Significance of Minimal Residual Disease in Patients with Chronic Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract 3269

Poster Board III-1

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for patients (pts) with chronic myeloid leukemia (CML). AlloHSCT is associated with long-term disease-free survival in 40% to 80% pts transplanted in early chronic phase of disease. The probability of relapse for pts transplanted in first chronic phase is 10% to 20% at 5 years, and is even higher (30% – 60%) for pts who received transplant in advanced phases of CML. The significance of minimal residual disease (MRD) in this clinical setting is uncertain. We enrolled 63 consecutive pts with CML who had received an alloHSCT between 1995 and 2007 and had BCR-ABL transcript quantity measured by RQ-PCR method on at least 2 occasions during follow-up in the period starting 6 months after alloHSCT. The reverse transcription was preformed using SuperScriptIII and random hexamers. Quantification of BCR-ABL was performed by RQ-PCR assay according to ‘Europe Against Cancer' protocol. BCR-ABL expression was normalized with endogenous control ABL gene and expressed as a ratio BCR-ABL/ABL. According to the amount of BCR-ABL transcript detected in blood or bone marrow after alloHSCT pts were allocated into 3 categories, including pts with no-detectable or stable very low-level of BCR-ABL transcripts (ratio BCR-ABL/ABL below 0.005%), pts with fluctuating-low level of BCR-ABL transcripts (0.005 – 0.01%) and pts with high-level of BCR-ABL transcripts (0.01 – 0.1%). We didn't find any relationships between different BCR-ABL levels after alloHSCT and clinical parameters at the time of CML diagnosis or transplantation, including Sokal, Hasford and Gratwohl scores. Median time from alloHSCT to molecular relapse (MR) was 38 months (range, 8.5 – 88.5 months). The 3-year progression rate into cytogenetic or hematological relapse of CML since MR was 70%. This progression occurred at a median time of 1.4 months (range, 0 – 3.2 months). We found strong correlation between the levels of BCR-ABL transcripts after alloHSCT and a risk of relapse. The incidence of MR was 0%, 26%, 71% for the low-level, fluctuating-low level and high-level of BCR-ABL transcript (p<.0001), respectively. Similarly the risk of cytogenetic and hematological relapse was 0%, 21%, 43% for these pts (p=.001), respectively. Five-year leukemia-free survival was 100%, 83.9% and 66.7% for the pts with low-level, fluctuating-low level and high-level BCR-ABL transcript (p=.003), respectively. There was no apparent relationship between the level of BCR-ABL transcript and overall survival. We conclude that pts with fluctuating-low and/or high levels of BCR-ABL transcripts are at higher risk of disease progression. Sequential RQ-PCR monitoring coupled with pre-emptive therapy can provide a valid strategy to reduce rates of relapse and development of a more individualized approach to management of pts with CML in major molecular response after alloHSCT.