Higher efficacy of oral etoposide for mobilization of peripheral blood stem cells in patients with multiple myeloma

This study compares the efficacy,toxicity,hematopoietic recovery,and cost of stem-cell mobilization using intermediate-dose cyclophosphamide(IDCy)plus granulocyte colony-stimulating factor(G-CSF)compared with etoposide(VP-16)plus pegylated granulocyte colony-stimulating factor(PEG-rhG-CSF)in multiple myeloma(MM)patients.Two hundred forty-four consecutive patients undergoing mobilization with IDCy(3-3.5g/m^(2))plus G-CSF(n=155)were compared with patients receiving VP-16 plus PEG-rhG-CSF(n=89),including oral etoposide(n=65)and intravenous etoposide(n=24).Compared with IDCy,VP-16 use was associated with significantly higher median peak peripheral blood CD34+cell count(8.20[range:1.84-84]×10^(6)/kg vs 4.58[range:0.1-27.9]×10^(6)/kg,P=.000),and ideal CD34+cell yield of more than 6×10^(6)/kg(56.8%vs 35.1%,P=.001),notably with a higher efficacy in oral VP-16 use compared with IDCy use(CD 34+cell counts:median peak peripheral blood 5.87 vs 4.58?106/kg and≥6×10^(6)/kg[48.4%vs 35.1%]).The median number of apheresis courses was reduced from two in the IDCy group to one in the VP-16 group(P=.000).IDCy use was associated with significantly more frequent episodes of neutropenia(70.2%vs 35.2%;P=.000),intravenous antibiotic use(13.2%vs 11.4%;P=.672),and hospitalization(P=.000).The recoveries of neutrophils and platelets after autologous stem-cell transplantation were significantly faster in the VP-16 group compared with the IDCy group(P=.000).Our data indicate robust stem-cell mobilization in MM patients with VP-16 delivered either orally or intravenously.When compared with intravenous VP-16,oral VP-16 mobilization was associated with significantly more convenient,lower average total costs,and especially decreased the risk of hospital visits and exposure.

A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors

Several obstacles to the production,expansion and genetic modification of immunotherapeutic T cells in vitro have restricted the widespread use of T-cell immunotherapy.In the context of HSCT,delayed naïve T-cell recovery contributes to poor outcomes.A novel approach to overcome the major limitations of both T-cell immunotherapy and HSCT would be to transplant human T-lymphoid progenitors(HTLPs),allowing reconstitution of a fully functional naïve T-cell pool in the patient thymus.However,it is challenging to produce HTLPs in the high numbers required to meet clinical needs.Here,we found that adding tumor necrosis factor alpha(TNFα)to a DL-4-based culture system led to the generation of a large number of nonmodified or genetically modified HTLPs possessing highly efficient in vitro and in vivo T-cell potential from either CB HSPCs or mPB HSPCs through accelerated T-cell differentiation and enhanced HTLP cell cycling and survival.This study provides a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified HTLPs for accelerating immune recovery after HSCT and for T-cell-based immunotherapy(including CAR T-cell therapy).

The more, the less： age and chemotherapy load are predictive of poor stem cell mobilization in patients with hematologic malignancies

Background Intensive treatment such as autologous peripheral blood stem cell （PBSC） transplantation is an important therapeutic strategy in many hematologic malignancies.A number of factors have been reported to impact PBSC mobilization,but the predictive factors varied from one study to another.This retrospective study assessed our current mobilization and collection protocols,and explored the factors predictive of PBSC mobilization in patients with hematologic malignancies.Methods Data of 64 consecutive patients with hematologic malignancies （multiple myeloma,n=22; acute leukemia,n=27; lymphoma,n=15） who underwent PBSC mobilization for over 1 year were analyzed.Four patients with response to treatment of near complete remission or better were administered granulocyte colony-stimulating factor （G-CSF） to mobilize PBSCs.Sixty patients received G-CSF followed by chemotherapy mobilizing regimens.Poor mobilization （PM） was defined as when ≤2.0×106 CD34＋ cells/kg body weight were collected within three leukapheresis procedures.Results The incidence of PM at the first mobilization attempt was 19% （12/64）.The PM group was older than the non-PM group （median age,51 vs.40 years; P=0.013）.In univariate analysis,there were no significant differences in gender,diagnosis,and body weight between the PM and non-PM groups.A combination of chemotherapy and G-CSF was more effective than G-CSF alone as a mobilizing regimen （P=0.019）.Grade Ⅲ or Ⅳ hematopoietic toxicity of chemotherapy had no significant effect on the mobilization efficacy.Supportive care and the incidence of febrile neutropenia were not significantly different between the two groups.In multivariate analysis,age （odds ratio （OR）,9.536;P=-0.002） and number of previous chemotherapy courses （OR 3.132; P=0.024） were two independent negative predictive factors for CD34＋ cell yield.PM patients could be managed well by remobilization.Conclusion Older age and a heavy load of previous chemotherapy are the negative risk factors for PBSC mobilization.