The Effect of Daratumumab, Lenalidomide, Dexamethasone (DRd) on Peripheral Blood Stem Cell Mobilisation (PBSC)

Abstract Peripheral blood stem cell (PBSC) mobilisation in multiple myeloma (MM) patients after exposure to daratumumab (D), a CD38 targeting monoclonal antibody, produces a lower stem cell yield possibly due to an effect on CD34+ stem cells (Hulin et al., 2021). Similarly, the GRIFFIN study reported greater plerixafor usage to facilitate PBSC mobilisation in patients randomised to DARA-Velcade, Lenalidomide and Dexamethasone (D-VRd) when compared to VRd (Voorhees et al., 2020). In addition, R use has previously been shown to impact adversely on PBSC yields (Kumar et al., 2007) with a recommendation to use cyclophosphamide (cyclo) assisted mobilisation for this group of patients (Mazumder et al., 2008). In this context there remains uncertainty about the role of plerixafor, compared to chemotherapy assisted mobilisation. Aim: To investigate the effect of DRd on PBSC mobilisation and to determine the outcomes of G-CSF (G) + cyclo and G +/-plerixafor mobilisation for patients with prior DRd exposure and to compare PBSC yields to patients mobilised after Velcade, Cyclophosphamide, Dexamethasone (VCD) based induction therapy Methods: The ALLG MM21 study (ACTRN12618001490268) is a multicentre study of transplant eligible refractory and/or relapsed MM patients. Patients were eligible if they had progressive disease or less than a partial response to prior VCD induction therapy. D at 16mg/m2 and d at 40mg was administered on Day 1,8,15 and 22 in combination with R 25mg D1-21 for the first 2 induction cycles. From cycle 3, D was administered fortnightly with R 10mg D1-28 and d 40mg weekly. PBSC mobilisation was undertaken after 2-3 cycles of DRd with a minimum of 14 days off R and D prior to proceeding. The PBSC mobilisation approach and the need plerixafor were based on institutional practice. Results: Fifty patients were enrolled on trial. Three patients experienced progressive disease and 3 patients died prior to mobilisation. A total of 44 patients underwent PBSC mobilisation,11 (25%) of these post-VCD but prior to starting DRd received G-only (Group A); 22/44 (50%) post-DRd received G + cyclo (Group B); and 11/44 (25%) post-DRd received G-only (Group C) (Figure 1). Based on low day 1 CD34+ counts 13/33 (33%) patients required plerixafor post-DRd and 2/11 (18%) post-VCD. Post-DRd 7/33 (21%) patients failed to collect more than 2 million cells/kg and 4 then failed a second attempt at mobilisation. All patients post-VCD/pre-DRd were successfully mobilised. Total PBSC yields were comparable between Groups A and B but significantly lower for Group C versus Group A (Table 1). Group B patients were then compared to a contemporaneous group of non-trial VCD treated and G only mobilised patients (n = 32) and found to have significantly inferior day 1 median peripheral blood (PB) CD34+ cell counts (Table 2, Figure 1). Seven patients (21%) who received G + cyclo experienced grade 3/4 infections with 5 of the 7 demonstrating day 1 PB CD34+ cell counts of <5 per/µl. There were more apheresis days with median 2.5 days (1-5) in the G+ cyclo (Group B) compared to the other G-only or G+ plerixafor groups (median 2 days (1-3)). Conclusions: PBSC collection after DRd salvage was characterised by lower CD34+ cell mobilisation and lower overall PB CD34+ yields when compared to patients mobilised after receiving VCD. Cyclo assisted mobilisation but not G + plerixafor abrogated this effect. Further evaluation of strategies to mitigate against the impact of DR containing induction are required. Figure 1 Figure 1. Disclosures Indran: Jansse-Cilag Pty Ltd.: Other: Registration costs , Patents & Royalties. Quach: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees. Janowski: BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees. Estell: Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Spencer: Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria. OffLabel Disclosure: The combination of Daratumumab, Lenalidomide and Dexamethasone therapy is not approved on the Pharmaceutical Benefits Scheme in Australia.

Download Full-text

Lower Hematopoietic Progenitor Cell Counts and Yields at Subsequent Donations Is Influenced By a Shorter Inter-Donation Interval between the First and Subsequent Mobilizations

Blood ◽

10.1182/blood-2019-123492 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1962-1962

Author(s):

Sandhya R. Panch ◽

Brent R. Logan ◽

Jennifer A. Sees ◽

Bipin N. Savani ◽

Nirali N. Shah ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Peripheral Blood ◽

Research Funding ◽

Time Interval ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Peripheral Blood Cd34 ◽

Cell Counts ◽

Cd34 Cells

Introduction: Approximately 7% of unrelated hematopoietic stem cell (HSC) donors are asked to donate a subsequent time to the same or different recipient. In a recent large CIBMTR study of second time donors, Stroncek et al. incidentally found that second peripheral blood stem cell (PBSC) collections had lower total CD34+ cells, CD34+ cells per liter of whole blood processed, and CD34+ cells per kg donor weight. Based on smaller studies, the time between the two independent PBSC donations (inter-donation interval) as well as donor sex, race and baseline lymphocyte counts appear to influence CD34+ cell yields at subsequent donations. Our objective was to retrospectively evaluate factors contributory to CD34+ cell yields at subsequent PBSC donation amongst NMDP donors. Methods. The study population consisted of filgrastim (G-CSF) mobilized PBSC donors through the NMDP/CIBMTR between 2006 and 2017, with a subsequent donation of the same product. evaluated the impact of inter-donation interval, donor demographics (age, BMI, race, sex, G-CSF dose, year of procedure, need for central line) and changes in complete blood counts (CBC), on the CD34+ cell yields/liter (x106/L) of blood processed at second donation and pre-apheresis (Day 5) peripheral blood CD34+ cell counts/liter (x106/L) at second donation. Linear regression was used to model log cell yields as a function of donor and collection related variables, time between donations, and changes in baseline values from first to second donation. Stepwise model building, along with interactions among significant variables were assessed. The Pearson chi-square test or the Kruskal-Wallis test compared discrete variables or continuous variables, respectively. For multivariate analysis, a significance level of 0.01 was used due to the large number of variables considered. Results: Among 513 PBSC donors who subsequently donated a second PBSC product, clinically relevant decreases in values at the second donation were observed in pre-apheresis CD34+ cells (73.9 vs. 68.6; p=0.03), CD34+cells/L blood processed (32.2 vs. 30.1; p=0.06), and total final CD34+ cell count (x106) (608 vs. 556; p=0.02). Median time interval between first and second PBSC donations was 11.7 months (range: 0.3-128.1). Using the median pre-apheresis peripheral blood CD34+ cell counts from donation 1 as the cut-off for high versus low mobilizers, we found that individuals who were likely to be high or low mobilizers at first donation were also likely to be high or low mobilizers at second donation, respectively (Table 1). This was independent of the inter-donation interval. In multivariate analyses, those with an inter-donation interval of >12 months, demonstrated higher CD34+cells/L blood processed compared to donors donating within a year (mean ratio 1.15, p<0.0001). Change in donor BMI was also a predictor for PBSC yields. If donor BMI decreased at second donation, so did the CD34+cells/L blood processed (0.74, p <0.0001). An average G-CSF dose above 960mcg was also associated with an increase in CD34+cells/L blood processed compared to donors who received less than 960mcg (1.04, p=0.005). (Table 2A). Pre-apheresis peripheral blood CD34+ cells on Day 5 of second donation were also affected by the inter-donation interval, with higher cell counts associated with a longer time interval (>12 months) between donations (1.23, p<0.0001). Further, independent of the inter-donation interval, GCSF doses greater than 960mcg per day associated with higher pre-apheresis CD34+ cells at second donation (1.26, p<0.0001); as was a higher baseline WBC count (>6.9) (1.3, p<0.0001) (Table 2B). Conclusions: In this large retrospective study of second time unrelated PBSC donors, a longer inter-donation interval was confirmed to be associated with better PBSC mobilization and collection. Given hematopoietic stem cell cycling times of 9-12 months in humans, where possible, repeat donors may be chosen based on these intervals to optimize PBSC yields. Changes in BMI are also to be considered while recruiting repeat donors. Some of these parameters may be improved marginally by increasing G-CSF dose within permissible limits. In most instances, however, sub-optimal mobilizers at first donation appear to donate suboptimal numbers of HSC at their subsequent donation. Disclosures Pulsipher: CSL Behring: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding; Bellicum: Consultancy; Amgen: Other: Lecture; Jazz: Other: Education for employees; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medac: Honoraria. Shaw:Therakos: Other: Speaker Engagement.

Download Full-text

Differences in Stem Cell Collection Practices and Related Outcomes Between Centers That Conduct and Do Not Conduct Aphaeresis on Weekends

Blood ◽

10.1182/blood.v118.21.1925.1925 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1925-1925

Author(s):

Nelson J. Chao ◽

Lisa M Bernard ◽

George Carrum ◽

Henry C. Fung ◽

Daniel T Grima ◽

...

Keyword(s):

Stem Cell ◽

Cell Count ◽

Peripheral Blood ◽

Research Funding ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Advisory Committees ◽

Cell Counts ◽

Collection Practices ◽

Stem Cell Collection

Abstract Abstract 1925 After mobilization, the timing of aphaeresis can be highly variable, often depending on rise in peripheral blood stem cell levels. Some centers that conduct autologous stem cell transplant (ASCT) do not conduct aphaeresis for stem cell collection on weekends. We examined stem cell collection practices and related outcomes in centers that do and do not conduct weekend aphaeresis. Methods: A retrospective, multi-center chart review was conducted of multiple myeloma (MM) and lymphoma patients mobilized between January 1, 2006 and December 31, 2007 for ASCT. Patients were excluded if they were mobilized with plerixafor (Mozobil®) or were enrolled in a clinical trial of mobilization regimens. Data collected included demographics, disease and treatment history, mobilization regimen, blood counts, aphaeresis, remobilization, cells transplanted, time to engraftment, and resource use. Stem cell collection practices and related clinical outcomes were analyzed separately for sites that did and did not conduct weekend aphaeresis. Results: Data were collected for 292 consecutive patients in the different centers (91 patients from 4 sites that performed weekday only aphaeresis and 201 patients from 7 sites who performed aphaeresis on weekends and weekdays). Weekday only aphaeresis sites were more likely to conduct GCSF alone mobilization compared to weekend sites (42% vs. 21%, p<0.005). Approximately half the patients at each site had MM. The day of the week that aphaeresis was initiated differed dramatically between groups with 74% of chemo-mobilization patients starting aphaeresis on a Monday in the weekday only group compared to 26% in the other group. Approximately 15% of chemo-mobilization patients started aphaeresis on a weekend in the group that conducted weekend aphaeresis. No chemo-mobilization patients began aphaeresis on a Friday in the weekday only aphaeresis group compared to 11% in the other group. Sixteen of all aphaeresis procedures occurred on the weekend on the sites that conducted weekend aphaeresis. Significant differences were found between weekend and weekday only sites, with regards to total cells collected (16.01 × 106/kg vs. 9.2 × 106/kg, p<0.05) and cells collected on day one of aphaeresis (10.8 × 106/kg vs 5.5 × 106/kg, p<0.05) for chemo-mobilization patients. Use of peripheral blood stem cell counts differed markedly, with counts conducted on the first day of aphaeresis in 18% of weekday only group patients and 61% of weekend group patients. Discussion: Significant differences in the management of patients were observed between sites that conduct and don't conduct weekend aphaeresis. Weekday only aphaeresis sites used a more regimented collection schedule with most collections starting on a Monday, potentially missing the “peak” day of cell collection. Sites that conducted weekend aphaeresis used a more cell-count based approach and were more likely to monitor peripheral blood stem cell counts. Collection success appears to be superior with the cell-count based approach that includes greater use of chemo-mobilization, cell count monitoring and weekend collection. Disclosures: Chao: Genzyme: Research Funding. Bernard:Cornerstone Research: Employment, Equity Ownership. Fung:Genzyme: Consultancy, Honoraria, Speakers Bureau. Grima:Cornerstone Research Group Inc.: Employment, Equity Ownership. Holmberg:Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Otsuka: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Research Funding. Brown:Cornerstone Research: Employment. Horwitz:Genzyme: Honoraria, Research Funding. Shaughnessy:Genzyme: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millenium: Honoraria, Speakers Bureau; Otsuka: Honoraria, Speakers Bureau. Tricot:Otsuka: I have an ongoing clinical study supported by Otsuka.

Download Full-text

Timing of Daratumumab Administered Pre-Mobilization in Multiple Myeloma Impacts Pre-Harvest Peripheral Blood CD34+ Cell Counts and Plerixafor Use

Blood ◽

10.1182/blood-2020-140811 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 15-16

Author(s):

Danny Luan ◽

Paul J Christos ◽

Michael Ancharski ◽

Danielle Guarneri ◽

Roger Pearse ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Peripheral Blood ◽

Research Funding ◽

Stem Cell Mobilization ◽

Newly Diagnosed ◽

Advisory Committees ◽

Peripheral Blood Cd34 ◽

Hematopoietic Recovery ◽

Cell Mobilization

Background: Daratumumab (DARA) is a monoclonal antibody which targets CD38 on plasma cells and B cell progenitors. DARA has been effectively combined with other therapies in newly diagnosed and relapsed/refractory multiple myeloma (RRMM), while DARA-based induction regimens in transplant-eligible patients (pts) are increasingly being used in clinical practice. Given that hematopoietic stem cells also express CD38, DARA may potentially affect stem cell mobilization and hematopoietic reconstitution following autologous stem cell transplant (ASCT). Although no clinically significant impact of DARA on stem cell mobilization or hematopoietic recovery was described in large phase 3 trials of triplet induction regimens +/- DARA in newly diagnosed MM, stem cell yields were lower and plerixafor more commonly used in the DARA-containing arms [Moreau et al, Lancet 2019; Voorhees et al, Blood 2020]. Significantly longer time to neutrophil (PMN) engraftment was also reported in pts receiving DARA-based induction who underwent upfront ASCT [Al Saleh et al, Am J Hematol 2020]. In this study, we examine the impact of timing of DARA administration pre-mobilization on day 4 pre-harvest peripheral blood CD34 cell count, stem cell apheresis yield, and post-ASCT engraftment. Methods: Between 1/1/2016 and 12/31/2019, newly diagnosed and RRMM pts receiving DARA-based induction regimens with ≥1 dose of DARA administered within 1 month prior to stem cell mobilization were identified retrospectively and compared to matched controls receiving similar induction regimens without DARA. Granulocyte colony-stimulating factor (G-CSF) was administered per institutional standards and plerixafor added based on day 4 pre-harvest peripheral blood CD34 counts. PMN and platelet engraftment post-ASCT was defined as the first of 3 consecutive days with sustained PMN count >500 x 106/L and independence from platelet transfusion in the preceding 7 days with a count >20 x 109/L, respectively. Pre-harvest peripheral blood CD34 counts and stem cell apheresis yields were obtained from the Cellular Therapy Laboratory at NewYork-Presbyterian Hospital. The study was approved by the Weill Cornell Medicine IRB. Results: We identified 16 pts who received DARA-based induction with ≥1 dose of DARA administered within 1 month of apheresis (DARA group) and 16 non-DARA-containing regimen-matched controls (non-DARA group). Demographics of the DARA and non-DARA groups were well matched (Table 1). DARA pts received their last dose of DARA a mean of 17.3 days prior to the first day of apheresis, with 8 pts receiving their last dose within 2 weeks and the remaining 8 pts between 2 weeks and 1 month prior. Overall, mobilization outcomes were inferior in the DARA group (Table 2). DARA pts had significantly lower day 4 pre-harvest peripheral blood CD34 counts compared to non-DARA pts (17.2 vs 35.4 cells/µL; P=0.0146). Institutional algorithm required plerixafor to be given for day 4 CD34 count ≤40 cells/µL. Fifteen of the 16 DARA pts received plerixafor vs. 11 non-DARA pts (P=0.07). Additionally, DARA pts required significantly more apheresis days (2.4 vs 1.6 days; P=0.0279). Differences in stem cell yield were not significant (8 vs 10 x106cells/kg; P=0.1391). Hematopoietic recovery post-ASCT was not affected by DARA administered in the month preceding mobilization. Conclusions: In summary, we report lower day 4 pre-harvest peripheral blood CD34 count, increased requirement for plerixafor, and longer apheresis duration in newly diagnosed and RRMM pts receiving DARA within 1 month ofstem cell mobilization. These limitations are largely overcome by plerixafor usage which, combined with G-CSF, resulted in successful stem cell collection in all patients. Limitations in our study include small sample sizes, retrospective control selection, and fewer pts in the DARA group achieving ≥VGPR prior to mobilization. Nevertheless, our findings are consistent with inferior mobilization outcomes reported in the DARA-containing arms of phase 3 trials of triplet induction +/- DARA and highlight the nearly universal requirement for plerixafor usage when DARA is administered within a month prior to apheresis. Prospective study of day 4 pre-harvest peripheral blood CD34 counts and other predictors of stem cell yield should be incorporated into future clinical trials of CD38 monoclonal antibody-based induction regimens for transplant-eligible MM pts. Disclosures Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Niesvizky:GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Rosenbaum:Amgen: Research Funding; GlaxoSmithKline: Research Funding; Akcea: Honoraria; Celgene: Honoraria; Janssen: Research Funding.

Download Full-text

Factors Influencing Long-Term Hematopoietic Function Following Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.2186.2186 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2186-2186

Author(s):

Alissa Visram ◽

Natasha Kekre ◽

Christopher N. Bredeson ◽

Jason Tay ◽

Lothar B. Huebsch ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Peripheral Blood ◽

Research Funding ◽

Infection Rates ◽

Advisory Committees ◽

Cd34 Cells ◽

Significant Difference

Abstract Background/Objective: Mobilized peripheral blood hematopoietic progenitor cells are the most common stem cell source for autologous hematopoietic stem cell transplantation (auto-HSCT). Successful short-term stem cell engraftment requires collection of at least 2x106 CD34+ cells/kg. The American Society of Bone Marrow Transplantation (ASBMT) recommends a stem cell infusion target of 3-5 x106 cells/kg (Giralt et al. 2014). However, the number of CD34+ cells to reinfuse to ensure long-term engraftment has not been established. Plerixafor, a reversible CXCR4 antagonist, increases CD34+ cell yield at collection even in patients who are predicted poor mobilizers (PPM). Although plerixafor could be used universally for all collections, this may not be the most cost-effective strategy (Veltri et al. 2012). This study sought to determine the minimum number of CD34+ cells/kg required for adequate long-term hematopoiesis, identify factors associated with poor long-term hematopoiesis, and determine if plerixafor mobilization improved long-term peripheral blood counts. Methods: A retrospective chart review was conducted on patients who underwent auto-HSCT between January 2004 and September 2013 at The Ottawa Hospital, for management of hematological malignancies. Peripheral blood cell counts were collected from 1 to 5 years after auto-HSCT, or until disease relapse. Poor long-term hematopoiesis was defined as an ANC <1 x109/L, hemoglobin <100 g/L, or platelets <100 x109/L. Patients were stratified into groups based on the infused CD34+ concentration (in cells/kg), and the proportion of patients with poor long-term hematopoiesis at 1, 2, 3, 4, and 5 years post auto-HSCT was compared with chi square tests. Long-term clinical outcomes (platelet and packed red blood cell transfusions, and post auto-HSCT infection rates) were compared between plerixafor-mobilized patients and PPM (defined as patients with pre-collection CD34+ <2 x 106 cells/kg) with standard mobilization regimens. Results: This study included 560 patients who underwent auto-HSCT, 210 with multiple myeloma and 350 with lymphoma. At 1 and 5 years post auto-HSCT 377 and 104 patients were included, respectively. A dose dependent improvement 1 year after auto-HSCT was seen in patients who received 0-2.99 x 106 CD34+ cells/kg (24.4%, n= 41) compared to patients who received 5-9.99 x 106 CD34+ cells/kg (11%, n=154, p=0.051) and ³10 x 106 CD34+ cells/kg (4.5%, n=66, p=0.006). Though there was a trend towards lower CD34+ infusions and poorer hematopoietic function (see table 1), there was no statistically significant difference in hematopoietic function based on CD34+ infusion concentrations after 1 year post auto-HSCT. 10 patients received <2 x106 CD34+ cells/kg, of whom the rate of inadequate hematopoiesis was 33% at 1 year (n=6) and 0% (n=1) at 5 years post auto-HSCT. Factors that increased the risk of poor hematopoiesis over the course of study follow up, based on a univariate analysis, included advanced age (OR 1.189, p=0.05), multiple prior collections (OR 2.978, p=0.035), and prior treatment with more than two chemotherapy lines (OR 2.571, p=0.02). Plerixafor-mobilized patients (n=25), compared to PPM (n=197), had a significantly higher median CD34+ cell collection (4.048 x109/L and 2.996 x109/L cells/kg, respectively, p=0.005). There was no significant difference in overall cytopenias, transfusion requirements, or infection rates between plerixafor-mobilized and PPM patients over the course of the study follow up. Conclusion: Low pre-collection CD34+ counts, advanced age, multiple prior collections, and more than two prior chemotherapy treatments adversely affected long-term hematopoiesis post auto-HSCT. We support the transfusion target of 3-5 x 106 cells/kg, as proposed by the ASBMT, given that at 5 years post auto-HSCT there was no statistical or clinically significant difference in hematopoietic function with higher CD34+ infusion targets. While mobilization with plerixafor significantly increased overall CD34+ cell collection when compared with PPM, long-term hematopoietic function and clinical outcomes were not different. This finding supports the practise of limiting plerixafor use only to patients who are PPM, thereby facilitating adequate stem cell collection and early engraftment, as opposed to universal plerixafor mobilization. Disclosures Sabloff: Lundbeck: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Canada: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding; Alexion: Honoraria.

Download Full-text

Peripheral Blood Stem Cell Collection In Patients Undergoing Induction Therapy with Lenalidomide Based Regimens: Failure Rates and Salvage Approaches

Blood ◽

10.1182/blood.v116.21.2253.2253 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2253-2253

Author(s):

Shirshendu Sinha ◽

Morie Gertz ◽

Martha Lacy ◽

Angela Dispenzieri ◽

Suzanne Hayman ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Peripheral Blood ◽

Research Funding ◽

Colony Stimulating Factor ◽

Advisory Committees ◽

Cd34 Cells ◽

Cell Mobilization ◽

Stimulating Factor ◽

Stem Cell Collection

Abstract Abstract 2253 Background: Lenalidomide based combinations are among the most common initial therapies for myeloma. Previous studies have suggested that lenalidomide therapy can result in suboptimal stem cell collection in patients eligible to undergo autologous stem cell transplantation, especially older patients after prolonged exposure to the drug. Many salvage approaches are used when attempting repeat stem cell collection in this patient group. Patients and Methods: Two hundred twenty four patients who underwent stem cell collection following lenalidomide-dexamethasone induction from July 2004 and December 2009 were included in the current analysis. Data pertaining to the duration of lenalidomide therapy, stem cell mobilization regimen, and the collection yields were collected from the medical records. Results: The median age at mobilization was 60.6 years (range; 29, 76) and 136 (60%) were male. There were a total of 245 collection attempts from among 224 patients, 21 (9.8%) patients attempting to remobilize after failing to collect the desired numbers of stem cells at the first attempt. We first analyzed the results of the initial collection attempt. The median duration of lenalidomide therapy prior to stem cell collection was 4 months (range; 1, 26). The mobilization strategies were GCSF (Granulocyte Colony Stimulating Factor) alone in 151 (67%) patients, cyclophosphamide (CTX) followed by GCSF in 29 (13%) patients, and GCSF plus AMD3100 in 44 (20%) patients. Among those receiving AMD3100, it was added either due to peripheral blood CD34 cell count not reaching the threshold for initiation of harvest or for poor first day CD34 cells collection in 34 patients and given in a planned fashion in 10 patients. Overall 15 patients (7%) failed to reach the peripheral CD34 cell counts required to initiate apheresis, and among those starting apheresis 6 patients failed to collect at least 2 million CD34 cells/kg; a cumulative failure rate of 9%. Another 18 (8%) patients failed to collect at least 4 million CD34 cells /kg. The CD34 cells yield on day 1, the total yield, number of collections, the average daily yield and the percentage of the targeted cells collected for each mobilization strategy including failure rates are detailed in the table. Twenty-one patients reattempted stem cell mobilization; including 14 that failed a first attempt and 7 did who not achieve the intended goal even though they collected more than 2 million CD34 cells/kg. The mobilization regimens were GCSF alone, CTX + GCSF, GCSF + GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) and GCSF + AMD in 5, 8, 3, and 4 patients respectively. All patients collected at least 2 million CD34 cells /kg and 14 patients (70%) collected more than 4 million CD34 cells /kg. The median CD34 cells collected with the second attempt was 5.4 million/kg (rang; 2, 19.5) bringing the median total collection for these 21 patients to 9.6 million/kg (2.6-19.6). Overall, of the 224 patients studied, all but the 6 patients who failed initially and did not attempt a second collection collected at least 2 million CD34 cells /kg and 197 (88%) collected at least 4 million CD34 cells/kg. Conclusion: While the overall failure rate of stem cell collection in patients receiving initial therapy with lenalidomide is 10%, a risk adapted approach of adding AMD3100 appear to decrease the risk of failure. However, majority of patients failing a stem cell harvest attempt can be salvaged with a second collection allowing these patients to proceed to a stem cell transplant if desired. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding. Lacy: Celgene: Research Funding. Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees. Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Download Full-text

Detection of Minimal Residual Disease in Patients with Multiple Myeloma by PCR-Based IGH Gene Clonality Analysis Using DNA Extracted From Archival Bone Marrow Slides

Blood ◽

10.1182/blood.v118.21.1879.1879 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1879-1879

Author(s):

Hiroyuki Takamatsu ◽

Yoshiyasu Ogawa ◽

Noriko Kobayashi ◽

Kazue Obata ◽

Tadashi Narisawa ◽

...

Keyword(s):

Stem Cell ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Residual Disease ◽

Pcr Primers ◽

Specific Primers ◽

Specific Pcr ◽

Clonality Analysis ◽

Group A ◽

Group B

Abstract Abstract 1879 Background: Multiple myeloma (MM) can be cured by allogeneic stem cell transplantation (SCT), which induces PCR-negative molecular remission (MR) in patients with MM. Autologous peripheral blood stem cell transplantation (ASCT) followed by maintenance therapy can also induce PCR-negative MR in MM patients, with a progression-free survival (PFS) rate of 100% at 42 months (JCO 2010). Accordingly, it is essential to assess the depth of remission using clonotype-specific PCR primers in the treatment of MM. To prepare primers for amplification of rearranged regions of the IgH gene specific to individual MM patients, fresh or frozen bone marrow (BM) or peripheral blood cells containing MM cells are required. However, these materials are not always available, particularly when patients are diagnosed and treated at local hospitals. Archival BM slides that had been prepared for diagnosis may serve as a source of DNA for PCR-based minimal residual disease (MRD) detection. Therefore, we examined whether DNA extracted from archival BM slides was useful for designing clonotype-specific IgH PCR primers for MRD detection in autografts as well as in the BM in the post-ASCT setting. Patients and Methods: Twenty-two Japanese patients (9 men and 13 women; median age, 56 years; age range, 48–68) with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients had achieved a very good partial response (VGPR) or complete response (CR) after ASCT. BM slides from 19 MM patients, which had been stored in a steel box at room temperature for 19 to 90 months (median, 60 months), and fresh BM cells from 3 MM patients, obtained at first diagnosis, were subjected to DNA extraction using the QIAamp DNA Micro Kit (QIAGEN). The IGH Gene Clonality Assay Kit (InVivoScribe Technologies) was used to detect IgH gene rearrangements in the extracted DNA. The CDR III region of the IgH gene was sequenced to design clonotype-specific primers for amplification of the rearranged sequence in MM patients. BM slides prepared at 3 to 12 months post-ASCT were also subjected to DNA extraction, followed by MRD detection using clonotype-specific PCR primers. Results: IgH gene clonality was detected in 6 of 8 (75%) unstained slides and 4 of 5 (80%) Giemsa-stained slides that had been preserved for less than 5 years. For slides that had been preserved for more than 5 years, IgH gene clonality was detected in 5 of 11 (45%) unstained slides and 1 of 4 (25%) Giemsa-stained slides. Clonotype-specific IgH PCR primers were prepared in 9 of 19 cases (47%) using BM slides and in 3 of 3 cases (100%) using fresh BM cells. DNA in peripheral blood stem cell autografts of 12 patients who had achieved a VGPR or CR after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences; rearranged sequences were amplified in four patients. Within 2 years post-ASCT, 3 of 4 (75%) patients with MRD-positive autografts (Group A) developed progressive disease, whereas all of the 8 patients with MRD-negative autografts (Group B) remained in remission. Group A showed a higher risk of progression than Group B (P = 0.023) (Figure 1A), although overall survival was comparable between the two groups (P =0.371). When BM slides (10 patients) and fresh BM cells (2 patients) obtained after ASCT were examined for the presence of MRD using clonotype-specific PCR primers, the rearranged IgH fragments were amplified in 5 of 12 patients. PFS of 5 MRD-positive patients tended to be shorter than that of 7 MRD-negative patients (P = 0.147) (Figure 1B). Conclusions: Archival BM slides can be used as a source of DNA to prepare clonotype-specific primers for MRD detection in MM patients whose cyropreserved myeloma cells are not available for DNA preparation. Furthermore, MRD status determined by PCR-based clonality analysis was useful in predicting prognosis of patients with MM. This approach enables us to select appropriate consolidation/maintenance therapy in MM patients based on their MRD status. A large multi-institutional study is currently underway to verify the clinical relevance of MRD detection using this technique. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Phase 1 Study of Elotuzumab in Combination with Autologous Stem Cell Transplantation and Lenalidomide Maintenance for Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.3448.3448 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3448-3448 ◽

Cited By ~ 1

Author(s):

Keren Osman ◽

Ajai Chari ◽

Samir Parekh ◽

Christine Pun ◽

Gillian Morgan ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Board Of Directors ◽

Peripheral Blood ◽

Research Funding ◽

Phase 1 ◽

Consolidation Therapy ◽

Open Label ◽

Advisory Committees ◽

Myeloma Cells

Abstract Introduction: Elotuzumab is a humanized monoclonal antibody directed against SLAMF7 that is approved for use in relapsed multiple myeloma patients in combination with lenalidomide and dexamethasone. This agent appears to have several modes of action, including facilitation of antibody-dependent, cell-mediated cytotoxicity (ADCC) through binding to SLAMF7 on myeloma cells and activation of natural killer (NK) cells to kill tumor cells through ligation of the target. We initiated a single-center, open label, phase 1 trial based on the hypothesis that the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard-of-care autologous hematopoietic stem cell transplantation (auto-SCT) and lenalidomide maintenance for consolidation therapy in myeloma patients after induction therapy will be safe and feasible. We hypothesize that early PBMC reconstitution post-auto-SCT will restore a viable NK cell population for activation by elotuzumab, which may target residual myeloma cells and promote tumor-specific humoral and cellular immune responses against myeloma cells. Subsequent maintenance therapy with elotuzumab and lenalidomide may amplify this response, resulting in long-term maintenance of the minimal residual disease state. Methods. This is a Phase 1b, open-label, trial investigating elotuzumab and autologous PBMC reconstitution with auto-SCT consolidation therapy and lenalidomide maintenance. The primary objective of this study is to assess the safety and tolerability of elotuzumab and autologous PBMC reconstitution in the setting of auto-SCT and lenalidomide maintenance in multiple myeloma patients. The secondary objectives are to assess myeloma disease status and progression-free survival (PFS) after one year of treatment. Subjects must achieve partial response or better by IMWG criteria with induction chemotherapy, be eligible for auto-SCT by institutional standards, and meet inclusion/exclusion criteria. Fifteen subjects are planned in this pilot study. The treatment plan is as follows: In addition to standard peripheral blood stem cell mobilization and harvest, subjects undergo steady-state leukopheresis for PBMC collection. Subjects receive standard melphalan conditioning (day -1) and autologous stem cell rescue (day 0). Autologous PBMC are reinfused on day +3 post-stem cell infusion and cycle 1 of elotuzumab 20 mg/kg IV is given on day +4. Subjects receive subsequent cycles of elotuzumab every 28 days up to cycle 12. Lenalidomide maintenance at 10 mg orally daily days 1-21 of every 28-day cycle begins with cycle 4 of elotuzumab, and may continue off study beyond cycle 12 at the investigator's discretion. Bone marrow aspirates and peripheral blood are collected for correlative studies at screening, cycle 2, cycle 4, and at the end of study after cycle 12. For the primary endpoint analysis, the safety population includes all subjects who received at least one dose of study treatment. The evaluable population constitutes all subjects who received at least four of the first five planned doses of elotuzumab. Results: Fourteen of the planned 15 subjects have been enrolled in the study. Demographic and staging data reflect the general transplant-eligible myeloma patient population at our institution. All 14 of these subjects are included in the safety population, having received at least 1 dose of elotuzumab. Nine of 14 subjects have completed at least 4 of the first 5 planned elotuzumab infusions and are evaluable. The majority of adverse events, including infusion reactions attributable to elotuzumab, have been grade 2 or lower. Grade 3 or higher hematologic AEs, including anemia, neutropenia, lymphopenia, thrombocytopenia, and non-hematologic AEs including nausea, vomiting, and dehydration, were attributable to the auto-SCT procedure. There were no delays in hematopoietic reconstitution observed. One episode of grade 3 hypertension was attributed to elotuzumab infusion and resolved with supportive care. No AEs were attributed to PBMC reconstitution. Conclusions: The combination of elotuzumab and PBMC reconstitution with standard auto-SCT and lenalidomide maintenance for consolidation therapy of multiple myeloma appears to be safe and feasible. One subject withdrew for personal reasons. The trial is ongoing and is expected to complete accrual and the clinical results will be updated for presentation. Disclosures Chari: Celgene: Consultancy, Research Funding; Array Biopharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Takeda: Consultancy, Research Funding. Geerlof:Bristol-Myers Squibb: Employment. Jagannath:Novartis: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Cho:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agenus, Inc.: Research Funding; Genentech Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Research Funding; Ludwig Institute for Cancer Research: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Predictive Factors for Survival in Sickle Cell Disease: A Cohort Study Using Etendard Data

Blood ◽

10.1182/blood-2018-99-113767 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 7-7

Author(s):

Laurent Savale ◽

Gylna Loko ◽

François Lionnet ◽

Bernard Maitre ◽

Anoosha Habibi ◽

...

Keyword(s):

Overall Survival ◽

Cohort Study ◽

Sickle Cell Disease ◽

Board Of Directors ◽

Transthoracic Echocardiography ◽

Research Funding ◽

Cell Disease ◽

Advisory Committees ◽

Group A ◽

Group B

Abstract Introduction The prospective ETENDARD study (NCT00434902) evaluated 398 outpatients with sickle cell disease (SCD) enrolled between February 2007 and March 2009 at referral centers in France. All patients were homozygous for hemoglobin S or had Sβ0 thalassemia. This study estimated the prevalence of pulmonary hypertension (PH) related to SCD to be 6%, based on the presence of a tricuspid regurgitation velocity (TRV) ≥2.5 m/s and a mean pulmonary arterial pressure (mPAP) measured by right-sided heart catheterization (RHC) ≥25 mmHg (Parent et al, New Engl J Med 2011). The long-term prognostic value of TRV≥2.5 m/s according to the level of mPAP measured by RHC has not been clearly established. Methods Using updated 10-year follow up data from the ETENDARD cohort study, we analyzed the overall survival of patients according to their TRV/mPAP status, as follows: patients with a TRV<2.5 m/s (group A), patients with a TRV≥2.5 m/s and a mPAP<25 mmHg (group B), and patients with a TRV≥2.5 m/s and a mPAP≥25 mmHg (group C). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards modeling was used to compute hazard ratios (HR) along with their 95% confidence intervals (CI95). Results The 398 enrolled patients were followed-up for a mean time of 106±26 months (median 112 months, interquartile range 106-119). TRV was≥2.5 m/s in 109 patients (27.4%). RHC was performed in 98 of them and confirmed PH diagnosis (mPAP≥25 mmHg) in 24 (6%). Overall survival was significantly decreased in patients with a TRV≥2.5 m/s (groups B/C vs. A; HR=2.5 [CI95 1.3-4.7], p=0.006, Figure 1A). However, after accounting for mPAP level, no statistically significant difference was found between patients with a TRV<2.5 m/s and those with TRV≥2.5 m/s and mPAP<25 mmHg (group A vs. B, log-rank p=0.54), while patients with a TRV≥2.5 m/s and a confirmed diagnosis of PH by RHC (mPAP≥25 mmHg) had a significantly decreased survival in comparison with the two other groups (groups A/B vs. C, p<0.0001, Figure 1B), yielding the following HRs in Cox analysis: HR=1.0 (group A), HR=1.3 (group B, CI95 0.5-3.0, p=0.59] and HR=6.0 (group C, CI95 2.7-13.3, p<0.0001). At time of inclusion, patients with confirmed diagnosis of PH by RHC (group C) were older and characterized by lower 6-min walk distance, higher rate of leg ulcers, lower PaO2 and forced vital capacity, and higher levels of alkaline phosphatase, lactate deshydrogenase and γ-glutamyl transferase (all p<0.05). Clearance of creatinine was significantly lower in both groups with TRV≥2.5 m/s. All these parameters and systemic arterial pressures at time of inclusion were associated with a higher risk of mortality in univariate analysis. Conclusion While an isolated VRT≥2.5 m/s on transthoracic echocardiography was found to be a moderate prognostic factor for overall survival, our findings reveal highly contrasted outcomes depending on the mPAP values measured by RHC. Only the combination of a VRT≥2.5 m/s and a mPAP≥25 mmHg is associated with a worse prognosis, confirming that a RHC is mandatory in case of PH suspicion on transthoracic echocardiography in SCD patients. Disclosures Bartolucci: Addmedica: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; Fondation Fabre: Research Funding; Novartis US: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Sparing Anti-Bacterial Prophylaxis in Acute Myeloid Leukemia during Post Induction Aplasia Does Not Impact on Bacteriemiae Incidence and Early Death: A Retrospective Single Center Study

Blood ◽

10.1182/blood-2018-99-117222 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4001-4001 ◽

Cited By ~ 1

Author(s):

Chiara Frairia ◽

Irene Urbino ◽

Ernesta Audisio ◽

Semra Aydin ◽

Stefano D'Ardia ◽

...

Keyword(s):

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Rectal Swab ◽

Advisory Committees ◽

Gram Negative ◽

Single Center Study ◽

Group A ◽

Group B ◽

Acute Myeloid

Abstract Introduction: Acute myeloid leukemia (AML) patients are at high risk of infections during post chemotherapy neutropenia, especially after induction. The anti-bacterial prophylactic approach raised concerns about the emergence of chemo-resistant pathogens and the increased incidence of Gram negative bacteriaemiae during consolidation therapy. The present study aimed at evaluating the need of anti-bacterial prophylaxis or not during induction. Methods: To address this point, we set up a retrospective single center study enrolling all consecutively newly diagnosed AML patients admitted in our institution; acute promyelocytic leukemia patients were excluded. All patients received an intensive standard induction chemotherapy. Patients were divided in two groups on the basis of anti-bacterial prophylaxis (levofloxacin 500 mg OD during aplasia and until neutrophil recovery or until intravenous antibiotic treatment was needed) given (Group A) or not (Group B). Group A consisted in consecutive patients treated from June 2001 to December 2016 and group B in those consecutively treated from January 2017 to May 2018. Clinical and microbiological data were collected and compared between the two groups. The primary endpoint was the number of bacteriaemiae. Statistical analysis was performed using Chi-square test for categorical variables while continuous variables were compared by Student's t-test; p value of <0.05 was considered significant. Results: A total of 402 consecutive AML patients were enrolled from June 2001 to May 2018. A total of 223 were male while 179 were female, the median age at diagnosis was 54 years (19-76). After induction, a complete remission was achieved in 280 patients (70%), 96 were resistant (24%) and 26 died (6%). Anti-bacterial prophylaxis was administered in 343 patients (group A) while 59 patients experienced aplasia without anti-bacterial prophylaxis (group B). Baseline characteristics were equally distributed among the patients in both groups with the exception of age (median 55 years vs 62 in group A vs B, respectively p<0.0001). In group A, 313 patients developed fever (91%), while 30 (9%) remained afebrile; in the group B, 56 patients developed fever (95%), while 3 (5%) remained afebrile (p=0.3439). The median number of fever days was similar in both groups (group A vs B: median 6 days, range 0-42 and median 5, range 0-17, respectively, p=0.0873). The incidence of bacteriemiae was 25% (n=87) in group A compared to 32% (n=19) in group B (p=0.2708). Considering the total number of bacteriemiae, the incidence of gram-negative infections were 32% (n=28) vs 47% (n=9), wherease gram-positive infections were 68% (n=59) vs 53% (n=10) in the group A vs B, respectively (p=0.2084). Klebsiella pneumonia carbapenemase-producing (KPC) positive blood cultures were detected in two patients in group A, one with KPC positive rectal swab, while in group B there was a case without evidence of KPC on rectal swab. A septic shock was evidenced in 5% (n=17) vs 11% (n=6) of patients with fever during induction in group A and B respectively (p=0.1320). Early induction deaths were similar in both groups with 22 deaths in group A (6%) and 4 in group B (7%), respectively (p=0.9160). In group A, we observed 80 (23%) pneumonia, 53 (15%) respiratory failure and 35 (10%) neutropenic colitis. In group B we observed 17 (29%) pneumonia, 17 (29%) respiratory failure and 18 (29%) neutropenic colitis. Conclusions: Our study showed that omitting levofloxacin prophylaxis did not cause an increase incidence of bacteriaemiae in a homogeneous cohort of AML patients. Neither fever incidence nor duration, septic shocks, early induction deaths and the rate of Gram-negative and Gram-positive cultures were different between the two groups. Our results underline the safety of a prophylaxis sparing approach that may reduce the emergence of drug-resistance Gram-negatives during the consolidation phases. Prospective studies are needed to confirm these data and to assess the impact of prophylaxis during consolidation phase. Disclosures Vitolo: Sandoz: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Download Full-text

The Impact of Degree of Anticoagulation on Thrombotic and Other Complications in Hospitalized COVID-19 Patients

Blood ◽

10.1182/blood-2021-148775 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1051-1051

Author(s):

Rena Zheng ◽

Alexandra Solomon ◽

Madeline DiLorenzo ◽

Iniya Rajendran ◽

Joseph Park ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

High Dose ◽

Advisory Committees ◽

Icu Admission ◽

Group A ◽

Group B ◽

The Impact ◽

D Dimer ◽

Privately Held

Abstract Introduction: In hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the frequency of venous thromboembolism (VTE) is increased. Retrospective studies suggested that an elevated D-dimer level is associated with increased mortality and predictive of thrombosis in these patients. In the spring of 2020, our institution developed a risk protocol for stratification of hospitalized COVID-19 patients into high, intermediate, or low risk groups, based upon history of thrombosis and D-dimer level. These patients were treated with full-dose anticoagulation, high- or standard-dose prophylaxis, respectively. The goal of this project was to determine the impact of this protocol on VTE frequency, need for intensive care unit (ICU) admission, organ failure and in-hospital mortality while assessing the frequency of hemorrhagic complications when compared to standard prophylactic anticoagulation. Methods: We performed a retrospective chart review of adults hospitalized between March 1 - June 1, 2020 who tested positive for SARS-CoV-2 by nasopharyngeal polymerase chain reaction (PCR). Patients were excluded if they were initially admitted to the ICU. VTE was defined as either a deep vein thrombosis (DVT) on Duplex ultrasound and/or pulmonary embolism (PE) on computed tomography (CT) angiogram. We collected demographic data, medical histories, laboratory and radiologic data on all subjects. Data were analyzed using the Chi Square test and Fisher's Exact Test to establish significant association with clinical outcomes between 3 anticoagulation regimens. Statistical significance was assessed at the p<0.05 level. Results: Data were analyzed from 910 patients; 496 (54.6%) were male and the mean age was 57.8 ± 16.9 years. 419 (46%) subjects were Black, 151 (16.6%) Caucasian, 133 (14.6%) Latinx. Diabetes mellitus (35.3%) and hypertension (59.8%) were common in our cohort as were tobacco (12.6%) and alcohol (20.4%) use. Only 69 (7.6%) were treated with chronic anticoagulation and 216 (23.7%) were on antiplatelet agents. 123 (13.5%) required an ICU transfer and the overall mortality was 5.3%. Most patients, 809 (88.9%), received standard prophylactic anti-coagulation initially (Group A); 32 (3.5%) received high dose prophylaxis (Group B) and 69 (7.6%) received therapeutic dose anticoagulation (Group C). In the entire cohort, 46 (5.1%) developed VTE; 29 (3.6%) in Group A, 2 (6.3%) in Group B, and 15 (22%) in Group C (p<0.0001). ICU admission was required for 102 (12.6%) in Group A, 7 (21.9%) in Group B, and 14 (20.3%) in Group C (p=0.075). 73 ICU patients (8%) required vasopressors, including 57 (7%) in Group A, 6 (18.8%) in Group B and 10 (14.5%) in Group C (p=0.175). 81 ICU patients (8.9%) required mechanical ventilation, including 66 (8.2%) in Group A, 6 (18.8%) in Group B, and 9 (13%) in Group C (p=0.513). One patient in Group B developed an intracerebral hemorrhage. Gastrointestinal hemorrhage occurred in 11 (1.2%) of the cohort; similar rates were observed across treatment arms. The overall in-hospital mortality was 5.3% in this cohort (4.7% in Group A, 12.5% in Group B, and 8.6% in Group C, p=0.064). Conclusion: The rate of VTE in COVID-19 patients receiving any form of anti-coagulation was low. There was an increased rate of VTE, but not rates of ICU admission, mortality, mechanical ventilation nor vasopressor use in those receiving either high dose prophylaxis or therapeutic anticoagulation, suggesting an increased propensity for thrombosis either related to prior thrombotic events or reflected by increased D-dimer levels. These findings need to be confirmed in prospective studies. Disclosures DiLorenzo: Abbott: Current holder of individual stocks in a privately-held company; Merck & Co: Current holder of individual stocks in a privately-held company; Glaxo Smith Kline: Current holder of individual stocks in a privately-held company. Sloan: Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Stemline: Honoraria. Weinberg: Janssen Pharmaceuticals: Other: Serve on data safety monitoring boards; Merck & Co: Current holder of individual stocks in a privately-held company. Klings: CSL Behring: Other: Consultant; Omeros: Other: Consultant; Bluebird Bio: Other: Consultant; Bayer: Research Funding; Novartis: Research Funding; FORM therapeutics: Research Funding.

Download Full-text