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Introduction:
RIC allogeneic HCT is an evolving post-remission treatment modality for medically complicated patients with AML. Previous reports demonstrated no benefit from consolidation therapy prior to myeloablative (MA) HCT; however, the impact of pre-HCT consolidation therapy in RIC/NMA HCT is largely unknown.
Methods and Patients:
Using the Center for International Bone Marrow Transplant Registry, we studied 604 adults with AML in CR1 undergoing RIC (approximately 33% non-myeloablative (NMA)) HCT from 2000-2010. We evaluated outcomes based on pre-HCT exposure to consolidation chemotherapy (no consolidation versus cytarabine based consolidation). The impact of standard patient, disease, and transplant variables were analyzed. Overall survival (OS), disease free survival (DFS) relapse, and transplant related mortality (TRM) are described.
Of the 604 patients, 402 (67%) received consolidation and 202 (33%) received none. Those who received consolidation therapy had a higher percentage of exposure to 7+3 or similar induction regimens (89% versus 78%, p <0.01), a higher percentage of CR1 after 1 cycle of induction (81% versus 67%%, p <0.01), a higher percentage of intermediate risk karyotype (48% versus 38%, p=0.03), and a higher proportion of ATG or Campath exposure (42% versus 34%, p=0.06). Those receiving no consolidation more frequently received Fludarabine + Melphalan conditioning (25% versus 13%, p=0.01) and had a pre-existing MDS/MPD (34% versus 19%, p <0.01). Donor source and GVHD prophylaxis were similar between groups.
Results:
Univariate analysis revealed similar rates of engraftment, acute and chronic graft versus host disease (GVHD), relapse incidence, TRM, OS and DFS between groups (Table). Multivariate analysis confirmed the lack of impact of pre-HCT consolidation on relapse, TRM, OS, or DFS. Higher (> 2 grams/m2/day) versus lower dose cytarabine did not influence results. Unfavorable karyotype was the main factor associated with higher rates of relapse (HR 1.865, p<0.0001) and was also associated with inferior OS (HR 1.74, p<0.001) and DFS (HR 1.645, p<0.0001).
Conclusion: Post transplant outcomes are not improved by pre-HCT consolidation therapy prior to RIC conditioning. Based on these data, donor searches for eligible patients should begin soon after AML diagnosis to facilitate transition to HCT upon CR1 without delay.
| No consolidation (N=202) | Consolidation (N=402) | p-value | ||
Outcome | N | Prob (95% CI) | N | Prob (95% CI) | p-value |
Grade 3-4 AGVHD | 202 |
| 402 |
|
|
100-day |
| 16 (12-22) |
| 13 (10-16) | 0.27 |
CGVHD | 195 |
| 395 |
|
|
3-year |
| 41 (34 -49) |
| 41(36-47) | 0.96 |
TRM | 197 |
| 393 |
|
|
3-year |
| 28 (22-35) |
| 21 (17-25) | 0.06 |
Relapse | 197 |
| 393 |
|
|
3-year |
| 38 (31-46) |
| 39 (34-45) | 0.84 |
DFS | 197 |
| 393 |
|
|
3-year |
| 34 (27-41) |
| 41 (35-46) | 0.15 |
Overall Survival | 202 |
| 402 |
|
|
3-year |
| 36 (29-43)% |
| 42 (37-47)% | 0.15 |