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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.
An evidence-based and risk-adapted GSF versus GSF plus plerixafor mobilization strategy to obtain a sufficient CD34(+) cell yield in the harvest for autologous stem cell transplants
Balint, M. T., Lemajić, N., Jurišić, V., Pantelić, S., Stanisavljević, D., Kurtović, N. K., Balint, B.
Translational oncology. 2024;39:101811
Abstract
BACKGROUND Plerixafor is a bicyclam molecule with the ability to reversibly bind to receptor CXCR-4 thus leading to an increased release of stem cells (SC) into the circulation. This study aims to evaluate the efficacy of G-CSF plus plerixafor versus G-CSF alone mobilizing regimens on the basis of CD34(+) cell yield and engraftment kinetics following hematopoietic SC transplants. METHODS The study incorporated 173 patients with plasma cell neoplasms (PCN), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), undergoing mobilization and following autologous SC-transplant. For patients with mobilization failure and those predicted to be at risk of harvesting inadequate CD34(+) yields (poor-responders), plerixafor was administered. Data was collected and compared in relation to the harvesting protocols used, cell quantification, cell-engraftment potential and overall clinical outcome. RESULTS A total of 101 patients received plerixafor (58.4 %) and the median CD34(+)increase was 312 %. Chemotherapy-mobilized PCN-patients required less plerixafor administration (p = 0.01), no difference was observed in lymphoma groups (p = 0.46). The median CD34(+)cell yield was 7.8 × 10(6)/kg bm. Patients requiring plerixafor achieved lower, but still comparable cell yields. Total cell dose infused was in correlation with engraftment kinetics. Patients requiring plerixafor had delayed platelet engraftment (p = 0.029). CONCLUSIONS Adequately selected plerixafor administration reduces "mobilization-related-failure" rate and assure a high-level cell dose for SC transplants, with superior "therapeutic-potential" and safety profile. The mobilization strategy that incorporates "just-in-time" plerixafor administration, also leads to a reduction of hospitalization days and healthcare resource utilization. For definitive conclusions, further controlled/larger clinical trials concerning correlation of CD34(+) cell count/yield, with hematopoietic reconstitution are required.
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3.
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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4.
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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5.
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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6.
[Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma]
Ji, M. M., Shen, Y. G., Gong, J. C., Tang, W., Xu, X. Q., Zheng, Z., Chen, S. Y., He, Y., Zheng, X., Zhao, L. D., et al
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2023;44(2):112-117
Abstract
Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.
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7.
A novel PEGylated form of granulocyte colony-stimulating factor, mecapegfilgrastim, for peripheral blood stem cell mobilization in patients with hematologic malignancies
Wen, J., Zhou, Q., Shi, L., Xu, F., Liu, Y., Su, J., Zhang, Y., Qu, W., Yue, J.
BMC cancer. 2023;23(1):694
Abstract
BACKGROUND The Pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) has longer half-life and is given once only, which is more comfortable for patients. We aimed to evaluate the efficacy of mecapegfilgrastim for hematopoietic stem cell (HSC) mobilization in patients with hematologic malignancies and to explore the potential factors related to HSC mobilization. METHODS A retrospective analysis was performed on patients who underwent HSC mobilization in the hematology department of Mianyang Central Hospital from April 2016 to November 2022. The number of CD34 + cells collected was compared between the patients receiving mecapegfilgrastim (PEG group) and those receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF group), and the possible factors for mobilization failure were analyzed. RESULTS The success rates of collecting CD34 + cells in the PEG group and rhG-CSF group were 80.6% and 67.7%, respectively (χ = 1.444, P = 0.229). The median CD34 + cell counts were 3.62 × 10^6/kg and 2.92 × 10^6/kg (P = 0.178), respectively. After combination with plerixafor for mobilization, the median number of CD34 + cells collected in the PEG group and rhG-CSF group were 3.64 × 10^6/kg and 3.92 × 10^6/kg, respectively, with no significant difference (P = 0.754). There was no significant difference in hematopoietic cell recovery or infection between the groups (P > 0.05). Multivariate analysis showed that more than 5 cycles of chemotherapy (OR = 15.897, 95% CI: 1.766-143.127, P = 0.014), a precollection WBC count < 32 × 10^9/L (OR = 14.441, 95% CI: 2.180-95.657, P = 0.006) and a precollection to premobilization lymphocyte ratio < 1.7 (OR = 11.388, 95% CI: 2.129-60.915, P = 0.004) were independent risk factors for HSC mobilization failure. CONCLUSIONS The HSC mobilization efficacy of mecapegfilgrastim in patients with hematologic malignancies was comparable to that of rhG-CSF, and combination with plerixafor for mobilization was feasible and effective. Patients with more than 5 cycles of chemotherapy before HSC mobilization, a precollection WBC count lower than 32 × 10^9/L, and a precollection lymphocyte count less than 1.7 times the premobilization lymphocyte count have a high probability of HSC mobilization failure.
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8.
[Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients]
Guan, F. S., He, D. H., Li, Y., Zhang, Y., Zheng, G. F., Zhu, Y. Y., He, J. S., Zhang, E. F., Cai, Z., Zhao, Y.
Zhongguo shi yan xue ye xue za zhi. 2023;31(4):1056-1060
Abstract
OBJECTIVE To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma. METHODS The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34(+) cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection. RESULTS A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34(+) cells < 5 cells/μl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection. CONCLUSIONS Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34(+) cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.
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9.
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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10.
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.