1.
Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF
Garciaz, S., Sfumato, P., Granata, A., Imbert, A. M., Fournel, C., Calmels, B., Lemarie, C., Chiaroni, J., Blaise, D., Boher, J. M., et al
PloS one. 2020;15(3):e0228878
Abstract
We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.
2.
A matched-pair analysis reveals marginally reduced CD34+ cell mobilization on second occasion in 27 related donors who underwent peripheral blood stem cell collection twice at the same institution
Velier, M., Granata, A., Bramanti, S., Calmels, B., Furst, S., Legrand, F., Harbi, S., Faucher, C., Devillier, R., Blaise, D., et al
Transfusion. 2019
Abstract
BACKGROUND In a small proportion of cases, hematopoietic function is insufficient after allogeneic hematopoietic stem cell transplantation, as a result of poor graft function or graft failure. These complications are common indications of re-mobilization of the initial donor, either for a second allograft or for an infusion of CD34+ Selected stem Cell Boost (SCB). METHODS AND MATERIALS We retrospectively reviewed the results of two cycles of CD34+ cell mobilization and collection. CD34+ cells mobilized and collected at each cycle were compared. When CD34+ cell selection from the collected allogeneic mononuclear cells was indicated, it was performed with the Clinimacs Plus(R) medical device, and results from in-process and final quality checks were analyzed. To assess the efficacy of CD34+ SCB, transfusion needs before and after the infusion of selected CD34+ cells were calculated. RESULTS The median peripheral blood concentration of CD34+ cells/muL was marginally reduced during the second cycle (35.6 vs 33.8, p < 0.05); results revealed a strong correlation between paired values (r = 0.85). The cumulative number of collected CD34+ cells were similar for both cycles; the total processed blood volume was higher during the second cycle (p = 0.023). For CD34+ immune-selection procedures, CD34+ cell recovery and purity were respectively 57% and 95%, with a median T-cell depletion of 6.7 log. Recipients' needs for platelet and red blood cell transfusions were significantly reduced after CD34+ SCB. CONCLUSION This study confirms the feasibility of a second cycle of mobilization in healthy related donors and the benefits of CD34+ SCB on hematopoietic reconstitution.
3.
Incidence of Second Primary Malignancies after Autologous Transplantation for Multiple Myeloma in the Era of Novel Agents
Sahebi, F., Iacobelli, S., Sbianchi, G., Koster, L., Blaise, D., Reményi, P., Russell, N. H., Ljungman, P., Kobbe, G., Apperley, J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018;24(5):930-936
Abstract
The advent of novel agents for multiple myeloma (MM) is cause for a re-examination of the incidence of second primary malignancies (SPMs). We examined the SPM rate in MM patients who were enrolled in the prospective observational CALM (Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma) study. Between 2008 and 2012, 3204 patients with MM underwent a first autologous hematopoietic stem cell transplantation. Plerixafor was used as a mobilizing agent for patients with poor (or potentially poor) stem cell mobilization as defined by the respective centers. A total of 135 patients developed SPMs, with a cumulative incidence of 5.3% (95% confidence interval, 4.4 to 6.3) at 72 months. Ninety-four patients developed solid tumors, 30 developed hematologic malignancies, and 11 developed an SPM of an unknown type. The cumulative incidence of known hematologic and solid malignancies were 1.4% and 3.6%, respectively, at 72 months. In a univariate analysis, use of radiotherapy, type of induction regimen, hematopoietic stem cell dose, poor mobilizer status, plerixafor use, and sex did not influence the cumulative incidence of SPMs. Only age over 65 years was statistically associated with an increased incidence. Overall, the incidence of SPMs was comparable to earlier estimations of SPMs in MM.