Abstract
Minimal residual diseases (MRD) are the problem of disease recurrence for childhood acute leukemia. Different levels of MRD determined with multi-parameter flow cytometry (MP-FCM) have been revealed prognostic for both adult and childhood acute leukemia in several recent studies. However, the MRD levels at the time of complete remission and the various check point during further treatment have not been reported.
Methods: 122 cases (Male 73, Female 49, aged 2 month to 15yrs with a median of 6.5yrs) with childhood acute leukemia treated in our hospital from 2001.3 ~ 2004.7 were enrolled into this study. A total of 610 BM samples were detected with three or four color MP-FCM based on individualized leukemia-associated aberrant immunophenotypes (LAIP) in each patient according to their initial complete immunophenotypic profiles (B lineage ALL: 79 cases, T lineage ALL: 11 cases; AML: 32 cases). A total of 99 LAIPs (B lineage ALL: 48, T lineage ALL: 16, AML: 31, HAL: 4) were identified and single LAIP was used in most patients, but some patients needed more than one (2 or 3) LAIPs to detect their MRDs. At least 100,000 events were collected for each analysis. ALL and AML patients were treated with Chinese Childhood Cancer Study Group (CCCSG) ALL-protocol-1998 and AML-protocol-1998, respectively.
Results: The CR rates for B lineage ALL, T lineage ALL and AML were 99.3%, 94.7% (overall ALL 98.8%) and 89.1%, respectively. The 1 yr/2 yrs of event free survival (EFS) for the three types of leukemia was 92.5%/85.2%, 78.3%/68.9% and 68.3%/56.4%, respectively. At the time of first CR after induction therapy, MRD level of B lineage ALL (79 cases) was 0.166%±0.057% (mean ± SE), significantly lower than those of T lineage ALL (11 cases, 0.783%±0.328%, t = 3.1926, P = 0.002) and AML (32 cases, 1.191%±0.257, t = 5.5177, P < 0.00001), respectively. No significance was identified between the MRD levels of T lineage ALL and AML (t = 0.8488, P = 0.40). The MRD level of the overall ALL (T + B lineage: 90 cases) was also significantly lower than that of AML (32 cases) (t = 5.0249, P < 0.00001). With further detection of MRD following the continuous consolidation and maintenance therapy, some patients relapsed and were excluded the study, and some had not reached the time for detection. At the time of 6 months after first CR, the MRD level of B lineage ALL (53 cases, 0.224%±0.065%) was not statistically different from that of T lineage ALL (7 cases, 0.627% ± 0.276%, t = 1.767, P = 0.083), while it was significantly higher than that of AML (16 cases, 0.966%±0.347%, t =3.334, P = 0.0014). At the time of 1 yr after CR, the MRD level in ALL (50 cases, 0.347%±0.090%) was not significantly different from that of AML (7 cases, 0.094%±0.072, t = 1.043, P = 0.31). At the time of 2 yrs after CR, the MRD level in ALL (49 cases, 0.302%±0.105%) was also not significantly different from that of AML (8 cases, 0.485%±0.246%, t = 0.6599, P = 0.51).
Conclusions: MRD level of B lineage ALL is significantly lower than those of T lineage ALL and AML at the time of first CR, being true at the time of 6 months after CR. The differences are lost at 12 and 24 months after CR indicating that MRD detection with MP-FCM are well associated with the prognosis of childhood acute leukemia. Continuous follow-up to accumulate more cases is now underway.
14q32 translocations are associated with mixed-lineage expression in childhood acute leukemia
