Publications by authors named "Reuben P Jacob"

6 Publications

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Universal Engraftment after Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts.

Transplant Cell Ther 2021 May 13. Epub 2021 May 13.

Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.

As a result of the COVID-19 pandemic, most centers performing allogeneic hematopoietic cell transplantation (allo-HCT) have switched to the use of cryopreserved grafts. Previous investigators have suggested that cryopreserved allografts may heighten risk of nonengraftment. To date, no study has investigated the effect of cryopreservation of CD34-selected hematopoietic progenitor cells (CD34 HPCs) used as the sole graft source. In this study, we sought to evaluate outcomes after unrelated donor or matched sibling allo-HCT with cryopreserved CD34 HPCs. This was a single-center analysis of adult patients with hematologic malignancies who underwent allo-HCT with cryopreserved CD34-selected allo-HCT grafts between January 2010 and June 2017. All patients received ablative conditioning and antirejection prophylaxis with rabbit antithymocyte globulin. G-CSF-mobilized leukapheresis products underwent CD34 selection using the CliniMACS Reagent System. Cells were then cryopreserved in DMSO (final concentration 7.5%) to -90 °C using a controlled-rate freezing system before being transferred to vapor-phase liquid nitrogen storage. In internal validation, this method has shown 92% mean CD34 cell viability and 99.7% mean CD34 cell recovery. Engraftment was defined as the first of 3 consecutive days of an absolute neutrophil count of ≥0.5. Platelet recovery was recorded as the first of 7 consecutive days with a platelet count ≥20 K/μL without transfusion. Kaplan-Meier methodology was used to estimate overall survival (OS) and relapse-free survival (RFS), and cumulative incidence functions were used to estimate rates of relapse, nonrelapse mortality (NRM), and acute graft-versus-host disease (GVHD). A total of 64 patients received a cryopreserved CD34-selected graft. The median CD34 cell count before cryopreservation was 6.6 × 10/kg (range, 1.4 to 16.1 × 10/kg), and the median CD3 cell count was 2.0 × 10/kg (range, 0 to 21.1 × 10/kg). All patients were engrafted, at a median of 11 days post-HCT (range, 8 to 14 days). One patient had poor graft function in the setting of cytomegalovirus viremia, necessitating a CD34-selected boost on day +57. The median time to platelet recovery was 16 days (range, 13 to 99 days). The estimated 2-year OS was 70% (95% confidence interval [CI], 58% to 83%) with cryopreserved grafts versus 62% (95% CI, 57% to 67%) with fresh grafts (hazard ratio [HR], 0.86; 95% CI, 0.54 to 1.35; P = .5). The estimated 2-year RFS in the 2 groups was 59% (95% CI, 48% to 74%) versus 56% (95% CI, 51% to 61%; HR, 1.01; 95% CI, 0.68 to 1.51; P > .9). The cumulative incidence of relapse at 2 years was 29% (95% CI, 17% to 41%) versus 23% (95% CI, 19% to 27%; P = .16), and the cumulative incidence of NRM at 2 years was 17% (95% CI, 9% to 28%) versus 23% (95% CI, 19% to 28%; P = .24). The cumulative incidence of grade II-IV acute GVHD by day +100 was 16% with cryopreserved grafts (95% CI, 8% to 26%) and 16% (95% CI, 13% to 20%; P = .97) with fresh grafts. Moderate to severe chronic GVHD by day +365 occurred in only 1 recipient of a cryopreserved graft (2%). Our data show that in patients with hematologic malignancies who received cryopreserved allogeneic CD34 HPCs, engraftment, GVHD, and survival outcomes were consistent with those seen in recipients of fresh allogeneic CD34 HPC grafts at our center. Our laboratory validation and clinical experience demonstrate the safety of our cryopreservation procedure for CD34-selected allografts.
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http://dx.doi.org/10.1016/j.jtct.2021.04.026DOI Listing
May 2021

A simplified CD34+ based preharvest prediction tool for HPC(A) collection.

Transfusion 2021 May 11;61(5):1525-1532. Epub 2021 Mar 11.

Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Hematopoietic stem cell transplantation is an important treatment that is dependent on the collection of sufficient CD34+ hematopoietic progenitor cells. The peripheral blood CD34 count (PB CD34+ counts) measured by flow cytometry can be used in predicting CD34+ stem cell yields hours before the completion of collection. Previously described formulas to predict the yield have used many different variables. As such, there is currently no consensus on an industry-standard algorithm or formula.

Study Design And Methods: Retrospective reviews of same-day PB CD34+ counts and the ensuing absolute CD34+ yields of mobilized donors (allogeneic and autologous) were used to develop and validate a formula using regression analysis to predict the CD34+ stem cell yield. A metric of prediction correlation, using root mean square error (RMSE), was used to assess the robustness of our prediction formula in addition to comparisons with two other published formulas, as well as subset analysis.

Results: A formula in the form of y = mx with r = 0.95 and 95% confidence intervals was generated and validated. The ratio of actual to predicted yield demonstrated a high correlation coefficient (r = 0.96) with linear regression and overall RMSE of 228.4, which was lower than the two prior studies (calculated RMSE = 330.8 and 405.2). Subset analyses indicated male patients, lymphoma patients, and patients >60 years of age demonstrated lower RMSEs.

Conclusion: We have demonstrated a simple yet robust formula that can be used prospectively to accurately predict the CD34+ stem cell yield in both autologous and allogeneic donors, which also accounts for recipient weight.
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http://dx.doi.org/10.1111/trf.16356DOI Listing
May 2021

Identifying correlations between donor demographics and isohemagglutinin titers as a potential method to screen for low-titer group O whole blood.

Transfus Apher Sci 2021 Feb 20;60(1):102970. Epub 2020 Oct 20.

Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, United States; Stanford Blood Center, Stanford Medicine, Stanford, CA 94305, United States. Electronic address:

Background: With more hospitals using low-titer group O whole blood in trauma resuscitation, having an efficient screening method for low-titer donors is critical. Our blood center uses an automated screen for high-titer isohemagglutinins in our platelet donations while collecting detailed donor demographic information. Using this data, we can identify key demographics often associated with titer status, thereby helping develop a donor-triaging method for titering.

Study Design And Methods: Titer results were read with an automated microplate system as either high or low, based on agglutination, with a cutoff equivalent to 1:256 (both anti-A and anti-B). Donor demographic data analyzed included date of donation, blood group, age, gender, and ethnicity.

Results: 57,508 donations were collected from 2073 unique donors between 2014 and 2018. We found the following demographics to be correlated with titer status: gender, ABO blood group, age, and ethnicity. Variability in titer status was identified in 215 individuals. This represented around 10 % of the total unique donors and was split equally amongst gender. We also found that donors between the ages of 41-60 ha d the highest likelihood of having variability in titer status, peaking at 13 %, and this proportion declined past age 60.

Conclusion: Titer status is associated with the following donor demographics: gender, ABO type, age, and ethnicity. We also discovered that variability in titer status is correlated with age. In blood centers that do not have automated and routine titer screening procedure, these findings could be used as a method to efficiently identify low-titer donors a-priori.
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http://dx.doi.org/10.1016/j.transci.2020.102970DOI Listing
February 2021

The impact of transfused blood products on deceased donor HLA typing.

Hum Immunol 2019 Dec 15;80(12):976-982. Epub 2019 Oct 15.

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States. Electronic address:

Accurate deceased donor HLA typing assumes that the blood sample tested contains only DNA from the organ donor. Prior to procurement, many organ donors are transfused at least one unit of red blood cells (RBC). Non-organ donor DNA acquired from transfusions may result in incorrect and/or ambiguous HLA typing. To address this question, we investigated the impact of RBC transfusion on organ donor HLA typing by using different in vitro transfusion models: leukoreduced (LR) and non-LR RBCs. Various quantities of LR and non-LR RBCs were added to normal peripheral blood and HLA typing was performed by real time PCR. Our results show that HLA typing of deceased donors can be impacted dependent upon the type and quantity of transfused RBCs. Importantly, if LR RBCs are given, HLA typing is unlikely to be affected, precluding the need to delay typing and obtain an alternative source of donor DNA.
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http://dx.doi.org/10.1016/j.humimm.2019.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341027PMC
December 2019

Stability of anti-A blood group titers among blood group B renal transplant candidates.

Transfusion 2018 12 28;58(12):2747-2751. Epub 2018 Sep 28.

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia.

Background: As deceased donor kidney allocation is based in part on blood type compatibility, group B candidates are disadvantaged due to their disproportionate representation on the wait list compared to the group B donor pool. To mitigate this discrepancy, group B candidates can receive group A or A B donor kidneys if their anti-A titers are below a predetermined cutoff. Currently, eligibility is reverified quarterly to UNet based on individual center protocols, which can vary due to a lack of set guidelines for monitoring ABO titers in these patients. Our goal was to assess the stability of anti-A titers in blood group B renal transplant candidates over time to provide data that could aid in the development of standardized ABO titer protocols.

Study Design And Methods: Titers performed between January 2011 and December 2015 were assessed for 191 group B patients with two or more documented titers.

Results: Fifty patients (26%) were ineligible, as the first titer exceeded the cutoff of 8. Of the remaining 141 patients, 19 (13%) became ineligible as the second titer exceeded 8. Thirty-nine patients (28%) had no change in titer between samples, while 71 (50%) had a titer change that never exceeded 8. Only 12 patients (8.5% of total) experienced a titer change that affected eligibility after the second test.

Conclusion: Although patients experience some variability in anti-A titers over time, in most cases, stability did not affect candidate eligibility. Our results indicate that regular testing beyond the second titer may be unnecessary and represent test overutilization.
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http://dx.doi.org/10.1111/trf.14923DOI Listing
December 2018

TROP-2 expression in papillary thyroid carcinoma: Potential Diagnostic Utility.

Diagn Cytopathol 2016 Jan 19;44(1):26-31. Epub 2015 Oct 19.

Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia.

TROP-2 is a type I transmembrane glycoprotein which is over-expressed in various malignancies, and is related to epithelial cell adhesion molecule (EpCAM), also called TROP-1, gp40, and KSA. In this study, we evaluated TROP-2 expression in papillary thyroid carcinoma (PTC) and compared it to other thyroid neoplastic and non-neoplastic lesions. Immunohistochemical (IHC) evaluation for TROP-2 was performed on 137 thyroid fine needle aspiration (FNA) cell blocks (CB) which included classic PTC (64), follicular variant PTC (FVPTC) (10), anaplastic thyroid carcinoma (AC) (2), medullary carcinoma (MC) (8), follicular neoplasms (FN) (8), Hurthle cell neoplasms (HCN) (9), follicular lesion of uncertain significance (FLUS) (12), and benign thyroid nodule (BTN) (24). IHC for TROP-2 expression was also performed on 331 BTN and malignant tumor tissue sections in tissue microarray (TMA). Membranous staining in >5% of tumor cells was considered positive. TROP-2 stained 61 of 64 PTC CB, 7 of 10 FVPTC CB, and 9 of 12 FLUS CB. All other cases were negative for TROP-2. TROP-2 showed a sensitivity of 95.31% and specificity of 89% for classic PTC in FNA CB. In TMA samples, TROP-2 stained 54 of 60 classic PTC cases and hence showed a high sensitivity and specificity. All BTN in CB and TMA were negative. We conclude that TROP-2 is a highly sensitive and specific IHC marker for identifying classic PTC. TROP-2 may play an important role in diagnosing classic PTC, especially in equivocal cases. This study also identifies a strong role for TROP-2 in separating PTC from BTN.
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http://dx.doi.org/10.1002/dc.23382DOI Listing
January 2016