Browsing by Author "Shpall, Elizabeth J"

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    A Randomized, Placebo-Controlled, Phase II Trial of Intravenous Allogeneic Non-HLA Matched, Unrelated Donor, Cord Blood Infusion for Ischemic Stroke.
    (Stem cells translational medicine, 2024-02) Laskowitz, Daniel T; Troy, Jesse; Poehlein, Emily; Bennett, Ellen R; Shpall, Elizabeth J; Wingard, John R; Freed, Brian; Belagaje, Samir R; Khanna, Anna; Jones, William; Volpi, John J; Marrotte, Eric; Kurtzberg, Joanne
    Stroke remains a leading cause of death and disability in the US, and time-limited reperfusion strategies remain the only approved treatment options. To address this unmet clinical need, we conducted a phase II randomized clinical trial to determine whether intravenous infusion of banked, non-HLA matched unrelated donor umbilical cord blood (UCB) improved functional outcome after stroke. Participants were randomized 2:1 to UCB or placebo within strata of National Institutes of Health Stroke Scale Score (NIHSS) and study center. Study product was infused 3-10 days following index stroke. The primary endpoint was change in modified Rankin Scale (mRS) from baseline to day 90. Key secondary outcomes included functional independence, NIHSS, the Barthel Index, and assessment of adverse events. The trial was terminated early due to slow accrual and logistical concerns associated with the COVID-19 pandemic, and a total of 73 of a planned 100 participants were included in primary analyses. The median (range) of the change in mRS was 1 point (-2, 3) in UCB and 1 point (-1,4) in Placebo (P = 0.72). A shift analysis comparing the mRS at day 90 utilizing proportional odds modeling showed a common odds ratio of 0.9 (95% CI: 0.4, 2.3) after adjustment for baseline NIHSS and randomization strata. The distribution of adverse events was similar between arms. Although this study did not suggest any safety concerns related to UCB in ischemic stroke, we did not show a clinical benefit in the reduced sample size evaluated.
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    CD34+ cell content of 126 341 cord blood units in the US inventory: implications for transplantation and banking.
    (Blood advances, 2019-04) Barker, Juliet N; Kempenich, Jane; Kurtzberg, Joanne; Brunstein, Claudio G; Delaney, Colleen; Milano, Filippo; Politikos, Ioannis; Shpall, Elizabeth J; Scaradavou, Andromachi; Dehn, Jason
    CD34+ cell dose is critical for cord blood (CB) engraftment. However, the CD34+ content of the CB inventory in the United States is unknown. We examined the CD34+ cell content of 126 341 red blood cell-depleted US units banked from January 2007 to September 2017 with a total nucleated cell (TNC) count of ≥90 × 107 and a cryovolume of 24-55 mL. Median pre-cryopreservation TNC content was 127 × 107 (interquartile range [IQR], 108-156 × 107); CD34+ cell content was 44 × 105 (IQR, 29 to 67 × 105). The median CD34+:TNC ratio was 0.34%. TNC and CD34+ cell content correlation was weak (r = 0.24). Of 7125 units with TNCs of ≥210 × 107, only 47% had CD34+ content of ≥100 × 105 However, some units had high CD34+ content for a given TNC count. Only 4% of CB units were acceptable as single-unit grafts (TNCs, ≥2.5 × 107/kg; CD34+ cells, ≥1.5 × 105/kg) for 70-kg patients; 22% of units were adequate for 70-kg patients using lower dose criteria (TNCs, ≥1.5 × 107/kg; CD34+ cells, ≥1.0 × 105/kg) suitable for a double-unit graft. These findings highlight that units with the highest TNC dose may not have the highest CD34+ dose, units with unexpectedly high CD34+ content (a ratio of >1.0%) should be verified, and the US CB inventory of adequately sized single units for larger patients is small. They also support the ongoing use of double-unit grafts, a focus on banking high-dose units, and development of expansion technologies.
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    Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2015-04) Ballen, Karen K; Logan, Brent R; Laughlin, Mary J; He, Wensheng; Ambruso, Daniel R; Armitage, Susan E; Beddard, Rachel L; Bhatla, Deepika; Hwang, William YK; Kiss, Joseph E; Koegler, Gesine; Kurtzberg, Joanne; Nagler, Arnon; Oh, David; Petz, Lawrence D; Price, Thomas H; Quinones, Ralph R; Ratanatharathorn, Voravit; Rizzo, J Douglas; Sazama, Kathleen; Scaradavou, Andromachi; Schuster, Michael W; Sender, Leonard S; Shpall, Elizabeth J; Spellman, Stephen R; Sutton, Millicent; Weitekamp, Lee Ann; Wingard, John R; Eapen, Mary
    Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.
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    Impact of selection of cord blood units from the United States and swiss registries on the cost of banking operations.
    (Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 2013-02) Bart, Thomas; Boo, Michael; Balabanova, Snejana; Fischer, Yvonne; Nicoloso, Grazia; Foeken, Lydia; Oudshoorn, Machteld; Passweg, Jakob; Tichelli, Andre; Kindler, Vincent; Kurtzberg, Joanne; Price, Thomas; Regan, Donna; Shpall, Elizabeth J; Schwabe, Rudolf

    Background

    Over the last 2 decades, cord blood (CB) has become an important source of blood stem cells. Clinical experience has shown that CB is a viable source for blood stem cells in the field of unrelated hematopoietic blood stem cell transplantation.

    Methods

    Studies of CB units (CBUs) stored and ordered from the US (National Marrow Donor Program (NMDP) and Swiss (Swiss Blood Stem Cells (SBSQ)) CB registries were conducted to assess whether these CBUs met the needs of transplantation patients, as evidenced by units being selected for transplantation. These data were compared to international banking and selection data (Bone Marrow Donors Worldwide (BMDW), World Marrow Donor Association (WMDA)). Further analysis was conducted on whether current CB banking practices were economically viable given the units being selected from the registries for transplant. It should be mentioned that our analysis focused on usage, deliberately omitting any information about clinical outcomes of CB transplantation.

    Results

    A disproportionate number of units with high total nucleated cell (TNC) counts are selected, compared to the distribution of units by TNC available. Therefore, the decision to use a low threshold for banking purposes cannot be supported by economic analysis and may limit the economic viability of future public CB banking.

    Conclusions

    We suggest significantly raising the TNC level used to determine a bankable unit. A level of 125 × 10(7) TNCs, maybe even 150 × 10(7) TNCs, might be a viable banking threshold. This would improve the return on inventory investments while meeting transplantation needs based on current selection criteria.
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    Progress toward curing HIV infection with hematopoietic cell transplantation.
    (Stem cells and cloning : advances and applications, 2015-01) Petz, Lawrence D; Burnett, John C; Li, Haitang; Li, Shirley; Tonai, Richard; Bakalinskaya, Milena; Shpall, Elizabeth J; Armitage, Sue; Kurtzberg, Joanne; Regan, Donna M; Clark, Pamela; Querol, Sergio; Gutman, Jonathan A; Spellman, Stephen R; Gragert, Loren; Rossi, John J
    HIV-1 infection afflicts more than 35 million people worldwide, according to 2014 estimates from the World Health Organization. For those individuals who have access to antiretroviral therapy, these drugs can effectively suppress, but not cure, HIV-1 infection. Indeed, the only documented case for an HIV/AIDS cure was a patient with HIV-1 and acute myeloid leukemia who received allogeneic hematopoietic cell transplantation (HCT) from a graft that carried the HIV-resistant CCR5-∆32/∆32 mutation. Other attempts to establish a cure for HIV/AIDS using HCT in patients with HIV-1 and malignancy have yielded mixed results, as encouraging evidence for virus eradication in a few cases has been offset by poor clinical outcomes due to the underlying cancer or other complications. Such clinical strategies have relied on HIV-resistant hematopoietic stem and progenitor cells that harbor the natural CCR5-∆32/∆32 mutation or that have been genetically modified for HIV-resistance. Nevertheless, HCT with HIV-resistant cord blood remains a promising option, particularly with inventories of CCR5-∆32/∆32 units or with genetically modified, human leukocyte antigen-matched cord blood.
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    Unlicensed Umbilical Cord Blood Units Provide a Safe and Effective Graft Source for a Diverse Population: A Study of 2456 Umbilical Cord Blood Recipients.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2020-04) Ballen, Karen; Logan, Brent R; Chitphakdithai, Pintip; Kuxhausen, Michelle; Spellman, Stephen R; Adams, Alexia; Drexler, Rebecca J; Duffy, Merry; Kemp, Ann; King, Roberta; Babic, Aleksandar; Delaney, Colleen; Karanes, Chatchada; Kurtzberg, Joanne; Petz, Lawrence; Scaradavou, Andromachi; Shpall, Elizabeth J; Smith, Clayton; Confer, Dennis L; Miller, John P
    Umbilical cord blood (UCB) transplantation (UCBT) is a curative procedure for patients with hematologic malignancies and genetic disorders and expands access to transplantation for non-Caucasian patients unable to find a fully matched unrelated donor. In 2011, the US Food and Drug Administration required that unrelated UCBT be performed using either licensed UCB or unlicensed UCB under the Investigational New Drug (IND) program. The National Marrow Donor Program manages an IND under which 2456 patients (1499 adults and 957 children, 564 with malignant diseases and 393 with nonmalignant diseases) underwent single or double UCBT between October 2011 and December 2016. The median patient age was 31 years (range, <1 to 81 years), and 50% of children and 36% of adults were non-Caucasian. The median time to neutrophil engraftment (ie, absolute neutrophil count ≥500/mm3) was 22 days for adults, 20 days for pediatric patients with malignant diseases, and 19 days for pediatric patients with nonmalignant diseases, with corresponding rates of engraftment at 42 days of 89%, 88%, and 90%. In these 3 groups of patients, the incidence of acute graft-versus-host disease (GVHD) grade II-IV was 35%, 32%, and 24%; the incidence of chronic GVHD was 24%, 26%, and 24%; and 1-year overall survival (OS) was 57%, 71%, and 79%, respectively. In multivariate analysis, younger age, lower Hematopoietic Cell Transplantation-Specific Comorbidity Index, early-stage chemotherapy-sensitive disease, and higher performance score were predictive of improved OS for adults. In a subset analysis of children with malignancies undergoing single UCBT, the use of either licensed UCB (n = 48) or unlicensed UCB (n = 382) was associated with similar engraftment and survival. The use of unlicensed UCB units is safe and effective and provides an important graft source for a diverse population.