CLAT Combinated With HLA-mismatched G-PBSC(Microtransplantation)for Refractory Acute Myeloblastic Leukemia

BackgroundPatients with refractory acute myeloblastic leukemia had poor outcomes and there was no effective standard-of-care therapy existed.This study aimed to analyze the efficacy and safety of CLAT regimen(Cladribine,cytarabine and topotecan)and CLAT combinated with HLA-mismatched G-PBSC infusion(microtransplantation)in patients with refractory acute myeloblastic leukemia(AML).Methods1)CLAT:The induction chemotherapy consisted of cladribine 5 mg/m2/d intravenously for 5 consecutive days(day 1～5)and topotecan 1.25 mg/m2/d persral for 5 days(day 1～5)for priming combined with cytarabine of 1.0 g/m2/d q12h for 5 days(day 1～5).G-CSF of 300 4g/day subcutaneous injection on day 6 until ANC>1.0×109/L.2)Microtransplantation:To evaluate outcomes in patients with refractory AML who receive granulocyte colony-stimulating factor(G-CSF)-mobilized HLA-mismatched donor peripheral-blood stem cells after the CLAT regimen of chemotherapy treatment.Apheresis of HLA-mismatched donor peripheral mononuclear cells was carried out with a COBE-spectra 6.0 blood cell separator on days 5 and 6 after the donor was subcutaneously injected with 10 ug/kg/d G-CSF in 2 days.The patient received the target dose of 2.0×108、kg for mononuclear cells or 1.0×108/kg of G-PBSC cells for CD3 cells 24～72 hours after the CLAT treatment.Results1)CLAT:Total of thirty-five patients with refractory AML were enrolled in this study.There were 25 males and 10 females with a median age of 31 years(range 14～58years).21 patients were primary refractory AML,and 14 patients were secondary refractory AML.17(48.6%)of 35 patients achieved complete remission(CR)or complete remission with incomplete marrow recovery(CRi),and 1(2.9%)patients achieved partial remission.Overall,the overall response rate was 51.4%.Ater two courses of CLAT treatment,19(54.3%)of 35 patients achieved CR/CRi.The most common treatment-emergent adverse events were hematological toxicity and infections.Grade IV myelosuppression events were 100%.The median duration of neutrophils<0.5×109/L and PLT<20×109/L is 14(range 3～46)days and 11.5(range 2～40)days.2)Microtransplantation:Nine patients with the median age 34(range 20～44)years,including 7 males and 2 female were enrolled.After the first cycle,4(44.4%)of 9 patinets achieved CR and 3(33.3%)patients achieved PR,the overall response rate was 66.7%.5(55.6%)of 9 patients achieved CR/CRi after the second cycle treatment.The median recovery time for neutrophils and platelets were 14(range 7～21)days and 8(range 0～19)days.Conclusion:CLAT regimen was well tolerated and showed a promising clinical efficacy in patients with refractory AML.Infusions of G-CSF-mobilized HLA-mismatched donor peripheral-blood stem cells can promote hematopoietic recovery and improve outcome but avoid GVHD.