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The Impact of CD34(+) Cell Collection Yields for Autologous Transplant on Survival Outcomes in Multiple Myeloma
Lebel, E., Lajkosz, K., Masih-Khan, E., Reece, D., Trudel, S., Tiedemann, R., Prica, A., Kukreti, V., Chen, C.
Clinical lymphoma, myeloma & leukemia. 2023
Abstract
INTRODUCTION According to previous data, higher yields of stem-cells collected to support autologous transplantation may predict for improved outcomes. We aimed to assess the association between high stem-cells collection and survival outcomes in multiple myeloma (MM) MATERIALS AND METHODS We reviewed all patients who underwent autologous transplantation for MM at our center over a 10-year period, and initially used a predefined threshold of 8 × 10(6)/kg used in previous studies. RESULTS Six hundred twenty-one patients were analyzed. Higher mobilization did not correlate with favorable outcomes post-transplant. The most efficient mobilizers, collecting ≥8 × 10(6)/kg (n = 478) achieved a shorter median progression-free survival (PFS) of 24.1m versus 34.5m in patients collecting 4.5 to 8 × 10(6)/kg (n = 129). A small group (n = 14) collecting ≤4.5 × 10(6)/kg but minimum of 2 × 10(6)/kg to support autologous transplantation exhibited the worst outcomes (median PFS 11.4m). Further analysis of potential confounders identified greater use of bortezomib induction in the lower mobilizers, however, sensitivity analysis in patients receiving bortezomib revealed similar results- worst outcomes to the most efficient mobilizers. CONCLUSION Although bortezomib is not considered stem-cell toxic, it may be associated with lower stem cell collection yields. Bortezomib's efficacy at induction may partially explain the improved outcomes, however, other factors may be involved, and are discussed. We can conclude that with our large cohort and long follow-up, high stem-cell mobilization does not appear to predict for a long-term survival advantage.
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Impact of residual tumor cells in the stem cell collection on multiple myeloma patients receiving autologous stem cell transplantation
Xu, J., Yan, W., Fan, H., Liu, J., Li, L., Du, C., Deng, S., Sui, W., Xu, Y., Qiu, L., et al
Annals of hematology. 2023
Abstract
Autologous stem cell transplantation (ASCT) is the standard therapy for patients with transplant-eligible multiple myeloma (TEMM). However, the ideal depth of response required before ASCT and the impact of residual tumor cells in the stem cell collection (SCC) on survival remains unclear. Here we collected data of 89 patients with TEMM undergoing ASCT and analyzed the minimal residual disease of SCC (cMRD) and bone marrow (BM) (mMRD) before transplantation. Before ASCT, 31.5% and 76.4% of patients achieved MRD negativity in BM and SCC, respectively. Tumor cells were less in SCC samples than that in BM samples. Neoplastic cells in SCC could be observed in patients with different responses after induction therapy, and there were no significant differences in the percentage and level of cMRD among these subgroups (P > 0.05). No correlation was found between the cMRD status and the response patients achieved after ASCT (P > 0.05). The median follow-up was 26.8 months. mMRD negativity before ASCT was associated with longer PFS (55.9 vs. 27.1 months; P = 0.009) but not OS (not reached vs. 58.9 months; P = 0.115). Patients with different cMRD statuses before ASCT experienced similar PFS (40.5 vs. 76.4 months for negativity vs. positivity; P = 0.685) and OS (not reached vs. 58.8 months for negativity vs. positivity; P = 0.889). These results suggested that detectable cMRD does not significantly predict the inferior post-ASCT response or shorter survival, and patients are eligible to undergo ASCT upon achieving partial response.
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Prolonged Lenalidomide Induction Does Not Significantly Impair Stem Cell Collection in Multiple Myeloma Patients Mobilized With Cyclophosphamide or Plerixafor: A Report From The Covid Era
Rybinski, B., Rapoport, A. P., Badros, A. Z., Hardy, N., Kocoglu, M.
Clinical lymphoma, myeloma & leukemia. 2022
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Abstract
INTRODUCTION Induction therapy for multiple myeloma is traditionally capped at 6 cycles of lenalidomide due to concerns that longer treatment compromises the ability to collect sufficient stem cells for autologous stem cell transplantation (ASCT). However, during the COVID-19 pandemic, many of our patients received prolonged lenalidomide induction due to concerns about proceeding to ASCT. We investigated whether prolonged induction with lenalidomide affects the efficacy of stem cell collection among patients mobilized with cyclophosphamide and/or plerixafor. PATIENTS AND METHODS This single center, retrospective study included patients who were treated with lenalidomide induction regimens, received mobilization with cyclophosphamide or plerixafor, and underwent apheresis in preparation for ASCT. 94 patients were included, 40 of whom received prolonged induction with >6 cycles of lenalidomide containing regimen. RESULTS Patients who received prolonged induction were more likely to require >1 day of apheresis (38% vs. 15%; OR 3.45; P = .0154), and there was a significant correlation between the duration of lenalidomide treatment and the apheresis time required to collect sufficient cells for transplant (R(2) = 0.06423, P = .0148). However, there was no significant difference between patients who received prolonged induction and those who did not with respect to CD34(+) stem cell yields at completion of apheresis (9.99 vs. 10.46 cells/Kg, P = .5513) or on the first day of collection (8.29 vs. 9.59 cells/Kg, P = .1788). CONCLUSION Among patients treated with >6 cycles of lenalidomide, mobilization augmented with cyclophosphamide and/or plerixafor will likely facilitate sufficient stem cell harvest to permit ASCT.
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Impact of daratumumab based induction on stem cell collection parameters in Swedish myeloma patients
Lemonakis, K., Tatting, L., Lisak, M., Carlson, K., Crafoord, J., Blimark, C. H., Santamaria, A. I., Wichert, S., Lenhoff, S., Hansson, M.
Haematologica. 2022
Abstract
Not available.
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Stem cell yield and transplantation in transplant-eligible newly diagnosed multiple myeloma patients receiving daratumumab + bortezomib/thalidomide/dexamethasone in the phase 3 CASSIOPEIA study
Hulin, C., Offner, F., Moreau, P., Roussel, M., Belhadj, K., Benboubker, L., Caillot, D., Facon, T., Garderet, L., Kuhnowski, F., et al
Haematologica. 2021
Abstract
Not available.
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Autologous stem-cell collection following VTD or VRD induction therapy in multiple myeloma: a single-center experience
Laurent, V., Fronteau, C., Antier, C., Dupuis, P., Tessoulin, B., Gastinne, T., Mahé, B., Blin, N., Dubruille, V., Lok, A., et al
Bone marrow transplantation. 2020
Abstract
Triplet-drug regimen bortezomib-thalidomide-dexamethasone (VTD) and bortezomib-lenalidomide-dexamethasone (VRD) are considered as standard of care induction prior autologous stem-cell transplantation (ASCT) in myeloma. In addition to improve response rate, induction therapy should preserve an adequate stem-cell collection. In the present retrospective study, we analyzed stem-cell collection in 325 newly diagnosed myeloma patients who received either VTD or VRD induction before ASCT. Stem-cell mobilization consisted of intravenous cyclophosphamide plus G-CSF. Plerixafor was administered preemptively to rescue mobilization. In comparison with VTD, VRD induction was associated with a more frequent use of plerixafor (19.3% versus 5.4%, p?=?0.004) and with an increased number of apheresis to reach adequate collection (>2 apheresis required in 42.3% versus 30.2%, p?=?0.05). Moreover, more patients experienced collection failure in the VRD group (6% versus 1.8%, p?=?0.004). The median number of CD34-positive cells (×10(6)/kg) was lower in the VRD group: 8.5 versus 9.3 (p?=?0.05) in the VTD group. The vast majority of patients underwent ASCT (93% versus 98%, in VRD and VTD group, respectively). These data highlight the need of optimal stem-cell collection strategy, especially in the context of tandem transplantation and incorporation of anti-CD38 monoclonal antibody into induction.
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Optia(R) continuous mononuclear collection (CMNC) system is a safe and efficient system for hematopoietic progenitor cells-apheresis (HPC-a) collection and yields a lower product hematocrit (HCT%) than the COBE(R) spectra system: A retrospective study
Pandey, S., Cottler-Fox, M.
Journal of clinical apheresis. 2018
Abstract
PURPOSE We evaluated the Optia(R) continuous mononuclear collection (CMNC) system for hematopoietic progenitor cell-apheresis (HPC-A) collection (Terumo BCT, Lakewood, CO) compared to the COBE(R) Spectra (Terumo BCT, Lakewood, CO), including both large volume leukapheresis (LVL) and non-LVL collections. METHODS We performed a retrospective data analysis of all autologous HPC-A collections with the Optia(R) CMNC system (n = 93; LVL = 59, non-LVL = 34) since implementation at our institution and compared it with a similar number of concurrent collections utilizing the COBE(R) Spectra (n = 96; LVL = 68, non-LVL = 28). The population studied included multiple myeloma (62 patients/171 collections) and lymphoma (5 patients/18 collections). Mobilization was achieved using chemotherapy + G-CSF (n = 108), chemotherapy + G-CSF + plerixafor (n = 67), G-CSF alone (n = 10), or G-CSF + plerixafor (n = 4). Based on our minimum predicted collection formula and the collection goal, 7-30 L of whole blood was processed. Per protocol, a minimum of 2 days of collection was performed. RESULTS HPC-A collected on Optia(R) CMNC had lower %HCT than those collected on COBE(R) Spectra (3.7 versus 4.3%, P = .029). There were no statistically significant differences between the two devices for other variables examined, including preapheresis WBC count and CD34+ cell count, procedure time, whole blood volume processed, collection efficiency (CE2), % platelet loss and throughput. CE2 for both devices was higher when <30 L of whole blood volume was processed. A linear correlation was noted between the preapheresis CD34+ cell count and CD34+ cells collected. No adverse events or bleeding episodes were noted, even when acetyl salicyclic acid (ASA) was given. CONCLUSIONS Optia(R) CMNC system is equivalent to the COBE(R) Spectra, with significantly lower product HCT%.
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Impact of apheresis automation on procedure quality and predictability of CD34(+) cell yield
Besson, N., Topholm Bruun, M., Stauffer Larsen, T., Nielsen, C.
Journal of clinical apheresis. 2018
Abstract
Success of peripheral blood stem cell (PBSC) collections depends on patient biological parameters and stable apheresis device performance. We investigated product quality and factors influencing main apheresis procedure outcomes including CD34(+) collection efficiency (CE), product volume or platelet CE. We also assessed different CD34(+) cell yield prediction algorithms. Autologous PBSC collections by Spectra Optia from myeloma and lymphoma patients were analyzed. Complete blood count (CBC) from patient preprocedure and from collected products were assessed. (1) Product yield was calculated, (2) Product CBC was correlated with patient preprocedure variables, and (3) Predictions of CD34(+) yields based on (a) product CD34(+) cell concentration in samples after two or four chamber flushes or (b) traditional CE2 benchmark, were compared. 62 procedures in 41 patients were analyzed. 84% of all procedures were run without operator intervention. Median CD34(+) CE2 was 56.9% (48.8%-65.2%) and quite stable irrespective of patient conditions, with minor influence from patient white blood cell (WBC) precounts (rs = -.47; P < .001). Platelet loss correlated with WBC precount (rs = .46; P < .001), product volume (rs = .71; P < .0001) and number of chambers collected (rs = .72; P < .0001). CD34(+) cell yield was better predicted based on (a) product CD34(+) cell concentration from samples after 2 and 4 chamber flushes, respectively (rs = .969; P < .0001 and rs = .9648; P < .0001) than based on (b) CE2 formula (rs = .8262, P < .0001). Spectra Optia provides good quality PBSC products with stable and predictable yield regardless of starting conditions. CD34(+) sampling of product after few chamber flushes could be used to predict CD34(+) yield.
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Performance assessment and benchmarking of autologous peripheral blood stem cell collection with two different apheresis devices
Wuchter, P., Hundemer, M., Schmitt, A., Witzens-Harig, M., Pavel, P., Hillengass, J., Goldschmidt, H., Ho, A. D., Lisenko, K.
Transfusion Medicine. 2017;27(1):36-42
Abstract
BACKGROUND Collection of peripheral blood stem cells (PBSCs) for autologous transplantation is a well-established process. As a new generation of leukapheresis (LP) machines has been launched, measures of benchmarking and quality control need to be defined in order to ensure consistent collection performance. OBJECTIVES The goal of this project was to establish and evaluate a benchmarking system for autologous PBSC collection. METHODS This retrospective study evaluated PBSC collection data of 198 patients with symptomatic multiple myeloma in first-line therapy who underwent LP in 2013 and 2014 at our institution. Half the patients in 2014 were assigned randomly to undergo LP with the new Terumo BCT Spectra Optia (Terumo BCT, Garching, Germany), while the COBE Spectra (Terumo BCT) was used in all other cases. In 2014, we implemented a previously described formula for predicting daily CD34+ cell collection. As a benchmark, we developed the performance ratio: collected/predicted CD34+ cells. RESULTS There was no significant difference in the number of collected CD34+ cells, the collection efficiency (collected/processed CD34+ cells) and performance ratio between the two collection devices and between LP procedures in 2013 and 2014. CONCLUSIONS We present a comprehensive benchmarking tool that is easy to implement, requires minimal expense and allows specific adjustment of LP parameters for optimisation of LP performance. With this approach, we could confirm the equal efficiency of the two compared apheresis systems. Copyright © 2016 British Blood Transfusion Society.
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Circulating hematopoietic progenitors and CD34(+) cells predicted successful hematopoietic stem cell harvest in myeloma and lymphoma patients: experiences from a single institution
Yu, J. T., Cheng, S. B., Yang, Y., Chang, K. H., Hwang, W. L., Teng, C. L.
Journal of Blood Medicine. 2016;7:5-11
Abstract
BACKGROUND Previous studies have shown that the numbers of both circulating hematopoietic progenitor cell (HPC) and CD34(+) cell are positively correlated with CD34(+) cell harvest yield. However, the minimal numbers of both circulating HPCs and CD34(+) cells required for performing an efficient hematopoietic stem cell (HSC) harvest in lymphoma and myeloma patients have not been defined in our institution. PATIENTS AND METHODS Medical records of 50 lymphoma and myeloma patients undergoing peripheral blood HSC harvest in our institution were retrospectively reviewed. The minimal and optimal HSC harvest yield required for the treatment was considered to be >2x10(6) CD34(+) cells/kg and >5x10(6) CD34(+) cells/kg, respectively. RESULTS The minimally required or optimal HSC yield obtained was not influenced by age (>60 years), sex, underlying malignancies, disease status, multiple rounds of chemotherapy, or history of radiotherapy. The numbers of both circulating HPC and CD34(+) cell were higher in patients with minimally required HSC yields (P=0.000 for HPC and P=0.000 for CD34(+) cell) and also in patients with optimal HSC yields (P=0.011 for HPC and P=0.006 for CD34(+) cell). The cell count cutoff for obtaining minimally required HSC harvest was determined to be 20/mm(3) for HPCs and 10/mm(3) for CD34(+) cells. Furthermore, the cell count cutoff for obtaining optimal HSC harvest was determined to be 60/mm(3) for HPCs and 35/mm(3) for CD34(+) cells. CONCLUSION A total of 60/mm(3) of HPCs and 35/mm(3) of CD34(+) cells in peripheral blood predicted optimal HSC harvest in lymphoma and myeloma patients.