My principal research interests have been the assessment of the immunological consequences of hematopoietic stem cell transplantation including both acute and chronic graft versus host disease and immune reconstitution and the use of hematopoietic stem cell transplantation to treat genetic diseases. My laboratory was the first to suggest that chronic graft versus host disease was an autoimmune disease directed at histocompatibility antigens shared by donors and recipients. The observation leaded to the assessment of the role of thymic dysfunction in the pathogenesis of chronic graft versus host disease. As a pediatric immunologist I have investigated the role of hematopoietic stem cell transplantation initially in the treatment of primary immune deficiency diseases and later the treatment of metabolic diseases, which lead to my involvement in the early gene transfer clinical trials.

Academic Appointments

Boards, Advisory Committees, Professional Organizations

  • Chairperson, Data Safety Monitoring Board for Cell and Gene Therapy, National Heart, Lung and Blood Institute (2002 - Present)


All Publications

  • The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Cooke, K. R., Luznik, L., Sarantopoulos, S., Hakim, F. T., Jagasia, M., Fowler, D. H., van den Brink, M. R., Hansen, J. A., Parkman, R., Miklos, D. B., Martin, P. J., paczesny, s., Vogelsang, G., Pavletic, S., Ritz, J., Schultz, K. R., Blazar, B. R. 2017; 23 (2): 211-234
  • The Biology of Chronic Graft-Versus-Host Disease: a Task Force Report From the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease. Biology of blood and marrow transplantation Cooke, K. R., Luznik, L., Sarantopoulos, S., Hakim, F. T., Jagasia, M., Fowler, D. H., van den Brink, M. R., Hansen, J. A., Parkman, R., Miklos, D. B., Martin, P. J., paczesny, s., Vogelsang, G., Pavletic, S., Ritz, J., Schultz, K. R., Blazar, B. R. 2016


    Chronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes. The biology of chronic GVHD remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD.

    View details for DOI 10.1016/j.bbmt.2016.09.023

    View details for PubMedID 27713092

  • National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Paczesny, S., Hakim, F. T., Pidala, J., Cooke, K. R., Lathrop, J., Griffith, L. M., Hansen, J., Jagasia, M., Miklos, D., Pavletic, S., Parkman, R., Russek-Cohen, E., Flowers, M. E., Lee, S., Martin, P., Vogelsang, G., Walton, M., Schultz, K. R. 2015; 21 (5): 780-792


    Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, or of a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include the following: (1) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity; (2) prognostic risk to develop chronic GVHD; and (3) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well documented following established quality control guidelines for sample acquisition, processing, preservation, and testing, at intervals that are both calendar and event driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for use in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a 4-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines.

    View details for DOI 10.1016/j.bbna.2015.01.003

    View details for Web of Science ID 000353856700002

    View details for PubMedID 25644957

  • Primary Immune Deficiency Treatment Consortium (PIDTC) report. journal of allergy and clinical immunology Griffith, L. M., Cowan, M. J., Notarangelo, L. D., Kohn, D. B., Puck, J. M., Pai, S., Ballard, B., Bauer, S. C., Bleesing, J. J., Boyle, M., Brower, A., Buckley, R. H., van der Burg, M., Burroughs, L. M., Candotti, F., Cant, A. J., Chatila, T., Cunningham-Rundles, C., Dinauer, M. C., Dvorak, C. C., Filipovich, A. H., Fleisher, T. A., Bobby Gaspar, H., Gungor, T., Haddad, E., Hovermale, E., Huang, F., Hurley, A., Hurley, M., Iyengar, S., Kang, E. M., Logan, B. R., Long-Boyle, J. R., Malech, H. L., McGhee, S. A., Modell, F., Modell, V., Ochs, H. D., O'Reilly, R. J., Parkman, R., Rawlings, D. J., Routes, J. M., Shearer, W. T., Small, T. N., Smith, H., Sullivan, K. E., Szabolcs, P., Thrasher, A., Torgerson, T. R., Veys, P., Weinberg, K., Zuniga-Pflucker, J. C. 2014; 133 (2): 335-347 e11


    The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

    View details for DOI 10.1016/j.jaci.2013.07.052

    View details for PubMedID 24139498

  • T lymphocyte abnormalities in juvenile systemic sclerosis patients CLINICAL IMMUNOLOGY Reiff, A., Weinberg, K. I., Triche, T., Masinsin, B., Mahadeo, K. M., Lin, C., Brown, D., Parkman, R. 2013; 149 (1): 146-155


    Multi-center evaluations of pediatric patients with juvenile systemic sclerosis (jSSc) have suggested that the pathogenesis of jSSc may differ from that of systemic sclerosis (SSc) in adult patients. Therefore, we undertook to identify abnormalities in the T lymphocytes of jSSc patients and to determine if they differed from the abnormalities reported in the T lymphocytes of adult SSc patients. We identified decreases in the frequency of resting regulatory T lymphocytes and an increased frequency of CD45RA expressing effector memory (EMRA) CD4 T lymphocytes, which were characterized by an increased frequency of CCR7 protein expressing cells. Neither the increases in the EMRA subpopulation nor the increased CCR7 protein expression have been reported in adult SSc patients. The decrease in resting regulatory T lymphocytes in jSSc patients may permit the expansion of the disease initiating CD4 T lymphocytes present in the CCR7 expressing EMRA CD4 T lymphocyte subpopulation.

    View details for DOI 10.1016/j.clim.2013.07.005

    View details for Web of Science ID 000325510100016

    View details for PubMedID 23994768

  • Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans BLOOD Candotti, F., Shaw, K. L., Muul, L., Carbonaro, D., Sokolic, R., Choi, C., Schurman, S. H., Garabedian, E., Kesserwan, C., Jagadeesh, G. J., Fu, P., Gschweng, E., Cooper, A., Tisdale, J. F., Weinberg, K. I., Crooks, G. M., Kapoor, N., Shah, A., Abdel-Azim, H., Yu, X., Smogorzewska, M., Wayne, A. S., Rosenblatt, H. M., Davis, C. M., Hanson, C., Rishi, R. G., Wang, X., Gjertson, D., Yang, O. O., Balamurugan, A., Bauer, G., Ireland, J. A., Engel, B. C., Podsakoff, G. M., Hershfield, M. S., Blaese, R. M., Parkman, R., Kohn, D. B. 2012; 120 (18): 3635-3646


    We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

    View details for DOI 10.1182/blood-2012-02-400937

    View details for Web of Science ID 000311624800007

    View details for PubMedID 22968453

  • Anti-CD52 Antibody-Mediated Immune Ablation with Autologous Immune Recovery for the Treatment of Refractory Juvenile Polymyositis JOURNAL OF CLINICAL IMMUNOLOGY Reiff, A., Shaham, B., Weinberg, K. I., Crooks, G. M., Parkman, R. 2011; 31 (4): 615-622


    Autologous hematopoietic stem cell transplantation (HSCT) has been used for the treatment of both adult and pediatric autoimmune diseases. However, HSCT has significant side effects (neutropenia, thrombocytopenia, infertility, cardiotoxicity) and costs (HSC collection/harvesting, blood product support). In an attempt to avoid the toxicities and costs associated with HSCT, we investigated whether immune ablation similar to that achieved following myeloablative HSCT could be achieved by the intensive administration of an anti-CD52 antibody (Campath-1H antibody). The first patient treated with the treatment regime, who had refractory juvenile polymyositis, achieved immune ablation (the elimination of pre-therapy antigen-specific T lymphocyte immunity) and has had stable clinical improvement for more than 6 years.

    View details for DOI 10.1007/s10875-011-9533-7

    View details for Web of Science ID 000293851600012

    View details for PubMedID 21541793

  • Study of thymic size and function in children and adolescents with treatment refractory systemic sclerosis eligible for immunoablative therapy CLINICAL IMMUNOLOGY Reiff, A., Krogstad, P., Moore, S., Shaham, B., Parkman, R., Kitchen, C., Weinberg, K. 2009; 133 (3): 295-302


    Following hematopoietic stem cell transplantation (HSCT), thymic reconstitution of peripheral T lymphocytes is essential to avoid a chronically immunodeficient state and disease recurrence. The purpose of this study was to determine if children and adolescents with treatment refractory SSc, awaiting HSCT, have sufficient thymic function to reconstitute T lymphocyte function after transplantation. Thirteen children with systemic scleroderma were enrolled and assessed by physical exam, chest MRI, measurement of autoantibodies, B and T cell immuno-phenotyping, and quantization of T cell receptor rearrangement excision circles (TREC) as a marker of thymopoiesis. MRI detected thymic tissue in 9/13 children. TREC levels were detectable in all but one child but were significantly reduced (p<0.001) when compared to a control population. SSc patients also had a reduced percentage of naïve (CD45RA+CD31+) CD4+ T lymphocytes, further indicating diminished thymopoiesis. Our data suggest that thymic function in children with SSc might be insufficient for an adequate immunoreconstitution following transplantation in some patients. A thorough evaluation of immune and thymic functions to identify those patients prior to HSCT is recommended.

    View details for DOI 10.1016/j.clim.2009.08.010

    View details for Web of Science ID 000271779600002

    View details for PubMedID 19793681

  • Progressive declines in neurocognitive function among survivors of hematopoietic stem cell transplantation for pediatric hematologic malignancies JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Shah, A. J., Epport, K., Azen, C., Killen, R., Wilson, K., De Clerck, D., Crooks, G., Kapoor, N., Kohn, D. B., Parkman, R., Weinberg, K. I. 2008; 30 (6): 411-418


    Neurocognitive function of pediatric patients is of great concern after hematopoietic stem cell transplantation (HSCT). We evaluated the neurocognitive function of pediatric patients pre-HSCT, 1, 3, and 5 years post-HSCT. All patients had a hematologic malignancy and received therapy to their central nervous system. Healthy siblings were tested as a comparison group. Pediatric patients with a hematologic malignancy did not have a significant decrease in their cognitive function before HSCT compared with their siblings except in areas of academic achievement. Our study population had significant declines in visual motor skills and memory test scores within the first year post-HSCT. By 3 years post-HSCT, there was an improvement in the visual motor development scores and memory scores, but there were new deficits in verbal skills. By 5 years post-HSCT, there were progressive declines in verbal skills (P=0.005), performance skills (0.04), and new deficits seen in long-term verbal memory scores (0.04). On the basis of the raw scores, most of these tests showed that patients had an inability to acquire new skills at a rate comparable to their age-matched healthy peers. However, long-term memory scores showed definite declines. The greatest decline in neurocognitive function occurred in those patients who received cranial irradiation either as part of their initial therapy or as part of their HSCT conditioning. Pediatric patients who received HSCT for hematologic malignancies have neurocognitive deficiencies that are both acute and chronic. Although some patients have acute deficits that appear and improve over time, other patients have progressive declines in neurocognitive function that are chronic.

    View details for Web of Science ID 000256535200001

    View details for PubMedID 18525456

  • The effects of Campath 1H upon graft-versus-host disease, infection, relapse, and immune reconstitution in recipients of pediatric unrelated transplants BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Shah, A. J., Kapoor, N., Crooks, G. M., Weinberg, K. I., Azim, H. A., Killen, R., Kuo, L., Rushing, T., Kohn, D. B., Parkman, R. 2007; 13 (5): 584-593


    Graft-versus-host disease (GVHD) is a cause of serious morbidity and mortality in >50% of recipients of unrelated hematopoietic stem cell transplantation (HSCT). We performed a trial using Campath 1 H pre- and post-HSCT in an attempt to decrease the incidence of GVHD without increasing the risk of infection or relapse. Patients were retrospectively compared to a population of patients who received antithymocyte globulin (ATG) pre- and post-HSCT. Twenty-seven patients were evaluated for this study. Fourteen patients received Campath 1H and 13 patients received ATG. Demographics of patients who received Campath 1H consisted of 9 males and 5 females, with a median age of 13 years (3-17.8 years). Thirteen patients received unrelated bone marrow and 1 patient received unrelated PBSC. Demographics of patients receiving ATG consisted of 9 males, 4 females with a median age of 7.4 years (21 months-19 years). Twelve patients received unrelated bone marrow and 1 patient received unrelated PBSC. Diagnoses were similar between the 2 groups. Patients who received Campath1H received a total dose of 52 mg/m(2) pre-HSCT and 20 mg/m(2) post-HSCT. Patients who received ATG received a total dose of 60 mg/kg pre-HSCT and 100 mg/kg post-HSCT. GVHD prophylaxis and supportive care measures were similar in both groups, including aggressive antimicrobial therapy. There was a significant difference in the incidence of severe (grade III and grade IV) GVHD between the 2 groups (Campath [0 of 14] versus ATG [6 of 13], P = .006). Among the patients who were transplanted for leukemia, there was no significant difference between the 2 groups in terms of relapse (Campath [2 of 14] versus ATG [4 of 9], P = 0.16). The 100-day survival between the 2 groups was not significantly different. Patients receiving Campath 1H had the presence of CD3(+) T cells (>30 cells/mL) in their peripheral blood later than in those who received ATG (64.5 days [Campath 1H] versus 27days [ATG], P = .001). The median time to the development of a normal PHA response occurred later in the Campath 1H arm (283 days[(Campath 1H] versus 88 days [ATG], P = .0001). The median time to an antigen specific response also occurred later in those receiving Campath 1H (365 days [Campath 1H] versus 150 days [ATG], P = .004). There was no significant difference between the 2 groups in terms of fungal or viral infections. Campath 1H is effective in decreasing the incidence of GVHD without increasing the risk of relapse. Although there is a significant delay in immune reconstitution, there was no increase in infectious complications or relapse in recipients of Campath 1H. Further studies are warranted to assess if a lack of difference in infection rates are still demonstrated in larger cohorts.

    View details for DOI 10.1016/j.bbmt.2007.01.076

    View details for Web of Science ID 000246252600010

    View details for PubMedID 17448918