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Post-remission strategies for patients with acute lymphoblastic leukemia (ALL) are limited to the multiagent chemotherapy and allogeneic stem cell transplant (allo-SCT), and cellular therapies are seldom involved. Although chemotherapy combined with mismatched granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell infusion (microtransplant, MST) has been studied in patients with acute myeloid leukemia, its efficacy in ALL is still undetermined. We enrolled 48 patients receiving hyper-CVAD-based MST between July 1, 2009, and January 31, 2018. No acute or chronic graft-versus-host disease occurred in patients receiving MST. Four-year overall survival (OS) and leukemia-free survival (LFS) were 62% and 35%, respectively, and the 4-year relapse rate was 65%. No patient experienced non–relapse mortality. Subgroup analysis showed that OS rates were comparable between groups with different age, risk stratification, minimal residual disease status prior to MST and immunophenotype. Adult patients tended to achieve better 4-year LFS (62% vs. 26%, P = .058) and lower hematologic relapse rate (38% vs. 74%, P = .058) compared with adolescent and young adult patients. Donor chimerism/microchimerism was detectable ranging from 0.002% to 42.78% in 78% (42/54) available samples within 14 days after each infusion and at 3 months or one year after the last cell infusion. Multivariate analyses demonstrated that white blood cells

Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) have poor prognosis, and the efficacy of chemotherapy plus tyrosine kinase inhibitors (TKIs) followed by mismatched donor stem cell infusion (microtransplantation, MST) has not been determined. We retrospectively summarized 45 patients including 11 undergoing MST with TKIs, 17 receiving allogeneic transplant and 17 undergoing chemotherapy with TKIs. Improved 4-year overall survival rate was observed in the MST group (91%) compared with either transplant group (31%, P = .005) or chemotherapy group (36%, P = .013). The MST group also had higher 2-year and 4-year leukemia-free survival rates (91% and 72%, respectively) compared with either transplant group (33%, P = .005 and 33%, P = .021, respectively) or chemotherapy group (41%, P = .017 and 31%, P = .023, respectively). 2-year and 4-year cumulative incidences of hematologic relapse were lower in the MST group (9% and 28%, respectively) compared with those in the chemotherapy group (56%, P = .025 and 67%, P = .034, respectively). In patients undergoing MST, donor microchimerism was detected (1.07 × 10(-5) to 6.6 × 10(-4) copies from 9 to 1499 days) in 7 patients, and donor/patient-derived HLA*0201/2402(+)WT1(+)CD8(+) T cells were found from 0.05% to 0.67% in 6 patients. MST may provide a favorable treatment for patients with Ph(+) ALL.

Supplemental material, Supplementary_figure_and_table for Co-infusion of high-dose haploidentical donor cells and CD19-targeted CART cells achieves complete remission, successful donor engraftment and significant CART amplification in advanced ALL by Changlin Yu, Bo Cai, Yao Wang, Zhiqiang Wu, Kaixun Hu, Qiyun Sun, Jianhui Qiao, Yanhong Fang, Hongli Zuo, Yi Wang, Zheng Dong, Zechuan Zhang, Yajing Huang, Zhiqing Liu, Tieqiang Liu, Huisheng Ai, Weidong Han and Mei Guo in Therapeutic Advances in Medical Oncology

Preparation, detection, and quantification of CD19-directed chimeric antigen receptor-modified T (CAR-T) cells. (DOCX 17Â kb)

Preparation and quality control of mesenchymal stem cells (MSC). (DOCX 12Â kb)

This paper extends the stochastic perturbation method to vector-valued and matrix-valued functions. The numerical method for the response and reliability of uncertain structures is formulated using matrix calculus, Kronecker algebra and perturbation theory. Random variables and system derivatives are conveniently arranged into two-dimensional matrices and generalized mathematical formulae are obtained. The results derived are easily amenable to computational procedures.

This study was performed to assay whether leukemia-associated antigen (LAA)-specific CTLs of recipient origin existed in the blood of patients who achieved full donor chimerism (FDC) soon after nonmyeloablative transplantation (NST). In 15 patients who received haplo-identical NST, WT1(+) CD8(+) CTLs were detected with WT1/HLA-A*0201 pentamer, and the donor-recipient chimerism levels were analyzed by three methods. Results showed that WT1(+) CD8(+) CTLs could be detected in patients with HLA-A*0201 expressing only in recipient, and cells of recipient origin existed in the blood of patients who achieved FDC, which suggested that LAA-specific CTLs of recipient origin may exist in patients achieving FDC soon after NST.