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Introduction
The effect of early response of AML to induction chemotherapy on transplant outcomes is not well-characterized. We hypothesize that higher blast count in an early post-induction bone marrow biopsy (Day 14 marrow) is associated with inferior outcomes after allogeneic HCT for AML in first remission (CR1).
Methods
We retrospectively reviewed 42 AML patients (median age 60 years, range 29-71) treated at Seidman Cancer Center from 2008 to 2014 who had early marrow evaluation (median 13 days, range 7-14) after induction chemotherapy and received allogeneic transplant in CR1. Blast % was calculated from 200 total nucleated cells counted on marrow aspirate. Variables examined included age, performance status, de novo vs. secondary AML, cytogenetics, FLT3 / NPM status, incomplete count recovery (CRi), number of induction cycles, conditioning regimen, graft source, minimal residual disease (MRD) and presence of acute and chronic graft-versus-host disease (GVHD). Relapse-free survival (RFS) was defined as time from transplant to relapse or death in remission. Survival distribution from time of transplant was estimated using Kaplan-Meier methods and difference of survival and RFS between groups was examined by log-rank. Effect of continuous variables on survival was estimated using Cox model.
Results
Patient characteristics are summarized in Table 1. RFS at 2 years did not differ between those with <6% or >5% marrow blasts at Day 14 (58 vs. 58%, p=.7). Survival at 2 years also did not differ between the 2 groups (43 vs. 49%, p=1; Figure 1). Use of different blast cutoff values did not elicit a difference in 2-year RFS or survival. A higher blast percentage did not result in increased hazard of death (HR 1, p=.72). Having ≥2 induction cycles (32 vs. 53%, p=.18), graft source of cord blood vs. other (28 vs. 58%; p=.16), and ECOG performance status 1 vs. 0 (27 vs. 42%; p=.32) may be associated with inferior survival at 2 years, although this did not reach statistical significance likely due to limited sample size.
Conclusion
Apparent chemotherapy resistance based on higher residual blast percent early after induction chemotherapy likely carries no significant risk of adverse outcome after AML transplant in first remission. Utility of the Day 14 marrow evaluation in predicting outcomes after allogeneic transplant in CR1 remains unclear.
Table 1.
Variable | n | Mean (STD) | Median (range) |
Age (yr) | 42 | 57.1 (11.5) | 59.5 (29, 71) |
Early marrow blast % | 42 | 21.4 (27.1) | 6 (0, 90) |
Factor | Frequency | Factor | Frequency |
Secondary AML |
| Cytogenetics |
|
N | 33 | Favorable/intermediate | 1/16 |
Y | 9 | Unfavorable/unknown | 23/2 |
FLT3 |
| NPM |
|
Negative | 20 | Negative | 25 |
Positive | 9 | Positive | 2 |
# of inductions |
| MRD present |
|
1 | 20 | N | 28 |
2 | 21 | Y | 11 |
3 | 1 | Graft |
|
Consolidation |
| Matched sibling | 14 |
N | 11 | Matched unrelated | 16 |
Y | 31 | Cord | 31 |
CR incomplete |
| Myeloablative |
|
N | 25 | N | 35 |
Y | 17 | Y | 7 |
