Key Points• Matching for MICA significantly reduces the incidence of acute and chronic GVHD in otherwise HLA 10/ 10-matched unrelated-donor HCT.• Our results formally define MICA as a novel major histocompatibility complex-encoded human transplantation antigen.
The limited number of progenitor stem cells in umbilical cord blood (UCB) enforces the optimization and strict control of all the procedures involved in its therapeutic use--ie, collection, processing, cryopreservation, thawing, and transportation--to ensure graft potency at transplantation. For this reason, international UCB standards recommend storage of a cell sample attached to the UCB unit as a quantitative and functional control of the unit selected for transplantation. To validate the use of the sample attached to the UCB unit as a quality-control tool for the final product, UCB units (n = 20) stored in liquid nitrogen with the Bioarchive system were analyzed. The UCB units and their attached segments were thawed, and the number and viability of total nucleated cells, mononucleated cells, CD45 + cells, and CD34+ cells were determined, as were colony-forming cell counts. There was no significant difference between UCB units and segments for any of the parameters assessed. Additionally, the linear correlation coefficient (R2) in these paired samples was 0.85 and 0.78 for CD34+ cells and colony-forming cells, respectively. In conclusion, the cell sample in the tube segment physically linked to the transplant UCB bag predicts the total cell content and functionality of the unit and may serve as a source for final quality control of the UCB unit before transplantation.
The cryopreservation of PBPC components at standard concentrations and 3.3 (1.8-6.2)-fold cell concentrations has no adverse effect on the function of HPCs after thawing.
The automatic washing method described is as effective as the manual method in terms of viability and progenitor cells recovery, but faster and easier for the operators to perform. Overall, our data suggest that the automatic method is safe and suitable for the routine washing of thawed CB grafts in the clinic.
BackgroundAlthough adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells (CD19-CAR T-cells) achieves high rates of complete response in patients with B-cell acute lymphoblastic leukemia (B-ALL), relapse is common. Bone marrow (BM) mesenchymal stem/stromal cells (BM-MSC) are key components of the hematopoietic niche and are implicated in B-ALL pathogenesis and therapy resistance. MSC exert an immunosuppressive effect on T-cells; however, their impact on CD19-CAR T-cell activity is understudied.MethodsWe performed a detailed characterization of BM-MSC from pediatric patients with B-ALL (B-ALL BM-MSC), evaluated their immunomodulatory properties and their impact on CD19-CAR T-cell activity in vitro using microscopy, qRT-PCR, ELISA, flow cytometry analysis and in vivo using a preclinical model of severe colitis and a B-ALL xenograft model.ResultsWhile B-ALL BM-MSC were less proliferative than those from age-matched healthy donors (HD), the morphology, immunophenotype, differentiation potential and chemoprotection was very similar. Likewise, both BM-MSC populations were equally immunosuppressive in vitro and anti-inflammatory in an in vivo model of severe colitis. Interestingly, BM-MSC failed to impair CD19-CAR T-cell cytotoxicity or cytokine production in vitro using B-ALL cell lines and primary B-ALL cells. Finally, the growth of NALM6 cells was controlled in vivo by CD19-CAR T-cells irrespective of the absence/presence of BM-MSC.ConclusionsCollectively, our data demonstrate that pediatric B-ALL and HD BM-MSC equally immunosuppress T-cell responses but do not compromise CD19-CAR T-cell activity.
This retrospective study presents data from 105 consecutive multiple myeloma and lymphoma patients who had PB CD34+ cell counts o 10/μL on day 4 of steady-state G-CSF mobilization for autologous hematopoietic cell transplantation. Our results confirm the capacity of plerixafor to improve mobilization outcomes in this clinical setting. In addition, they show that the effectiveness of plerixafor, compared with G-CSF only, translates to patients with very low (o 3.5/μL) circulating CD34+ cell counts: overnight CD34+ cell count expansion (5.3-vs 1.7-fold), overall CD34+ cell yield (2.29 vs 0.15 × 10 6 CD34+ cells per kg) and patients yielding ⩾ 2 × 10 6 CD34+ cells per kg (63% vs 3%). Furthermore, our data also show that preemptive plerixafor is significantly more effective and more efficient than in remobilization: CD34+ cell yield in the first apheresis (3.28 vs 2.0 × 10 6 CD34+ cells per kg) and overall (3.73 vs 2.44 × 10 6 CD34+ cells per kg), patients yielding ⩾ 2 × 10 6 CD34+ cells per kg in the first apheresis (85% vs 44%) and overall (92% vs 64%), all this requiring less days and doses of plerixafor treatment (1.08 vs 1.48). These data would advocate using plerixafor as an early preemptive intervention based on day 4 circulating CD34+ counts, including very high-risk patients with very low circulating levels.
These results support the use of 7.5-10% as the optimal DMSO concentration and the maximum exposure time should be limited to <1 h prior to freezing and 30 min post-thaw.
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