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G-CSF causes decrease in peripheral blood platelet counts unrelated to leukapheresis during autologous stem cell mobilization
Poster Abstract Presentations that compared to ovalbumin injected positive control group, both low and high dosage injected experimental groups showed mild symptoms of anaphylactic response. We propose that MSC-derived exosomes has little antigenicity at least in guinea pig, which are considered to be biologically safe in humans. 202 FDP-2B:THE NEW GENERATION OF CGMP COMPLIANT LYOPHILIZED PLATELET RICH PLASMA. S. RAJINDRA1 & S. CHOON2 1 Laboratory, StemTech International Sdn.Bhd, Cyberjaya, Selangor Darul Ehsan, Malaysia, 2Department of Orthopaedic Surgery, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), University of Malaya, Kuala Lumpur, Malaysia Background & Aim: Platelet Rich Plasma (PRP) is a fraction of peripheral blood by concentration of platelets that generates clinically useful levels of various growth factors such as platelet-derived growth factor (PDGF), fibroblast growth factors (FGF) and epithelial growth factor (EGF). However, due to intensive time and labour, it can be difficult to prepare an adequate and consistent amount of platelets. Thus, we have generated a new method of PRP which could be isolated before hand and stored for further use. Methods, Results & Conclusion: Fresh PRP with 2 billion platelets/vial and freeze-dried PRP (FDP-2B) which were also stored in 2 billion platelets/vial has been prepared from peripheral blood of 8 healthy human volunteers (300 mL/person) ages 20-50 years old. Every vial of the fresh PRP from each donor were sent for growth factor studies right after the processing from the whole blood while the rest of the vials from each donor were freeze-dried and stored at three different temperatures of 4,-20 and -80°C. The growth factors (PDGF, FGF and EGF) concentration were examined after freezing and tested on day 10th, 1 month, 3 month, 6 month and 1 year post freeze drying. The successful samples processed for storage is 100%. All the three growth factors studied were present in both the fresh PRP(2B) and FDP-2B. However, it was observed that for every sample studied, the lyophilized PRP (FDP2B) shows a significant increase (p<0.05) in all growth factors as compared to the fresh PRP. The results of our study suggest that freeze-drying is an effective technique in preserving PRP bioactivity. Furthermore, we have developed the product in a cGMP environment, taking into account the bacterial and fungal culture testing for each donor in order to improve the safety of the procedure and to ensure it is free from contamination. In conclusion, our results suggest that freeze-dried human PRP maintains the growth factor levels that are comparable to those of fresh PRP(2B), even after the storage with potential clinical value. 205 G-CSF CAUSES DECREASE IN PERIPHERAL BLOOD PLATELET COUNTS UNRELATED TO LEUKAPHERESIS DURING AUTOLOGOUS STEM CELL MOBILIZATION M.S. Bakeer3,2, A. Zubair2 & V. Roy1 1 Hematology-Oncology, Mayo Clinic, Jacksonville, Florida, United States, 2 Mayo Clinic, Jacksonville, Florida, United States, 3Internal Medicine, AlAzhar university, Cairo, Egypt Background & Aim: Autologous transplant utilizing G-CSF mobilized peripheral blood stem cells (PBSC) is an established treatment for various conditions. PBSC collection has been reported to be associated with decrease in platelet counts, attributed to leukapheresis. Whether G-CSF directly affects platelet counts is unclear and studies show conflicting findings. We studied the change in platelet count, prior to start of leukapheresis, in patients receiving G-CSF for PBSC mobilization for autologous stem cell transplant Methods, Results & Conclusion: Myeloma patients undergoing PBSC collection in our institution were retrospectively studied. Patients received 10 mg/kg G-CSF SQ daily. Stem cell collection started on day 4 (after 3 doses of G-CSF) if blood CD34 count on day 4 was at least 10 cells/mL (Good mobilizer). If not (Poor mobilizer), patients received plerixafor and another dose of G-CSF on day 4 followed by collection starting day 5. Complete blood count was measured before G-CSF on day 0 and on days 2,3,and 4 prior to start of leukapheresis. 163 patients were studied, median age 61 yr (39-74), 99(61%) were men. Platelet count (Mean § SE) on day 0 was 230§5.9, which dropped to 192§4.4 (p<0.0001) on day 2, 190§4.6 on day 3, and 163§3.8 on day 4. Platelets decreased to a greater extent in poor mobilizers (n=74) compared to good mobilizers (n=89) (17.9%v11.9% on day 2, p=0.016; 18.2v12.3% on day 3, p=0.034). Platelet decrease was weakly correlated with CD34 count on day 3 (p=0.06). There was no correlation of age, sex, race, BMI or day 0 neutrophil count with day 0 platelet count or decrease in platelet count after G-CSF.
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There was no correlation of platelet decline with transplant outcomes - time to neutrophil or platelet engraftment, transfusion requirement, or infections. We show a direct effect of G-CSF on platelet counts unrelated to leukapheresis. The decline is more severe in poor mobilizers. This together with known association of thrombocytopenia with poor mobilization, and expected further drop after leukapheresis is an important consideration when assessing safety and efficacy of G-CSF based mobilization in patient with low platelet count. The mechanism of G-CSF induced thrombocytopenia is likely multifactorial. Possibilities include G-CSF induced differentiation and proliferation of myeloid progenitors at the expense of megakaryocytic lineage, G-CSF induced activation and consumption (Platelets are known to have functional G-CSF receptors), or sequestration from G-CSF induced splenomegaly.
Platelet count at baseline (Day 0) and after treatment with G-CSF 206 FACTORS PREDICTING PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION WITH PLERIXAFOR IN MULTIPLE MYELOMA PATIENTS WHO HAD INADEQUATE MOBILIZATION WITH G-CSF. M.S. Bakeer3,2, A. Zubair2 & V. Roy1 1 Hematology-Oncology, Mayo Clinic, Jacksonville, Florida, United States, 2 Mayo Clinic, Jacksonville, Florida, United States, 3Internal Medicine, Al-Azhar University, Cairo, Egypt Background & Aim: Autologous transplant utilizing G-CSF mobilized peripheral blood stem cells (PBSC) is considered standard practice for eligible multiple myeloma (MM) patients. G-CSF is often utilized as the preferred agent and Plerixafor added if there is inadequate PBSC mobilization with G-CSF alone. To the best of our knowledge, there are no studies predicting the response of the poor mobilizers to plerixafor. Methods, Results & Conclusion METHODS: MM patients undergoing PBSC collection in our institution were retrospectively studied. Patients received 10 mg/kg G-CSF SQ daily. Stem cell collection started on day 4 (after 3 doses of G-CSF) if blood CD34 count on day 4 was at least 10 /mL (Good mobilizer). If not (Poor mobilizer), patients received 240 mg/kg plerixafor SQ and another dose of G-CSF on day 4 followed by collection starting day 5. Complete blood count was measured before G-CSF (day 0) and on days +2, +3, and +4, . and CD34 count on day +5 . Based on day +5 CD34 count patients were categorized into two groups; Above Median (AM) with CD34 count above median or Below Median (BM; CD34 =< median). We analyzed associations of various variables with BM versus AM CD34 category using JMP statistical software. Results: 73 patients were studied. Median age 61 yr, (39-74), 44 (61%) were men. Median CD34 count on day +5 was 41.9/mL, 37 were in BM and 36 in AM groups. Disease duration prior to mobilization strongly correlated with plerixafor response (25.9m v 15.1m in BM v AM, p=0.02) . Mean day 0, day 2 and day 3 platelet count was higher in AM compared to BM (236 v 192,P =0.0075 on day 0, 182 v 148, p=0.0003 on day 2, and 195 v 152 p=0.0001 on day 3). Platelet count dropped from day 0 to day 2 in the whole cohort but
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There was no correlation of platelet decline with transplant outcomes - time to neutrophil or platelet engraftment, transfusion requirement, or infections. We show a direct effect of G-CSF on platelet counts unrelated to leukapheresis. The decline is more severe in poor mobilizers. This together with known association of thrombocytopenia with poor mobilization, and expected further drop after leukapheresis is an important consideration when assessing safety and efficacy of G-CSF based mobilization in patient with low platelet count. The mechanism of G-CSF induced thrombocytopenia is likely multifactorial. Possibilities include G-CSF induced differentiation and proliferation of myeloid progenitors at the expense of megakaryocytic lineage, G-CSF induced activation and consumption (Platelets are known to have functional G-CSF receptors), or sequestration from G-CSF induced splenomegaly.
Platelet count at baseline (Day 0) and after treatment with G-CSF 206 FACTORS PREDICTING PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION WITH PLERIXAFOR IN MULTIPLE MYELOMA PATIENTS WHO HAD INADEQUATE MOBILIZATION WITH G-CSF. M.S. Bakeer3,2, A. Zubair2 & V. Roy1 1 Hematology-Oncology, Mayo Clinic, Jacksonville, Florida, United States, 2 Mayo Clinic, Jacksonville, Florida, United States, 3Internal Medicine, Al-Azhar University, Cairo, Egypt Background & Aim: Autologous transplant utilizing G-CSF mobilized peripheral blood stem cells (PBSC) is considered standard practice for eligible multiple myeloma (MM) patients. G-CSF is often utilized as the preferred agent and Plerixafor added if there is inadequate PBSC mobilization with G-CSF alone. To the best of our knowledge, there are no studies predicting the response of the poor mobilizers to plerixafor. Methods, Results & Conclusion METHODS: MM patients undergoing PBSC collection in our institution were retrospectively studied. Patients received 10 mg/kg G-CSF SQ daily. Stem cell collection started on day 4 (after 3 doses of G-CSF) if blood CD34 count on day 4 was at least 10 /mL (Good mobilizer). If not (Poor mobilizer), patients received 240 mg/kg plerixafor SQ and another dose of G-CSF on day 4 followed by collection starting day 5. Complete blood count was measured before G-CSF (day 0) and on days +2, +3, and +4, . and CD34 count on day +5 . Based on day +5 CD34 count patients were categorized into two groups; Above Median (AM) with CD34 count above median or Below Median (BM; CD34 =< median). We analyzed associations of various variables with BM versus AM CD34 category using JMP statistical software. Results: 73 patients were studied. Median age 61 yr, (39-74), 44 (61%) were men. Median CD34 count on day +5 was 41.9/mL, 37 were in BM and 36 in AM groups. Disease duration prior to mobilization strongly correlated with plerixafor response (25.9m v 15.1m in BM v AM, p=0.02) . Mean day 0, day 2 and day 3 platelet count was higher in AM compared to BM (236 v 192,P =0.0075 on day 0, 182 v 148, p=0.0003 on day 2, and 195 v 152 p=0.0001 on day 3). Platelet count dropped from day 0 to day 2 in the whole cohort but