Impact Of CD34 Research Articles

The Impact of CD34+ Cell Collection Yields for Autologous Transplant on Survival Outcomes in Multiple Myeloma

IntroductionAccording to previous data, higher yields of stem-cells collected to support autologous transplantation may predict for improved outcomes. We aimed to assess the association between high stem-cells collection and survival outcomes in multiple myeloma (MM) Materials and MethodsWe reviewed all patients who underwent autologous transplantation for MM at our center over a 10-year period, and initially used a predefined threshold of 8 × 106/kg used in previous studies. ResultsSix hundred twenty-one patients were analyzed. Higher mobilization did not correlate with favorable outcomes post-transplant. The most efficient mobilizers, collecting ≥8 × 106/kg (n = 478) achieved a shorter median progression-free survival (PFS) of 24.1m versus 34.5m in patients collecting 4.5 to 8 × 106/kg (n = 129). A small group (n = 14) collecting ≤4.5 × 106/kg but minimum of 2 × 106/kg to support autologous transplantation exhibited the worst outcomes (median PFS 11.4m). Further analysis of potential confounders identified greater use of bortezomib induction in the lower mobilizers, however, sensitivity analysis in patients receiving bortezomib revealed similar results- worst outcomes to the most efficient mobilizers. ConclusionAlthough bortezomib is not considered stem-cell toxic, it may be associated with lower stem cell collection yields. Bortezomib's efficacy at induction may partially explain the improved outcomes, however, other factors may be involved, and are discussed. We can conclude that with our large cohort and long follow-up, high stem-cell mobilization does not appear to predict for a long-term survival advantage.

The Impact of CD34+ Cell and Immunefector Cell Dose on Transplant Outcomes

The Impact of CD34+ Cell and Immunefector Cell Dose on Transplant Outcomes

Impact of the number of cryopreserved CD34+ cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: Experience from the GOA study.

Prospective data on the impact of CD34+ cell loss during cryopreservation and the amount of cryopreserved CD34+ cells infused after high-dose therapy on hematologic recovery and post-transplant outcome in multiple myeloma (MM) are scarce. This post-hoc study aimed to investigate factors associating with CD34+ cell loss during cryopreservation and the effects of the infusion of a very low number (<1.0 × 106 /kg, group A), low number (1-1.9 × 106 /kg, group B), and optimal number (≥2 × 106 /kg, group C) of thawed viable CD34+ cells on hematologic recovery, progression free survival, and overall survival after autologous stem cell transplantation among 127 patients with MM. In group C, pegfilgrastim use (P=0.001), plerixafor use (P=0.039), and older age ≥ 60 years (P=0.026) were associated with less loss of CD34+ cells during cryopreservation. Better mobilization efficacy correlated with greater CD34+ cell loss in group B (P=0.013 and P=0.001) and in group C (P < 0.001 and P < 0.001). Early platelet engraftment was slowest in group A (20 d vs 12 d in group B vs 11 d in group C, P=0.003). The infused viable CD34+ cell count <1.0 × 106 /kg seemed not to have influence on PFS (P=0.322) or OS (P=0.378) in MM patients. Cryopreservation impacts significantly on the CD34+ cell loss. A very low number of graft viable CD34+ cells did not affect PFS or OS.

Immune phenotypes and T-cell density at the invasive margin correlate with prognosis in epithelial vulvar cancer.

5599 Background: Tumor infiltrating lymphocytes (TILs) in the cancer microenvironment are of prognostic value in many solid tumors. However, only little is known about TILs infiltration and its predictive value in vulvar cancer. Methods: Immunohistochemistry and automated digital image analysis was applied to measure the densities of CD3+ (DAKO, Santa Clara, US; #IR503) and CD8+ (DAKO, Santa Clara, US; #IR623) TILs at the invasive margin (IM) and in the center of 530 vulvar carcinomas. Results: At the IM the mean immune cell density was significantly higher compared to the center of the tumor (CD3: 1772±1105, CD8: 769±644 cells/mm2 vs. CD3: 518±570, CD8: 301±445 cells/mm2, p≤0.0001). An elevated density of CD3+ T-cell at the IM was significantly associated with low tumor stage (p = 0.0012). The 2-years OS and PFS rate was significantly different between the group with a high (OS: 82%, PFS: 65%), moderate (OS: 76%, PFS: 55%), or low CD3+ T-cell density at the IM (OS: 64%, p = 0.008, PFS: 44%, p = 0.02). The prognostic impact of CD3+ cells in the center of the tumor was weaker compared to the IM (OS p = 0.046, PPS p = 0.031) and lacking for CD8+ T-cell densities at any location (p≥0.14 each). Unsupervised clustering of CD3+ and CD8+ T-cell densities identified three major subgroups corresponding to the immune desert (137 patients), immune excluded (220 patients) and immune inflamed phenotypes (133 patients). Survival analysis revealed a particular poor prognosis for the immune desert phenotype for OS (0.0071) and PFS (0.0027). Conclusions: This study demonstrates a prognostical relevance of the immunphenotype and the distribution of CD3+ T-cells in vulvar cancer. Their value for therapeutic decision making has to be determined in the future.

339 - Impact of CD34+ Graft Cell Dose on Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation: A Systemic Review and Meta-Analysis

339 - Impact of CD34+ Graft Cell Dose on Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation: A Systemic Review and Meta-Analysis

323 - Impact of CD34+ Cell Dose on Outcome Among Children Undergoing Autologous Hematopoietic Stem Cell Transplant for High-Risk Neuroblastomas

323 - Impact of CD34+ Cell Dose on Outcome Among Children Undergoing Autologous Hematopoietic Stem Cell Transplant for High-Risk Neuroblastomas

Cytokine Release Syndrome Following Peripheral Blood Stem Cell Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide

Post-transplantation cyclophosphamide (PTCy) is a safe and efficacious graft-versus-host-disease (GVHD) prophylaxis following hematopoietic cell transplantation (HCT) from a haploidentical (haplo) donor. Cytokine release syndrome (CRS) is a common complication of this platform. Early fever post-haplo-HCT using bone marrow grafts is associated with higher CD3+ cell dose and CRS. However, the impact of CD3+ and CD34+ cell dose on CRS post-haplo-HCT using peripheral blood stem cell (PBSC) grafts is unknown. Our goals were to evaluate the incidence of CRS following PBSC transplantation (PBSCT) and to identify factors that can be modified to prevent the development of severe CRS in this setting. In 271 patients, we investigated factors associated with the development of CRS following haplo-PBSCT and examined the impact of CRS on clinical outcomes. Ninety-three percent of the patients developed CRS of any grade post-haplo-PBSCT. In multivariate analysis, severe CRS (grade 3-4 versus grade 0-1) was associated with higher nonrelapse mortality (hazard ratio [HR], 6.42; 95% confidence interval [CI], 2.68 to 15.39; P < .001), worse 1-year overall survival (HR, 3.40; 95% CI, 1.63 to 7.08; P=.005), and worse disease-free survival (HR, 4.02; 95% CI, 1.99 to 8.08; P < .001). Moderate to severe CRS (grade 2-4) did not impact 1-year relapse or acute GVHD (grade II-IV and III-IV) at 100 days (P=.71 and .19, respectively). Importantly, higher CD3+ cell dose, but not CD34+ cell dose, predicted a higher incidence of grade 2-4 CRS (HR, 1.20; 95% CI,1.07 to 1.36; P=.003) and grade 3-4 CRS (HR, 1.40; 95% CI, 1.05 to 1.86; P=.022). Both older age (HR, 8.57; 95% CI, 1.73 to 42.36; P < .001) and non-total body irradiation-based reduced-intensity conditioning with fludarabine/melphalan (HR, 15.38; 955 CI, 2.06 to 114.67; P < .001) were predictive of grade 3-4 CRS. Overall, we observed that severe CRS (grade 3-4) negatively affected transplantation outcome, and that higher CD3 cell dose was associated with the development of any grade CRS and severe CRS.

Poster: CT-037: The Impact of CD34+ Cell Dose on the Outcome of Allo-HSCT in Adult SAA Patients Conditioned with a Non-ATG-Based Regimen with Post-Transplantation Cyclophosphamide from Fully Matched-Sibling Donors

Poster: CT-037: The Impact of CD34+ Cell Dose on the Outcome of Allo-HSCT in Adult SAA Patients Conditioned with a Non-ATG-Based Regimen with Post-Transplantation Cyclophosphamide from Fully Matched-Sibling Donors

CT-037: The Impact of CD34+ Cell Dose on the Outcome of Allo-HSCT in Adult SAA Patients Conditioned with a Non-ATG-Based Regimen with Post-Transplantation Cyclophosphamide from Fully Matched-Sibling Donors

<h3>Context and Objective</h3> Allo-HSCT is an established treatment for SAA. In this study, we aimed at investigating the correlations between the CD34+ dose and early TRM, 1-year OS, and GVHD incidence. In addition, we aimed at finding a cut-off for the optimal CD34+ dose. <h3>Design</h3> We retrospectively reviewed the records of SAA patients who underwent allo-HSCT between 2017 and 2020. The median follow-up time was 23 months. <h3>Setting</h3> Nasser's Institute Hospital BMT, Cairo, Egypt. <h3>Patients or Other Participants</h3> Twenty-three SAA patients aged 20 years and older underwent allo-HSCT. Patients were conditioned with fludarabine, cyclophosphamide, and post-transplantation cyclophosphamide (FLU/Cy/PTCy). <h3>Interventions</h3> Patients received fludarabine (40 mg/m²/d from d-3 to d-1), cyclophosphamide (25 mg/kg/d from d-5 to d-2), and PTCy (50 mg/kg/d from d+3 to d+4). All patients received PBSC. Cyclosporine (3 mg/kg/d) was started from d+5. <h3>Main Outcome Measures</h3> 6-months TRM and 1-year OS. <h3>Results</h3> The median age at transplantation was 31 years (range: 20–55 years), and the median CD34+ dose was 6.1 × 10⁶/kg (range: 2.9–7.0 × 10⁶/kg). Neutrophil engraftment occurred in 15 patients (65.2%) and platelet engraftment in 12 patients (52.2%). The median time to engraftment was 18 days for neutrophils (range: 15–26 days) and 15 days for platelets (range: 9–27 days). Within the specified follow-up period, 12 patients died, where 7 deaths (58.3%) occurred before d+15. The primary cause of death was septic shock, which occurred in 6 patients (50%). The median survival was 5.5 months. No patient had aGVHD, and only 2 patients (8.70%) had pulmonary cGVHD. Receiver operating characteristic analysis identified a CD34+ dose of 6 × 10⁶/kg as an optimal cut-off to predict 6-month mortality with 66.7% sensitivity and 81.8% specificity (AUC: 0.75). CD34+ doses higher than 6 × 10⁶/kg correlated with lower 6-months TRM (30.8% <i>vs</i> 80.0%, <i>P</i> = 0.036) and higher 1-year OS (69.2% <i>vs</i> 20.0%, <i>P</i> = 0.016). <h3>Conclusions</h3> CD34+ doses higher than 6 × 10⁶/kg correlated with a significantly lower TRM and a better OS in SAA patients undergoing allo-HSCT conditioned with FLU/Cy/PTCy. However, further research is mandatory to confirm the cut-off for the optimal CD34+ dose.

Impact of CD34+ Stem Cell Dose on Engraftment Period in Allogeneic Peripheral Blood Stem Cell Transplanted Patients

Haematopoietic progenitor stem cells acquired from the peripheral blood have been increasingly used to treat patient with haematological malignancy. The success of the allogeneic peripheral blood stem cell transplantation (PBSCT) is significantly dependent on amount of CD34+ stem cell infused which will determine the rate of the haematopoietic recovery and engraftment. This study was aimed to correlate the amount of CD34+ cell infused with the period of engraftment. This retrospective study was conducted on 62 patients with haematopoietic malignancy who have received PBSCT at Universiti Kebangsaan Malaysia Medical Centre from year 2011 to 2015. The impact of CD34+ stem cell infusion on neutrophil and platelet engraftment and obtaining complete chimerism was studied. Patients were divided into two groups based on the amount of CD34+ stem cell. Group A consisted of 9 patients and infused with &lt;5x106 cells/kg CD34+ cell while Group B consisted of 53 patients and infused with ≥5x106 cells/kg CD34+ stem cell. Data were collected and analysed. Group B patients were significantly associated with faster neutrophil engraftment: 12 (10-14) days while group A were 15 (10-21) days, (p=0.002). Platelet engraftment was also faster in group B: 17(12-25) days compared to group A: 18 (15-30) days. Complete chimerism in group B occurred in 30 (15-90) days and in group A was 60 (30-240) days. Platelet engraftment (p=0.149) and complete chimerism (p=0.021) were not significantly influenced by the CD34+ cell count. This study has shown that infusion of ≥5x106 cells/kg CD34+ stem cell shorten the time to haematopoietic engraftment particularly of neutrophilic engraftment.

Low-dose peripheral blood stem cell graft after high-dose chemotherapy - an evaluation of hematopoietic reconstitution

BackgroundHigh-dose (HD) chemotherapy followed by autologous blood stem-cell transplantation (ASCT) is the standard treatment for multiple myeloma (MM) patients. However, the collection of sufficient peripheral blood stem cell (PBSC) grafts can be challenging, and the question arises whether reinfusion of low-dose grafts will lead to a hematopoietic recovery.MethodsThe hematopoietic recovery of 148 MM patients who underwent HD melphalan chemotherapy and received PBSC transplants with varying CD34+ cells doses (3–4 × 106 [n = 86], 2–2.5 × 106 [n = 53], < 2 × 106 [n = 9] per kg body weight [bw]) was analyzed in this retrospective single-center study.ResultsAll patients reached hematopoietic reconstitution, even those who received < 2 × 106 CD34+ cells/kg bw. 62 (42%) patients received granulocyte-colony-stimulating factor (G-CSF). The median duration to leukocyte recovery ≥1.0 × 109/L was 12 days in every group. The median duration to platelet recovery ≥20 × 109/L was 11, 13 and 13 days, respectively. In the multivariate analysis, a low number of reinfused CD34+ cells was associated with prolonged time until leukocyte reconstitution (p = 0.010, HR 0.607) and platelet recovery (p < 0.001, HR 0.438). G-CSF support significantly accelerated leukocyte (p < 0.001, HR 16.742) but not platelet reconstitution.ConclusionIn conclusion, reinfusion of low- and even very-low-dose PBSC grafts leads to sufficient hematopoietic reconstitution. No severe adverse events were observed during or after HD chemotherapy and ASCT in the analyzed cohort. While the impact of CD34+ cell dose is marginal, G-CSF significantly accelerates the leukocyte recovery.

Impact of CD34+ Cell Dose on Clinical Outcomes after Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from Haploidentical Donors in AML Patients. a Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

The absolute number of infused CD34+ donor cells represents a critical step towards the achievement of durable marrow engraftment after allogeneic hematopoietic stem cell transplantation (HSCT). Previous observations have reported controversial conclusions on the impact of CD34+ cell doses and post-transplant clinical end-points. We conducted a retrospective analysis on 414 adult patients (median age 54 years; range, 18-74) with acute myeloid leukemia (AML) in first (70%) and second (30%) complete remission who had received a T-cell replete allogeneic HSCT from a haploidentical donor, using peripheral blood stem cells (PBSC), between 2006-2018, based on ALWP-EBMT registry data. Graft vs. host disease (GVHD) prophylaxis was post-transplant cyclophosphamide (PT-Cy)-based in 293 (71%) patients and anti-lymphocyte serum (ATG)-based in 121 (29%) patients. Conditioning was myeloablative in 179 (43%) patients and reduced-intensity in 235 (57%) patients. Median number of infused CD34+ cells was 6.58 × 106/kg (range, 2.2-31.2). After a median follow-up of 23.3 months (range, 12.1-41.8) 2-year overall survival (OS) was 64.5% (95% CI 59.3-69.7) with a leukemia-free survival (LFS) of 57.3% (95% CI 51.8-62.7) and non-relapse mortality (NRM) of 23.3% (95% CI: 19.0-27.7). The cumulative incidence of grade II-IV and III-IV acute GVHD at day-100 were 32.3% (95% CI: 27.8 - 36.9) and 14.6% (95% CI: 11.3 - 18.2), respectively. Incidence of 2-years chronic GVHD overall and extensive were 36.3% (95% CI: 30.9 - 41.6) and 14.4% (95% CI: 10.7 - 18.6), respectively. GVHD-free/relapse-free survival was 43.5% (95% CI: 38 - 48.9) at 2-years. We found the optimal CD34+/kg threshold defining high-dose (n= 334) versus low-dose (n= 80) to be 4.96 × 106, using the Hothorn and Zeileis method (Hothorn, T. and Zeileis, A. Biometrics 2008;64(4):1263–1269). Recipients of > 4.96 × 106/kg CD34+ cells experienced lower NRM (hazard ratio [HR] 0.48; 95% CI: 0.29-0.75) and prolonged LFS (HR 0.62; 95% CI 0.43-0.90) and OS (HR 0.59; 95% CI: 0.40-0.87) than recipients of ≤ 4.96 × 106/kg CD34+ cell dose. Patients who received ATG as GVHD prophylaxis experienced less grades II-IV acute GVHD respect those in the PT-Cy cohort (HR 0.56; 95% CI: 0.36-0.87) without any differences in grades III-IV acute GVHD incidence at day 100 between the two groups. On Cox analysis, a female donor to male recipient combination was associated with higher extensive chronic GVHD incidence compared to other donor-recipient sex combinations, with CD34+ categorized according to the optimal threshold of 4.96 × 106 (HR 2.21; 95% CI: 1.23-3.97; p=0.008). AML patients who underwent a PBSC T-cell replete HSCT from haploidentical donors receiving ≥ 4.96 × 106 CD34+/kg cells experienced a lower NRM and extended survival rates compared to those receiving ≤ 4.96 × 106/kg CD34+. The latter findings may have a significant practical impact and can guide prospective approaches.

Investigating the Relationship between CD34+and CD3+ Cell Doses, One-Year Graft-Versus-Relapse-Free-Survival, Graft-Versus-Host Disease, and Overall Survival in Haploidentical Hematopoietic Stem Cell Transplantation Using Post Transplant Cytoxan: A Single Center Experience

Background Haploidentical hematopoietic cell transplantation (haplo-HCT) is a popular alternative to traditional HLA-matched HCT. The dose of CD34+ cells used during haplo-HCT to ensure favorable outcomes using PTCy has not yet been reported though 2-5.00 × 106 cells/kg is common. The optimal dose of CD3+ cells is also unknown but recent data suggests ≤3.00 × 108 cells/kg may prevent the development of acute GVHD. The importance of studying the impact of CD34+/CD3+ cell dosing may improve outcomes in this setting. Methods We retrospectively analyzed adult patients at USC Norris Cancer Hospital who received haplo-HCT from 2014 to 2019. The primary end-point assessed was 1-year GVHD-free/relapse-free survival (GRFS). Secondary end-points included 1-, 2-, and 3-year relapse-related mortality (RRM) and overall survival (OS) in addition to 1-year transplant related mortality (TRM) and incidence of acute and chronic GVHD. Results 67 adult haplo-HCT recipients were reviewed with 50% (n = 33) male and 49% (n = 32) female. The age range was 21-71 years old (median = 44) and the most common underlying hematologic disorders included AML (40%), ALL (38%), and aplastic anemia (7.7%). 67% received myeloablative conditioning while 33% received reduced intensity. 70% (n = 47) received peripheral blood and 30% (n = 20) received bone marrow stem cells. The mean CD34+ and CD3+ doses were 6.07 × 106 cells/kg and 2.94 × 108 cells/kg. The mean time to recovery of platelets, ANC, and lymphocytes was 25, 18, and 37 days respectively. CD34+ ≥5.00 × 106 cells/kg was associated with shorter time to lymphocyte recovery (p = 0.0265) though recovery less than 30 days was not associated with OS (p = 0.5268). Incidence of 1-year GRFS was 71% (n= 46) and 1-, 2-, and 3-year RRM were 4.6%, 6%, and 7.7% respectively. 1-year TRM was 15.3% with 50% of deaths from acute GVHD. 1-, 2-, and 3-year OS were 80%, 78%, and 77%. 33% (n = 22) and 30% (n = 20) developed acute and chronic GVHD. Subgroup analysis of those who received CD34+ dose ≥7.00 × 106 cells/kg (n = 24) and ≥10 × 106 cells/kg (n = 7) were found to have 1-year OS of 87.5% and 85.7% compared with 77% and 80% in those that received lower doses (p= 0.2229 and p = 1.00). Discussion Our results demonstrate 71% survived 1 year without experiencing at least 1 GRFS event compared with reports of 24-35% and 3-year OS of 77% when compared with 48%. The mean CD34+ dose of our population is higher than the standard which may have lead to improved outcomes however the CD34+/CD3+ dose was not significantly associated with our end-points but significantly associated with shorter time to lymphocyte recovery, a factor that has been reported to be associated with decreased RRM and therefore improved OS. Subgroup analysis of higher CD34+ doses also did show improved 1-year OS though not significant. Further research with a prospective study identifying the optimal CD34+/CD3+ cell dose is warranted to improve haplo-HCT outcomes.

Impact of Donor-Derived CD34+ Infused Cell Dose on Outcomes of Patients Undergoing Allo-HCT Following Reduced Intensity Regimen for Myelofibrosis:a Study from the Chronic Malignancies Working Party of the EBMT

Introduction: Cellular composition of grafts is believed to be one of the significant determinants of outcomes of reduced-intensity conditioning (RIC) allogenic hematopoietic cell transplantation (allo-HCT). However, inconsistent results of the influence of CD34+ cells dose on the incidence of graft-versus-host disease (GVHD), disease control and survival have been reported in studies published thus far. Allo-HCT remains the only potentially curative treatment modality for eligible patients with myelofibrosis (MF). As patients with this diagnosis were underrepresented or not included in the above mentioned analyses, this EBMT registry study aimed to determine impact of CD34+ cell counts on allo-HCT results in this population. Methods: Six hundred and fifty seven patients with primary or secondary MF transplanted with use of peripheral blood (PB) as a source of stem cells after RIC regimen (Fludarabine/Melphalan, N=536 (82%); Fludarabine/Busulphan, N=121 (18%)) between 2000 and 2016 were included. Stem cell donor type was HLA-identical sibling (MSD; N=249, 38%) or unrelated (UD; N=408, 62%). Use of ex vivo T-cell depletion and post-transplant cyclophosphamide to prevent GVHD were the exclusion criteria. Median patient age was 58 (range, 22-76) years. In-vivo T-cell depletion was used in 526 (80%) of cases. Median transplanted CD34+ dose was 6.6 (2-29) x 10^6 per kg of recipient body weight. Median follow-up was 46 (2-194) months. Patient and transplant characteristics are summarized in Table 1. Results: We did not observe any impact of CD34+ cells dose on outcome variables in the whole study group. However, in an analysis adjusted for donor type, among patients transplanted from a MSD, the 2yr overall survival (OS) probability was 77% for those transplanted with higher doses of CD34+ cells (defined as &gt;7.0 x 10^6/kg) compared to 60% for lower CD34+ counts (below 7.0 x 10^6/kg), P=0.007 (Figure 1). The corresponding probabilities of 2yr non-relapse mortality (NRM) were 16% and 29% (P=0.04), respectively (Figure 2). In multivariate analysis, for patients transplanted from a MSD, higher CD34+ dose was an independent predictor for better survival (HR 0.56; P=0.01) and lower risk of NRM (HR 0.54; P=0.02). We did not find any association between CD34+ counts with probability of engraftment, the incidence of acute (aGVHD) and chronic (cGVHD) nor disease relapse. The effect of cell dose was not seen in the UD cohort. Factors associated independently with an unfavorable outcome in the whole study group were: older patient age and transplantation from CMV seronegative donors to seropositive recipients for OS and NRM and use of an UD and female donor for NRM. Allo-HCT from UD was also an independent predictor for higher incidence of aGVHD and lower probability of engraftment. Use of in vivo T-cell depletion was a protective factor for aGVHD. It was in turn associated with higher risk of relapse. Conclusions: Our analysis suggests a potential survival benefit for MF patients treated with RIC PB-allo-HCT from MSD with higher doses of CD34+ cells (threshold &gt; 7.0 x 10^6/kg). We suggest that this factor should be taken into consideration when planning and performing hematopoietic cell apheresis. Disclosures Kröger: Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Robin:Novartis Neovii: Research Funding. Chevallier:Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria. Mielke:Bellicum: Consultancy, Honoraria, Other: Travel (via institution); EBMT/EHA: Other: Travel support; Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau; IACH: Other: Travel support; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; ISCT: Other: Travel support; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; DGHO: Other: Travel support; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau. Snowden:Janssen: Honoraria; Mallinckrodt: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; IDMC: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Blaise:Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria. Hernandez Boluda:Incyte: Other: Travel expenses paid. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria.

CD34+ Cell Dose Effects on Clinical Outcomes of Patients with Acute Myeloid Leukemia after T-Replete Haploidentical Allogeneic Hematopoietic Stemcell Transplantation Using Peripheral Blood Stem Cells. a Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

The absolute number of infused CD34+ donor cells represents a critical step towards the achievement of a meaningful marrow engraftment after allogeneic hematopoietic stem cell transplantation (HSCT). Previous observations have reported controversial conclusions regarding the impact of CD34+ donor cell doses and post-transplant clinical end-points. The vast majority of analysis conducted so far have considered myeloablative and reduced-intensity conditioning allogeneic HSCT setting, with HLA-matched sibling and/or unrelated donors. The T-cell replete haploidentical setting has not been extensively studied yet. We conducted a retrospective analysis on 414 adult patients (median age 54 years; range, 18-74) with acute myeloid leukemia (AML) in first (70%) and second (30%) complete remission who had received a T-cell replete allogeneic HSCT from a haploidentical donor, using peripheral blood stem cells (PBSC), between 2006-2018, based on ALWP-EBMT registry data. Median donor age was 37 years (range, 20-71). Time from disease diagnosis to HSCT was 6.3 months (range, 1.3-97.9). Seventy-three (18%) patients had secondary-AML. Eighty-seven patients (21%) had unfavorable cytogenetics. Karnofsky performance-status at the time of HSCT was ≥ 90 in 318 (77%) patients. Graft vs. host disease (GVHD) prophylaxis was post-transplant cyclophosphamide (PT-Cy)-based in 293 (71%) patients and anti-lymphocyte serum (ATG)-based in 121 (29%) patients. Conditioning was myeloablative in 179 (43%) patients and reduced-intensity in 235 (57%) patients. Median number of infused CD34+ cells was 6.58 x 106/kg (range, 2.2-31.2). Thirteen patients (3.2%) experienced graft failure while the remaining 399 (96.8%) engrafted uneventfully. Neutrophils engraftment at day 30 was 91.2% (95% Confidence interval [CI]: 88 - 93.6) while sustained platelets engraftment (&gt;20.000/uL at 6-months) was observed in 83.7% (95% CI: 79.6 - 87). Median time to neutrophils and platelets engraftment were 20 (range, 10-79) and 21 days (range, 1-37) respectively. After a median follow-up of 23.3 months (range, 12.1-41.8) 2-year overall survival (OS) was 64.5 % (95% CI 59.3-69.7) with a leukemia-free survival (LFS) of 57.3 % (95% CI 51.8-62.7) and non-relapse mortality (NRM) of 23.3 % (95% CI: 19.0-27.7). The cumulative incidence of grade II-IV and III-IV acute GVHD at day-100 were 32.3 % (95% CI: 27.8 - 36.9) and 14.6 % (95% CI: 11.3 - 18.2), respectively. Incidence of 2-years chronic GVHD overall and extensive were 36.3 % (95% CI: 30.9 - 41.6) and 14.4 % (95% CI: 10.7 - 18.6), respectively. GVHD-free/relapse-free survival was 43.5 % (95% CI: 38 - 48.9) at 2-years. We found the optimal CD34+/kg threshold defining high-dose (n= 334) versus low-dose (n= 80)to be 4.96 x 106, using the Hothorn and Zeileis method (Hothorn, T. and Zeileis, A. Generalized maximally selected statistics. Biometrics 2008;64(4):1263-1269). Patients in the high-dose group experienced higher rates of engraftment compared to those in the low-dose group both for neutrophils (92.1% vs. 87.3%, p= 0.005) and platelets (86% vs. 73.3%, p= 0.001) while median time to neutrophils engraftment was 19 days (range, 10-79) in the high-dose group and 22 days (range, 14-46) in the low-dose group (p= 0.0001). Recipients of &gt; 4.96 x 106/kg CD34+ cells experienced lower NRM (hazard ratio [HR] 0.48; 95% CI:0.29-0.75) and prolonged LFS (HR 0.62; 95% CI 0.43-0.90) and OS (HR 0.59; 95% CI:0.40-0.87) than recipients of ≤ 4.96 x 106/kg CD34+cell dose. Patients who received ATG as GVHD prophylaxis experienced less grades II-IV acute GVHD respect those in the PT-Cy cohort (HR 0.56; 95% CI: 0.36-0.87) without any differences in grades III-IV acute GVHD incidence at day 100 between the two groups. On Cox analysis, a female donor to male recipient combination was associated with higher extensive chronic GVHD incidence compared to other donor-recipient sex combinations, with CD34+ categorized according to the optimal threshold of 4.96 x 106 (HR 2.21; 95% CI:1.23-3.97; p= 0.008). AML patients who underwent a PBSC T-cell replete HSCT from haploidentical donors receiving ≥ 4.96 x 106CD34+/kg cells experienced a lower NRM and extended survival rates compared to those receiving ≤ 4.96 x 106/kg CD34+. The latter findings may have a significant practical impact and can guide prospective approaches. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Blaise:Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria. Chevallier:Jazz Pharmaceuticals: Honoraria; Daiichi Sankyo: Honoraria; Incyte: Consultancy, Honoraria. Socie:Alexion: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

Impact of CD34+ pre-counting and plerixafor on autologous peripheral blood stem cell collection in Japanese university hospitals in eight years

ObjectiveOver the past decade, there have been two major advancements in autologous peripheral blood stem cell (PBSC) collection, namely enumeration of CD 34+ cells for apheresis prediction and use of plerixafor to assist mobilization of PBSC. This study aimed to investigate changes in the efficacy of PBSC collection from two Japanese university hospitals over an eight-year period. Study design and methodsA series of 399 PBSC collection procedures from 239 patients with solid malignant tumors (ST, n = 42), malignant lymphoma (ML, n = 91), multiple myeloma (MM, n = 99), and others (amyloidosis and leukemia, n = 7) from two university hospitals from 2011 to 2018 were retrospectively analyzed. We also analyzed the effects of CD34+ pre-counting and plerixafor administration in improving CD34+ cell yield. ResultsUsing CD34+ pre-count as a reference, the frequency of apheresis was reduced and the yield of CD34+ cells increased in patients with ST. When administrating plerixafor, especially with a CD34+ pre-count <20/μL, the yield of CD34+ cells was significantly increased in patients with ML (p = 0.02) and MM (p = 0.03). ConclusionsWe verified that CD34+ cell counting and plerixafor administration contributed to effective PBSC collections in our hospitals for the eight-year study period. In patients with ST, CD34+ pre-count threshold for starting apheresis was ≥10/μL. CD34+ pre-count (<20/μL) was useful to select appropriate patients for plerixafor administration among the patients with ML and MM.

Improved Overall Survival, Relapse-Free-Survival, and Less Graft-vs.-Host-Disease in Patients With High Immune Reconstitution of TCR Gamma Delta Cells 2 Months After Allogeneic Stem Cell Transplantation.

T-cell receptor (TCR) γδ cells are perceived as innate-like effector cells with the possibility of mediating graft-vs. -tumor (GVT) without causing graft-vs.-host disease (GVHD) in the setting of hematopoietic allogeneic stem cell transplantation (HSCT). We conducted a prospective study to assess the clinical impact of TCR γδ cell immune reconstitution on overall survival, relapse-free-survival, relapse and GVHD. The impact of CD3, CD4, and CD8 T cells together with NK cells including subtypes were analyzed in parallel. A total of 108 patients with hematological malignancies transplanted with HLA-matched, T cell replete stem cell grafts were included for analyses of absolute concentrations of CD3, CD4, and CD8 positive T cells and NK cells together with a multi-color flow cytometry panel with staining for TCRαβ, TCRγδ, Vδ1, Vδ2, CD3, CD4, CD8, HLA-DR, CD196, CD45RO, CD45RA, CD16, CD56, CD337, and CD314 at 28, 56, 91, 180, and 365 days after transplantation. Immune reconstitution data including subsets and differentiation markers of T and NK cells during the first year after transplantation was provided. Patients with TCR γδ cell concentrations above the median value of 21 (0–416) × 106 cells/L 56 days after transplantation had significantly improved overall survival (p = 0.001) and relapse-free survival (p = 0.007) compared to patients with concentrations below this value. When day 56 cell subset concentrations were included as continuous variables, TCR γδ cells were the only T cell subsets with a significant impact on OS and RFS; the impact of TCR γδ cells remained statistically significant in multivariate analyses adjusted for pre-transplant risk factors. The risk of death from relapse was significantly decreased in patients with high concentrations of TCR γδ cells 56 days after transplantation (p = 0.003). Also, the risk of acute GVHD was significantly lower in patients with day 28 TCR γδ cell concentrations above the median of 18 × 106 cells/L compared to patients with low concentrations (p = 0.01). These results suggest a protective role of TCR γδ cells in relapse and GVHD and encourage further research in developing adaptive TCR γδ cell therapy for improving outcomes after HSCT.

The prognostic impact of CD3, CD8, FoxP3, and IL17 tumor-infiltrating immune cells in periampullary cancer differs by morphological type and adjuvant chemotherapy.

53 Background: The prognostic impact of tumor-infiltrating T lymphocytes has been evaluated in periampullary carcinoma, but previous studies have not taken into consideration the different morphological subtypes of cancers derived from the periampullary region. Herein, we investigated the prognostic impact and distribution of tumor-infiltrating CD3+, CD8+, FoxP3+ T lymphocytes as well as IL-17+cells in periampullary adenocarcinoma, with particular reference to morpohological subtyoe. Methods: Counts of CD3+, CD8+, FoxP3+ T lymphocytes, and IL-17+cells were assessed using immunohistochemistry on tissue microarrays with tumors from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinoma; 110 of pancreatobiliary type (PB-type) and 65 of I intestinal type (I-type). Results: Distribution of all evaluated immune cells differed significantly between PB- and I-type tumors. In I-type tumors, the ratios of IL-17+/FoxP3+ and IL-17+/CD3+ were independent factors of poor prognosis. Notably, the unfavorable prognostic impact of IL-17+ was only evident in cases that had not received adjuvant chemotherapy. In PB-type tumors, CD3+was an independent marker of good prognosis. Conclusions: The results from this study highlight that the composition and prognostic importance of various subsets of infiltrating immune cells in periampullary adenocarcinoma differ by morphological subtype, and potentially by adjuvant chemotherapy.

Prognostic impact of CD3 infiltrating t-cells in the tumor microenvironment with clinical factors for solid organ transplant (SOT) recipients with post-transplant lymphoproliferative disorders (PTLD).

e19033Background: Prognostication in post-transplant lymphoproliferative disorders (PTLD) is limited to clinical factors, with no validated tissue biomarkers. It is suggested that the degree of CD3...

IB-02 * ROLE OF TUMOR INFILTRATING LYMPHOCYTES AND PDL1 EXPRESSION IN GLIOBLASTOMA (GBM) AND BRAIN METASTASES (BM): COMPARATIVE ANALYSIS

BACKGROUND: Differences in the adaptive immune response to various kinds of brain tumors have been poorly characterized. METHODS: We immunostained 287 neurosurgical specimens: 170 BM (lung cancer: 77 (45.3%); breast cancer: 17 (10.0%); melanoma 44 (25.9%); renal cell carcinoma 10 (5.9%) others 22 (7.7%)) and 117 GBM for CD3 (n = 287), CD8 (n = 287), PD1 (n = 287) and PDL1 (n = 234) and used previously published semiquantitative evaluation criteria. RESULTS: TIL infiltration of variable density (sparse to dense) was found in 161/170 (94.7%) BM and 78/117 (66.6%) GBM. TILs were predominantly present in the tumor stroma and perivascular areas in BM and in perivascular area in GBM. Dense infiltration with CD3+ TILs (p < 0.001), CD8+ TILs (p < 0.001) and PD1+ TILs (p < 0.001) was observed more frequently in BM than GBM. Among BM, we found significant differences in the composition of immune infiltrates with renal cell carcinoma BM showing the highest density of CD3+ and PD1+ TILs. Membranous PDL1 expression on tumor cells was evident in 25/117 (21.4%) BM and 44/117 (37.6%) GBM. Expression of PDL1 in over 5% of tumor cells was more frequently observed in GBM than in BM (p = 0.006). Dense infiltration of CD3+ TILs (9 vs. 12 months; p = 0.015) correlated with favorable survival prognosis in BM patients, while no prognostic impact of TIL infiltration was evident in GBM. Expression of PDL1 in over 5% of tumor cells was not associated with survival prognosis in BM (11 vs. 11 months; p = 0.395) or GBM (15 vs. 14 months; p = 0.859). CONCLUSION: We found high TIL densities and prognostic impact of CD3+ immune infiltrates in BM. GBM was characterized by sparse TIL infiltrates, higher expression of PDL1 and lack of prognostic impact of immune infiltrates. Our results indicate clinically relevant differences in the immune response to brain tumor types and may be of interest for studies with immunomodulatory agents.