| Objectives:By open clinical trials,we make an observation aboutlow dose arsenous acid/retinoid induction programme treating Myelodysplastic Syndromes(MDS)of children.Exploring the influence of HLA-DR15 gene to clinical effect and WT1 gene to living state.Investigating the possible pharmacomechanism of the project on MDS of children.Methods:(1)Clinical data:Observed patients are 31 inpatients of MDS of children from pediatrics of our institute,and 17 cases are measurable(RCC 13 cases,RAEB-Ⅰ 3 cases,RAEB-Ⅱ 1 case),Males and females are 9 cases and 8 cases respectively,median age is 9 years old(3～14),median course of disease is 16 months(0.25～96).Diagnostic classifications are based on Blood Disease Diagnosis and Curative Effect Standard written by Zhang Zhinan(the third edition)and MDS Classification Standard issued by WHO in 2008.Standard of prognostic evaluation refers to the Revised International Prognostic Scoring System(IPSS-R)for Myelodysplastic Syndromes of adults in 2012.(2)Therapeutic methods:Gradation treatments of low dose arsenous acid/retinoid induction programme on MDS of children include two levals,one is low dose arsenous acid/retinoid project for RCC subtype,and another one is low dose arsenous acid/retinoid combined with low dose Ara-C for RAEB-Ⅰ or RAEB-Ⅱ subtypes.Main drugs are ATO 0.08mg·kg-1·time-1·d-1(maximum dose less than 5mg·d-1),venous transfusion,each treatment course is 1～28 days,ATRA 10-20mg·m-2·d-1,two times a day,taking orally,treatment course is same as ATO,low dose Ara-C protocol:5-10mg·m-2·d-1(maximum dose less than 10mg·d-1)subcutaneous injection or venous transfusion,each treatment course is 1～7 or 1～14 days.Therapy interval is 2～4weeks or more than 8 weeks,and it depends on the extent of disease.(3)Evaluation of therapeutic efficiency:It is based on the standard of therapeutic evaluation of MDS established by IWG in 2006.(4)Carrying on HLA-DR15 gene and WT1 gene testing for medullary cells of partial patients by PCR gene detection method.Results:(1)The short term effective rate of low dose arsenous acid/retinoid induction programme for MDS of children is 88.24%(15/17),and the patients acquiring short term clinical effects after one courese account for 60%(9/15);course of disease less than 24 months of 11 children all acquired short-term clinical efficacy,superior to the patients of long disease process(P<0.05),we have not found the degree of disease influencing the short term clinical effects(P>0.05);as to the date of follow-up,76.47%(13/17)of patients acquired stable and above survival state,median PFS is 18 months(5～51),median OS is 27 months(5～79),it has not been found that the degree and course of disease will impact the survival state for those who have acquired short term clinical efficacy(P>0.05).Currently,there are still 10 patients in maintenance treatment,median treatment coursesare 12.5 ones(3～21),the protocol is found safe and well-tolerated.(2)5/11 cases of RCC who applied this therapy showed the positive expression of HLA-DR15 gene,and there is no significant difference about the short term efficiency between the HLA-DR15 positive group and negative group(P>0.05).(3)Partial patients whose WT1 gege increase abnormally account for 76.92%(10/13),4/6 cases are RCC subtype,6/7 cases are RAEB subtype.Conclusions:(1)The project achieved 88.24%of shot term clinical efficiency,and improved the quality of life of MDS patients.(2)It may be the effective mechanism of this plan for induction hematopoietic cell differentiation,apoptosis and immunoregulation for MDS patients.(3)The abnormal increase of WT1 gene may be one of the dangerous factors of children of RAEB subtype. |
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