PCR to determine the likelihood of relapse in AML patients

Acute Myeloid Leukemia (AML) is a rare form of cancer affecting the Myeloid cells in the blood. It most commonly results from a mutation in the FMS-related Tyrosine Kinase 3 (FLT3) gene. The current treatment for AML is Allogenic Stem Cell Transplantation; the transfer of stem cells from a healthy donor to the patient following chemotherapy or radiation.

 

 

The University of Texas MD Anderson Cancer Center used the Polymerase Chain Reaction (PCR) to investigate how the status of the disease at the time of the transplant impacts the risk of relapse and survival of AML patients with the FLT3 mutation. In particular they investigated the significance of Minimal Residual Disease (MRD) detection prior to the transplant. Results of the study were published in The American Journal of Hematology.

It was found that AML patients with the FLT3 mutation can be detected by PCR. The morphologic and molecular remission status of the disease in these patients at the time of the transplant influenced their likelihood of relapse and survival following the transplant. This study suggests that using PCR to detect disease status prior to the transplant could be a valuable tool to predict the patients likelihood of relapse, enabling planning for alternative treatments.

“Abstract: In patients with AML with FMS-like tyrosine kinase 3 (FLT3) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes after transplant remains unclear. We identified 200 patients with FLT3-AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n=119), high-risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR-HR, n=31), and morphological evidence of active disease (AD, n=50). The median follow-up was 27 months, and the 2-year overall and progression-free survival were 43% and 41%, respectively. Relapse was highest in the AD group (85%) and the CR-HR FLT3 MRD positive group (72%), followed by CR-HR FLT3 MRD negative (58%), CR1/CR2 FLT3 MRD positive (39%), and lowest in the CR1/CR2 FLT3 MRD negative group (23%). On multivariate analysis, independent factors influencing the risk of relapse were detectable morphological disease and FLT3 MRD by PCR pre-transplant. Factors that did not influence the relapse risk included: age, graft type, graft source, type of FLT3 mutation, or conditioning intensity. Morphologic and molecular remission status at the time of transplant were key predictors of disease relapse and survival in patients with FLT3-AML.”

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