The Clinical Observation Of The Therapeutic Effects And Reactions For An Optimal Therapeutic Strategy In Treating Newly-diagnosed Acute Promyelocytic Leukemia

APL is a special subtype of AML and distinct from other acuteleukemias very often accompanied with fatal hemorrhage and its earlymortality rate is very high.Since arsenic and all-trans retinoic acidwere used to treat APL ,this situation has been changed.We hasestablished a new way in the treatment of APL. The use of arsenic is anew method in treatment of APL.With the development of medicine andscience ,arsenic has showed me a very remarkable effect.But with thefurther research about the therapy of APL,people found that arsenic andall-trans retinoic acid may be used in the induction of newly diagnosedAPL, which can improve the disturbance of coagulation function, whoseCR rate respectively is high and early mortality rate is low.But if thepatients of APL who had achieved HCR1 continued to use As2O3 or ATRA toconsolidate and maintain,both can't effectively clean the malignancyclone,so the molecular biological CR rate(MCR) is low,and the continualadministration of As2O3 may cause the accumulation of arsenic andoccasionally show up the toxical effects.Meanwhile the ATRA inclined toappear the drug-resistance,so recently some people has raised thatduring the course of the therapy of APL,continual chemotherapy canachieve the higher CR(including MCR),and the higher rate of EFS than thegroup of the single agent As2O3,and lower early mortality andchemotherapy-relative risk.The research about the optimal opportunityto adopt chemotherapy seldom can be found,so we want to assess theclinical effectiveness and side effects and try to find the optimaltherapeutic strategy.Methods:132 previously untreated patients(including 6 casesoccurred early death) of APL who were diagnosed as APL from January,2002to February,2006 were chosen. The ages were 7-70 years old.The medianage was 34.7 ± 13.3.55 patients are males and 46 patients arefemales.Except 3/101 patients were lack of intimate data, the other 98patiens had finished the As2O3 treatment for at least one course withoutreceiving the treatment with arsenic trioxide and the traditionalChinese medicine before hospitalization.These patients had no severevisceral malfunction.The female patients were not in the gestationalperiod and lactational period.Induction therapy:The patients don't useAs2O3 until CR.Consolidation therapy:The patients of Group A were giventhe treatment with the alternation of As2O3 and chemotherapy.The patientsof Group B were given As2O3 alone.In addition,all patients received thepertinent supportive care during the treatment period.We observedwhether the patient had the side effects,such as headache,ostalgia,mucosa dehydration/ulcer,bleeding,edema and regularly examedCBC,bone marrow aspiration for cytology and biopsy,blood coagulationroutine,hepatic and renal funtion,ECG.They received the PML/RAR αexamination before and after every course.Meanwhile compared with thepatients diagnosed between December,1988 and April,1992.The data wereanalyzed by SPSS.Results:1.Hematological remission:98 patients among 101 patientshad achieved HCR by As2O3 alone.The CR rate was 97%.The median time ofCR was 32.0±6.7d (Range:18-49d).2.Cytogenetical remission:Among 101patients 69 patients showed up the typical chromosome abnormality,that's t(15;17)(q22;q21). 3.Molecular biological remission:96/101patients's fusion genes of PML/RAR α were positive(95%) at thebeginning of the treatments.79 patients (Group A:36 patients;Group B:43patients)received the consolidation and maintenance therapy andreceived the PML/RARαfusion gene exmination.Till January,2005, GroupA:29 patients'fusion genes became negative. The mean course was 4.6±1.9 courses.Group B:10 patients'fusion genes of PML/RARαbecamenegative. The mean course was 7.9±3.0 .The CR rate of Group A was muchhigher than that of Group (BP<0.05). The MCR time of Group A was shorterthan that of Group (BP<0.05). 4.Relative factors analysis of bone marrowdepression during the chemotherapy in Group B after CR:Comparing the bonemarrow depression of the first chemotherapy between the group whichapplied chemotherapy immediately after CR( Group 1) and the group whichdidn't apply chemotherapy immediately after CR (Group 2).The time ofWBC<10×109/L and the time from the lowest counts of WBC to the normalof Group 1 are longer than those of Group 2,and the rates of infectionis higher than those of Group 2(P<0.05).5.DIC:There were 22.8% patientswith blood coagulation disfunctions,5.9% patients who had been diagnosedas DIC,no patients died in the early days of treatment because ofhemorrhage.With the treatment of As2O3,the patients'blood coagulationdisfunctions all had gotten to become better and the symptom of thepatients of DIC was relieved. 6.CNS-L:6 patients was diagnosed asCNS-L.7.Relapse and survival: 1>The period of induction therapy:10patients of 132 cases died and the rate was 7.6%.2>The period ofconsolidation and maintenance therapy:the later mortalities was 2.5%.The median time of the patients'treatments was 13.3m(Range:2-41m).Therelapse rate of Group A:0% in the 1st year,2.7% in the 2nd year,2.7% over2 years;The relapsed rate of Group B:12.2% in the 1st year,22.0% in the2nd year,4.9% over 2 years.There was noticeable difference between thatof Group A and B(P<0.05). 8.Side effect: (1)The influence of As2O3on CBC:Stage of induction remission:1)change of WBC: the percentage ofthe patients with WBC≥ 10×109/L and the average counts of WBC afterthe treatment are higher than that before treatment(P<0.05),whichinduce hyperleukocytosis.The incidence of the hyperleukocytosis is31.7%;Consolidation:43.1% patients presented the decrease of WBC andthere is no difference of Hb and PLT between before and after treatment(P>0.05).(2) Other side effects: The incidence of hepatic damage is33.7%;the incidence of retention of sodium and water was 31.7%;theincidence of dermal and mucosal irritation was 26.7%;the incidence ofsymptoms of nervous system was 18.8%;the incidence of the symptoms ofdigestive system was 14.9%;the incidence of the systems ofcardiovascular system was 13.9%. None of these patients emerged renaldamage.Conclusion:1. 1.The optimal therapeutic strategy for the newlydiagnosed APL patients :(1)The stage of induction is As2O3±ATRA,whoseCR rate is high(97%) ,the rate of DIC (5.9%)and the mortality ofinduction(7.6%) are low.(2)The stage of consolidation and maintenanceapplying chemotherapy in 3st course or later after CR1 whosechemotherapy-induced mortality is lower and the molecular biological CRis higher and appeared earlier is better than the other ones. 2.For theMICM diagnosis,evaluating the therapeutic effect and the prognosisexactly,conventional G-banding could't obtain the very accuratecytogenetical result and the sensitivity of PCR method is higher. 3.Theinfluence of As2O3 on blood routine:The stage of introductionremission:The WBC increased after the treatment and thehyperleukocytosis can be induced(31.7%).Meanwhile in the clinicalobservation, the other main side effects of As2O3 and ATRA can beobserved ,that's hepatic damage,the symptoms of digestive system ,nervous system and cardiovascular system,the retention of sodium andwater,dermal and mucosal dehydration,etc.Most of the side effects arelight and reversible which need the corresponding treatments and havenothing with the use of As2O3 and ATRA.The question is still furtherresearched when is the optimal opportunity alternating chemotherapyduring the stage of consolidation and maintenance.