The Clinical Study Of HLA-haploidentical Lymphocyte Infusions For 59 Patients With Refractory Solid Tumors

Objective:Observe the short-term efficacy,the toxicity,and the quality of life about HLA-haploidentical lymphocyte infusions for refractory solid tumors,and explore its clinical value.Data and Methods:Patients with phase IV solid tumors who were failed by conventional therapy,understand and are willing to accept HLA haploidentical lymphocyte infusions,then sign the informed consent. All patients received routine therapy 4 to 8 weeks before DLI or simultaneously. Patients with gastric cancer received conventional doses of"Taxane+ Oxaliplatin"or"Capecitabine"4 to 8 weeks before DLI;patients with RCC take"Thalidomide"orally during DLI;patients with HCC undergo a TACE with"Cisplatin+Epirubicin"4 to 8 weeks before DLI;the other acceptted common radiotherapy or chemotherapy before DLI. Donor/recipient's loci determination for six sites among HLA-A,HLA-B,HLA-DR,is needed for the pairs. We must detect ABO blood type,HBsAg,anti-HIV,anti-HCV and syphilis antibody for the suitable donors. The eligible donors have a collection of MNCs on the CS-3000Plus blood cell separator,according to the"lymphocyte collection procedures",and the circulating blood volume is 8000ml. The MNCs is about 55ml,diluted into 200ml by 145ml of normal saline. The mixture above will accept 60Go irradiation (DT 25Gy),then infuse into the patients. Repeat the infusion every 4～8 weeks,detect the value of CD3/HLA-DR and CD25 pre-DLI and post-DLI,observe the occurrence of GVHD. Acute GVHD is clinically graded asⅠ～Ⅳbased on Glucksberg criteria,and chronic GVHD is classified as mild,moderate and severe according to National Institutes of Health consensus development project on standards for cGVHD. 4 weeks after each infusion,there is a conventional evaluation,which is classified into CR,PR,SD and PD on the basis of RECIST,the percentage of CR and PR plus SD is regarded as the disease control rate. Meanwhile,we evaluate the quality of life in terms of Karnofsky Performance Status standards.Results:①From February 2004 to August 2008,59 patients with refractory solid tumors accepted (0.983±0.425)×108 CD3+cells/Kg weight of DLIs,all can be evaluated. 1 of 16 cases with gastric cancer achieved CR,8 SD,and 7 PD,the DCR is 56.25%,and the median OS is 15.7 months (8.5 to 52.1 months);the DCR of 13 patients with RCC is 46.15%,including 1 CR and 5 SD,and the median OS is 28.3 months (8.9 to 46.4 months);in 11 cases of HCC,6 had SD and 5 PD,the DCR is 54.55%,and the median OS is 9.6 months (3.6 to 51.2 months). The other malignants were 19 cases,one achieved PR,6 SD,and 12 PD,the DCR is 36.84%,and the median OS is 16.3months (7.4 to 54.8 months).②The DCR with 2～7 times of DLIs is higher than only once(P <0.05);the DCR of the group with >1.0×108CD3+ cells/Kg is higher than the other one with <1.0×108CD3+cells/Kg(P <0.005);46 patients had a detection of CD3/HLA-DR and CD25 before and after DLI,the DCR of the group with CD3/HLA-DR rising is higher than the decline one(P <0.005),and the change of CD25 is similar(P<0.05);the difference of DCR between different diseases,combinations of donor/recipient and loci-mismatched numbers are no signi- ficant(P>0.50).③The toxicities can be assessed in all patients,and 10 cases (16.95%) occurred in gradeⅠ～Ⅱof aGVHD,not gradeⅢ～ⅣaGVHD or cGVHD.④The KPS score has a improvement with 10 points or more in 29 patients after DLI.Conclusion:①HLA haploidentical lymphocyte infusions may have some effects for patients with relapsed or refractory solid tumors.②The toxicities is not significant in HLA haploidentical lymphocyte infusions for relapsed or refractory solid tumors.③Whether HLA haploidentical lymphocyte infusions for relapsed or refractory solid tumors can improve the overall survival or not remains to be seen.