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Does PBSC Product Platelet Content Affect Outcomes of Autologous Peripheral Blood Stem Cell Transplant?
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
We recognize patients undergoing autologous BMT, may not show as robust a response to mobilization drugs as healthy donors. We recommend data collection in patients with sickle cell trait and sickle cell disease undergoing PBSC collections to define the tolerability of new mobilization regimens.
193 Does PBSC Product Platelet Content Affect Outcomes of Autologous Peripheral Blood Stem Cell Transplant? Raisa Pinto 1, Najla El Jurdi 1, Fahrettin Covut 1, Reshmi Parameswaran 2, Soumya Panigrahi 3, Paolo Caimi 1, Katharine Downes 1, Robert Maitta 1, James J. Driscoll 4, Marcos de Lima 1, Ehsan Malek 1. 1 University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 2 Pathology, Case Western Reserve University, Cleveland, OH; 3 Medicine, Case Western Reserve University, Cleveland, OH; 4 Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH Hematopoietic recovery after transplantation with mobilized peripheral stem cell (PBSC) is faster than with bone marrow, however the underlying mechanism(s) remains largely unknown. Different platelet (Plt) content is one of the major differences between these two products. Exposure to platelet agonists during mobilization lead to platelet activation
S155
(Nomura et al. Stem Cell, 2004). Studies using preclinical models showed platelet-derived particles attach to CD34 cells and accelerate engraftment (Janowska-Wieczorek et al. Blood. 2001). Furthermore, human CD34 hematopoietic stem-progenitor cells express platelet-binding antigens (sialomucin p-selelctin antigen and integrin Mac-1) suggesting the potential effect of platelets on CD34 homing and engraftment. Our objective was to determine the possible influence of platelet content of peripheral blood stem cell products on engraftment. Methods: Collection profiles of 94 patients (pts) who underwent ASCT to treat multiple myeloma from 2007 to 2014 in our institution were analyzed. Fifty three (56%) and 40 (42%) pts achieved partial response and very good partial response or better, respectively, before undergoing ASCT. Median number of prior regimens was 2 (1-6). Melphalan dosing was 200 mg/ m2 in 91 pts and 140 mg/m2 in another 3 pts. Median time from diagnosis to ASCT was 11.7 months. All pts underwent leukapheresis using the COBE Spectra cell separator (COBE BCT, Inc., Lakewood, CO). Twenty one pts were collected after Cytoxan and G-CSF, 8 with G-CSF alone and 65 with G-CSF and Plerixafor. Median number of collections was 2 (range, 1-4). The median viability of the collection product was 99.8%. Median number of collected Plt was 3.95 × 10^3/kg (range: .3-14).Pts were classified as PltHigh (n = 47) vs. PltLow (n = 47) if their collected Plt were above or below the median value, respectively. Result: Platelet size was significantly larger in the first day of collection in comparison to subsequent days (10.27 vs. 9.92 fL,
Figure 1. (A) Higher platelet volume collected on the first day. (B) Higher ratio of collected CD34 to Platelet on first dat in compare to subsequent days.
Figure 2. The total number of collected CD34 was inversely correlated with collected Platelet in patients who had more than one-day collection.
S156
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
Figure 3. (A) Neutrophil engraftment between Plthigh and Pltlow group. (B) Platelet engraftment between Plthigh and Pltlow group.
P < .04). (Figure 1A). Also, the ratio of CD34 cells to Plt was higher in the first day of collection in comparison to subsequent days (2.57 vs. 2.12, P < .045) (Figure 1B). The total number of collected CD34 cells was inversely correlated with collected Plt in pts who had more than one-day collection. Mean time to neutrophil and platelet engraftment was not statistically different between PltHigh vs. PltLow (10. 21 vs. 11.49, days P = .09; 19.95 vs. 20.9 days, P = .16, respectively). Median progression free survival was not different between the two groups with a median follow up of 30 months (27.7 vs. 25.7 months, P = .23). Conclusion: Although there was a trend towards faster engraftment with PltHigh than PltLow, it did not reach statistical significance. Further studies paired with pertinent platelet and megakaryocyte assays are needed to delineate the possible influence of platelets on CD34 homing and engraftment (Figures 2, 3).
194 Impact of Lenalidomide on Hematopoietic Myeloid and Erythroid Progenitors: Peripheral Stem Cell Collection May Not be Affected Fahrettin Covut 1, Raisa Pinto 1, Talib Dosani 2, Judah Friedman 3, James J. Driscoll 4, Katharine Downes 1, Robert Maitta 1, Marcos de Lima 1, Ehsan Malek 1, Najla El Jurdi 1. 1 University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 2 University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH; 3 University Hospitals Geauga Medical Center, Chardon, OH; 4 Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH
Triplet regimens that include the immunomodulatory agent lenalidomide (LEN) have emerged as standard-of-care frontline therapy for multiple myeloma. Peripheral blood stem cell collection (PBSC) occurs frequently after only a few cycles of LEN, mostly due to reported deleterious effect of this agent on collections. This approach prevents a subset of patients (pts) from achieving the deepest possible response prior to transplant. Plerixafor antagonizes binding SDF-1 to its cognate receptor CXCR4, results in rapid mobilization of hematopoietic stem cells, and may ameliorate the suppressive effect of LEN on PBSC. Here, we examined the effect of LEN before PBSC collection on early erythroid, Burst-forming Erythroid Unit (BFU-E), and myeloid progenitors, Granulocyte-Monocyte Colony-forming Units (CFUGM), and its effect on autologous stem cell transplant (ASCT) outcomes. Methods: Ninety four pts who underwent first ASCT from 2007 to 2014 at our institution were included. Median age was 59 years old at the time of ASCT. Fifty three (56%) and 40 (42%) pts achieved partial response and very good partial response or better, respectively, before undergoing ASCT. Median number of prior regimens were 2 (1-6). Median time from diagnosis to ASCT was 11.7 months. All pts underwent leukapheresis using the COBE Spectra cell separator. Twenty one pts were collected after Cytoxan and G-CSF, 8 with G-CSF alone and 65 with G-CSF and Plerixafor. Median number of collections was 2 (range, 1-4). Pts that received LEN containing regimens as the immediate line of therapy before PBSC collection (LENpos, n = 51) were compared to those who did not (LENneg, n = 43). Pts that received pomalidomide-containing regimen before PBSC were excluded.
Figure 1. Correlation of collected total nucleated cells (TNC) with Myeloid (A) and Erythroid progenitors (B) in LENpos vs. LENneg groups.
We recognize patients undergoing autologous BMT, may not show as robust a response to mobilization drugs as healthy donors. We recommend data collection in patients with sickle cell trait and sickle cell disease undergoing PBSC collections to define the tolerability of new mobilization regimens.
193 Does PBSC Product Platelet Content Affect Outcomes of Autologous Peripheral Blood Stem Cell Transplant? Raisa Pinto 1, Najla El Jurdi 1, Fahrettin Covut 1, Reshmi Parameswaran 2, Soumya Panigrahi 3, Paolo Caimi 1, Katharine Downes 1, Robert Maitta 1, James J. Driscoll 4, Marcos de Lima 1, Ehsan Malek 1. 1 University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 2 Pathology, Case Western Reserve University, Cleveland, OH; 3 Medicine, Case Western Reserve University, Cleveland, OH; 4 Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH Hematopoietic recovery after transplantation with mobilized peripheral stem cell (PBSC) is faster than with bone marrow, however the underlying mechanism(s) remains largely unknown. Different platelet (Plt) content is one of the major differences between these two products. Exposure to platelet agonists during mobilization lead to platelet activation
S155
(Nomura et al. Stem Cell, 2004). Studies using preclinical models showed platelet-derived particles attach to CD34 cells and accelerate engraftment (Janowska-Wieczorek et al. Blood. 2001). Furthermore, human CD34 hematopoietic stem-progenitor cells express platelet-binding antigens (sialomucin p-selelctin antigen and integrin Mac-1) suggesting the potential effect of platelets on CD34 homing and engraftment. Our objective was to determine the possible influence of platelet content of peripheral blood stem cell products on engraftment. Methods: Collection profiles of 94 patients (pts) who underwent ASCT to treat multiple myeloma from 2007 to 2014 in our institution were analyzed. Fifty three (56%) and 40 (42%) pts achieved partial response and very good partial response or better, respectively, before undergoing ASCT. Median number of prior regimens was 2 (1-6). Melphalan dosing was 200 mg/ m2 in 91 pts and 140 mg/m2 in another 3 pts. Median time from diagnosis to ASCT was 11.7 months. All pts underwent leukapheresis using the COBE Spectra cell separator (COBE BCT, Inc., Lakewood, CO). Twenty one pts were collected after Cytoxan and G-CSF, 8 with G-CSF alone and 65 with G-CSF and Plerixafor. Median number of collections was 2 (range, 1-4). The median viability of the collection product was 99.8%. Median number of collected Plt was 3.95 × 10^3/kg (range: .3-14).Pts were classified as PltHigh (n = 47) vs. PltLow (n = 47) if their collected Plt were above or below the median value, respectively. Result: Platelet size was significantly larger in the first day of collection in comparison to subsequent days (10.27 vs. 9.92 fL,
Figure 1. (A) Higher platelet volume collected on the first day. (B) Higher ratio of collected CD34 to Platelet on first dat in compare to subsequent days.
Figure 2. The total number of collected CD34 was inversely correlated with collected Platelet in patients who had more than one-day collection.
S156
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
Figure 3. (A) Neutrophil engraftment between Plthigh and Pltlow group. (B) Platelet engraftment between Plthigh and Pltlow group.
P < .04). (Figure 1A). Also, the ratio of CD34 cells to Plt was higher in the first day of collection in comparison to subsequent days (2.57 vs. 2.12, P < .045) (Figure 1B). The total number of collected CD34 cells was inversely correlated with collected Plt in pts who had more than one-day collection. Mean time to neutrophil and platelet engraftment was not statistically different between PltHigh vs. PltLow (10. 21 vs. 11.49, days P = .09; 19.95 vs. 20.9 days, P = .16, respectively). Median progression free survival was not different between the two groups with a median follow up of 30 months (27.7 vs. 25.7 months, P = .23). Conclusion: Although there was a trend towards faster engraftment with PltHigh than PltLow, it did not reach statistical significance. Further studies paired with pertinent platelet and megakaryocyte assays are needed to delineate the possible influence of platelets on CD34 homing and engraftment (Figures 2, 3).
194 Impact of Lenalidomide on Hematopoietic Myeloid and Erythroid Progenitors: Peripheral Stem Cell Collection May Not be Affected Fahrettin Covut 1, Raisa Pinto 1, Talib Dosani 2, Judah Friedman 3, James J. Driscoll 4, Katharine Downes 1, Robert Maitta 1, Marcos de Lima 1, Ehsan Malek 1, Najla El Jurdi 1. 1 University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH; 2 University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH; 3 University Hospitals Geauga Medical Center, Chardon, OH; 4 Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH
Triplet regimens that include the immunomodulatory agent lenalidomide (LEN) have emerged as standard-of-care frontline therapy for multiple myeloma. Peripheral blood stem cell collection (PBSC) occurs frequently after only a few cycles of LEN, mostly due to reported deleterious effect of this agent on collections. This approach prevents a subset of patients (pts) from achieving the deepest possible response prior to transplant. Plerixafor antagonizes binding SDF-1 to its cognate receptor CXCR4, results in rapid mobilization of hematopoietic stem cells, and may ameliorate the suppressive effect of LEN on PBSC. Here, we examined the effect of LEN before PBSC collection on early erythroid, Burst-forming Erythroid Unit (BFU-E), and myeloid progenitors, Granulocyte-Monocyte Colony-forming Units (CFUGM), and its effect on autologous stem cell transplant (ASCT) outcomes. Methods: Ninety four pts who underwent first ASCT from 2007 to 2014 at our institution were included. Median age was 59 years old at the time of ASCT. Fifty three (56%) and 40 (42%) pts achieved partial response and very good partial response or better, respectively, before undergoing ASCT. Median number of prior regimens were 2 (1-6). Median time from diagnosis to ASCT was 11.7 months. All pts underwent leukapheresis using the COBE Spectra cell separator. Twenty one pts were collected after Cytoxan and G-CSF, 8 with G-CSF alone and 65 with G-CSF and Plerixafor. Median number of collections was 2 (range, 1-4). Pts that received LEN containing regimens as the immediate line of therapy before PBSC collection (LENpos, n = 51) were compared to those who did not (LENneg, n = 43). Pts that received pomalidomide-containing regimen before PBSC were excluded.
Figure 1. Correlation of collected total nucleated cells (TNC) with Myeloid (A) and Erythroid progenitors (B) in LENpos vs. LENneg groups.