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1.
Early Impact of Mobilization Process on Cardiac Function and Size in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation
Vaitiekiene, A., Kulboke, M., Bieseviciene, M., Bartnykaite, A., Kireilis, B., Rinkuniene, D., Jankauskas, A., Zemaitis, J., Gaidamavicius, I., Gerbutavicius, R., et al
Journal of clinical medicine. 2024;13(3)
Abstract
Background: The hematopoietic stem cell transplantation (HSCT) process is known to cause cardiac toxicity of different grades. In this paper, we aimed to evaluate the impact of mobilization procedure of hematopoietic stem cells for autologous HSCT process for left and right ventricle sizes and functions. Material and Methods: The data of 47 patients undergoing autologous HSCT were analyzed. All patients underwent hematopoietic stem cell mobilization with chemotherapy and filgrastim at 10 µg/kg/d. Echocardiography was performed two times: before enrolling in the transplantation process and after mobilization before the conditioning regimen for transplantation. Changes in left and right ventricle (RV) diameter and systolic and diastolic function of the left ventricle and systolic function of the RV were measured. Results: A statistically significant difference was observed in the change of right ventricular function (S')-it slightly decreased. Mean S' before mobilization was 13.93 ± 2.85 cm/s, and after mobilization it was 12.19 ± 2.64 cm/s (p = 0.003). No statistically significant change in left ventricular diameter and systolic and diastolic function and RV diameter was observed. Conclusions: The mobilization procedure in patients undergoing autologous HSCT is associated with reduced RV systolic function. S' could be used as a reliable tool to evaluate early cardiotoxicity in HSCT patients and guide further follow-up.
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2.
Anti-CD38 monoclonal antibody impairs CD34+ mobilization and affects clonogenic potential in multiple myeloma patients
Zappaterra, A., Civettini, I., Cafro, A. M., Pezzetti, L., Pierini, S., Anghilieri, M., Bellio, L., Bertazzoni, P., Grillo, G., Minga, P., et al
Blood transfusion = Trasfusione del sangue. 2024
Abstract
BACKGROUND Induction with daratumumab-based regimens followed by autologous stem cell transplantation is the current standard for newly diagnosed multiple myeloma (NDMM) patients eligible for intensive chemotherapy. However, concerns emerged regarding potential negative effects following daratumumab-based treatment on CD34+ mobilization. We here compared CD34+ mobilization and clonogenic potential between daratumumab and non-daratumumab based therapy without upfront plerixafor administration among patients affected by NDMM. MATERIALS AND METHODS Clinical, mobilization and clonogenic data from 41 consecutively enrolled NDMM patients were analyzed. Patients underwent collection of autologous CD34+ by apheresis at the ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, from January 2021 to March 2023. Clonogenicity analysis was performed on BFU-E and CFU-GM. RESULTS Seventy-five percent of daratumumab-treated patients underwent >1 apheresis, compared to 24% of non-daratumumab patients (p=0.0017). Daratumumab-treated patients had significantly lower CD34+ count (mean 38 vs 79/μL, respectively; p=0.0011), with a median CD34+ harvest of 3.98×10(6)/kg (range 1.68-9.18) vs 6.87×10(6)/kg (range 1.63-16.85) in non-daratumumab-treated (p=0.0006). In multivariate analysis the likelihood of undergoing >1 apheresis was significantly higher in older patients (OR 1.2, 95% CI 1-1.4, Z=2.10, p=0.03) and daratumumab-treated patients (OR 15, 95% CI 2.8-129, p=0.004). Moreover, daratumumab-based induction therapy demonstrated an independent negative association with BFU-E colony formation (p=0.0148), even when accounting for patient age and CD34+ levels. DISCUSSION Our findings underscore the impact of daratumumab-based treatment on CD34+ mobilization in a real-life, upfront plerixafor-free population of NDMM patients. Higher probability of requiring multiple apheresis occurred among daratumumab-treated patients. Interestingly, the observation that daratumumab might negatively impact BFU-E colony formation, independent of CD34+ cell count, offers novel biological perspectives. Appropriate strategies should be adopted by the Apheresis teams to mitigate these potential negative effects.
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3.
Efficacy of prophylactic antibiotics for the prevention of neutropenic fever in patients with multiple myeloma receiving high-dose cyclophosphamide for stem cell mobilization
Hou, L. Q., Liu, J. R., Gu, J. L., Chen, M. L., Kuang, L. F., Huang, B. H., Zou, W. Y., Li, J.
Annals of hematology. 2024
Abstract
High-dose cyclophosphamide (HD-Cy) (3 g/m(2)) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 10(6)/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 10(6)/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.
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4.
Impact of daratumumab on stem cell mobilization and collection, engraftment and early post-transplant complications among multiple myeloma patients undergoing autologous stem cell transplantation
Eleutherakis Papaiakovou, E., Terpos, E., Kanellias, N., Migkou, M., Gavriatopoulou, M., Ntanasis-Stathopoulos, I., Fotiou, D., Malandrakis, P., Theodorakakou, F., Spiliopoulou, V., et al
Leukemia & lymphoma. 2023;:1-8
Abstract
Autologous stem cell transplantation (ASCT) remains a standard therapy for multiple myeloma (MM) patients. Our study aimed to assess the impact of daratumumab-containing induction on stem cell (SC) mobilization, apheresis and hospitalization. We evaluated 200 newly diagnosed MM patients that were mobilized for SC collection and which received induction with (N = 40) or without daratumumab (N = 160). Dara group patients required more frequent use of plerixafor, larger collection volumes, and had lower SC yield. 87.5% (35/40) of dara group patients achieved the planned yield of ≥ 5 × 10^6 CD34+/kg for at least one transplant compared to 96.2% (154/160) of patients in the non-dara group. Dara group patients had delayed hematopoietic recovery (11 vs 10 days for PMN > 0.5 × 10E9/l), required more transfusions (4 vs 2 plts), prolonged hospitalization (20 vs 18 days), more febrile episodes and prolonged antibiotic administration. Despite daratumumab effect patients finally achieved a successful stem cell collection and proceeded to transplant.
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5.
Mobilization of hematopoietic stem cells with lenograstim in multiple myeloma patients: Prospective multicenter observational study (KMM122)
Jung, E. H., Byun, J. M., Shin, D. Y., Do, Y. R., Jo, J. C., Lee, S. M., Yoon, S. S.
Cancer medicine. 2023
Abstract
BACKGROUND Current guidelines recommend using filgrastim or tbo-filgrastim to mobilize hematopoietic progenitor cells in an autologous setting. However, previous studies have suggested other forms of granulocyte colony-stimulating factor (G-CSF) are equally efficacious, possibly with fewer leukaphereses required. Thus, we prospectively studied the efficacy of lenograstim, a glycosylated recombinant form of G-CSF, in multiple myeloma (MM) patients. METHODS From November 2011 to January 2020, 98 MM patients undergoing autologous stem cell transplant (ASCT) from five academic centers in Korea were enrolled. Patients were mobilized with subcutaneous lenograstim (Neutrogin®) with fixed doses of 10 μg/kg for 4 days. RESULTS Most of the patients ( N = 90, 91.8%) achieved at least the targets of 2 × 10(6) CD34+ cells/kg body weight, and more than half of MM patients ( N = 57, 58.2%) reached a target of 5 × 10(6) CD34+ cells/kg body weight. The mobilization failure rate was 8.2% ( N = 8). The median number of CD34 + cell/kg using G-CSF only was 5.25 × 10(6) /kg (range 0.49-13.47). Adverse events included transfusion (TF, N = 53, 54.1%), bone pain ( N = 6, 6.1%), fever ( N = 2, 2.0%), and gastrointestinal troubles ( N = 2, 2.0%). There were no grade 3 or 4 adverse events during mobilization. Body surface area (BSA) at mobilization and platelet TF were factors associated with CD34+ collection. Most patients achieved neutrophil ( N = 93, 98.9%) and platelet ( N = 89, 95.7%) engraftment. CONCLUSION Lenograstim can safely and effectively mobilize stem cells in MM autologous settings.
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6.
Prediction of mobilized hematopoietic stem cell yield in patients with multiple myeloma: Usefulness of whole-body MRI-derived indices
Takasu, M., Higashino, R., Sueoka, T., Kawai, S., Tanitame, N., Tamura, A., Iida, M., Kawase, T., Ichinohe, T., Awai, K.
PloS one. 2023;18(3):e0283241
Abstract
INTRODUCTION High-dose chemotherapy followed by autologous stem cell transplant is the mainstay of treatment for multiple myeloma (MM). The purpose of this study was to evaluate the ability of MRI-derived indices to predict mobilized hematopoietic stem cell yield. MATERIALS AND METHODS In this exploratory pilot work, we retrospectively analyzed 38 mobilization procedures for MM. Successful mobilization procedure was defined as a total yield of >4.0×106 CD34+ cells/kg. Univariate and multivariate analyses were performed to identify factors with a significant effect on successful mobilization from among clinical characteristics including number of prior lines of therapy, period from diagnosis to harvest, type of monoclonal protein (M protein); and radiological characteristics including total diffusion volume (tDV), median apparent diffusion coefficient (ADC) of tDV, and mean fat fraction of bone marrow calculated by MRI. RESULTS Univariate analyses showed that relatively poor mobilization was significantly associated with M protein of Bence-Jones type and with median ADC of tDV (P = 0.02 and P = 0.004, respectively). Multivariate analyses using these two indices showed that median ADC of tDV was a significant predictive factor for adequate mobilization (P = 0.01), with an area under the curve of 0.784 (cutoff value, 1.18×10-3 mm2/s; sensitivity, 72.7%; specificity, 87.5%). CONCLUSION The present data indicate that median ADC of tDV is a predictive factor for relatively poor mobilization of hematopoietic stem cells in MM patients undergoing autologous stem cell transplant.
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7.
Stem cell collection after lenalidomide, bortezomib and dexamethasone plus elotuzumab or isatuximab in newly diagnosed multiple myeloma patients: a single centre experience from the GMMG-HD6 and -HD7 trials
Kauer, J., Freundt, E. P., Schmitt, A., Weinhold, N., Mai, E. K., Müller-Tidow, C., Goldschmidt, H., Raab, M. S., Kriegsmann, K., Sauer, S.
BMC cancer. 2023;23(1):1132
Abstract
BACKGROUND While quadruplet induction therapies deepen responses in newly diagnosed multiple myeloma patients, their impact on peripheral blood stem cell (PBSC) collection remains incompletely understood. This analysis aims to evaluate the effects of prolonged lenalidomide induction and isatuximab- or elotuzumab-containing quadruplet induction therapies on PBSC mobilization and collection. METHODS A total of 179 transplant-eligible patients with newly diagnosed MM treated at a single academic center were included. The patients were evaluated based on PBSC mobilization and collection parameters, including overall collection results, CD34(+) cell levels in peripheral blood, leukapheresis (LP) delays, overall number of LP sessions, and the rate of rescue mobilization with plerixafor. The patients underwent four different induction regimens: Lenalidomide, bortezomib, and dexamethasone (RVd, six 21-day cycles, n = 44), isatuximab-RVd (six 21-day cycles, n = 35), RVd (four 21-day cycles, n = 51), or elotuzumab-RVd (four 21-day cycles, n = 49). RESULTS The patients' characteristics were well balanced across the different groups. Collection failures, defined as the inability to collect three sufficient PBSC transplants, were rare (n = 3, 2%), with no occurrences in the isatuximab-RVd and elotuzumab-RVd groups. Intensified induction with six 21-day cycles of RVd did not negatively impact the overall number of collected PBSCs (9.7 × 10(6)/kg bw versus 10.5 × 10(6)/kg bw, p = 0.331) compared to four 21-day cycles of RVd. Plerixafor usage was more common after six cycles of RVd compared to four cycles (16% versus 8%). Addition of elotuzumab to RVd did not adversely affect overall PBSC collection (10.9 × 10(6)/kg bw versus 10.5 × 10(6)/kg bw, p = 0.915). Patients treated with isatuximab-RVd (six cycles) had lower numbers of collected stem cells compared to those receiving RVd (six cycles) induction (8.8 × 10(6)/kg bw versus 9.7 × 10(6)/kg bw, p = 0.801), without experiencing significant delays in LP or increased numbers of LP sessions in a multivariable logistic regression analysis. Plerixafor usage was more common after isatuximab plus RVd compared to RVd alone (34% versus 16%). CONCLUSIONS This study demonstrates that stem cell collection is feasible after prolonged induction with isatuximab-RVd without collection failures and might be further explored as induction therapy. TRIAL REGISTRATION Patients were treated within the randomized phase III clinical trials GMMG-HD6 (NCT02495922, 24/06/2015) and GMMG-HD7 (NCT03617731, 24/07/2018). However, during stem cell mobilization and -collection, no study-specific therapeutic intervention was performed.
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8.
Stem Cell Mobilization for Multiple Myeloma Patients Receiving Daratumumab-Based Induction Therapy: A Real- World Experience
Thurlapati, A., Roubal, K., Davis, J. A., Shah, S. Z., Smith, D., McGann, M., Gaffney, K., Cendagorta, A., Maldonado, A., Weeda, E., et al
Transplantation and cellular therapy. 2023;29(5):340.e1-340.e4
Abstract
For patients with newly diagnosed multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT), hematopoietic stem cell mobilization can be affected by induction chemotherapy. In clinical trials, the addition of daratumumab (dara) to a triplet backbone lowered hematopoietic stem cell yield, necessitating the administration of plerixafor to achieve the desired yield for ASCT. Here we describe our experience of stem cell mobilization and collection after dara-based and non-dara-based induction regimens. This single-center retrospective analysis included patients with newly diagnosed MM who had received induction chemotherapy and were candidates for upfront HDT-ASCT. Based on the induction regimen used, patients were divided into 2 groups, RVd (lenalidomide, bortezomib, and dexamethasone) and DRVd (RVd with the addition of dara). Based on our institutional practice, patients received pegylated growth colony-stimulating factor (G-CSF) on day -3 (at 0900 hours) in combination with plerixafor on day -1 (at 2300 hours) as a preemptive mobilization strategy. Patients continued apheresis for 1 to 3 days until the goal dose of hematopoietic stem cells was collected (2.5 × 10(6) cells/kg for one ASCT and 5.0 × 10(6) cells/kg for 2 ASCTs). Patients with a suboptimal stem cell yield on day 1 received additional doses of plerixafor with or without G-CSF. A total of 101 patients with newly diagnosed MM who underwent mobilization between July 2021 and June 2022 were analyzed. The median patient age was 61 years (range, 36 to 80 years), and 51.5% of the cohort was female. Patients received a median of 5 (range, 2 to 12) cycles of induction chemotherapy, with a median of 4 (range, 2 to 12) cycles of DRVd and 6 (range, 3 to 12) cycles of RVd. The median number of CD34(+) cells collected in the DRVd and the RVd groups was 6.54 × 10(6)/kg and 6.78 × 10(6)/kg, respectively. Target CD34(+) stem cells were collected in a median of 1 day (range, 1 to 4 day) in each group. On average, more patients in the DRVd group compared to the RVd group received additional doses of plerixafor (51% versus 43%) and additional doses of GCSF (19% versus 14%) to achieve the target stem cell yield. There were no mobilization failures or grade 3+ mobilization-related adverse events reported in either group. The addition of daratumumab to the RVd induction regimen did not lead to any clinically significant differences in stem cell yield or number of collection days, provided that the patient received preemptive G-CSF and plerixafor. Patients with suboptimal collection on day 1 were able to collect adequate stem cells with additional doses of plerixafor with or without G-CSF.
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9.
Non-interventional Study Evaluating the Mobilization of Stem Cells by Plerixafor Before Salvage Autologous Stem Cell Transplant in Relapsed Multiple Myeloma (IFM-2015-03)
van de Wyngaert, Z., Malard, F., Hulin, C., Caillot, D., Mariette, C., Facon, T., Touzeau, C., Perrot, A., Moreau, P., Hebraud, B., et al
Clinical hematology international. 2023;:1-5
Abstract
INTRODUCTION Despite the implementation of new therapeutic agents, management of relapsed multiple myeloma (MM) remains a challenge. Salvage autologous hematopoietic cell transplant (AHCT) remains a valid therapeutic option for eligible patients who achieve prolonged response after a first AHCT. However, a second graft is not always available, and these patients may need a second mobilization. PATIENTS AND METHODS This prospective, non-interventional, multicenter study aimed to collect data on the feasibility of salvage AHCT using a plerixafor-based hematopoietic cell mobilization in relapsed MM, according to the plerixafor label in France. Adult patients with relapsed MM eligible for a second AHCT and mobilized using granulocyte- colony stimulating factor (G-CSF) and plerixafor were included. RESULTS Of the 23 patients, 17 achieved a successful hematopoietic cell mobilization and 13 were able to proceed to a second AHCT. Median age was 62.9 years (min-max 51-71). Ten patients (77%) were male. Eleven (85%) received AHCT as a third-line treatment or more. Median time between first and second AHCT was 5.4 years (range, 2.6-16.3). Among 18 evaluable patients, mobilization was successful for 17 (94%) of them [95% CI 84-100], with no reported side effects. Among the 13 patients who underwent salvage AHCT, the median time to engraftment was 14 days (min-max 11-29). One-year progression-free and overall survival were 88.9% [95% CI 43.3-98.4] and 100%, respectively. CONCLUSION This study demonstrated that plerixafor allows safe and efficient mobilization in relapsed MM patients who are candidates for a salvage AHCT. TRIAL REGISTRATION NCT02439476 Registered 8 May 2015, https://clinicaltrials.gov/ct2/show/NCT02439476 .
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10.
Inflammation-related mRNA expression in patients with multiple myeloma undergoing hematopoietic stem cell mobilization
Nowicki, M., Wierzbowska, A., Szymańska, B., Nowicki, G., Szmigielska-Kapło, A.
Experimental hematology. 2023
Abstract
Mobilization of CD34+ cells is a key element in the therapy of patients with multiple myeloma undergoing autologous stem cell transplantation. The use of chemotherapy and the granulocyte colony-stimulating factor can significantly affect the expression of inflammation-related proteins and the migration of hematopoietic stem cells. We assessed the mRNA expression of selected proteins involved in the inflammatory landscape in MM patients (n=71). The aim of the study was to evaluate C-C motif chemokine ligand 3, 4, 5 (CCL3, CCL4, CCL5), leukocyte cell-derived chemotaxin 2 (LECT2), tumor necrosis factor (TNF), and formyl peptide receptor 2 (FPR2) levels in the course of mobilization and their role in the CD34+ collection efficacy. mRNA expression from peripheral blood plasma was evaluated by RT-PCR. We observed a deep decline in CCL3, CCL4, LECT2, and TNF mRNA expression on the day of the first apheresis (day A) as compared to baseline. A negative correlation was observed between CCL3, FPR2, LECT2, TNF level, and the CD34+ cells count in peripheral blood on day A, and the number of CD34+ cells obtained at first apheresis . Our results indicate that the investigated mRNAs significantly alter and may regulate the migration of CD34+ cells during mobilization. Moreover, in case of FPR2 and LECT2, the results obtained in patients differ from the murine models.