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Dive into the research topics where Kristin Baird is active.

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Featured researches published by Kristin Baird.


Cancer Research | 2005

Gene Expression Profiling of Human Sarcomas: Insights into Sarcoma Biology

Kristin Baird; Sean Davis; Cristina R. Antonescu; Ursula Harper; Robert L. Walker; Yidong Chen; Arthur A. Glatfelter; Paul H. Duray; Paul S. Meltzer

Sarcomas are a biologically complex group of tumors of mesenchymal origin. By using gene expression microarray analysis, we aimed to find clues into the cellular differentiation and oncogenic pathways active in these tumors as well as potential biomarkers and therapeutic targets. We examined 181 tumors representing 16 classes of human bone and soft tissue sarcomas on a 12,601-feature cDNA microarray. Remarkably, 2,766 probes differentially expressed across this sample set clearly delineated the various tumor classes. Several genes of potential biological and therapeutic interest were associated with each sarcoma type, including specific tyrosine kinases, transcription factors, and homeobox genes. We also identified subgroups of tumors within the liposarcomas, leiomyosarcomas, and malignant fibrous histiocytomas. We found significant gene ontology correlates for each tumor group and identified similarity to normal tissues by Gene Set Enrichment Analysis. Mutation analysis done on 275 tumor samples revealed that the high expression of epidermal growth factor receptor (EGFR) in certain tumors was not associated with gene mutations. Finally, to further the investigation of human sarcoma biology, we have created an online, publicly available, searchable database housing the data from the gene expression profiles of these tumors (http://watson.nhgri.nih.gov/sarcoma), allowing the user to interactively explore this data set in depth.


Pediatrics | 2012

Allowing Adolescents and Young Adults to Plan Their End-of-Life Care

Lori Wiener; Sima Zadeh; Haven Battles; Kristin Baird; Elizabeth D. Ballard; Janet Osherow; Maryland Pao

OBJECTIVE: The objective of this study was to assess and compare the usefulness, helpfulness, and stress associated with reviewing a previously adapted advance care planning guide, My Thoughts, My Wishes, My Voice, in comparison with the widely used adult document Five Wishes by adolescents and young adults (AYAs) living with a serious illness. METHODS: Fifty-two participants (age 16–28) living with metastatic or recurrent cancer or HIV infection (acquired at birth or early in life) were presented pages randomly from My Thoughts, My Wishes, My Voice and, Five Wishes, and asked to rank 25 items on several factors, including how likely they would be to complete each statement. Participant opinion on suggested changes in content, design, format, and style was obtained and resulted in development of a new document. RESULTS: AYAs living with a life-threatening illness want to be able to choose and record (1) the kind of medical treatment they want and do not want, (2) how they would liked to be cared for, (3) information for their family and friends to know, and (4) how they would like to be remembered. CONCLUSIONS: AYA views of what should be included in an advance care planning guide were incorporated into a new document, Voicing My Choices, that provides youth, families and providers an opportunity to reduce the silence around the dying process by allowing an opportunity to share one’s voice. We provide guidance on how to incorporate this tool into care.


Blood | 2015

Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T cell depleted stem cell transplantation

Nirali N. Shah; Kristin Baird; Cynthia Delbrook; Thomas A. Fleisher; Mark E. Kohler; Shakuntala Rampertaap; Kimberly Lemberg; Carolyn Katovich Hurley; David E. Kleiner; Melinda S. Merchant; Stefania Pittaluga; Marianna Sabatino; David F. Stroncek; Alan S. Wayne; Hua Zhang; Terry J. Fry; Crystal L. Mackall

Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL-activated NK cells (aNK-DLI) following HLA-matched, T-cell-depleted (1-2 × 10(4) T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3(+)-depleted, CD56(+)-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL(+)IL-15Rα(+) artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104.


Journal of Clinical Oncology | 2012

Phase I Trial and Pharmacokinetic Study of Lexatumumab in Pediatric Patients With Solid Tumors

Melinda S. Merchant; James I. Geller; Kristin Baird; Alexander J. Chou; Susana Galli; Ava Charles; Martha Amaoko; Eunice H. Rhee; Anita P. Price; Leonard H. Wexler; Paul A. Meyers; Brigitte C. Widemann; Maria Tsokos; Crystal L. Mackall

PURPOSE Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors. PATIENTS AND METHODS This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age≤21 years with recurrent or progressive solid tumors. RESULTS Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response. CONCLUSION Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.


Pediatric Clinics of North America | 2010

Chronic Graft-Versus- Host Disease (GVHD) in Children

Kristin Baird; Kenneth R. Cooke; Kirk R. Schultz

Five-year survival rates for childhood cancer now exceed 80% and with the significant progress made by the transplant community in developing less toxic conditioning regimens and in the treatment of posttransplant complications, allo-hematopoietic stem cell transplantation (HSCT) contributes significantly to that population of long-term survivors. In this context, the acute and long-term toxicities of chronic graft-versus-host disease (cGVHD) have an ever-increasing effect on organ function, quality of life, and survival; patients and families who initially felt great relief to be cured from the primary disease, now face the challenge of a chronic debilitating illness for which preventative and treatment strategies are suboptimal. Hence, the development of novel strategies that reduce and or control cGVHD, preserve graft-versus-tumor effects, facilitate engraftment and immune reconstitution, and enhance survival after allo-HSCT represents one of the most significant challenges facing physician-scientists and patients.


Biology of Blood and Marrow Transplantation | 2009

Voriconazole-Induced Phototoxicity Masquerading as Chronic Graft-versus-Host Disease of the Skin in Allogeneic Hematopoietic Cell Transplant Recipients

Asha R. Patel; Maria L. Turner; Kristin Baird; Juan Gea-Banacloche; Sandra A. Mitchell; Steven Z. Pavletic; Barbara Wise; Edward W. Cowen

Systemic fungal infections pose a significant risk to patients following allogeneic hematopoietic cell transplantation (alloHCT). Voriconazole (Vfend, Pfizer) is an oral second-generation triazole antifungal agent that offers a broad spectrum of coverage against fungal species and is frequently utilized in the post-HCT setting. Herein, we describe 5 patients who were initially believed to be experiencing a flare of cutaneous chronic graft-versus-host disease (cGVHD), but who were actually exhibiting phototoxicity caused by voriconazole. A high index of suspicion for this adverse reaction in the post-alloHCT setting will prevent misdiagnosis and avoid inappropriate therapy for cGVHD.


Clinical Cancer Research | 2016

Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors

Melinda S. Merchant; Matthew Wright; Kristin Baird; Leonard H. Wexler; Carlos Rodriguez-Galindo; Donna Bernstein; Cindy Delbrook; Maya Lodish; Rachel J. Bishop; Jedd D. Wolchok; Howard Streicher; Crystal L. Mackall

Purpose: Ipilimumab is a first-in-class immune checkpoint inhibitor approved for treatment of metastatic melanoma but not studied in children until this phase I protocol. Experimental Design: This study examined safety, pharmacokinetics, and immunogenicity, and immune correlates of ipilimumab administered to subjects ≤21 years old with recurrent or progressive solid tumors. Dose escalation cohorts received 1, 3, 5, or 10 mg/m2 intravenously every 3 weeks in a 3 + 3 design. Response was assessed after 6 weeks and 12 weeks, and then every 3 months. Treatment was continued until disease progression or unacceptable toxicity. Results: Thirty-three patients received 72 doses of ipilimumab. Patients enrolled had melanoma (n = 12), sarcoma (n = 17), or other refractory solid tumors (n = 4). Immune-related adverse events included pancreatitis, pneumonitis, colitis, endocrinopathies, and transaminitis with dose-limiting toxicities observed at 5 and 10 mg/kg dose levels. Pharmacokinetics revealed a half-life of 8 to 15 days. At day 21, subjects had increased levels of cycling T cells, but no change in regulatory T-cell populations. Six subjects had confirmed stable disease for 4 to 10 cycles (melanoma, osteosarcoma, clear cell sarcoma, and synovial sarcoma). Conclusions: Ipilimumab was safely administered to pediatric patients using management algorithms for immune-related toxicities. The spectrum of immune-related adverse events is similar to those described in adults; however, many of the pediatric toxicities were evident after a single dose. Although no objective tumor regressions were observed with ipilimumab as a single agent, subjects with immune-related toxicities had an increased overall survival compared with those who showed no evidence of breaking tolerance. Clin Cancer Res; 22(6); 1364–70. ©2015 AACR.


The Journal of Allergy and Clinical Immunology | 2012

Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency

Chimene Kesserwan; Robert A. Sokolic; Edward W. Cowen; Elizabeth Garabedian; Kerstin Heselmeyer-Haddad; Chyi Chia Richard Lee; Stefania Pittaluga; Clarymar Ortiz; Kristin Baird; Dolores Lopez-Terrada; Julia A. Bridge; Alan S. Wayne; Fabio Candotti

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is a rare malignant skin tumor associated with a characteristic chromosomal translocation (t[17;22][q22;q13]) resulting in the COL1A1-platelet-derived growth factor β(PDGFB) fusion gene. This malignancy is rarely diagnosed in childhood. OBJECTIVE We observed an unexpected high incidence of this DFSP in children affected with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) and set out to evaluate the association of these 2 clinical entities. METHODS Twelve patients with ADA-SCID were evaluated with a complete dermatologic examination and skin biopsy when indicated. Conventional cytogenetic and molecular analyses (fluorescence in situ hybridization, RT-PCR, or both) were performed when possible. RESULTS Eight patients were found to have DFSP. Six patients had multicentric involvement (4-15 lesions), primarily of the trunk and extremities. Most lesions presented as 2- to 15-mm, round atrophic plaques. Nodular lesions were present in 3 patients. In all cases CD34 expression was diffusely positive, and diagnosis was confirmed either by means of cytogenetic analysis, molecular testing, or both. The characteristic DFSP-associated translocation, t(17;22)(q22;q13), was identified in 6 patients; results of fluorescence in situ hybridization were positive for fusion of the COL1A1 and PDGFB loci in 7 patients; and RT-PCR showed the COL1A1-PDGFB fusion transcript in 6 patients. CONCLUSIONS We describe a previously unrecognized association between ADA-SCID and DFSP with unique features, such as multicentricity and occurrence in early age. We hypothesize that the t(17;22)(q22;q13) translocation that results in dermal overexpression of PDGFB and favors the development of fibrotic tumors might arise because of the known DNA repair defect in patients with ADA-SCID. Although the natural course of DFSP in the setting of ADA-SCID is unknown, this observation should prompt regular screening for DFSP in patients with ADA-SCID.


Leukemia | 2012

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity

Lana Grković; Kristin Baird; Seth M. Steinberg; Kirsten M. Williams; Drazen Pulanic; Edward W. Cowen; Sandra A. Mitchell; Fran Hakim; Kathryn J. Martires; Daniele Avila; Tiffani Taylor; Rachel B. Salit; Scott D. Rowley; Dan Zhang; Daniel H. Fowler; Michael R. Bishop; Ronald E. Gress; Steven Z. Pavletic

Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P=0.043), higher platelets (P=0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinicians intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P=0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.


Archives of Dermatology | 2011

Localization of Sclerotic-type Chronic Graft-vs-Host Disease to Sites of Skin Injury Potential Insight Into the Mechanism of Isomorphic and Isotopic Responses

Kathryn J. Martires; Kristin Baird; Deborah E. Citrin; Fran Hakim; Steven Z. Pavletic; Edward W. Cowen

BACKGROUND The mechanisms responsible for the variable manifestations of chronic cutaneous graft-vs-host disease (cGVHD) are poorly understood. Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury (isomorphic and isotopic responses), a recognized phenomenon in morphea, suggests a potential common pathway between cGVHD and other sclerotic skin conditions. OBSERVATIONS Four cases of sclerotic-type cGVHD developed at the site of disparate skin injuries (ionizing radiotherapy, repeated needle sticks, central catheter site, and varicella-zoster virus infection). We review the spectrum of previously reported cases of sclerotic and nonsclerotic cGVHD relating to external forces on the skin. CONCLUSIONS Localization of sclerotic-type cGVHD may occur after many types of skin injury, including UV and ionizing radiotherapy, needle sticks, viral infection, and pressure or friction. Recognition of this phenomenon may be helpful for the early diagnosis of sclerotic disease. Recent insights into the immunological consequences of minor skin injury may provide important clues to the underlying pathogenesis of cGVHD-mediated skin disease.

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Edward W. Cowen

National Institutes of Health

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Steven Z. Pavletic

National Institutes of Health

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Sandra A. Mitchell

National Institutes of Health

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Seth M. Steinberg

National Institutes of Health

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Ronald E. Gress

National Institutes of Health

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Daniele Avila

National Institutes of Health

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Alan S. Wayne

University of Southern California

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Kirsten M. Williams

Children's National Medical Center

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Leora E. Comis

National Institutes of Health

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