Shelly Heimfeld
University of Washington
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Featured researches published by Shelly Heimfeld.
Blood | 2010
Jonathan A. Gutman; Cameron J. Turtle; Thomas J. Manley; Shelly Heimfeld; Irwin D. Bernstein; Stanley R. Riddell; Colleen Delaney
We investigated the potential role of an immune reaction in mediating the dominant engraftment of 1 cord blood unit in 14 patients who received a double-unit cord blood transplantation (CBT). In 10 patients, dominant engraftment of a single donor unit emerged by day 28 after CBT. In 9 of these 10 patients, a significant subset of CD8(+) CD45RO(+/-)CCR7(-) T cells, present in peripheral blood mononuclear cells and derived from the engrafting cord blood unit, produced interferon-gamma (IFN-gamma) in response to the nonengrafting unit. No significant population of IFN-gamma-secreting cells was detectable when posttransplantation peripheral blood mononuclear cells were stimulated against cells from the engrafted unit (P < .001) or from a random human leukocyte antigen disparate third party (P = .003). Three patients maintained persistent mixed chimerism after CBT, and no significant IFN-gamma-secreting cells were detected after similar stimulations in these patients (P < .005). Our data provide the first direct evidence in human double-unit CBT recipients that immune rejection mediated by effector CD8(+) T cells developing after CBT from naive precursors is responsible for the failure of 1 unit to engraft. Future investigations based on these findings may result in strategies to predict a dominant unit and enhance graft-versus-leukemia effect.
Blood | 2010
Marcello Rotta; Barry E. Storer; Rainer Storb; Paul J. Martin; Shelly Heimfeld; Amanda Peffer; David G. Maloney; H. Joachim Deeg; Frederick R. Appelbaum; Marco Mielcarek
We retrospectively analyzed outcomes among 567 patients with hematologic malignancies who had hematopoietic cell transplantation from human leukocyte antigen-identical sibling donors between 2001 and 2007 for a correlation between statin use and risk of graft-versus-host disease (GVHD). Compared with allografts where neither the donor nor recipient was treated with a statin at the time of transplantation (n = 464), statin use by the donor and not the recipient (n = 75) was associated with a decreased risk of grade 3-4 acute GVHD (multivariate hazard ratio, 0.28; 95% confidence interval, 0.1-0.9). Statin use by both donor and recipient (n = 12) was suggestively associated with a decreased risk of grade 3 or 4 acute GVHD (multivariate hazard ratio, 0.00; 95% confidence interval, undefined), whereas statin use by the recipient and not the donor (n = 16) did not confer GVHD protection. Risks of chronic GVHD, recurrent malignancy, nonrelapse mortality, and overall mortality were not significantly affected by donor or recipient statin exposure. Statin-associated GVHD protection was restricted to recipients with cyclosporine-based postgrafting immunosuppression and was not observed among those given tacrolimus (P = .009). These results suggest that donor statin treatment may be a promising strategy to prevent severe acute GVHD without compromising immunologic control of the underlying malignancy.
Bone Marrow Transplantation | 2000
J Yu; Wendy Leisenring; W Fritschle; Shelly Heimfeld; Howard M. Shulman; William I. Bensinger; Leona Holmberg; Rowley S
Enumeration of CD34+ cells in the peripheral blood before apheresis predicts the quantity of those cells collected, although the cytometric techniques used are complex and expensive. We found that a subpopulation of lysis-resistant cells in the peripheral blood, identified by the Sysmex SE9500 and designated as HPC, can serve as a surrogate marker predictive of the yield of CD34+ cells. Spearmans rank statistics were used to examine the correlation between WBC, MNC, HPC and CD34+ cells in the peripheral blood and final CD34+ cell yield for 112 samples of peripheral blood and matching apheresis collections from 66 patients and donors. The results indicate that WBC and MNC in the peripheral blood were poor predictors of CD34 content, while HPC gave a correlation coefficient of 0.62. The positive predictive values of different cutoff levels of HPC in the peripheral blood ranging from 5 to 50 × 106/l increased from 0.80 to 0.93 when the target collection was 1 × 106cells/kg. However, for patients with HPC levels below various cutoff levels, the proportion of the collections not reaching that target goal ranged between 0.36 and 0.43, indicating that most collections will still exceed the target goal of CD34+ cells. When the target collection was 2.5 × 106 CD34+ cells/kg, the positive predictive value was lower and negative predictive value was higher. Bone Marrow Transplantation (2000) 25, 1157–1164.
Bone Marrow Transplantation | 2001
Scott D. Rowley; J. Yu; Theodore A. Gooley; Shelly Heimfeld; Leona Holmberg; David G. Maloney; William Bensinger
The number of CD34+ cells collected during apheresis is related to the volume of blood processed. In large-volume apheresis (LVL) procedure, more cells can be collected than were originally present in the peripheral blood at the start of the collection procedure. We prospectively studied the levels of CD34+ cells in the blood and apheresis product during LVL procedures for 21 patients with acute myelogenous leukemia or multiple myeloma. These patients experienced a slow decline in blood CD34+ cell concentrations during the apheresis procedure. No patient demonstrated a sustained rise in CD34+ cell counts as a result of the procedure. The number of CD34+ cells collected exceeded the number calculated to be in the peripheral blood at the start of the procedure by an average of 3.0-fold. The efficiency of collection for CD34+ cells averaged 92.6% and did not vary with speed of blood processing, diagnosis, or mobilization regimen. The calculated release of CD34+ cells from other reservoirs into the peripheral blood averaged 3.71 × 106/min (range, 0.36–13.7 × 106/min), and correlated (r = 0.82) with the concentration of these cells in the peripheral blood at the start of the procedure. These data show that the apheresis procedure used in this study does not affect the release of CD34+ cells in a cytokine-treated patient. LVL will result in collection of larger quantities of CD34+ cells than procedures involving processing of smaller volumes of blood, but the number of cells collected is limited by the rate of release of these cells into the peripheral circulation where they are accessible for collection. Bone Marrow Transplantation (2001) 28, 649–656.
Biology of Blood and Marrow Transplantation | 2013
Filippo Milano; Shelly Heimfeld; Ted Gooley; Jack Jinneman; Ian Nicoud; Colleen Delaney
Single-donor dominance is observed in the majority of patients following double-unit cord blood transplantation (dCBT); however, the biological basis for this outcome is poorly understood. To investigate the possible influence of specific cell lineages on dominance in dCBT, flow cytometry assessment for CD34(+), CD14(+), CD20(+), CD3(-)CD56(+), CD3(+)CD56(+) (natural killer), and T cell subsets (CD4(+), CD8(+), memory, naïve, and regulatory) was performed on individual units. Subsets were calculated as infused viable cells per kilogram of recipient actual weight. Sixty patients who underwent dCBT were included in the final analysis. Higher CD3(+) cell dose was statistically concordant with the dominant unit in 72% of cases (P = .0006). Further T cell subset analyses showed that dominance was correlated more with the naive CD8(+) cell subset (71% concordance; P = .009) than with the naive CD4(+) cell subset (61% concordance; P = .19). These data indicate that a greater total CD3(+) cell dose, particularly of naïve CD3(+)CD8(+) T cells, may play an important role in determining single-donor dominance after dCBT.
Bone Marrow Transplantation | 2016
S. Gallo; Ann E. Woolfrey; Lauri Burroughs; Barry E. Storer; Mary E.D. Flowers; Parameswaran Hari; Michael A. Pulsipher; Shelly Heimfeld; Hans-Peter Kiem; Storb R
A total of 21 patients with severe aplastic anemia (SAA) underwent marrow transplantation from HLA-identical siblings following a standard conditioning regimen with cyclophosphamide (50u2009mg/kg/day × 4 days) and horse antithymocyte globulin (30u2009mg/kg/day × 3 days). Post-grafting immunosuppression consisted of a short course of methotrexate (MTX) combined with cyclosporine (CSP). The transplant protocol tested the hypothesis that the incidence of chronic GvHD could be reduced by limiting the marrow grafts to ⩽2.5 × 108 nucleated marrow cells/kg. None of the patients rejected the graft, all had sustained engraftment and all are surviving at a median of 4 (range 1–8) years after transplantation. Chronic GvHD developed in 16% of patients given ⩽2.5 × 108 nucleated marrow cells/kg. Post-grafting immunosuppression has been discontinued in 20 of the 21 patients. In conclusion, limiting the number of transplanted marrow cells may have resulted in minimal improvement in the incidence and severity of chronic GvHD.
Molecular Therapy | 2015
Jennifer E. Adair; Kevin G. Haworth; Guy Sauvageau; Shelly Heimfeld; Hans-Peter Kiem
Lentivirus (LV) mediated gene therapy of CD34+ hematopoietic stem and progenitor cells (HSPCs) has demonstrated clinical success for a variety of diseases. However, current state-of-the-art requires ex vivo HSPC gene transfer in a dedicated Good Manufacturing Practices (GMP) facility, limiting treatment to highly developed countries capable of supporting GMP infrastructure. We developed a flexible, overnight platform for efficient isolation and LV gene modification of bone marrow and mobilized peripheral blood CD34+ HSPCs in a closed, table top system, the Prodigy CliniMACS™, with limited requirement for additional equipment. We performed all experiments with only a biosafety cabinet and personal protective equipment to simulate anticipated conditions in clinical facilities of underdeveloped countries. Given the economic burden of mobilization, we initially designed the process for bone marrow. A total of 7 custom programs were developed based on current device memory limitations: (1) hetastarch sedimentation to deplete red blood cells (RBCs), (2) labeling CD34+ cells in the RBC-depleted product, (3) immunomagnetic enrichment of CD34+ cells, (4) initial transduction (MOI = 20 IU/cell), (5) culture overnight, (6) second transduction (MOI = 20 IU/cell) and additional culture, and (7) harvest and formulation of the final product. Addition of a pyrimidoindole derivative, UM729, permitted efficient transduction of CD34+ HSPCs in £18 hours. The process took 70%). Perform-and-report testing and xenotransplantation of these gene-modified cells into immunodeficient mice for further functional testing are in progress. These data demonstrate preclinical safety and feasibility of this portable strategy for ex vivo LV gene transfer into HSPCs, representing the first globally applicable advance in translation of HSPC gene therapy.
Blood | 1999
Leona Holmberg; Michael Boeckh; Heather Hooper; Wendy Leisenring; Rowley S; Shelly Heimfeld; Oliver W. Press; David G. Maloney; Peter A. McSweeney; Lawrence Corey; Richard T. Maziarz; Frederick R. Appelbaum; William I. Bensinger
Blood | 2001
J. Maciej Zaucha; Theodore A. Gooley; William I. Bensinger; Shelly Heimfeld; Thomas R. Chauncey; Renata Zaucha; Paul J. Martin; Mary E.D. Flowers; Jan Storek; George E. Georges; Rainer Storb; Beverly Torok-Storb
Biology of Blood and Marrow Transplantation | 2006
H. Joachim Deeg; Barry E. Storer; Michael Boeckh; Paul J. Martin; Jeannine S. McCune; David Myerson; Shelly Heimfeld; Mary E.D. Flowers; Claudio Anasetti; Doney K; John A. Hansen; Hans-Peter Kiem; Richard A. Nash; Paul V. O’Donnell; Jerald P. Radich; Bart L. Scott; Mohamed L. Sorror; E. Houston Warren; Robert P. Witherspoon; Ann E. Woolfrey; Frederick R. Appelbaum; Rainer Storb