HDA方案再诱导治疗儿童难治性急性淋巴细胞白血病

Treatment of pediatric patients with refractory acute lymphoblastic leukemia with IHDA regimen

目的观察以去甲氧柔红霉素（IDA）及大剂量阿糖胞苷（HD—Ara—C）组成的IHDA方案再诱导治疗儿童难治急性淋巴细胞白血病（ALL）的疗效及不良反应。方法应用IHDA方案再诱导治疗12例难治性ALL患儿，获得完全缓解（CR）后进入后续序贯治疗或及时进行异基因造血干细胞移植（allo—HSCT）；如1个疗程未获cR，待WBC〉2．0×109／L，再进行1个疗程的化疗。方案组成：IDA，10mg／（m2·d），第1—3天；Ara—C，1．0g／m2，q12h，第1—3天；评价其疗效及血液学、非血液学不良反应。结果12例难治性ALL患儿应用IHDA1个疗程后，CR／部分缓解（PR）／未缓解（NR）分别为4／3／5例；2个疗程后CR／PR／NR分别为5／3／4例。2个疗程后CR率为41．7％（5／12例），PR率为25．0％（3／12例），NR率为33．3％（4／12例），总有效率（CR＋PR）达66．7％（8／12例）。患儿均发生Ⅳ级骨髓抑制，经应用人粒细胞集落刺激因子（G—CSF）及输注血小板并予抗感染治疗，未出现严重感染及出血；部分患儿出现肝脏、心脏及神经损害等不良反应，经对症支持治疗后均可逆转，12例患儿均未发生化疗相关死亡。随访至2015年10月，CR5例中再次复发2例，1例为B—ALL，应用嵌合抗原受体T淋巴细胞免疫疗法治疗后再次CR，目前接受allo—HSCT治疗中；1例为T—ALL，改用FLAG（泼尼松＋氟达拉滨＋Ara—C＋G—CSF）挽救性化疗无效死亡；其他3例持续CR，缓解时间分别为26、10、4个月。余7例患儿中，进行强行造血干细胞移植3例，放弃治疗2例，失访2例。结论IHDA方案对部分难治性ALL患儿再诱导治疗有效，不良反应可以耐受，为应用allo—HSCT创造了机会。

Objective To observe the efficacy and adverse effect of IHDA [ Idarubicin （IDA） ＋ high -dose Cytarabine（ HD- Ara- C）I as a remedy regimen in the treatment of pediatric patients with refractory acute lympho- blastic leukemia（ALL）. Methods Twelve children with refractory ALL were treated by IHDA regimen as follows： IDA, 10 mg/（ m2 d） , dl - 3 ;Ara - C, 1.0 g/m2, q l 2h, dl - 3. The children who achieved complete remission （CR） could get into the following sequential regimens or allogeneic hematopoietic stem cell transplantation（ allo - HSCT）. The same regimen was given to the children who didn＇t achieve CR when WBC 〉 2.0 × 109/L. The efficacy and hematology or non - hematology adverse effect were evaluated. Results CR/partial remission （PR）/non - remission （NR） were respectively 4/3/5 cases after giving the first regimen, and CR./PR/NR were 5/3/4 cases after giving the second regi- men,respectively. The overall remission was 66.7% （8/12 cases） , of which 5 cases（41.7% ） achieved CR,3 cases （25.0%） reached PR and 4 cases（33.3% ） reached NR. Grade IV myelosuppression occurred in all patients, but no severe infection and hemorrhage happened after the application of granulocyte colony stimulating factor （ G - CSF ） , platelet transfusion and anti - infection treatment. Some reversible side effects like liver toxicity, myocardial damage and nerve injury were observed in some patients. There was no chemotherapy related mortality in all the patients. Two cases relapsed again followed up to October 2015. One achieved CR after applying chimeric antigen receptor T - cell immuno- therapy and was receiving allo - HSCT now. Another was dead after applying FLAG （ Prednisone ＋ Fludarabine ＋ Ara - C ＋ G - CSF） save regimen. The time of the other 3 cases achieving CR was 26,10,4 months, respectively. Among the remaining 7 cases, 3 cases were forced to receive hematopoietic stem cell transplantation, 2 cases abandoned treatment and 2 cases failed to follow - up. Conclusions The IHDA regimen is a well - effective and tolerated treatment for pe- diatric patients with refractory ALL, and could create an opportunity for the application of allo- HSCT.