Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation

ABSTRACT Introduction: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. Objective: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. Materials and methods: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. Results: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). Conclusion: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

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.

Expression Changes of Hypoxia-Inducible Factor-1α in G-CSF Induced Hematopoietic Stem Cell Mobilization / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and its relative mechanism of hypoxia-inducible factor-1α(HIF-1α) in bone marrow(BM) of mice during G-CSF mobilization of hematopoietic stem cells (HSC) .@*METHODS@#Flow cytometry was used to detect the proportion of Lin-Sca-1+ c-kit+ (LSK) cells in peripheral blood of C57BL/6J mice before and after G-CSF mobilization. And the expression of HIF-1α and osteocalcin (OCN) mRNA and protein were detected by RQ-PCR and immunohistochemistry. The number of osteoblasts in bone marrow specimens of mice was counted under the microscope.@*RESULTS@#The proportion of LSK cells in peripheral blood began to increase at day 4 of G-CSF mobilization, and reached the peak at day 5, which was significantly higher than that of control group (P<0.05). There was no distinct difference in the expression of HIF-1α mRNA between bone marrow nucleated cells and osteoblasts of steady-state mice (P=0.073), while OCN mRNA was mainly expressed in osteoblasts, which was higher than that in bone marrow nucleated cells (P=0.034). After mobilization, the expression level of HIF-1α increased, but OCN decreased, and the number of endosteum osteoblasts decreased. The change of HIF-1α expression was later than that of OCN and was consistent with the proportion of LSK cells in peripheral blood.@*CONCLUSION@#The expression of HIF-1α in bone marrow was increased during the mobilization of HSC mediated by G-CSF, and one of the mechanisms may be related to the peripheral migration of HSC induced by osteoblasts inhibition.

Predictive value of peripheral blood CD34-positive cell count for the stem cell mobilization effect of plerixafor in patients with multiple myeloma / 白血病·淋巴瘤

Objective:To explore the predictive value of peripheral blood CD34-positive cell count for the stem cell mobilization effect of plerixafor in patients with multiple myeloma (MM).Methods:The clinical data of 12 MM patients who used plerixafor for stem cell mobilization in the First Affiliated Hospital of Guangxi Medical University from December 2019 to February 2021 were retrospectively analyzed. The changes of peripheral blood CD34-positive cell count and the collection status of stem cell in all patients before and after the mobilization of plerixafor were analyzed.Results:Twelve patients were included in this study. These patients were in international staging system (ISS) stage Ⅱ-Ⅲ, and the induction therapy was mainly VRD regimen. The CD34-positive cell count was increased after the use of plerixafor in all patients no matter which mobilization strategies were used before plerixafor. The CD34-positive cell count was 3.63/μl (0.72-13.53/μl) and 32.11/μl (8.52-53.68/μl) before and after the use of plerixafor, and the difference was statistically significant ( Z = -0.40, P<0.001); the median increasing time was 11.50 times (1.61-23.71 times). The mobilization failure occurred in 1 patient. The CD34-positive cell count in his blood was less than 1/μl before the use of plerixafor; though increased 11.83 times after the use of plerixafor, the CD34-positive cell count was still less than 10/μl. Pearson analysis showed that among the patients with CD34-positive cell count less than 4/μl before the use of plerixafor, there was a positive correlation in peripheral blood CD34-positive cell count before and after the use of plerixafor ( r = 0.80, P = 0.032). Conclusions:The peripheral blood CD34-positive cell count has a certain predictive value for the stem cell mobilization effect of plerixafor in MM patients.

A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation.@*RESULTS@#CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1).@*CONCLUSION@#The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;

Effects of peripheral blood CD34 + cells count on the collection timing and results of peripheral blood stem cells / 肿瘤研究与临床

Objective:To investigate the variation trend of peripheral blood CD34 + cells during the hematopoietic stem cell mobilization and its influence on the collection timing and results. Methods:The clinical data of 62 patients with hematologic diseases undergoing autologous peripheral blood hematopoietic stem cell mobilization from April 2012 to March 2017 in Shanxi Provincial Cancer Hospital were analyzed. Mobilization regimen used chemotherapy combined with granulocyte colony-stimulating factor (G-CSF) to monitor the number of white blood cells (WBC), mononuclear cells (MNC), CD34 + cells in peripheral blood and apheresis concentrates, and the correlation with CD34 + cells was analyzed. Furthermore, the receiver operating characteristic (ROC) curve was used to establish the threshold to start apheresis. Results:MNC (5.66±1.11)×10 8/kg and CD34 + cell count (2.15±1.20)×10 6/kg were obtained in 62 patients who received 136 times collection in total. The peak of peripheral blood CD34 + cells count appeared at day 4-5 after the treatment of G-CSF, and then it went down. CD34 + cell count in the product was correlated with the peripheral blood CD34 + cell count collected on the day ( r = 0.879, P < 0.01), and it was also correlated with the peripheral blood WBC and MNC collected on the day as well as MNC count in the product (all P < 0.05). Furthermore, the ROC curve analysis demonstrated that peripheral blood CD34 + cells count > 23/μl was the optimal threshold for stem cell collection on the day, 85.2% of patients reaching up to the threshold could be successfully collected at one time. Conclusions:The variation trend of peripheral blood CD34 + cell count can guide the best time of stem cell collection in clinic. Peripheral blood CD34 + cell count is the reliable index to predict CD34 + cells count in the products. Peripheral blood CD34 + cells count > 23/μl could be used as the collection threshold.

The therapeutic effect of G-CSF-mobilized autologous stem cells on radiation pulmonary injury in mice / 中华放射医学与防护杂志

Objective To investigate the effects of G-CSF-mobilized autologous stem cells in the prevention of radiation pulmonary injury.Methods Mice were divided into control group,irradiation group and treatment group.Mouse model of pulmonary fibrosis was established by exposing chest to a single dose of 14 Gy.Animals in the treatment group received recombinant human G-CSF (250 μg/kg daily for 5 d) before the irradiation in order to mobilize autologous stem cells in vivo.The general condition and mortality were documented after radiation injury.The pathological study with histological scoring,Masson staining and Sirius red staining with polarized light analysis were used to identify lung injury and the potential benefit of stem cell mobilization.Results Local chest irradiation of a single dose of 14 Gy was a suitable dose to create radiation-induced pulmonary fibrosis in mice.The death rate was 37.5％,which mainly happened around 11 weeks after injury.In contrast,all of the animals in G-CSF treated group survived.The ratio of lung to body mass was significantly increased in both irradiation group and treatment group (F =23.20,P＜0.05) around 3 months after the injury,with a higher ratio in irradiation group than that in treatment group (P＜0.05).Histological scoring for alveolar inflammation at 3 months after injury revealed statistically significant difference in irradiation group and treatment group compared with control group (F=11.93,P＜ 0.05).At this time point,the pathological observation showed lung tissue degeneration and necrosis with alveolitis and interstitial inflammation,as well as fibroblasts proliferation and focal collagen deposition in alveolar septa.At 4 month after the injury,the inflammation ininterstitial tissue was receded,but fibrosis and collagen deposition were significantly increased.In addition,at 3 and 4 months afterinjury,the pulmonary fibrosis was aggravated in irradiation group (F=28.73,16.85,P＜0.05),and significantly alleviated in the treatment group (P＜0.05).The similar results were confirmed in collagen content analysis (IOD) by Sirius red staining and image analysis (F =17.70,17.79,P＜ 0.05).Conclusions Autologous mobilization of stem cells could prevent the death of radiation-injured animals possibly by alleviating early lung injury and interstitial inflammation as well as the late pulmonary fibrosis,suggesting a therapeutic potential of autologous stem cell mobilization in radiation pulmonary fibrosis.

Analysis of factors influencing the mobilization and collection of autologous peripheral blood stem cells / 白血病·淋巴瘤

Objective@#To explore the factors influencing the mobilization and collection of autologous peripheral blood stem cells.@*Methods@#The clinical data of 62 patients who received autologous peripheral blood hematopoietic stem cell mobilization in Shanxi Provincial Cancer Hospital from April 2012 to March 2017 were collected. The effects of age, gender, disease type, chemotherapy cycle, disease status, different schemes and the number of CD34+ cells in peripheral blood of patients 1 d before collection on the number of CD34+ cells and the success rate of CD34+ cells collection were analyzed. Measurement data were compared by one-way ANOVA and t test; count data were compared by χ 2 test; multivariate analysis was performed by multiple linear regression analysis.@*Results@#There were statistically significant differences in the number of CD34+ cells between patients with chemotherapy >6 cycles and ≤6 cycles [(2.6±1.3)×106/kg vs. (5.8±2.2)×106/kg; t = 5.221, P < 0.01], and the difference in the success rate of CD34+ cell collection between the two groups was statistically significant [68.8% (11/16) vs. 97.8% (45/46); χ2 = 8.396, P = 0.004]. The difference in the CD34+ cells yield was not statistical significance between male and female patients [(5.4±2.2)×106/kg vs. (4.5±2.8)×106/kg; t = 1.302, P = 0.198)], but the collection success rate in males was higher than that in females [97.6% (40/41) vs. 76.2% (16/21)], and the difference was statistically significant (χ 2 = 5.017, P = 0.025). The success rate of CD34+ cell collection in patients with ≥10/μl CD34+ cell in the peripheral blood was significantly higher than that in patients with < 10/μl CD34+ cells 1 d before the collection[97.9% (47/48) vs. 64.3% (9/14)], and the difference was statistically significant (χ 2 = 10.668, P = 0.001). The differences in CD34+ cells yield and collection success rate between patients with different age, disease type, disease status and mobilization regimen were not statistically significant (all P > 0.05). Multi-factor analysis showed that > 6 cycles chemotherapy before mobilization was the adverse factor affecting stem cell collection (b = -3.435, P < 0.01).@*Conclusions@#The effective mobilization and collection of autologous peripheral blood stem cells are related to the number of chemotherapy cycles before mobilization. The stem cell mobilization and collection should be conducted as soon as possible when the chemotherapy is ≤ 6 cycles and the patient reaches partial remission or above. In addition, peripheral blood CD34+ cell count should be monitored during mobilization. When the peripheral blood CD34+ cell count is > 10/μl, the collection could be started on the next day to obtain a better collection effect, so as to improve the success rate of collection.

Analysis of factors influencing the mobilization and collection of autologous peripheral blood stem cells / 白血病·淋巴瘤

Objective To explore the factors influencing the mobilization and collection of autologous peripheral blood stem cells. Methods The clinical data of 62 patients who received autologous peripheral blood hematopoietic stem cell mobilization in Shanxi Provincial Cancer Hospital from April 2012 to March 2017 were collected. The effects of age, gender, disease type, chemotherapy cycle, disease status, different schemes and the number of CD34+cells in peripheral blood of patients 1 d before collection on the number of CD34+cells and the success rate of CD34+cells collection were analyzed. Measurement data were compared by one-way ANOVA and t test; count data were compared by χ2 test; multivariate analysis was performed by multiple linear regression analysis. Results There were statistically significant differences in the number of CD34+cells between patients with chemotherapy＞6 cycles and≤6 cycles [(2.6±1.3)×106/kg vs. (5.8±2.2)×106/kg;t＝5.221, P<0.01], and the difference in the success rate of CD34+cell collection between the two groups was statistically significant [68.8% (11/16) vs. 97.8% (45/46); χ 2＝ 8.396, P ＝ 0.004]. The difference in the CD34+cells yield was not statistical significance between male and female patients [(5.4±2.2)×106/kg vs. (4.5± 2.8)×106/kg; t ＝ 1.302, P＝ 0.198)], but the collection success rate in males was higher than that in females [97.6% (40/41) vs. 76.2% (16/21)], and the difference was statistically significant (χ2＝5.017, P ＝0.025). The success rate of CD34 + cell collection in patients with ≥10/μl CD34 + cell in the peripheral blood was significantly higher than that in patients with < 10/μl CD34+cells 1 d before the collection[97.9% (47/48) vs. 64.3% (9/14)], and the difference was statistically significant (χ 2 ＝ 10.668, P＝ 0.001). The differences in CD34+cells yield and collection success rate between patients with different age, disease type, disease status and mobilization regimen were not statistically significant (all P＞ 0.05). Multi-factor analysis showed that ＞6 cycles chemotherapy before mobilization was the adverse factor affecting stem cell collection (b ＝ -3.435, P< 0.01). Conclusions The effective mobilization and collection of autologous peripheral blood stem cells are related to the number of chemotherapy cycles before mobilization. The stem cell mobilization and collection should be conducted as soon as possible when the chemotherapy is ≤ 6 cycles and the patient reaches partial remission or above. In addition, peripheral blood CD34+cell count should be monitored during mobilization. When the peripheral blood CD34+cell count is ＞10/μl, the collection could be started on the next day to obtain a better collection effect, so as to improve the success rate of collection.

Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma

BACKGROUND: Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. METHODS: This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m² IV d 1, 2), etoposide (200 mg/m² IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). RESULTS: We successfully collected stem cells from all patients, with a median of 7.9×10⁶/kg of body weight (range, 4.4 to 17.3×10⁶/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). CONCLUSION: For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.

Efficacy and safety evaluation of mobilization and collection of unrelated allogeneic peripheral blood stem cells / 白血病·淋巴瘤

Objective To evaluate the efficacy and safety of the mobilization and collection of unrelated allogeneic peripheral blood stem cells. Methods The suitable stem cell mobilization plan was made in accordance with the hematopoietic stem cell mobilization plan of China Marrow Donor Program, the ruler of the hospital, and the donor's constitution. The unrelated allogeneic peripheral blood stem cells of 64 healthy donors were collected in the second Hospital of Shanxi Medical University from May 2012 to January 2017. The donor was infected one or several times with the mobilization agent granulocyte colony stimulating factor (G-CSF) by 5-10 μg·kg-1·d-1. After 3-4 days, peripheral blood hematopoietic stem cells were collected using COBE Spectra blood cell separator. Then, the effect and adverse reaction of donors were analyzed from different age and sex. Results It can achieve the acquisition requirements using 3 or 4 days of mobilization programs, mononuclear cells≥5.0×108/kg, CD34+cells≥2.0×106/kg. The single acquisition success rate (the target acquisition of the number of mononuclear cells and CD34+) up to 65 ％, collection efficiency reached 52％, which could reduce the risk of donor and the cost of patients. The quality of donor stem cell of young was better than that of older persons. Sixteen donors (25％) had mild adverse reactions, and no special treatment was required. Conclusions Allogeneic stem cell mobilization is safe. Starting from save medical resources and the interests of the donor the 3 day or 4 days of mobilization scheme could improve the success rate of the single mobilization. During the collection process, the condition of donor hypocalcemia should be observed and health education should be given to relieve the tension of donor.

PEG-rhG-CSF for peripheral blood stem cell mobilization in patients with relapsed or refractory malignant lymphoma / 中国肿瘤临床

Objective:To compare the efficacy and costs of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) and granulocyte colony stimulating factor (G-CSF) for hematopoietic stem cell mobilization and hematopoietic recovery after transplantation in patients with relapsed or refractory malignant lymphoma. Methods:From July 2014 to October 2016, 15 patients with malignant lymphoma using peripheral blood stem cell mobilization (PBSCM) for autologous peripheral stem cell transplantation (APBSCT) were treated in our institution and enrolled in the PEG-rhG-CSF group (experimental group). We analyzed data from other 15 patients with malignant lymphoma mobilized with G-CSF who were treated in our institution from January 2013 to August 2015 (control group). Results:Patients in both groups were successfully mobilized. The median amounts of CD34+cells collected in the experimental and control groups were 16.2×106/kg and 8.9×106/kg, respectively (P=0.414), and the median amount of mononuclear cell (MNC) was 12.4×108/kg and 9.9× 108/kg, respectively (P=0.519). In the experimental and control groups, the mean durations of mobilization were 10.66±1.45 and 9.33±1.83 days (P=0.234), the mean durations of neutropenia during mobilization were 4.20±2.17 and 3.80±2.04 days (P=0.608), the mean durations of absolute neutrophil count recovery after APBSCT were 10.14±1.29 and 10.93±2.69 days (P=0.327), and the mean durations of platelet recovery were 10.36±2.27 and 12.27±3.38 days (P=0.121). Mobilization and hematopoietic recovery after APBSCT were not significantly different between the two groups. The cost was lower in the experimental group than that in the control group (RMB 3,960 yuan versus RMB 11,479.3±2,401.3 yuan). Conclusion:High-dose chemotherapy combined with PEG-rhG-CSF is a promising, effective, and low-cost mobilization regimen for patients with relapsed or refractory malignant lymphoma.

Differences in Mobilization Efficiency between Small Children and Adults with Healthy Marrows / 임상소아혈액종양

BACKGROUND: We compared the yields of mobilized PBSCs from single day of normal volume leukapheresis (NVL) in children and adults, and factors affecting the yields, to understand differences in mobilization efficiency between adults and small children with healthy marrows.METHODS: This study involved 18 adult volunteer donors and 47 small children weighing less than 20 kg who participated in a clinical trial of cell therapy in children with cerebral palsy. Donor factors analyzed to identify predictors of the yield of apheresis included age, gender, weight and complete blood cell count (CBC) with differential counts as well as equipment parameters.RESULTS: The yields of total nucleated cells (TNCs) and CD34⁺cells in the apheresis products of the children were significantly lower than in those from healthy adults. However, the efficiency of recovery of PBSCs (total CD34⁺ cell counts/TNCs) was significantly higher in small children (0.48±0.30%) than in adults (0.10±0.05%) (P < 0.05). Multivariable analysis of adult donor factors showed that the processed volume and flow rate of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both), but not of CD34⁺cells. However, in multivariable analysis of child donor factors, body weight and circulating WBC count on the day of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both) and of CD34⁺cells (P < 0.05, for both).CONCLUSION: The predictors of PBSC yields from a single day of NVL in adults and small children are different. Also mobilization is more effective in small children than in adults.

Differences in Mobilization Efficiency between Small Children and Adults with Healthy Marrows / 임상소아혈액종양

BACKGROUND: We compared the yields of mobilized PBSCs from single day of normal volume leukapheresis (NVL) in children and adults, and factors affecting the yields, to understand differences in mobilization efficiency between adults and small children with healthy marrows. METHODS: This study involved 18 adult volunteer donors and 47 small children weighing less than 20 kg who participated in a clinical trial of cell therapy in children with cerebral palsy. Donor factors analyzed to identify predictors of the yield of apheresis included age, gender, weight and complete blood cell count (CBC) with differential counts as well as equipment parameters. RESULTS: The yields of total nucleated cells (TNCs) and CD34⁺cells in the apheresis products of the children were significantly lower than in those from healthy adults. However, the efficiency of recovery of PBSCs (total CD34⁺ cell counts/TNCs) was significantly higher in small children (0.48±0.30%) than in adults (0.10±0.05%) (P < 0.05). Multivariable analysis of adult donor factors showed that the processed volume and flow rate of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both), but not of CD34⁺cells. However, in multivariable analysis of child donor factors, body weight and circulating WBC count on the day of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both) and of CD34⁺cells (P < 0.05, for both). CONCLUSION: The predictors of PBSC yields from a single day of NVL in adults and small children are different. Also mobilization is more effective in small children than in adults.

Mobilization of hematopoietic progenitor cells for autologous transportation: consensus recommendations / Mobilização de células progenitoras hematopoéticas para transplante autólogo: recomendações de consenso

SUMMARY Selected patients with certain hematological malignancies and solid tumors have the potential to achieve long-term survival with autologous hematopoietic progenitor cell transplant. The collection of these cells in peripheral blood avoids multiple bone marrow aspirations, results in faster engraftment and allows treatment of patients with infection, fibrosis, or bone marrow hypocellularity. However, for the procedure to be successful, it is essential to mobilize a sufficient number of progenitor cells from the bone marrow into the blood circulation. Therefore, a group of Brazilian experts met in order to develop recommendations for mobilization strategies adapted to the reality of the Brazilian national health system, which could help minimize the risk of failure, reduce toxicity and improve the allocation of financial resources.

RESUMO Pacientes selecionados com certas neoplasias hematológicas e tumores sólidos têm o potencial de alcançar sobrevida de longo prazo com o transplante autólogo de células progenitoras hematopoéticas. A coleta dessas células no sangue periférico evita múltiplas aspirações de medula óssea, resulta em enxertia mais rápida, e permite o tratamento de pacientes com infiltração, fibrose ou hipocelularidade medular. Contudo, para o sucesso desse procedimento, é essencial mobilizar um número suficiente de células progenitoras da medula óssea para a circulação sanguínea. Por isso, um painel de especialistas brasileiros se reuniu com o objetivo de desenvolver recomendações para estratégias de mobilização adaptadas à realidade do sistema de saúde nacional, que pudessem contribuir para minimizar os riscos de falha, reduzir a toxicidade e melhorar a alocação de recursos financeiros.

Stem Cells and Lung Regeneration

Tissues such as the lung, liver, and pancreas that have a low steady-state cell turnover yet can respond robustly after injury to replace damaged cells. The airway epithelium is exposed to inhaled particles and pathogens that may lead to the development of a many infectious and inflammatory respiratory diseases. Lung transplantation is an accepted modality of treatment for end-stage lung diseases. Since the early 1990 s, more than 26,000 lung transplants have been performed at centers worldwide. However, the availability of donor tissues and organs is limited, which presents a serious limitation for widespread transplantation surgery. The appearance of bioengineered lung and tracheal tissue transplants is considered a promising alternative to the classical transplantation of donor organ/tissue. Stem cells therapy arises as a new therapeutic approach, with a wide application potential.

Mobilization and collection of CD34+ cells for autologous transplantation of peripheral blood hematopoietic progenitor cells in children: analysis of two different granulocyte-colony stimulating factor doses

The use of peripheral hematopoietic progenitor cells (HPCs) is the cell choice in autologous transplantation. The classic dose of granulocyte-colony stimulating factor (G- CSF) for mobilization is a single daily dose of 10 µg/kg of patient body weight. There is a theory that higher doses of granulocyte-colony stimulating factor applied twice daily could increase the number of CD34+ cells collected in fewer leukapheresis procedures. Objective: The aim of this study was to compare a fractionated dose of 15 µg G-CSF/kg of body weight and the conventional dose of granulocyte-colony stimulating factor in respect to the number of leukapheresis procedures required to achieve a minimum collection of 3 × 106 CD34+ cells/kg body weight. Methods: Patients were divided into two groups: Group 10 - patients who received a single daily dose of 10 µg G-CSF/kg body weight and Group 15 - patients who received a fractioned dose of 15 µg G-CSF/kg body weight daily. The leukapheresis procedure was carried out in an automated cell separator. The autologous transplantation was carried out when a minimum number of 3 × 106 CD34+ cells/kg body weight was achieved. Results: Group 10 comprised 39 patients and Group 15 comprised 26 patients. A total of 146 apheresis procedures were performed: 110 (75.3%) for Group 10 and 36 (24.7%) for Group 15. For Group 10, a median of three (range: 1-7) leukapheresis procedures and a mean of 8.89 × 106 CD34+ cells/kg body weight (±9.59) were collected whereas for Group 15 the corresponding values were one (range: 1-3) and 5.29 × 106 cells/kg body weight (±4.95). A statistically significant difference was found in relation to the number of apheresis procedures (p-value <0.0001). Conclusions: To collect a minimum target of 3 × 106 CD34+ cells/kg body weight, the administration of a fractionated dose of 15 µg G-CSF/kg body weight significantly decreased the number of leukapheresis procedures performed.

The mobilization of stem cells promote the recovery of the ischemia brain injury after cardiopulmonary resuscitation / 中华急诊医学杂志

Objective To explore the therapeutic potential and mechanism of stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) and AMD3100 to repair global cerebral ischemia injuries in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR).Methods Cardiac arrest was induced by asphyxia.Fifty-six SD rats were randomly assigned into four groups:G-CSF group,G-CSF + AMD3100 group,CPR control group and sham operated group.The animals were sacrificed at 3d and 6d after CPR respectively.The neurological status and morphological changes of damaged cerebrum,the apoptosis of nerve cells and vascular endothelial growth factor (VEGF) expressed in brain tissue and capillary density in hippocampus and temporal lobe cortex were measured and analyzed by means of neurological deficit score (NDS),adhesive tape removal test (TRT),ELISA,MRI and immunofluorescence.Results NDS in G-CSF + AMD3100 group (61.4 ± 10.7) was significantly higher than that in CPR control group (49.9 ± 10.4) at 3 d after CPR (P ＜0.05).And less time consumption for TRT found in G-CSF + AMD3100 group (85.5 ±28.9) s rather than was in CPR control group (148.1 ± 23.8) s and G-CSF group (118.5 ± 30.4) s (P ＜ 0.05).The severity of cerebral injury assessed by MRI was significantly milder at both 3 d and 6 d in the two stem cell mobilization groups.The apoptosis rate of nerve cells in G-CSF + AMD3100 group (0.23 ± 0.06) was significantly lower than that in G-CSF group (0.34 ±0.08) at 3 d after CPR,and that in both stem cell mobilization groups was lower than that in CPR control group (0.44 ± 0.09) (P ＜ 0.05).At 3 d and 6 d after CPR,the levels of VEGF in brain tissue were (106.2 ±23.3) pg/mL and (79.9 ± 18.4) pg/mL in G-CSF + AMD3100 group,and were (50.6 ± 13.7) pg/mL and (73.9 ± 16.6) pg/mL in G-CSF group,which were both significantly higher than that in CPR control group (23.1 ± 10.2) pg/mL and (36.2 ± 12.8) pg/mL (P ＜0.05).At 3 d after CPR,the cerebral capillary density (351.8 ±67.9) branches in every high power field (A/HPF) was significantly higher in G-CSF + AMD3100 group than that (301.4 ± 77.3) A/HPF in G-CSF group and (250.4 ± 48.0) A/HPF in CPR control group (P ＜ 0.05).The cerebral capillary density in G-CSF group elevated to (348.4 ±76.7) A/HPF at 6 d after CPR which was significantly higher than that at 3 d (P ＜0.05),and there was no difference between that at 3 d and 6 d in G-CSF + AMD3100 group.Conclusions The mobilization stem cells improve the impaired neurological function.The increased expression of VEGF in brain tissue,the neo-vascularization promoted by the mobilized stem cells and the inhibition of nerve cell apoptosis may be associated with the protective effects of the stem cell mobilization.

Analysis of the feasibility of early hospital discharge after autologous hematopoietic stem cell transplantation and the implications to nursing care

INTRODUCTION: Autologous hematopoietic stem cell transplantation is a conduct used to treat some hematologic diseases and to consolidate the treatment of others. In the field of nursing, the few published scientific studies on nursing care and early hospital discharge of transplant patients are deficient. Knowledge about the diseases treated using hematopoietic stem cell transplantation, providing guidance to patients and caregivers and patient monitoring are important nursing activities in this process. Guidance may contribute to long-term goals through patients' short-term needs. AIM: To analyze the results of early hospital discharge on the treatment of patients submitted to autologous transplantation and the influence of nursing care on this conduct. METHODS: A retrospective, quantitative, descriptive and transversal study was conducted. The hospital records of 112 consecutive patients submitted to autologous transplantation in the period from January to December 2009 were revisited. Of these, 12 patients, who remained in hospital for more than ten days after transplantation, were excluded from the study. RESULTS: The medical records of 100 patients with a median age of 48.5 years (19-69 years) were analyzed. All patients were mobilized and hematopoietic stem cells were collected by leukapheresis. The most common conditioning regimes were BU12Mel100 and BEAM 400. Toxicity during conditioning was easily managed in the outpatient clinic. Gastrointestinal toxicity, mostly Grades I and II, was seen in 69% of the patients, 62% of patients had diarrhea, 61% of the patients had nausea and vomiting and 58% had Grade I and II mucositis. Ten patients required hospitalization due to the conditioning regimen. Febrile neutropenia was seen in 58% of patients. Two patients died before Day +60 due to infections, one with aplasia. The median times to granulocyte and platelet engraftment were 12 days and 15 days, respectively, with median...

Factors Predicting Peripheral Blood Stem Cell Collection: Analysis of Korean Patients at a Single Center / 대한수혈학회지

BACKGROUND: Peripheral blood stem cell (PBSC) transplantation is a curative treatment in various hematologic malignancies and some solid cancers. Effective mobilization and collection of PBSC is essential for successful PBSC transplantation. The aim of this study was to investigate the useful factors for predicting PBSC collection using multivariate analysis. METHODS: We retrospectively reviewed the medical records of 170 allogeneic and 389 autologous donors at Chonnam National University Hwasun Hospital between 2005 and 2012. Donor groups were divided into three groups (failure group, suboptimal group, and optimal group) according to the total CD34+ yield. Donors were compared regarding age, sex, body weight, disease, complete blood count, hematopoietic progenitor cell (HPC) parameter of automated cell counter, process volume, number of leukapheresis procedures, prior mobilization history, type of vascular access and instrument. RESULTS: In allogeneic PBSC collections (n=170), the collection failure group showed lower baseline (premobilization) white blood cell (WBC) (P=0.004) and HPC (P<0.001) than the optimal group. In autologous PBSC collections (n=389), the collection failure group showed lower baseline HPC and more frequent prior mobilization history (P<0.001) than the suboptimal and optimal group. In multivariate analysis, older age, lower number of leukapheresis procedures, and prior mobilization history were risk factors associated with mobilization failure. CONCLUSION: Our data suggest that baseline WBC and HPC would be useful for predicting poor mobilizer in allogeneic PBSC collection, whereas baseline HPC would be useful in autologous PBSC collection. Conventional chemotherapy and G-CSF based remobilization would not be helpful to proven poor mobilizer in previous mobilization.