The Clinical Study On Therapeutic Strategy Of Newly-diagnosed Acute Promyelocytic Leukemia

Objective:To study the effect of different induction regimens and post-remission treatment in patients with acute promyelocytic leukemia (APL). Investigate preventive treatment of hyperleukocytosis in the induction treatment process and the clinical significance of detecting chromosome and PML / RARa fusion gene. Observe the effects of middle dose Ara-c(MD-Ara-c) on preventing central nervous system leukemia(CNSL).Methods:We retrospectively analyzed 305 cases data of newly diagnosed APL in the First Affiliated Hospital of Nanchang University from January,1989 to October,2007. Compared the complete remission(CR) rate, mortality rate and the duration for achieving CR in different induction regimens groups. Compared the leukocyte count peaks, the duration of hyperleukocytosis, the leukocyte increased multiples, the quantity of blood products infusion, the rate of hospital infection and the multiple site bleeding events, and the incidence of retinoic acid syndrome(RAS) in different groups chemo-therapied on different opportunity in the induction process of 99 patients who have newly confirmed diagnosis of APL with no higher leukocyte. Compared disease free survival(DFS),the relapse rate, mortality rate and The estimated 5-year overall survival in different post-remission treatment groups. Compared the incidence of CNSL between the treated with MD-Ara-c group and the no MD-Ara-C group during post-remission treatment. Compared the CR rate,the duration for achieving CR and the relapse rate in different chromosome karyotypes'groups. We also analyzed the data of the molecular biology remission and monitored the results of PML / RARa fusion gene.χ2 test, t test and Kaplan-Meier survival curve and Log-Rank test were used to statistic analysis.Results:1. Compared with ATRA single group, ATO single group , ARTA and ATO consecutive group, the complete mission(CR) rate was the highest(96.08%) in all-trans retinoic acid (ATRA) combined with Arsenic Trioxide(ATO) (ATRA+ATO)group, but there was no significant difference. In ATRA+ATO group, the duration to CR was shorter (32.62±4.32days) than the other three groups (P all <0.01). 2. On investigating the effect of preventive treatment of hyperleukocytosis on the induction treatment,in the preventive treatment group, the leukocyte count peaks, the duration of hyperleukocytosis and the leukocyte increased multiples were significantly lower than these in the general treatment group( P all <0.05), however, there was no significant difference in the quantity of blood products infusion, the hospital infection and the multi-site bleeding incidents (P all > 0.05),The incidence of RAS in the general treatment group is higher than it in preventive treatment group(7.27% VS 2.27%), but there is no statistical difference. 3. compared with ATRA+ATO+chemotherapy sequential group, ATRA+chemotherapy alternating group and ATO+ chemotherapy alternating group, the disease free survival was significant lower and the mortality rate was significant higher in single chemotherapy group(P all<0.05). The relapse rate of the sequential group was the lowest(19.23%), but there was significant difference only between the sequential group and the single chemotherapy group(P<0.05). The estimated 5-year overall survival(OS) of the sequential group was the highest (82.74±5.58)%, the single chemotherapy group was the lowest (P all < 0.05). 4. Variant chromosomal abnormalities group had the highest relapse rate (37.50%), but there were no significant difference compared with the patients with the other karyotypes groups(P all > 0.05), and there were no significant difference in the CR rates and The median duration to CR in different karyotypes groups. 5. We detected the PML/RARa fusion genes in 139 patients with APL at the beginning of the treatments, found the positive rate was 95.68%. it took(2.75±0.90) courses for the fusion genes of PML/RARa becoming negative. There were 11 patients whose PML/RARαfusion genes turned to positive from negative, 3 patients with Persistent Positive PML/RARαfusion genes, 2 patients whose PML/RARαfusion genes alternately changed between positive or weakly positive and negative more times, 2 patients with negative PML/RARαfusion genes had hematological relapse. However, 9 patients whose PML/RARαfusion genes turned to positive from negative, 3 patients whose PML/RARαfusion genes turned to weakly positive from negative, 3 patients whose PML/RARαfusion genes alternately changed betweent positive or weakly positive and negative had been Persistent negative and CR state after strengthened therapy in time. 6. 117 patients had received systemic post-remission treatment,and the incidence of CNSL was 7.69%. The incidence of patients who had ever received MD-Ara-c treatment was lower than it of patiens without receiving MD-Ara-c treatment(5.56% VS 11.11%), but there was no significant difference(P = 0.31).Conclusions:1. The induction regimen combined with ATRA+ATO increase CR rate, shorten the period to CR. To increase the second CR rate of relapsed cases, the regimen inculded ATO should be chosen on the second induction treatment. 2. In APL induction treatment, preventive chemotherapy can significantly decrease leukocyte peak, shorten the duration of hyperleukocytosis, and there are no significantly increase in the quantity of blood products infusion, the incidence of hospital infection and multiple site bleeding events. At the same time the preventive chemotherapy tend to reduce the incidence of RAS. 3. The post-remission treatment combining with ATRA, ATO and chemotherapy sequentially have a low relapse rate and significantly improve the long-term survival of APL patients. 4. atypical chromosome abnormality t(15;17) is not associated with poor prognosis, but The patient with variant chromosomal abnormality seemingly lean toward relapse, and need further studies. 5. Continuous detection of PML/RARαfusion transcripts is important for predicting hematological relapse, determination of the time to stop medicine and prognostication of recurrence. 6. MD-Ara-c have not shown a good preventive effect on CNSL, but seemingly lean toward preventing CNSL, and need more studies to further define the exact effect on reduceing the relapse rate in CNS of APL.