scholarly journals Impact of Natural Killer Cells Reconstitution on Outcomes after Allogenic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4880-4880
Author(s):  
Moazzam Shahzad ◽  
Amna Y Shah ◽  
Muhammad Usman Zafar ◽  
Ezza Tariq ◽  
Anam Hamid ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Hematopoietic Stem Cell ◽  
Research Funding ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Meta Analysis ◽  
Cell Transplant ◽  
Hematopoietic Stem

Abstract Background: Natural killer (NK) cells are the first cells to recover following allogeneic hematopoietic stem cell transplant (HSCT) and play a crucial role in enabling engraftment, preventing post-transplant infection and tumor relapse. In addition, NK cells also reduce the risk of graft versus host disease (GvHD) and increase the graft versus leukemia effect (GVL). The purpose of this systematic review and meta-analysis is to know the impact of NK cells reconstitution on outcomes of allogeneic HSCT. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was conducted on PubMed, Cochrane Library, and ClinicalTrials.gov through January 2021. We used MeSH terms and keywords for "hematologic malignancies" OR "hematopoietic stem cell transplantation" AND "natural killer cells." No filters or publication time limits were applied for the search. A total of 13 studies were included after screening 988 records and excluding duplicates, review, and non-relevant articles. An arbitrary value of NK cell count of 22.2 cell/ul was set as a cut-off to divide between high and low groups of NK where applicable. Quality evaluation was done using the NIH quality assessment tool and Inter-study variance was calculated using Der Simonian-Laird Estimator. Pooled analysis was done using the 'meta' package (Schwarzer et al. R programming language), and proportions with 95% confidence intervals (CI) were computed. Results: A total of 1623 patients were evaluated from 13 studies. (Table 1) The median age of patients was 44 (8.6-63) years and 33.5% were males. The median duration of follow-up was 18 (0.3-122) months. The median 2-year overall survival (OS) for high NK cohort and low NK cohort was 77% (95%CI 0.70-0.83, I 2 =82%, n=982) and 52%(95%CI 0.38-0.67, I 2 =95%, n=982), respectively. The pooled rate of relapse in high NK group was 8% (95%CI 0.01-0.19, I 2 =83%, n=226) and it was 20% (95%CI 0.06-0.39, I 2 =90%, n=226) for low NK group. The pooled incidence of acute GvHD was 24% (95%CI 0.09-0.42, I 2 =91%, n=336) and 44% (95%CI 0.26-0.62, I 2 =91%, n=336) for high and low NK cohorts, respectively. The pooled incidence for viral infection for high NK group was 17% (95%CI 0.01-0.47, I 2 =98%, n=508) while it was 29% (95%CI 0.04-0.65, I 2 =98%, n=508) for low NK group, respectively. Conclusion: Higher reconstitution of NK cells after allogeneic hematopoietic stem cell transplant has a favorable impact on outcomes, including better overall survival and low incidence of relapse, acute GvHD, and viral infections. Our findings suggest the need for further prospective studies to investigate utility of NK cells infusion early post-transplant to improve clinical outcomes and survival. Figure 1 Figure 1. Disclosures McGuirk: Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Astelllas Pharma: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding; Gamida Cell: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding.

Outcome of High Dose Melphalan with Autologous Hematopoietic Stem Cell Transplant In Myeloma Associated with AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2400-2400
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Research Funding ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
High Dose Melphalan

Abstract Abstract 2400 Background: Approximately 10% of patients with multiple myeloma (MM) have clinically overt primary systemic light-chain (AL) amyloidosis, and about 30% have concurrent occult AL amyloidosis. The impact of concurrent AL amyloidosis on the prognosis of myeloma is not well known. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) has shown significant activity in both MM and AL amyloidosis. Methods: We performed a retrospective analysis of patients who had concurrent MM and AL amyloidosis and underwent auto HSCT with high dose Melphalan at MDACC between 01/1998 to 05/2010. We identified 41 patients with concurrent MM and AL amyloidosis. Patient characteristics are summarized in Table 1. Twenty -six patients had occult AL amyloid, while 15 had clinically overt disease. Results: Median age at auto HSCT was 56 years (39-77), 58.5% being male with median follow up of 58.7 months from the time of diagnosis and 42.5 months from auto HCT. The median time from diagnosis to auto HCT was 8.9 mos (2.7-102.4 mos). 39% had Salmon Durie Stage III disease and 36.6% had more than one involved site at the time of transplant.Cytogenetic abnormalities were detected in 24.4% of patients. Post transplant hematologic responses were as follows: ≥CR=10 (24%), ≥VGPR=16 (39%), >PR=33 (80.5%), ≥stable disease= 40 (97.6%). Among the patients with overt organ involvement, one had early death. Of the 15 evaluable patients, organ responses were scored using the published consensus guidelines for amyloidosis and were as follows: PR=5 (33.3%), ≥SD=7 (46.7%). No correlation was seen between organ response and hematologic response. The 100-day treatment related mortality (TRM) was 0 and 1-year TRM of 2.4% which is comparable to patients transplanted for MM alone at our center. The median progression-free (PFS) and overall survival (OS) from auto HCT were 33.8 and 58.3 months, respectively.The median PFS and OS from diagnosis were 49.8 and 96 mos, respectively. In multivariate analysis, creatinine ≥ 2mg/dl was associated with a shorter PFS (p=0.043) and hemoglobin <10g/dl showed a trend towards a shorter PFS (p=0.093). None of these variables (Hb <10g/dl, Age>60yrs, Creatinine≥2mg/dl, B2M >3.5mg/l, BM plasma cells>30%) emerged as significant predictors of OS. There was no significant difference in outcome between patients with occult or symptomatic AL amyloidosis for OS (p=0.24) or PFS (P=0.9) Conclusion: In this analysis the outcome of patients with concurrent MM and AL amyloidosis was comparable to patients with MM alone. We believe these patients are acceptable candidates for auto HCT. Disclosures: Shah: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Weber: novartis-unpaid consultant: Consultancy; Merck- unpaid consultant: Consultancy; celgene- none for at least 2 years: Honoraria; millenium-none for 2 years: Honoraria; celgene, Millenium, Merck: Research Funding. Orlowski: Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding.

scholarly journals Outcomes of HMA and Venetoclax in Relapsed AML Post-Allogenic Hematopoietic Stem Cell Transplant

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Osama Diab ◽  
Haitham Abdelhakim ◽  
Joseph P. McGuirk ◽  
Tara Lin
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Complete Remission ◽  
Hematopoietic Stem Cell ◽  
Research Funding ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Pharmaceutical Research ◽  
Cell Transplant ◽  
Hematopoietic Stem

Background: There is no standard of care treatment for Acute Myeloid Leukemia (AML) in relapse post-allogeneic hematopoietic stem cell transplant (post-HSCT), with overall 5-year survival about 5-10%. Venetoclax (Ven) is a novel BCL2 inhibitor approved by the FDA for treatment of newly diagnosed AML in combination with hypomethylating agents (HMA) or low dose cytarabine for patients unfit for intensive induction. However, data in relapsed/refractory AML are limited, especially in the post-HSCT setting. In this retrospective study, we reviewed outcomes of patients with AML relapse post-HSCT who received Ven in combination with HMA in a single center. Methods: Charts of 17 patients who had AML relapse post-HSCT treated with combination of Ven and HMA between November 2018 - March 2020 at the University of Kansas Medical Center were reviewed. We utilized descriptive statistics for baseline characteristics and outcomes, and Kaplan-Meier log-rank test for calculating overall survival. Results Seventeen patients received Ven+HMA for AML relapse post-HSCT in our center. At the time of SCT, patients were in first complete remission (CR) (n=15); second CR (n=1) and primary failure induction (1). Median age was 62 at time of relapse (31-71) years, and 8 patients were female (47%). 9 patients (53%) had adverse risk AML (ELN 2017) 8 of them were in CR1 and 1 with primary induction failure. Common mutations included DNMT3a, ASLX-1, TET2 (3); TP53 (2); IDH1/2 (2); NPM1/FLT3 (1); NPM1/IDH2 (1); NPM1 (1 transplanted in CR2); FLT3 (1). 2/17 had received Ven+HMA prior to SCT; 4 patients received HMA alone prior to SCT. 11 patients (65%) were naïve to either Ven or HMA prior to relapse. Median time to relapse was 181 (44-851) days post-HSCT. 9 (53%) patients received Azacitidine+Ven and 8 (47%) received Decitabine+Ven. HMA+Ven was the first line of therapy post-HSCT relapse in 14 patients. 2 had donor lymphocyte infusion (DLI) after either MEC or dacogen but relapsed prior to Ven+HMA. 1 had IDH (2) inhibitor. Patients received median of 2 (1-10) cycles of HMA+Ven. Six (35%) patients achieved complete remission/complete remission with incomplete hematologic recovery (CR/CRi), and 2/6 patients had negative measurable residual disease by multiparameter flow cytometry. Median overall survival was 361 days from relapse (Figure 1). 3/14 patients received subsequent DLI with Ven+HMA. Disease progression was the most common cause of death in 8/9 of patients who died during the follow up period. Most common side effects included neutropenic fever (n=8, 47%) and acute graft versus host disease (aGVHD) (n=5, 30%). 2/5 developed new aGVHD on HMA+Ven with no prior history of aGVHD. However, aGVHD was mainly grade I-II and responsive to therapy. Discussion HMA+Venetoclax demonstrates potential activity in patients with AML relapse post-HSCT with a CR/CRi rate of 35%, comparable to other salvage therapies. There were no unexpected side effect in this high-risk population. Larger studies are needed to confirm efficacy and toxicity in this setting. Disclosures McGuirk: Pluristem Ltd: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Bellicum Pharmaceutical: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding. Lin:Aptevo: Research Funding; Abbvie: Research Funding; Bio-Path Holdings: Research Funding; Celgene: Research Funding; Gilead Sciences: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Ono Pharmaceutical: Research Funding; Pfizer: Research Funding; Prescient Therapeutics: Research Funding; Seattle Genetics: Research Funding; Tolero Pharmaceuticals: Research Funding; Trovagene: Research Funding; Genetech-Roche: Research Funding; Celyad: Research Funding; Astellas Pharma: Research Funding.

scholarly journals Outcomes with Natural Killer Cells Infusion after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1847-1847
Author(s):  
Muhammad Umair Mushtaq ◽  
Moazzam Shahzad ◽  
Amna Y Shah ◽  
Muhammad Usman Zafar ◽  
Ezza Tariq ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cell ◽  
Natural Killer Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Research Funding ◽  
Meta Analysis ◽  
Killer Cells ◽  
Hematopoietic Stem ◽  
Relapsed Disease

Abstract Background: Natural killer cells (NK) are known to be the first cells that recover after allogeneic hematopoietic stem cell transplant (HCT). NK cells have anti-leukemic and anti-viral properties and are also implicated in the graft versus leukemia (GVL) effect without causing graft versus host disease (GVHD). There is emerging evidence supporting the use of NK cells post-transplant as adoptive immunotherapy to prevent or treat the relapse of hematologic malignancies. Here, we present a systematic review and meta-analysis aimed to investigate the outcomes with NK cells infusion after HCT. Methods: A detailed literature search was conducted for the systematic review and meta-analysis according to the guidelines mentioned in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Population, intervention, comparison, and outcome (PICO) table was developed and three electronic databases (PubMed, Cochrane Library, and ClinicalTrials.gov) were searched through January 2021 using MeSH terms and keywords for "hematologic malignancy and natural killer cells" and "hematopoietic stem cell transplantation and natural killer cells". No filters or publication time limits were applied for the search. A total of 988 records were identified through database searching. After excluding duplicates, review, and non-relevant articles, we selected 9 studies that reported outcomes with NK cells infusion after HCT. Quality evaluation was done using the NIH quality assessment tool and Inter-study variance was calculated using the Der Simonian-Laird Estimator. Pooled analysis was done using the 'meta' package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. Results: We identified 9 studies with a total of 149 participants. Out of these, 53 patients were from 4 studies using NK cells for the treatment of relapsed disease after HCT (therapeutic studies) and 96 patients were from 5 studies using NK cells to prevent relapse after HCT (pre-emptive studies). Therapeutic use of NK cells for relapsed disease after HCT: A total of 53 patients from 4 studies were evaluated. The median age of patients was 44.5 (1.9-69) years, and 40% patients were male. The median follow-up was 20 (1-69) months. Overall survival (OS) was reported by two studies at 2 years and was 36.3% and 55%. The pooled complete response (CR) was 18% (95% CI 0.06-0.33, I 2 =0%, n=37) and overall response rate (ORR) was 45% (95% CI 0.20-0.71, I 2 =71%, n=53). The pooled relapse rate was 65% (95% CI 0.32-0.92, I 2 =75%, n=42). The pooled incidence of acute GVHD and chronic GVHD was 15% (95% CI 0.03-0.31, I 2 =41%, n=53) and 8% (95% CI 0.01-0.18, I 2 =0%, n=53) respectively. Pre-emptive use of NK cells to prevent relapse after HCT: A total of 96 patients from 5 studies were evaluated. The median age of patients was 33.5 (2-75) years, and 48% patients were males. The median follow-up was 23.1 (8-81.6) months. The median OS was 1 (0.63-5) years. The pooled CR was 45% (95% CI 0.21-0.70, I 2 =76%, n=83) and ORR was 89% (95% CI 0.57-1.00, I 2 =77%, n=42). The pooled relapse rate was 35% (95% CI 0.20-0.52, I 2 =55%, n=96). The pooled incidence of acute GVHD and chronic GVHD was 30% (95%CI 0.14-0.48, I 2 =61%, n=96) and 8% (95%CI 0.00-0.24, I 2 =73%, n=96) respectively. Conclusion: Infusion of NK cells after HCT to prevent relapsed disease results in favorable outcomes with an acceptable toxicity profile. Optimal use of NK cells infusions after HCT is in a pre-emptive fashion to prevent relapsed disease and the efficacy of NK cells infusions after HCT in the setting of overt hematologic relapse is modest. Our findings suggest the need for large prospective clinical trials to establish the potential benefit of NK cells infusion after HCT to prevent relapse of hematologic malignancies without increased non-relapse mortality. Figure 1 Figure 1. Disclosures Abhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. McGuirk: Bellicum Pharmaceuticals: Research Funding; Gamida Cell: Research Funding; Novartis: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Fresenius Biotech: Research Funding; Astelllas Pharma: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau.

CMV-Reactive NK Cells in Pediatric Post-Hematopoietic Stem Cell Transplant

2020 ◽  
Vol 52 (1) ◽  
pp. 353-359
Author(s):  
Nopporn Apiwattanakul ◽  
Suradej Hongeng ◽  
Usanarat Anurathapan ◽  
Samart Pakakasama ◽  
Supanart Srisala ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nk Cells ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem
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