing clofarabine to other salvage regimens in refractory AML and analysis of cost efficacy are warranted.

TABLE 1: Results for Aplasia and HCT after Clofarabine Salvage	Number (%) Patients	Number (%) Alive (thru 10/1/12)
Patients Receiving Clofarabine	15 (100%)	6 (40%)
+Aplasia	9   (60%)	5 (33%)
+Aplasia,  -AML	5	4 (27%)
+Aplasia , +AML	4	1  (7%)
-Aplasia	6   (40%)	1 (7%)
-Aplasia, -AML	2	1 (7%)
-Aplasia, +AML	4	0 (0%)
		Number (%) Alive after HCT
Patients receiving HCT	10  (67%)	6 (60%) *
+Aplasia	8	5 (50%)
+Aplasia, -AML	6	4
+Aplasia, +AML	2	1 **
-Aplasia	2	1 (10%)
-Aplasia, -AML	2
-Aplasia, +AML	0	0

*range day 100-365

**11 months post HCT