Abstract 3065

Introduction:

Current studies suggest that monitoring the minimal residual disease (MRD) of patients with malignant hematological disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is helpful for screening patients at high risk of relapse. WT1 and leukemia-associated aberrant immune phenotypes (LAIPs) were the major MRD parameters used to predict leukemia relapse after allo-HSCT. The aim of this study was to first evaluate the clinical value of various positive MRD standards for accurately predicting relapse based on WT1 and flow cytometry (FCM) data in a large sample of adult patients with actue leukemia (AL) in a single transplant center.

Methods:

In total, 824 AL patients treated with non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology from January 1, 2006 to November 30, 2011 were enrolled in this study. BM samples from patients were obtained at regular time points: +1 month, +2 months, +3 months, +4.5 months, +6 months, +9 months, +12 months and every 6 months thereafter for the MRD investigation after HSCT. WT1 expression was evaluated using TaqMan-based RQ-PCR technology and LAIPs were detected using 4/7-color FCM. At least one positive MRD marker, including WT1 or LAIP, was detected before transplantation in 90.8% (748 of 824) of the subjects. Positive FCM could be found in all 748 patients. Both FCM+ and WT1+ were detected before transplantation in 58.7% (484/824) of subjects. We compared the sensitivity and specificity of diverse, multiple-criteria MRD forecasting standards including one WT1+, two consecutive WT1+, one FCM+, two consecutive FCM+, concurrent WT1+ & FCM+, concurrent WT11.0+ & FCM+, MRDco+ and MRDco1.0+, based on WT1 and FCM assays.

Results:

Higher sensitivity was achieved without a loss of specificity in total 824 patients as well as in 748 patients with WT1+ or FCM+ before transplant when MRDco+ was used as the positive MRD standard (Table 1). Similar results were observed, even in 484 patients with acute myeloid leukemia (AML, n=308) and acute lymphoblastic leukemia (ALL, n=176) who had both abnormal WT1 and LAIPs values before transplant (Table 1). A multivariate analysis that included age, sex, disease status (CR1/CR2), donor type, number of chemotherapy courses before CR1, and MRD status (including the different MRD standards mentioned above) after transplantation showed that MRDco+ was an independent risk factor to predict leukemia relapse after allo-HSCT; it had the most powerful contribution to leukemia recurrence after transplant in both AML (HR=12.54, 95% CI: 7.01–22.42, P<0.001) and ALL (HR=12.84, 95% CI: 6.05–27.25, P<0.001) compared with other MRD standards.

Conclusions:

The combined use of FCM and WT1 monitoring were able to distinguish between patients with low and high risk of relapse. Diverse standards of positive MRD raised in this work were conductive to guide different interventive measures. Further studies should focus on exploring the new better parameters with both high sensitivity and specificity in predicting the recurrence of leukemia after allo-HSCT.

Table 1.

Sensitivity and specificity of combinative MRD criteria for predicting leukemia relapse in different groups after allo-HSCT.

GroupsSensitivitySpecificityRelapse ratep valueYouden's index
All subjects MRDco+ 41.3% 97.8% 81.0% vs 12.2% <0.001 0.391 
n = 824 MRDco1.0+ 31.0% 99.3% 90.6% vs 13.9% <0.001 0.303 
n = 748 MRDco+ 43.5% 97.9% 82.2% vs 11.6% <0.001 0.414 
 MRDco1.0+ 34.1% 99.2% 90.4% vs 13.1% <0.001 0.333 
AML MRDco+ 50.0% 97.2% 79.4% vs 9.9% <0.001 0.472 
n = 308 MRDco1.0+ 35.2% 99.2% 90.5% vs 12.2% <0.001 0.344 
ALL MRDco+ 37.8% 99.3% 93.3% vs 14.3% <0.001 0.431 
n = 176 MRDco1.0+ 35.1% 99.3% 92.9% vs 14.8% <0.001 0.344 
GroupsSensitivitySpecificityRelapse ratep valueYouden's index
All subjects MRDco+ 41.3% 97.8% 81.0% vs 12.2% <0.001 0.391 
n = 824 MRDco1.0+ 31.0% 99.3% 90.6% vs 13.9% <0.001 0.303 
n = 748 MRDco+ 43.5% 97.9% 82.2% vs 11.6% <0.001 0.414 
 MRDco1.0+ 34.1% 99.2% 90.4% vs 13.1% <0.001 0.333 
AML MRDco+ 50.0% 97.2% 79.4% vs 9.9% <0.001 0.472 
n = 308 MRDco1.0+ 35.2% 99.2% 90.5% vs 12.2% <0.001 0.344 
ALL MRDco+ 37.8% 99.3% 93.3% vs 14.3% <0.001 0.431 
n = 176 MRDco1.0+ 35.1% 99.3% 92.9% vs 14.8% <0.001 0.344 
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Disclosures:

No relevant conflicts of interest to declare.

Topics:
allogeneic hematopoietic stem cell transplant, flow cytometry, hematopoietic stem cell transplantation, leukemia, transplantation, allopurinol, acute lymphocytic leukemia, chemotherapy regimen, hematological diseases, leukemia, myelocytic, acute

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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