Abstract
Abstract 2038
Cytogenetic abnormalities in leukemic blasts at time of diagnosis are the most important prognostic factors in acute myelogenous leukemia (AML). However, approximately 50% of patients (pts) with AML have normal cytogenetics (NC-AML). Within this population, the presence of somatic mutations further refines the prognosis. Mutations such as the internal tandem duplication of FLT-3 (FLT-3 ITD), and mutations in NPM1 and IDH1 have been all been shown to have significant prognostic value in determining response to chemotherapy and overall survival (OS). FLT-3 ITD is present in approximately 30% of pts with NC-AML and is considered the most significant predictor of poor prognosis following chemotherapy. However, it is not clear whether the presence of FLT-3 ITD influences the outcome of patients who undergo hematopoietic stem cell transplant (HSCT). We therefore performed a retrospective analysis of all adult patients with NC-AML and FLT-3 ITD present at time of diagnosis who underwent HSCT at MSKCC between 2007 and 2012.
A total of 196 pts with AML underwent HSCT during this period. For this analysis, we excluded 112 pts with abnormal cytogenetics, 5 pts who had no cytogenetic testing performed, and 27 pts with normal cytogenetics who did not have molecular analysis performed.
A total of 52 pts with normal cytogenetics had molecular testing done; of these, 35 were FLT-3 negative (67%) and 17 were FLT-3 positive (33%). Characteristics of the 2 groups are shown below:
| FLT-3 Negative (n=35) | FLT-3 Positive (n=17) | |
|---|---|---|
| Median age years (range) | 55 (27–57) | 55 (19–71) |
| M/F | 22/13 | 7/10 |
| Transplanted in CR1 | 22 (63%) | 13 (76%) |
| Transplanted in CR-2 | 5 (14%) | 1 (6%) |
| Transplanted in other | 8 (23%) | 3 (18%) |
| Donor: Matched sib donor | 15 (43%) | 6 (35%) |
| Matched unrelated donor | 11 (31%) | 6 (35%) |
| Mismatched unrelated donor | 9 (26%) | 5 (29%) |
| Source: Bone marrow | 0 | 1 (6%) |
| Mobilized blood | 32 (91%) | 12 (71%) |
| Cord blood | 3 (9%) | 4 (24%) |
| Unmodified transplant | 10 (29%) | 6 (25%) |
| T-depleted transplant | 25 (71%) | 11 (65%) |
| Median f/u mos (range) | 22 (2–22) | 26 (3–44) |
| Relapses | 3 (9%) | 2 (12%) |
| Death (all causes) | 11 (31%) | 4 (24%) |
| Overall survival at 2 years: | 70% | 82% |
| FLT-3 Negative (n=35) | FLT-3 Positive (n=17) | |
|---|---|---|
| Median age years (range) | 55 (27–57) | 55 (19–71) |
| M/F | 22/13 | 7/10 |
| Transplanted in CR1 | 22 (63%) | 13 (76%) |
| Transplanted in CR-2 | 5 (14%) | 1 (6%) |
| Transplanted in other | 8 (23%) | 3 (18%) |
| Donor: Matched sib donor | 15 (43%) | 6 (35%) |
| Matched unrelated donor | 11 (31%) | 6 (35%) |
| Mismatched unrelated donor | 9 (26%) | 5 (29%) |
| Source: Bone marrow | 0 | 1 (6%) |
| Mobilized blood | 32 (91%) | 12 (71%) |
| Cord blood | 3 (9%) | 4 (24%) |
| Unmodified transplant | 10 (29%) | 6 (25%) |
| T-depleted transplant | 25 (71%) | 11 (65%) |
| Median f/u mos (range) | 22 (2–22) | 26 (3–44) |
| Relapses | 3 (9%) | 2 (12%) |
| Death (all causes) | 11 (31%) | 4 (24%) |
| Overall survival at 2 years: | 70% | 82% |
Both groups had similar clinical and transplant characteristics, relapse rates, and OS (p=NS in all categories). We conclude that in this relatively small group of pts (1) HSCT appears to overcome the negative prognostic effect of FLT-3 ITD and (2) use of a T cell depleted graft does not influence transplant outcomes. A larger cooperative group analysis will be needed to confirm these findings.
No relevant conflicts of interest to declare.
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