Susan F Leitman

National Heart, Lung, and Blood Institute, 베서스다, Maryland, United States

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Publications (237)1774.53 Total impact

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    ABSTRACT: Leukapheresis is often performed in cancer patients to harvest stem cells, manufacture therapeutic vaccines, or follow immunologic response to therapy. We have recently described the minimal impact of leukapheresis on normal donors. Here we provide additional immunologic data from patients with advanced cancer who underwent leukapheresis. Using data from cancer patients on clinical trials who had leukapheresis (n = 64) or peripheral blood draws only (n = 90) as controls for immune analysis, we evaluated the impact of leukapheresis on number and function of lymphocytes. In the leukapheresis group, median age was 63.5 (range 38-82); 87.5 % were male. Comparing pre- and post-leukapheresis values within the groups, with each patient as its own control, there was no significant difference in enzyme-linked immunosorbent spot (ELISPOT), antivector humoral response, absolute lymphocyte count (ALC), or T cell number. Twelve patients completed three leukaphereses with subsequent ELISPOT analysis; seven had increased responses to flu (1.1- to 2.3-fold) with an even distribution around no change. Nineteen patients had matched ALC values after completing three leukaphereses with no significant change from baseline. These data provide evidence that leukapheresis has no detectable effects on a cancer patient's immune system in terms of number or function. These results contribute to a growing body of evidence refuting the hypothesis that a patient's immune competence is meaningfully affected by the procedure. Limitations include a restriction to 2-L leukapheresis procedure and small sample size.
    No preview · Article · Aug 2015 · Cancer Immunology and Immunotherapy
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    P T Vo · J Pantin · C Ramos · L Cook · E Cho · R Kurlander · H Khuu · J Barrett · S Leitman · R W Childs
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    ABSTRACT: Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure, which if left untreated, is invariably fatal. Conventional therapies with immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation (HSCT) are highly effective. HSCT can offer a greater outcome in younger patients who have an available HLA match-related donor. Recent studies showing the addition of antithymocyte globulin (ATG) to the conditioning regimen improves engraftment and reduces the risk of graft-versus-host disease (GVHD). There are currently two ATG preparations in the USA, equine (or horse) and rabbit ATG. These agents are pharmacologically distinct, having significant differences in their pharmacokinetics and in vivo immunosuppressive effects [N Engl J Med 365(5):430-438, 2011]. Here, we report a case of two monozygotic twins with constitutional SAA that evolved to myelodysplastic syndrome (MDS) who both underwent allogeneic peripheral blood stem cell transplantation (PBSC) from the same single HLA antigen mismatched sibling donor with the only difference in the transplant regimen being the type of ATG used in the preparative regimen; one twin received horse ATG and the other received rabbit ATG during conditioning. This report emphasizes that dramatic differences in donor T cell chimerism and clinical outcomes including GVHD can occur as a consequence of the type of ATG that is utilized in the transplant conditioning regimen. These differences highlight that these agents should not be considered interchangeable drugs when used in this setting.
    Full-text · Article · Jun 2015 · Journal of Hematology & Oncology

  • No preview · Article · Jun 2015 · Cytotherapy
  • Antoinette Rabel · Susan F. Leitman · Jeffery L. Miller
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    ABSTRACT: The study aims to review a condition defined by the desire to consume ice in order to satisfy an addictive-like compulsion, rather than for purposes of hydration or pain relief. This condition is called ice pica, or pagophagia. Associations between ice pica and iron deficiency, suggestions for clinical screening of at risk populations, and recommendations for treatment and follow-up care are provided. An extensive literature review of original research articles, reviews, clinical practice manuscripts, and scientific publications on pica and pagophagia. A compulsion or craving for the consumption of ice is often overlooked in clinical practice. It is therefore important for clinicians to include ice pica as part of the review of systems for certain patient populations. Ice pica is frequently associated with iron deficiency, and iron supplementation is an effective therapy in most cases. Knowledge gained from screening for ice pica can generate valuable patient information and lead to the diagnosis and treatment of iron deficiency. The populations at risk include young women and blood donors of either sex. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
    No preview · Article · May 2015 · Journal of the American Association of Nurse Practitioners
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    ABSTRACT: Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia. We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single-center case series detailing our experience (1996-2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone- and granulocyte-colony-stimulating factor-stimulated donors. Twenty-three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor-stimulated GTs generated mean "same-day" neutrophil increments of 3.35 × 10(9) ± 1.24 × 10(9) /L and mean overall posttransfusion neutrophil increments of 2.46 × 10(9) ± 0.85 × 10(9) /L. Progressive decrements in neutrophil response to GTs in two cases were attributed to GT-related HLA alloimmunization. In patients with IF, donor-stimulated GTs may contribute to high response rates by effectively bridging periods of neutropenia or marrow suppression. However, their utility in the absence of neutrophil recovery remains questionable. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
    No preview · Article · Apr 2015 · Transfusion

  • No preview · Article · Feb 2015 · Biology of Blood and Marrow Transplantation
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    ABSTRACT: Background Therapeutic phlebotomy is increasingly used in patients with transfusional siderosis to mitigate organ injury associated with iron overload (IO). Laboratory response variables and therapy duration are not well characterized in such patients.Study Design and Methods We retrospectively evaluated 99 consecutive patients undergoing therapeutic phlebotomy for either transfusional IO (TIO, n = 88; 76% had undergone hematopoietic transplantation) or nontransfusional indications (hyperferritinemia or erythrocytosis; n = 11). Complete blood cell count, serum ferritin (SF), transferrin saturation, and transaminases were measured serially. Phlebotomy goal was an SF level of less than 300 μg/L.ResultsMean SF levels before phlebotomy among TIO and nontransfusional subjects were 3093 and 396 μg/L, respectively. Transfusion burden in the TIO group was 94 ± 108 (mean ± SD) RBC units; approximately half completed therapy with 24 ± 23 phlebotomies (range, 1-103). One-third were lost to follow-up. Overall, 15% had mild adverse effects, including headache, nausea, and dizziness, mainly during first phlebotomy. Prior transfusion burden correlated poorly with initial ferritin and total number of phlebotomies to target in the TIO group. However, number of phlebotomies to target was strongly correlated with initial SF (R2 = 0.8; p < 0.0001) in both TIO and nontransfusional groups. ALT decreased significantly with serial phlebotomy in all groups (mean initial and final values, 61 and 39 U/L; p = 0.03).Conclusions Initial SF but not transfusion burden predicted number of phlebotomies to target in patients with TIO. Despite good treatment tolerance, significant losses to follow-up were noted. Providing patients with an estimated phlebotomy number and follow-up duration, and thus a finite endpoint, may improve compliance. Hepatic function improved with iron offloading.
    No preview · Article · Oct 2014 · Transfusion
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    ABSTRACT: Background Granulocyte–colony-stimulating factor (G-CSF)-mobilized autologous hematopoietic progenitor cells (HPCs) may be collected by apheresis of patients with chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID) for use in gene therapy trials. CD34+ cell mobilization has not been well characterized in such patients.Study Design and Methods We retrospectively evaluated CD34+ cell mobilization and collection in 73 consecutive CGD and SCID patients and in 99 age-, weight-, and G-CSF dose–matched healthy allogeneic controls.ResultsIn subjects aged not more than 20 years, Day 5 preapheresis circulating CD34+ counts were significantly lower in CGD and SCID patients than in controls; mean peak CD34+ cell counts were 58 × 106, 64 × 106, and 87 × 106/L, respectively (p = 0.01). The SCIDs had lower CD34+ collection efficiency than CGDs and controls; mean efficiencies were 40, 63, and 57%, respectively (p = 0.003). In subjects aged more than 20 years, the CGDs had significantly lower CD34+ cell mobilization than controls; mean peak CD34+ cell counts were 41 × 106 and 113 × 106/L, respectively (p < 0.0001). In a multivariate analysis, lower erythrocyte sedimentation rate (ESR) at mobilization was significantly correlated with better CD34+ cell mobilization (p = 0.007). In SCIDs, CD34 collection efficiency was positively correlated with higher red blood cell (RBC) indices (mean RBC volume, R2 = 0.77; mean corpuscular hemoglobin [Hb], R2 = 0.94; mean corpuscular Hb concentration, R2 = 0.7; p < 0.007) but not Hb.ConclusionsCGD and SCID populations are characterized by significantly less robust CD34+ HPC mobilization than healthy controls. The presence of active inflammation or infection as suggested by an elevated ESR may negatively impact mobilization. Among SCIDs, markedly reduced CD34 collection efficiencies were related to iron deficiency, wherein decreased RBC size and density may impair apheresis cell separation mechanics.
    No preview · Article · Sep 2014 · Transfusion
  • Kamille A. West · Susan F. Leitman · Willy A. Flegel

    No preview · Article · Sep 2014 · Transfusion
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    ABSTRACT: In adults with sickle cell disease (SCD), markers of iron burden such as serum ferritin are associated with excessive production of the angiogenic protein placenta growth factor (PlGF) and high estimated pulmonary artery pressure. Enforced PlGF expression in mice stimulates production of the potent vasoconstrictor endothelin-1, producing pulmonary hypertension. We now demonstrate heme-bound iron (hemin) induces PlGF mRNA more than 200-fold in a dose- and time-dependent fashion. In murine and human erythroid cells, expression of Erythroid Krüppel-like Factor (EKLF) precedes PlGF, and its enforced expression in human erythroid progenitor cells induces PlGF mRNA. Hemin-induced expression of PlGF is abolished in EKLF-deficient murine erythroid cells but rescued by conditional expression of EKLF. Chromatin immunoprecipitation reveals that EKLF binds to the PlGF promoter region. SCD patients show higher level expression of both EKLF and PlGF mRNA in circulating blood cells, and markers of iron overload are associated with high plasma level of PlGF and early mortality. Finally, PlGF association with iron burden generalizes to other human diseases of iron overload. Our results for the first time demonstrate a specific mechanistic pathway induced by excess iron that is linked in humans with SCD and in mice to markers of vasculopathy and pulmonary hypertension. Studies were registered at, identifiers: NCT00007150, NCT00023296, NCT00081523, and NCT00352430.
    Full-text · Article · Jun 2014 · Blood

  • No preview · Article · Feb 2014 · Biology of Blood and Marrow Transplantation
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    Susan F Leitman
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    ABSTRACT: Hereditary hemochromatosis (HH) due to homozygosity for the C282Y mutation in the HFE gene is a common inherited iron overload disorder in whites of northern European descent. Hepcidin deficiency, the hallmark of the disorder, leads to dysregulated intestinal iron absorption and progressive iron deposition in the liver, heart, skin, endocrine glands, and joints. Survival is normal if organ damage is prevented by early institution of phlebotomy therapy. HH arthropathy is the symptom most affecting quality of life and can be debilitating. Genotype screening in large population studies has shown that the clinical penetrance of C282Y homozygosity is highly variable and can be very low, with up to 50% of women and 20% of men showing a silent phenotype. Targeted population screening for the HFE C282Y mutation is not recommended at present, but might be reconsidered as a cost-effective approach to management if counseling and care were better organized and standardized. Referral of patients to the blood center for phlebotomy therapy and use of HH donor blood for transfusion standardizes treatment, minimizes treatment costs, and may benefit society as a whole. Physician practices should be amended such that HH subjects are more frequently referred to the blood center for therapy.
    Preview · Article · Dec 2013 · Hematology
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    ABSTRACT: Plerixafor (Mozobil) is a CXCR4 antagonist that rapidly mobilizes CD34(+) cells into circulation. Recently, plerixafor has been used as a single agent to mobilize peripheral blood stem cells for allogeneic hematopoietic cell transplantation. Although G-CSF mobilization is known to alter the phenotype and cytokine polarization of transplanted T cells, the effects of plerixafor mobilization on T cells have not been well characterized. In this study, we show that alterations in the T cell phenotype and cytokine gene expression profiles characteristic of G-CSF mobilization do not occur after mobilization with plerixafor. Compared with nonmobilized T cells, plerixafor-mobilized T cells had similar phenotype, mixed lymphocyte reactivity, and Foxp3 gene expression levels in CD4(+) T cells, and did not undergo a change in expression levels of 84 genes associated with Th1/Th2/Th3 pathways. In contrast with plerixafor, G-CSF mobilization decreased CD62L expression on both CD4 and CD8(+) T cells and altered expression levels of 16 cytokine-associated genes in CD3(+) T cells. To assess the clinical relevance of these findings, we explored a murine model of graft-versus-host disease in which transplant recipients received plerixafor or G-CSF mobilized allograft from MHC-matched, minor histocompatibility-mismatched donors; recipients of plerixafor mobilized peripheral blood stem cells had a significantly higher incidence of skin graft-versus-host disease compared with mice receiving G-CSF mobilized transplants (100 versus 50%, respectively, p = 0.02). These preclinical data show plerixafor, in contrast with G-CSF, does not alter the phenotype and cytokine polarization of T cells, which raises the possibility that T cell-mediated immune sequelae of allogeneic transplantation in humans may differ when donor allografts are mobilized with plerixafor compared with G-CSF.
    No preview · Article · Nov 2013 · The Journal of Immunology
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    ABSTRACT: Hematopoietic stem cells can be procured from unrelated donors via either the bone marrow (BM) aspiration or peripheral blood stem cell (PBSC) collection methods. There is no evidence from prospective randomized trials in the unrelated donor setting about the relative health-related quality-of-life (HRQoL) benefits/costs to donors. The goals of this prospective longitudinal investigation were to describe and compare the donation-related HRQoL experiences of 332 BM and PBSC donors. Donors were interviewed before donation, 48 hours after donation, weekly until fully recovered, and at 6 and 12 months after donation. Before donation, BM donors had lower confusion, fewer concerns, and were more prepared for donation. Shortly after donation, BM donors reported more physical side effects. BM donors also reported more donation-related impact on their social activities. However, BM donors reported somewhat better psychological status and were more likely to indicate that the donation made their lives more meaningful. There were virtually no longer term differences in the experiences of the 2 donor groups, including no recovery time difference beginning 3 weeks after donation. Although BM donors may experience the process as more physically stressful and more psychologically beneficial in the short term, the longer term HRQoL consequences of BM and PBSC donors are similar.
    No preview · Article · Oct 2013 · Biology of Blood and Marrow Transplantation
  • S. R. Panch · Y. C. Yau · E. Kang · H. Malech · S. F. Leitman

    No preview · Conference Paper · Sep 2013
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    ABSTRACT: The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine and equine anti-thymocyte globulin. GVHD prophylaxis included cyclosporine A alone or in combination with either mycophenolate mofetil or methotrexate. To reduce the risk of graft-rejection/failure, un-manipulated G-CSF mobilized PBPCs obtained from an HLA-identical or single HLA-antigen mismatched relative were transplanted rather than donor bone marrow. Despite a high prevalence of pre-transplant HLA-alloimmunization (41%) and a heavy prior transfusion burden, graft-failure did not occur with all patients having sustained donor lympho-hematopoietic engraftment. The cumulative incidence of grade II-IV acute-GVHD and chronic-GVHD was 51.8% and 72% respectively; with 87.1% surviving at a median follow up of 4.5 years. A multivariate analysis showed pre-transplant alloimmunization and rapid donor T-cell engraftment (≥95% donor by day 30) were both significantly (P<0.05) associated with the development of chronic-GVHD (adjusted HR 2.13and 2.99 respectively).These data show fludarabine-based PBPC transplantation overcomes the risk of graft-failure in patients with BMFS, although rapid donor T-cell engraftment associated with this approach appears to increase the risk of chronic-GVHD. ( identifier: NCT00003838).
    No preview · Article · Sep 2013 · American Journal of Hematology

  • No preview · Article · May 2013 · Transfusion

  • No preview · Article · May 2013 · Transfusion
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    ABSTRACT: In experimental models, ex vivo induced T cell rapamycin-resistance occurred independent of T-helper 1 (Th1)/T-helper 2 (Th2) differentiation and yielded allogeneic CD4(+) T cells of increased in vivo efficacy that facilitated engraftment and permitted graft-versus-tumor (GVT) effects while minimizing graft-versus-host disease (GVHD). To translate these findings, we performed a phase II multi-center clinical trial of rapamycin-resistant donor CD4(+) Th2/Th1 (T-Rapa) cells after allogeneic matched-sibling donor hematopoietic cell transplantation (HCT) for therapy of refractory hematologic malignancy. T-Rapa cell products, which expressed a balanced Th2/Th1 phenotype, were administered as a pre-emptive donor lymphocyte infusion (DLI) at day 14 post-HCT. After T-Rapa cell infusion, mixed donor/host chimerism rapidly converted and there was preferential immune reconstitution with donor CD4(+) Th2 and Th1 cells relative to regulatory T cells and CD8(+) T cells. The cumulative incidence probability of acute GVHD was 20% and 40% at days 100 and 180 post-HCT, respectively. There was no transplant-related mortality. Eighteen of 40 patients (45%) remain in sustained complete remission (range of follow-up: 42 to 84 months). These phase II clinical trial results demonstrate the safety of this low-intensity transplant approach, and indicate the feasibility of subsequent randomized studies to compare T-Rapa cell-based therapy to standard transplantation regimens. Study registered at:; NCT 00077480.
    Full-text · Article · Feb 2013 · Blood
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    ABSTRACT: Pica and restless legs syndrome (RLS) are associated with iron depletion and deficiency. The presence of pica and RLS was prospectively assessed in blood donors. During a 39-month period, 1236 donors deferred for fingerstick hemoglobin (Hb) level of less than 12.5 g/dL and 400 nondeferred “control” donors underwent health screening and laboratory testing (complete blood count, ferritin, iron, transferrin). Pica and RLS were assessed by direct questioning. Deferred donors and iron-deficient control donors were given 325 mg of ferrous sulfate daily for 60 days. Reassessments were performed and additional iron tablets dispensed at subsequent visits. Pica was reported in 11% of donors with iron depletion or deficiency, compared with 4% of iron-replete donors (p < 0.0001). Pagophagia (ice pica) was most common and often of extraordinary intensity. Female sex, younger age, and lower mean cell volume and transferrin saturation values were strongly associated with pica. Donors with pica given iron reported a marked reduction in the desire to consume the nonnutritive substance by Days 5 to 8 of therapy, with disappearance of symptoms by Days 10 to 14. RLS was reported in 16% of subjects with iron depletion or deficiency compared with 11% of iron-replete donors (p = 0.012). Iron replacement generally resulted in improvement of RLS symptoms; however, at least 4 to 6 weeks of iron therapy was necessary. The presence of pica is associated with a high probability of iron depletion or deficiency in blood donors; however, RLS lacks a strong correlation in this population. Screening questions for pagophagia may be useful in the ascertainment of iron deficiency in donors and may identify those who would benefit from oral iron.
    No preview · Article · Jan 2013 · Transfusion

Publication Stats

15k Citations
1,774.53 Total Impact Points


  • 1989-2015
    • National Heart, Lung, and Blood Institute
      • Hematology Branch
      베서스다, Maryland, United States
  • 1987-2015
    • National Institutes of Health
      • • Center for Clinical Research
      • • Chemical Biology Laboratory
      • • Branch of Surgery
      • • Laboratory of Host Defenses
      베서스다, Maryland, United States
  • 2011-2013
    • University of Texas Medical Branch at Galveston
      • Department of Pathology
      Galveston, Texas, United States
  • 1994-2012
    • National Cancer Institute (USA)
      • • Center for Cancer Research
      • • Surgery Branch
      베서스다, Maryland, United States
  • 1989-2010
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      Maryland, United States
  • 2009
    • University of Utah
      Salt Lake City, Utah, United States
  • 2005
    • University of Milan
      Milano, Lombardy, Italy
    • National Human Genome Research Institute
      Maryland, United States
  • 2001-2005
    • Walter Reed Army Institute of Research
      Silver Spring, Maryland, United States
  • 2003
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • The University of the West Indies at Mona
      Kingston, Kingston, Jamaica
  • 2002
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      베서스다, Maryland, United States
  • 2000
    • National Marrow Donor Program
      Minneapolis, Minnesota, United States
  • 1997
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
  • 1996
    • Red Cross
      Washington, Washington, D.C., United States
  • 1991
    • George Washington University
      • Children's National Medical Center
      Washington, Washington, D.C., United States