The Analysis Of Prognostic Factors Of Acute Promyelocytic Leukemia

All-trans retinoic acid (ATRA),arsenic trioxide (ATO) and chemotherapy have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), which have reversed the most malignant and fatal form of acute leukemia into a highly curable subtype in all acute non-lymphocytic leukemia.But there are still about 12-30% APL patients died because of failure of induction treatment,relapse in the post-treatment and died of certain kind of compliance.So, recently,how to raise the curative effect furthermore,how to prolong survival time ,become the focus of reseach.This reseach tried to find out the negative prognostic factors and the relationship between these factors.If the negative factors can be interfered in the very early state,it may make senses to the stretching of survival time.Objective : :Analyse the prognostic factors of acute promyelocytic leukemia and the possible relationship among the factors.Method : 114 newly diagnosed patients were involved in the reaseach ,who were treat by ATO and/or ATRA as induction thrapy,and interval treatment of ATO,ATRA and chemotherapy as consolidation therapy. The patients were divided into different groups depend on different characte- ristics,measured by the hemotology complete remission,molecular complete remission,the rate of replase and death, and other indexes , observe the outcome of different groups after the ATRA±ATO induction treatment , which contained the ratio of early death,CR rate,CR- achieving time and the ratio of relapse. The data were analyzed by SPSS.Result:1..Age:There is obvious differernce among children,aged and the middle aged in the CR rate ,there is no difference in the time achieve CR by the three groups.3.Gender:The female seemed tohad better effect including CR rate,CR- achieving time,ED ratio and 3 years relapse–ratio than male ,but there was no obvious difference according to statistics. 4.Cell counts when first diagnosed.During the induction therapy,wbc>10×10~9/L group had the longest CR–achieving time,the lowest CR rate,the longest leukocytosis time ,the highest ED ratio,than 4.0×10~9/L100×10~9/L). there was no significant difference in DIC ratio among the three groups,but the lower group had the longest CR-achieving time,there was obvious difference between the plt>40×10~9/L patients and plt<40×10~9/L patients in CR achieving time,DIC ratio and relapse rate,but there was no difference between the normal lever and middle level. The relapse rate in plt<40×10~9/L group is higher than the other two groups,however ,there wa no difference between the two. According to the NCCN grading, the people in high risk had obvious difference in CR rate and ED ratio with people in poor risk and low risk. 5.Molecular biology subtype.114 newly diagnosed patients, 97 patients had PML/RARαL(+),and 12 patients S(+).There was obvious difference between the L(+) group and S(+)group of leukocytosis incidence rate,the leukocytosis time,DIC rate,CR-achieving time and CR rate. In the three year follow up ,33 L(+)cases were available in which seven patients relapsed,while two S(+)cases were available in which 1 patient relapsed,there was no difference between the two.6.Morphology subtype.According to the morphology of granules in the leukocytes,people were divided into two subtype:course granule subtype(M3a) and fine granule subtype (M3b),while the cases of M3a:M3b=4.7:1.There was obvious difference between the M3a group and M3b group in the wbc and plt count when firstly diagnosed,the incidence ratio of leukocytosis,the leukocytosis time,DIC rate ;There was no difference between the two in ED and CR rate. In the three year follow up,30 M3a cases were available in which six patients relapsed,while five M3b cases were available in which three patients relapsed .In this reseach ,it seemed that M3b had some relationship with leukocytosis and PML/RARαS (+).7. Cytogenetics:88 patients had their cytogenetic reports, 70 patients showed up typical chromosome abnormality t(15;17)(q22;q21)(typical group); 13 patients show up additional chromosome abnormality ( additional group) ;and two patients had normal karyotype(normal group); three cases had abnormal karyotype without (t15;17)(q22;q21)(abnormal group).The CR-achieving time in typical group,normal group and additional group,abnormal group were 32.56±3.21 day and 31.61±6.52 days ,the CR rate were 100% and 89.11% respectively,and there was no difference between the two in CR-achieving time,CR rate and three-year relapse.7. Induction treatment:114 cases, ATO and/or ATRA as induction therapy,seven patients gave up treatment,10cases were died in the early stage of APL,the ratio of early death was 10.31%,overall survival ratio was 90.65%, all the 97 patients achieve hemotology CR in the first induction therapy,the average time achieve CR is 31.5±6.9 days(20 -113days).The average time of the fusion gene transfered to negative was 4.3±1.4 courses of treatment。Two patients had CNS-L when diagnosed,five cases had CNS-L in the CR ,the ratio of CNS-L is 6.1%.Five patients had normal cerebral fluid after 1-3 courses of treatment and several times of intrathecal injection,the other two patients got well after times of intrathecal injection and prophylactic cerebral radiothera- py .After CR ,87 patients were followed up for one year,nobody died , one case relapsed ,so the one-year OS is 90.56%,the one-year relapse ratio is 1.15%;51 patients were followed up in two years, one patient died ,four patients relapsed;35 patients were follow up for three years ,one patient died ,so the three-year OS is 86.33% ,eight patients relapsed.In the all 114 cses ,83 patients,which accounts for 83% had the disturbance of blood coagulation ,and eight were diagnosed to have DIC,of which two cases were related to early death of cerebral hemorrhage during the induction theray ,the most commom adverse reaction is leukocytosis,then headache and edema,then liver disfuction,skin changes,the dryness of mucosa and digestive system disfunction.After giving corticoid and other symptomatic treatment, all the side effects were well tolerable ,and all the adverse reactions were reversible,left no permanent damage.Conclusion: 1.Age is one of the prognositic factors,children have better prognosis,while aged people have worse due to poorer chemotherapy tolerance and more complications.2.Gender is not one of the prognositic factors.3.Cell counts when first diagnosed:The wbc count more than 10×10~9/L and plt count less than 40×10~9/L are independent negative prognositic factors.According to the NCCN grading in this reseach, the combination of the wbc count more than 10×10~9/L and plt count less than 40×10~9/L is negative prognositic factor.4. the M3b group tends to have more dangerous course,but if proper treatment was available ,it could have the same effect with the M3a group in the early stage.But in the long run survivals, the M3b type is one of the prognositic factors,because of some relationship with leukocytosis and PML/RARαS (+) subtype.5. Molecular biology subtype.there was obvious difference between the L(+) group and S(+)group in CR-achieving time and CR rate.S(+) subtype is one of the prognositic factors。6.Cytogenetics:There was no difference between the typical,normal group and additional,abnormal group in CR-achieving time and CR rate。Because of the small sample,the influence of cytogenetic type to the survival is hard to assess.7.ATO and/or ATRA as induction therapy,had a comparative hemotology CR rate and long time relapse ratio.But the molecular remission rate in ATRA+chemotherapy is significantly higher than that after the first induction therapy.So furthermore reseach is needed to evaluate the good aspects and bad aspects of the two induction therapies.