[A new prognostic stratification for patients with acute myeloid leukemia].

OBJECTIVE: To evaluate the impact of the percentage of residual blasts in bone marrow at the end of induction chemotherapy (T1) or during myelosuppression phase (T2) on prognosis of de novo acute myeloid leukemia (AML) (non M(3)) in 105 cases. To refine AML risk-stratification by combining the percentage of residual blast cells (T1 or/and T2) with cytogenetic data based the South West Oncology Group (SWOG) criteria. METHODS: The data of 105 de novo AML (non M(3)) patients hospitalized between January 1st 1999 and February 1st 2008 were retrospectively reviewed. Results were analyzed with SPSS15.0 software. RESULTS: (1) Patients were divided into two subgroups by a cutoff of 5% residual bone marrow blasts at T1 or T2 time point. Patients with percentage of residual bone marrow blast cells < 5% had better complete remission (CR) rate, relapse-free survival (RFS) and overall survival (OS) than the patients with percentage > or = 5% at T1 or T2. The percentage of residual bone marrow blast cells at T1 was correlated with that at T2. (2) The prognosis of patients with intermediate karyotypes with percentage < 5% at T1 or T2 was similar to that of the patients with favorable karyotypes. The patients with intermediate karyotypes and percentage of residual bone marrow blasts > or = 5% at T1 or T2 are defined as a subgroup with prognosis similar to that of patients with unfavorable karyotypes. (3) COX regression analysis showed that the percentage of residual bone marrow blasts at T1 or T2 is an independent prognostic factor of AML. The percentage of residual bone marrow blasts at T1 may be more helpful in prognostication than that at T2. CONCLUSION: AML patients with percentage of residual bone marrow blasts < 5% after induction chemotherapy (T1 or T2) have better CR rate, RFS, OS than the patients with percentage > or = 5% at the same time point. Combination of cytogenetics and percentage of residual bone marrow blasts at T1 or T2 is helpful to divide patients with intermediate karyotypes into two subgroups with different prognosis. Thus, a better decision of treatment strategy can be designed.

[Correlation of single-cell gel electrophoresis and mitomycin C-induced chromosomal breakage for chromosomal instabiligy in children with Fanconi anemia].

OBJECTIVE: Fanconi anemia (FA) is characterized by bone marrow failure, congenital abnormalities and predisposition to neoplasia. Hypersensitivity of FA cells to the clastogenic effect of mitomycin C (MMC) provides a unique marker for the diagnosis before the beginning of hematological manifestations. The aim of this study was to evaluate the relationship between Single-Cell Gel Electrophoresis (SCGE) and mitomycin C-induced chromosomal breakage in children with FA. METHOD: Between January 2007 and June 2011, 248 children (< 15 years) with hypocytosis were included. Chromosomal breakage was induced by MMC 0 ng/ml, 40 ng/ml, and 80 ng/ml. SCGE was performed at the same time. We analyzed the results of the two methods and compared with each other. The receiver operating characteristic (ROC) curve was used to evaluate the parameters in SCGE. RESULT: Seventeen patients were diagnosed as FA and 231 as non-FA. Chromosomal breakage was found to be significantly higher in FA patients [(32.2 ± 4.8)%] than non-FA [(19.9 ± 3.0)%] and controls[(21.6 ± 4.8)%] when induced by MMC 80 ng/ml. The parameters of SCGE were significantly different between FA patients and non-FA or controls. All the parameters were rectilinearly correlated with MMC (P = 0.000). The most closely correlated parameter was the rate of comet cell (r = 0.848, P = 0.000). The results of ROC curves suggested the comet cell rate (0.999) was more important. CONCLUSION: SCGE might be used to discriminate between FA and non-FA individuals. The relationship between SCGE and MMC-induced chromosomal breakage was significant. The rate of comet cell was the important parameter.

[Role of IFN-γ + 874 genetic polymorphisms in allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To explore the impact of IFN-γ + 874 polymorphisms on the outcome in HLA matched sibling HSCT. METHODS: We used PCR-sequence-specific primer analysis (PCR-SSP) to analyze the polymorphisms of IFN-γ + 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008. RESULTS: Recipients having donors who possessed IFN-γ + 874 A/A genotype had significantly earlier neutrophil recovery compared with those having donors with non-A/A genotype (15 (11 - 27) days vs 18 (12 - 30) days, P = 0.029). And IFN-γ + 874 A/A in both recipients and donors further facilitated neutrophil recovery compared with others (13 (11 - 25) days and 19 (12 - 31) days, P = 0.019). Besides, IFN-γ + 874 A/A in recipients increased the probability of grade II-IV acute graft versus disease (aGVHD) and cytomegalovirus viraemia compared with IFN-γ + 874 T/A or T/T genotype (20% vs 4% P = 0.041, 43.6% vs 16.0% P = 0.032), which lead to increased 5-year transplant-related mortality (TRM) (33.7% ± 6.8% vs 12.0% ± 6.5%, P = 0.050) and decreased 5-year event free survival (EFS) \[(58.2 ± 6.7)% vs (84.0 ± 7.3)%, P = 0.032\] compared with the latter. IFN-γ + 874 A/A in both recipients and donors also significantly increased the probability of grade II-IV aGVHD and cytomegalovirus viraemia compared with the other (21.7% vs 5.9%, P = 0.050; 45.7% vs 20.6%, P = 0.020), which caused increased 5-year TRM \[(31.6 ± 7.5)% vs (13.6 ± 6.5)%, P = 0.048\] and decreased 5-year EFS \[(56.8 ± 7.3)% vs (79.4 ± 6.9)%, P = 0.037\] compared with the other. CONCLUSION: In HLA-matched sibling HSCT setting, the presence of IFN-γ + 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade II-IV aGVHD and CMV infection and increased EFS. While IFN-γ + 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.