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1.
Leukemia ; 34(12): 3370-3381, 2020 12.
Article in English | MEDLINE | ID: mdl-32690879

ABSTRACT

In the context of hematopoietic cell transplantation, hematopoietic stem cells and progenitor cells (HSC and HPC) are usually collected by apheresis following their mobilization by G-CSF alone or in combination with Plerixafor® when patients fail to respond to G-CSF alone. In medical practice, the quality of the hematopoietic graft is based on CD34+ cell content that is used to define "Good Mobilizer (GM)" or "Poor Mobilizer (PM)" patients but does not report the real HSC content of grafts. In this study, we assessed the HSC content within the CD34+ fraction of graft samples from 3 groups of patients: 1-GM patients receiving G-CSF only (GMG-CSF), 2-PM patients receiving G-CSF only (PMG-CSF), 3-PM patients receiving G-CSF + Plerixafor (PMG-CSF+P). Although HSC from the 3 groups of patients displayed very similar phenotypic profiles, expression of "stemness" genes and metabolic characteristics, their capacity to engraft NSG mice differed revealing differences in terms of HSC between groups. Indeed according to mobilization regimen, we observed differences in migration capacity of HSC, as well as differences in engraftment intensity depending on the initial pathology (myeloma versus lymphoma) of patients. This suggests that mobilization regimen could strongly influence the long term engraftment efficiency of hematopoietic grafts.


Subject(s)
Antigens, CD34/metabolism , Granulocyte Colony-Stimulating Factor/metabolism , Heterocyclic Compounds/therapeutic use , Animals , Benzylamines , Child , Cyclams , Female , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/metabolism , Humans , Lymphoma/drug therapy , Lymphoma/metabolism , Male , Mice , Middle Aged , Multiple Myeloma/drug therapy , Multiple Myeloma/metabolism , Stem Cells/drug effects , Stem Cells/metabolism
2.
J Clin Apher ; 35(4): 281-289, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32369661

ABSTRACT

INTRODUCTION: No randomized controlled clinical trial of therapeutic plasma exchanges (TPE) has yet been performed for moderate-to-severe relapses of multiple sclerosis (MS). OBJECTIVE: To compare TPE to sham-TPE in patients with a recent steroid-resistant moderate-to-severe MS relapse. METHODS: Patients presenting with an MS relapse of less than 2 months without improvement and 15 days after a course of steroids were randomized. Specific criteria were used for each relapse type to define moderate-to-severe disability. The primary endpoint was the proportion of patients with at least a moderate improvement based on objective and functional evaluation after 1 month. RESULTS: Thirty-eight patients were randomized. The intention-to-treat analysis included 14 patients in the TPE group and 17 in the Sham-TPE group. The proportion of patients with at least moderate improvement at 1 month did not differ between the groups (P = .72), although 57.1% of the TPE group had full recovery compared with 17.6% of the sham group. Considering optic neuritis (ON), a significant difference in the proportion of different levels of improvement was observed in favor of the TPE group (P = .04). The combined Kurtzke's functional systems scores were significantly more improved in the TPE group than in the sham-TPE group at months 1 (P < .01), 3 (P < .05), and 6 (P < .05). No major side effects were observed. CONCLUSIONS: A significant difference between TPE and Sham-TPE at the primary endpoint was only observed in patients with ON. Neurological function improved significantly more often in the TPE group than in the sham-TPE group.


Subject(s)
Multiple Sclerosis/blood , Multiple Sclerosis/therapy , Plasma Exchange/methods , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Disease Progression , Double-Blind Method , Female , Humans , Male , Middle Aged , Optic Neuritis/complications , Phenotype , Recurrence , Sample Size , Steroids/therapeutic use , Treatment Outcome , Young Adult
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