Decision-Tree Algorithm Optimize Hematopoietic Progenitor Cell-Based Prediction in Peripheral Blood Stem Cell Mobilization

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1903-1903
Author(s):  
Chia-Yun Wu ◽  
Tzeon-Jye Chiou ◽  
Chun-Yu Liu ◽  
Feng-Chang Lin ◽  
Jeong-Shi Lin ◽  
...  

Abstract Background and Objectives Enumeration of hematopoietic progenitor cells (HPC) using an automated hematology analyzer provides rapid, inexpensive, and less technically dependent prediction of peripheral blood stem cell (PBSC) mobilization. This study aimed to incorporate HPC enumeration along with other predictors for optimizing a successful harvest. Materials and Methods Between 2007 and 2012, 189 consecutive patients who proceeded to PBSC harvesting with a preharvest HPC ≥ 20 x 106 /L were recruited. A failed PBSC mobilization was defined as < 2 x 106 CD34+ cells/kg. Variables predicting a successful harvest identified by multivariate logistic regression and correlation analysis were subjected to classification and regression tree (CART) analysis. Results A total of 154 (81.5%) patients successfully achieved mobilization of CD34+ cells (median 8.18 x 106 CD34+ cells/kg). Five independent host predictors including age ≥ 60, a diagnosis of solid tumor, prior chemotherapy cycles ≥ 5, prior radiotherapy, and mobilization with G-CSF alone or high-dose cyclophosphamide, as well as laboratory markers including HPC and mononuclear cell (MNC) counts, were used for CART analysis. The number of host predictors with a cutoff at two, HPC cutoff at 28 x 106/L and MNC cutoff at 3.5 x 109 /L were best discriminative for successful prediction. In the decision tree algorithm, patients predicted as good mobilizers (0 to 2 risk factors) had a higher success rate (150/169, 88.8%) than that (4/20, 20.0%) of those predicted as poor mobilizers (3-5 risk factors). Moreover, patients predicted as good mobilizers and further with a HPC enumeration ≥ 28 x 106/L had a high probability of achieving successful mobilization (138/148, 93.2%). Conclusion Our CART algorithm incorporating host predictors, HPC enumeration and MNC count may improve prediction and thus increase the success of PBSC mobilization. Further prospective validation is necessary. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7099-7099
Author(s):  
M. Ozturk ◽  
F. Arpaci ◽  
S. Ataergin ◽  
A. Ozet ◽  
T. Cetin ◽  
...  

7099 Background: 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. However,in our previous randomized study we demonstrated that a 7.5 microg/kg/day dose of lenograstim has been as efficacious as 10 microg/kg/day of filgrastim. In this study, we investigated whether a reduced dose of lenograstim is equavalent to standard dose for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. Methods: A total of 49 consecutive patients were randomized to either low dose (7.5 microg/kg/day, n = 24) or standard dose (10 microg/kg/day, n = 25) of lenograstim. These two groups were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each dose of lenograstim was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, lenograstim was given at 5 microg/kg/day until leukocyte engraftment. Results: Successful mobilization with the first apheresis, was achieved in 10/24 (42%) patients in low dose group versus 14/25 (56%) patients in standard dose group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Conclusions: Lenograstim 7.5 microg/kg/day is as efficious as Lenograstim 10 microg/kg/day for autologous PBSC mobilization and transplantation. No significant financial relationships to disclose.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1922-1922
Author(s):  
Ryuji Tanosaki ◽  
Tomoko Kumazawa ◽  
Shigehisa Yoshida ◽  
Atsuya Nakano ◽  
Shizuka Yamagata ◽  
...  

Abstract Abstract 1922 The number of infused CD34+ cells is crucial to the success of peripheral blood stem cell transplantation (PBSCT). Although counting CD34+ cells currently depends solely on flow cytometry technology, the complexity of the procedure and the high cost of reagents (including monoclonal antibodies) are the main disadvantages. The SYSMEX SE-9000 (SE) and XE-2100 (XE) automated hematology analyzers quickly estimate the number of immature cells, referred to as hematopoietic progenitor cells (HPCs), at very low cost. The number of peripheral blood SE/XE-determined HPC (SE/XE-HPC) is used to determine the optimal timing of peripheral blood stem cell (PBSC) collection. However, SE/XE-HPCs are limited as a substitute for CD34+ cells because they are likely to be affected by co-existing immature cells (e.g. immature granulocytes), resulting in overestimation of the HPC count. Therefore, we developed a new technology for counting HPCs. The assay's mechanism is based on finely-tuned hemolysis reactions and chemical staining with a specific dye, and does not require monoclonal antibodies. The assay is followed by a flow cytometry-based optical detection technique that differs from the SE or XE former types, which use the electrical radiofrequency/direct currency impedance detection method. This modified program has been installed into an revised model of an automated hematology analyzer, the XN Prototype (SYSMEX corporation, Kobe, Japan), which enables us to cost-effectively obtain the number of new, marked HPCs, designated as 'XN-determined HPC (XN-HPC)', within 4 minutes using small (200 μL) samples. The purpose of this study is to evaluate the XN-HPC in comparison with CD34+ cells, and this is the first report of the results. Between 2008 and 2011, a total of 87 blood or G-CSF-mobilized apheresis samples were taken from healthy donors (n=20) or patients undergoing autologous PBSCT (n=5) at the National Cancer Center Hospital, Japan. Next, CD34+ cells and XN-HPCs were analyzed in the same samples. XN-HPCs were counted using the XN Prototype, and CD34+ cells were quantified using a flow cytometer (FACSCalibur, BD, New Jersey, USA) using the dual platform method according to the International Society of Hematology and Graft Engineering protocol. This study was approved by Institutional Review Board, and informed consent was obtained from all patients. There was a very good correlation between the numbers of XN-HPCs and CD34+ cells (R2=0.952) in all samples, at a wide range of CD34+ cell concentrations (range; 0.3–12830.5 cells /μL) (Fig. 1). The correlation was unaffected by WBC counts, use of EDTA as an anticoagulant, sample type, or timing of collections. The XN-HPC concentration in the 3L-apheresis products (3L-HPCs) correlated well with CD34+ cell concentration in the final products (R2=0.948). The estimated total number of XN-HPCs in the final products, which was calculated from the 3L-HPC concentration or pre-apheresis HPC concentration in the peripheral blood (PB-HPCs), also correlated well with the total number of CD34+ cells in the final products (R2=0.918 or 0.950, respectively), suggesting that the final amount of collected CD34+ cells could be predicted from the total number of HPCs in the final products, as well as from pre-apheresis PB-HPCs and from the intermediate products during apheresis (3L-HPCs). The change in PB-HPCs closely resembled that of CD34+ cells during the bone marrow recovery phase after chemotherapy (Fig. 2), also suggesting that XN-HPC might be a good indicator for the optimal timing of PBSC collection. In conclusion, XN-HPC could be a surrogate for CD34+ cells in PBSCT, and further investigation of their usefulness and clinical applications are warranted. Disclosures: Tanosaki: Sysmex Corporation: They provided hematology analyzers, a flow cytometer and reagents.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2037-2037
Author(s):  
Sun-Young Kong ◽  
Hyoeun Shim ◽  
Se-Na Lee ◽  
Jung-Hee Kong ◽  
Hyeon-Seok Eom ◽  
...  

Abstract Background The optimal peripheral blood stem cell (PBSC) collection is a key step for successful outcome in hematopoietic stem cell transplantation (HSCT). Many indicators including preharvest white blood cell (WBC), mononuclear cell (MNC), and CD34 positive cell counts have been used for deciding the adequate time for collection of PBSCs, but each indicator has limitations. Here we investigated hematopoietic progenitor cell (HPC) count as an indicator for PBSC collection. Methods: Data from 851 autologous PBSC collections from 233 patients at the National Cancer Center, Korea, were analyzed. The correlations between harvested CD34 cell counts with preharvest WBC, MNC, CD34 cell counts, and HPC were analyzed, as were correlations by disease and mobilizing agent. Also how the outcome for engraftment can be predicted based on HPC count was studied. Results: The median age of patients was 41 years (range 0.1-72 years). The most frequent diseases were multiple myeloma (n=64) and non-Hodgkin lymphoma (n=56). The correlation coefficient between collected CD34 cells and preharvest CD34 count was (r=0.669, p<0.001), followed by preharvest HPC count (r=0.419, p<0.001), preharvest MNC (r=0.190, p<0.001) and preharvest WBC (r=0.014, p=0.679). The most adequate cut-off value for obtaining >1x106 CD34+ cells/kg at first time of PBSC was 24.0 HPCs/μL with sensitivity and specificity of 67.7% and 74.3% respectively. The cutoff as 28.0 HPCs/μL was adequate for obtaining 2.0 x106 CD34+ cells/kg with sensitivity and specificity of 73.7% and 72.2% respectively. HPC was well correlated with CD34 in PBSC of patients with multiple myeloma (r=0.326, p=0.009), non-Hodgkin lymphoma (r=0.353, p=0.008), especially diffuse large B-cell lymphoma (r=0.810, p<0.001) and acute leukemia (r=0.998, p<0.001). HPC was a better indicator for non-cyclophosphamide (r=0.337, p<0.001) than cyclophosphamide-based chemomobilization (r=0.572, p=0.052). Infused number of HPCs did not affect the times to engraftment of platelets (p=0.896) and neutrophils (p=0.953), though CD34 count of infusion had positive effect on platelet engraftment (p=0.017). Conclusion: HPC count represented good correlation with CD34+ and high area under the curve. Considering advantages of ease for use and cost-effectiveness than those of CD34 count, HPC is a good surrogate marker to determine appropriate timing for PBSC. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2314-2314
Author(s):  
Francois Lefrere ◽  
Dominique bastit-Barrau ◽  
Suzanne Mathieu ◽  
Alain Bohbot ◽  
Philippe Bourrin ◽  
...  

Abstract &lt;&gt;The ACVBP regimen is commonly used in young poor-risk patients with DLBCL candidates to first line consolidative high-dose therapy followed by autologous stem cells transplantation in GELA trials. The combination with the monoclonal anti-CD20 antibody rituximab (R-ACVBP) is now routinely used, as induction treatment and to mobilize peripheral blood stem cell (PBSC). The aim of the present study was to assess the impact of rituximab on PBSC mobilization and collection in patients with newly diagnosed DLBCL receiving ACVBP chemotherapy. We reviewed the data from two prospective controlled trials. The first, conducted between 1999 and 2003, involved patients presenting with 2 or 3 adverse prognostic factors on the basis of the age-adjusted IPI (aa-IPI), treated by ACVBP (LNH 98B-3) (ASCO2007:8018). In the second trial (LNH 03-3B), conducted between 2004 and 2007, similar patients received the same initial inductive chemotherapy combined to rituximab (375mg/m2 at D1). 137 and 91 patients in the ACVBP and the R-ACVBP groups are here analyzed, respectively. Clinical and biological characteristics at diagnosis of the two groups of patients were similar (aa-IPI 2 and aa-IPI 3: 75% and 25%, respectively). The conditions for G-CSF administration and stem cell collections were identical. PBSC mobilizations were performed following the third or fourth cycle of (R)-ACVBP. The median delay between day 1 of chemotherapy and the first hemapheresis was identical for both groups. First hemapheresis was performed with a median peripheral white blood cell concentration of 16.2 x 109/l and 16.6 x 109/l for ACVBP and R-ACVBP groups, respectively. The median peak number of peripheral blood CD34+ cells observed the same day of first hemapheresis in ACVBP and R-ACVBP group was 69 x 106/l and 63 x 106/l, respectively (p = 0.5). The median number of CD34+ cells collected were 7.1 x 106 and 6.0 x 106 CD34 cells/kg for ACVBP and R-ACVBP groups (p = 0.12) while the median number of hemapheresis to target a minimal number of 3 x 106 CD34 cells/kg was identical, of one, in both groups. Failure of stem cell collection , defined as less than 3 x 106 CD34 cells/kg harvested, was observed in 8% and 4% of the patients who received ACVBP or R-ACVBP , respectively (p = 0.13). We conclude that rituximab combined to ACVBP regimen does not impair PBSC mobilization and collection.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1131-1131
Author(s):  
Evdokia S. Urnova ◽  
Larisa P. Mendeleeva ◽  
Olga S. Pokrovskaya ◽  
Marina A. Gracheva ◽  
Eduard G. Gemdzhian ◽  
...  

Abstract Background: Patients (pts) with multiple myeloma (MM) have an increased risk of thrombosis. Previous studies have shown that 3.7–4.6% of pts undergoing peripheral blood stem cell (PBSC) mobilization developed thrombotic complications. Aims: The aim of the study was to investigate the blood coagulation status in MM pts during PBSC mobilization. Methods: 20 pts: 12 males, 8 females at the age of 27 – 64 years (median 53) were included in the study. After bortezomib-containig induction therapy 5 of them achieved CR, 11 – VGPR and 6 – PR. PBSC mobilization was performed by using cyclophosphamide (CY, 4g/m2) and granulocyte colony-stimulating factor (G-CSF, 5mcg/kg/day). A central venous catheter (CVC) was placed on the day before CY administration and heparin-sulphate continuous infusion (500 IU/hour) as thromboprophylaxis was started. Subcutaneous injections of G-CSF were administrated when WBS decreased less 1 x 109/l. The procedures of stem cell collection were carried out when the number PB CD 34+ cells exceeded 10 x 103/ml. Hemostasis analysis was performed 5 times, namely before (point 0) and 24 hours after heparin administration (point 1), the next day after CY infusion (point 2), before G-CSF administration (point 3) and on the day of PBSC collection (point 4). Condition of hemostasis was assessed by the results of activated partial thromboplasin time (APTT, normal rate: 25 – 38 sec) and thrombin generation test, namely by using endogenous thrombin potential (ETP, normal rate: 760 – 1450 nM*min) in every point. Hypercoagulation was considered in cases when APTT < 25 sec and ETP > 1450 nM*min. And hypocoagulation was estimated by data APTT > 38 sec and ETP < 760 nM*min. Time series analysis performed using TIMESERIES procedure in SAS 9.3 (SAS Institute Inc. Cary, NC). Significance level of alpha was set at 0.05. Results: Before heparin administration (point 0) APTT evaluation showed normal coagulation in 18 pts (90%) and hypocoagulation in 2 pts (mean 34 sec, 95% CI 32 – 36 sec) (Figure 1). ETP was normal in 14 pts and increased in 6 cases (mean 1441 nM*min, 95% CI 1304 – 1578 nM*min) (Figure 2). Pts in CR demonstrated no significant difference in coagulation status compared to pts in VGPR or PR. On the next day after CVC incorporation and starting thromboprophylaxis (point 1), APTT and ETP have significantly changed (p < 0,05) to hypocoagulability in response to heparin infusion: mean data APTT became 38 sec (95% CI 36 – 41 sec) and mean ETP - 938 nM*min (95% CI 801 – 1074 nM*min). On the next day after CY administration (point 2) APTT was statistically significantly decreased (p < 0.05) reaching 35 sec (95% CI 34 – 36 sec). ETP had also changed but to a lesser degree, the mean was 1079 nM*min (95% CI 929 – 1229 nM*min). Hemostasis at point 3 was characterized by APTT mean 38 sec (95% CI 37 – 40 sec) and ETP mean 1057 nM*min (95% CI 911 – 1203 nM * min). On the day of PBSC collection mean values of measured parameters have not changed as compared to the previous point: APTT was 40 sec (95% CI 37 – 43 sec) and ETP was 1046 nM*min (95% CI 916 – 1176 nM*min) (Table 1). Thrombotic events were diagnosed in 2 cases of the total of 20 pts. There were two females, 54 and 56 years, both in CR MM. The first pt developed CVC-associated thrombosis. She had additional risk factors such as obesity (BMI – 44) and heterozygous MTHFR polymorphism. The second pt demonstrated acute violation of cerebral circulation which arose due to occlusion of the right internal carotid artery. She was a hard smoker and heterozygous FV Leiden polymorphism. Having confirmed thrombotic complications, the dose of heparin had been increased. Besides, folic acid was administrated for the first pt and combination of aspirin and pentoxifilline for the second. PBSC collection was successful for both pts. Summary: The results of our study identify latent hypercoagulation status in 30% pts of confirmed by elevated ETP. Those changes were registered despite of achievement CR or PR MM. Thrombotic complications have developed in 10% from our group. Notably, one should consider individual risk factors for each pt. Figure 1 Figure 1. Figure 2 Figure 2. Table 1. Measurements data of parameters of hemostasis Measuring point Mean APTT (95% CI) Mean ETP (95% CI) 0 33.6 (31.2-35.9)* 1441.1 (1304.3-1577.9)* 1 38.6 (35.7-41.6)* 937.6 (801.3-1074.0)* 2 35.2 (33.9-36.5)* 1079.0 (928.8-1229.2)* 3 38.1 (36.7-39.5) 1057.2 (911.4-1203.1) 4 39.6 (36.5-42.8) 1046.2 (916.0-1176.3) * Means in the same column are significantly different (P<0.05) Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Takahiro Shima ◽  
Teppei Sakoda ◽  
Tomoko Henzan ◽  
Yuya Kunisaki ◽  
Takahiro Maeda ◽  
...  

Peripheral blood stem cell (PBSC) transplantation is a key treatment option for hematological diseases and widely performed in clinical practice. Platelet loss is the major complication of PBSC apheresis, and platelet-rich plasma (PRP) return is recommended in case of severe platelet decrease following apheresis; however, little is known about the frequency and severity of platelet loss nor the efficacy of PRP return post-apheresis. To address these questions, we assessed changes in platelet counts following PBSC-related apheresis in 270 allogeneic (allo)- and 105 autologous (auto)-PBSC settings. We also evaluated efficacy of PRP transfusion on platelet recovery post-apheresis. Platelet counts reduced up to 70% post-apheresis in both allo- and auto-PBSC settings, while severe platelet count decrease (&lt; 50 x 109/L) was only observed in auto-PBSC patients (Figure 1). We next analyzed the relationship between severe platelet (&lt; 50 x 109/L) after apheresis and several clinical factors by using univariate and multivariate analysis for auto-PBSC patients. As shown in Table 1, in univariate analysis, severe platelet counts following auto-PBSC apheresis was found more frequently in patients with lower platelet count, lower percentage of CD34+ cells in PB at pre-apheresis, repeated round of apheresis, and smaller number of collected CD34+ cells. On the other hand, in multivariate analysis, the white blood cell (WBC) counts pre-apheresis was the only significant risk factor of severe platelet count following apheresis (p = 0.038). We finally analyzed the transitions of platelet counts in the setting of apheresis. The median platelet counts at pre-apheresis, post-apheresis, and post-PRP return were 187.0 x 109/L, 132.0 x 109/L, and 154.0 x 109/L for allo-PBSC apheresis, and 147.0 x 109/L, 111.0 x 109/L, and 127.0 x 109/L for auto-PBSC apheresis (p &lt; 0.0001 for all, allo-PBSC donors and auto-PBSC patients, respectively) (Figure 2), indicating that PRP return post-apheresis facilitated a rapid platelet recovery in both allo- and auto-settings. Collectively, our data suggest that WBC counts pre-apheresis is a useful predictor for severe platelet decrease following auto-PBSC apheresis and that PRP return is an effective mean to facilitate platelet recovery post-apheresis. Disclosures No relevant conflicts of interest to declare.


1997 ◽  
Vol 15 (2) ◽  
pp. 684-690 ◽  
Author(s):  
T Demirer ◽  
C D Buckner ◽  
B Storer ◽  
K Lilleby ◽  
S Rowley ◽  
...  

PURPOSE To evaluate the effects of chemotherapy regimens on peripheral-blood stem-cell (PBSC) yields in patients with breast cancer who receive granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS One hundred patients with breast cancer received cyclophosphamide 4 g/m2 for dose (CY) (n = 10), CY and etoposide 600 mg/m2 (CE) (n = 13), CE and cisplatin 105 mg/m2 (CEP) (n = 19), or CY and paclitaxel 170 mg/m2 (n = 58), followed by G-CSF. PBSC collections were initiated when the WBC count recovered to greater than 1 x 10(9)/L. A multivariate analysis was undertaken to evaluate the effects of different chemotherapy regimens and patient variables on PBSC collections as measured by the yield of CD34+ cells. RESULTS The medians of average daily CD34+ cell yields for patients who received paclitaxel plus CY, CE, and CEP with G-CSF were 12.9, 11.03, and 5.37 x 10(6)/kg, respectively, compared with 2.02 x 10(6)/kg in the reference group that received CY with G-CSF (P = < .0001, .002, and .09, respectively). On first-day collections, patients who received paclitaxel plus CY, CE, and CEP with G-CSF yielded medians of 11.07, 8.09, and 3.52 x 10(6) CD34+ cells/kg, respectively, compared with 0.90 x 10(6)/kg in the reference group that received CY with G-CSF (P = .0006, .02, and .09, respectively). The number of previous cycles of chemotherapy, previous radiotherapy, marrow involvement, and phase and stage of disease did not have statistically significant effects on CD34+ cell yield. CONCLUSION Combination chemotherapy regimens were superior to single-agent CY for the mobilization of CD34+ cells.


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