Abstract
Background: There are conflicting reports on the prognosis of patients with newly diagnosed c-KIT positive (CD117) AML. In addition there is controversy on the best way to define CD117 positivity by flow cytometry (FC). We retrospectively reviewed data on 95 patients with newly diagnosed AML during the years 1998–2002 to determine the prognostic value of CD117 expression. Methods: CD117 expression was determined by staining cells with antibodies to CD45 and CD117 (BD Biosciences San Jose, CA). CD45-stained cells without CD117 antibody were used as a negative control. FC was performed on FACSCalibur instruments and data acquired using CellQuest software (BD Biosciences). Using a CD45/orthogonal light scatter gate to isolate blasts, the mean fluorescence index (MFI) was calculated as the CD117 mean channel number (MCN) of the blasts/MCN auto fluorescence. Statistical analysis was performed using Cox proportional hazards (CPH) and log rank (LR) testing; Recursive Partitioning analysis was used to Identify CD117 MFI cut-point.
Results: The median age of patients was 59 years. 30% had a history of an antecedent hematological disorder. Good, normal, unfavorable, and other cytogenetics were seen in 10%, 49%, 30%, and 11% of patients, respectively. Patients were treated with anthracycline based induction therapy, followed by consolidation therapy (45% chemotherapy, 23% stem cell transplant). The complete remission (CR) rate was 69.5% (58.7% for age ≥60, 79.6% for age <60). Median Follow up was 16.5 months (m). Median PFS and median overall survival (OS) was 11.2 m (8.5 m for age ≥60, 12.7m for age <60) and 21.3m (19.9m for age ≥ 60, 37.1m for age <60), respectively. CD117 expression (MFI) did not correlate with age, cytogenetics, CR rates or OS. However, patients with CD117 MFI > 10.7 had a median PFS of 9.5m vs. 14.0m for MFI ≤ 10.7 (p=0.033, LR). Median FFP for MFI > 10.7 was 10.0m vs. 33.6m for MFI ≤ 10.7 (p=0.019, LR). On univariate CPH analysis, CD117 (MFI >10.7) was associated with worse PFS (HR: 1.86, 1.04–3.32, p=0.036) and FFP (HR: 2.38, 1.13–5.03, p=0.023). Multivariate CPH analysis showed increasing CD117 expression (per 5 unit MFI increase) was associated with worse FFP (HR: 1.19, 1.01–1.4, p=0.042).
Conclusion: CD117 expression does not correlate with age, cytogenetics, or OS. However, CD117 (MFI>10.7) is a poor PF for PFS and FFP in AML patients. Higher CD117 ratio is also an independent poor PF for FFP. Whether or not agents that inhibit CD117, such as Imatinib Mesylate, can improve prognosis is the basis of ongoing trials.
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