Day 14 Bone Marrow Stromal Microenvironment Independently Predicts Long Term Survival in Acute Myelogeneous Leukemia (AML)
R Dewar, R Kalluri. Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA; Harvard-MIT, Boston, MA
Background: Bone marrow microenvironment (BME) is important in hematopoietic regulation, leukemogenesis & stem cell homing. However, direct evidence linking BME to survival in AML is lacking. We characterize two microenvironmental (osteoblastic & vascular) niches by immuno-histochemistry in BM biopsies to show their relationships with survival in AML.
Design: New diagnosis AML (2003-05) were chosen. Bone marrow trephine biopsy at day 14 following chemo-induction were collected. AML M3, ALL, inadequate biopsy samples were excluded. From an intial screen of 36 cases, 22 trephine biopsies were retrieved & immunostained for the following stromal factors (characterizing BME): CD34, Fibroblast Specific factor-1 (FSP1), Stromal derived factor (SDF), α-SMA & Hypoxia Inducible factor-1α. Stromal characterization included vascular CD34, interstitial stromal CD34 (bi-phasic pattern), blastic CD34, α-SMA (endosteal), α-SMA (interstitial). Blinded 5 point scoring (0-4) was performed for each of these parameters. Unsupervised hierarchical cluster analysis was performed on the 22 cases for the 8 stromal parameters as shown below:
Results: Two BME patterns emerged separating the 22 cases into 2 groups (n=14 &8). After accounting for 2 cases that failed chemo-ablation and died in the first 30 days, survival analysis (Kaplan-Meier) showed statistically significant differences in survival between the two groups:
Conclusions: BME stromal profile, independent of AML sub-type is important for long term survival in AML patients who survive chemo-induction. Large, blinded, prospective studies along with stromal gene expression profiling is necessary for confirmation of these findings.
Tuesday, March 23, 2010 11:45 AM
Platform Session: Section B, Tuesday Morning