Hematopoiesis reconstitution and anti-tumor effectiveness of Pai-Neng-Da capsule in acute leukemia patients with haploidentical hematopoietic stem cell transplantation

BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.

Effects of adenovirus mediated vascular endothelial growth factor gene transfer on reconstitution of hematopoiesis in post-bone marrow transplantation mice

Background Bone marrow transplantation ( BMT) conditioning procedure isconsidered as the cause of damage to bone marrow microvasculature and the delay of hematopoiesisrecovery. However, hematopoiesis regulation post BMT by vascular endothelial growth factor ( VEGF)has not yet been studied. In this study, adenovirus were used to investigate the effects of VEGFgene transfer on preventing damages to bone marrow microenvironment and its promotion ofhematopoiesis in post-BMT mice. Methods Recombinant adenovirus (Ad)-enhanced green fluorescentprotein (EGFP)/hVEGF_(165) was injected via tail vein into BALB/c mice undergoing syngeneic BMT.During the different phases post BMT, the distribution of adenovirus and the plasma levels of hVEGFwere measured as well as the numbers of white blood cells (WBC) , platelet (PLT) and red blood cells(RBC) in peripheral blood. At the same time, the mice were injected with Chinese ink via tail vein,following which the tibias were separated and were used for analysis of bone marrowmicrovasculature surface area and cellularity. Results Significant expression of EGFP and hVEGF wasobserved in multiple organs at different phases post BMT, and the plasma level of hVEGF was up to(866. 67 ± 97. 13 ) pg/ml. The recovery of WBC, PLT and RBC of the group treated with recombinantadenovirus Ad-EGFP/hVEGF_(165) were significantly more rapid than those of other BMT groups (P <0.05 , respectively). At the 20th day post BMT, the percentage of bone marrow microvasculaturesurface area in group treated with VEGF [ (61.2 ± 4.0)% ] returned to normal level [ (62.0 ± 5. 0)% , P > 0. 05 ]. The restoration of hematopoiesis was retarded more than that of microvasculature.The cellularity of bone marrow in each group was still lower than that of normal control [ ( 62. 3± 4. 0 ) % , P < 0. 05 ] at the 30th day post BMT, but the percentage in group treated with VEGF atthe 20th and 30th days post BMT [(46.5 ± 5.0)% and (55.1 ± 4.5)%] exceeded those of other BMTgroups (P < 0. 05, respectively). Conclusion VEGF gene transfer mediated by adenovirus may protectthe hematopoietic microenvironment to promote the restoration of hematopoiesis in post-BMT mice.