Clinical Focus

  • Blood and Marrow Transplantation, Pediatric
  • Hematology/Oncology/Stem Cell Transplant, Pediatric
  • Pediatric Hematology-Oncology

Academic Appointments

Administrative Appointments

  • Clinical Director, Pediatric Stem Cell Transplant (2008 - Present)
  • Section chief, Pediatric Stem Cell Transplantation (2010 - Present)

Honors & Awards

  • President's award, Best Woman Candidate in India in Medical School Examinations (1979)

Professional Education

  • Residency:Children's Hospital Medical Center (1995) OH
  • Residency:MGM Medical College (1983) India
  • Medical Education:MGM Medical College (1983) India
  • Internship:MGM Medical College (1981) India
  • MD, Indore University, Pediatrics (1983)
  • M.B.B.S, Indore University (1980)

Community and International Work

  • volunteer donor recruitment for bone marrow transplants


    increasing the minority participation in the unrelated volunteer donor pool

    Partnering Organization(s)


    Populations Served

    Indian subcontinent


    Bay Area

    Ongoing Project


    Opportunities for Student Involvement


Research & Scholarship

Current Research and Scholarly Interests

I trained extensively in India as a pediatric Hematologist-Oncologist.Due to a strong interest in pursuing translational research in the field I chose to come to USA.During my stay at children's hospital medical center (CHMC) in Cincinnati, Ohio I developed a strong interest in the field of stem cell biology and transplantation.My experience in this field also included extensive training and expertise obtained at the hospital for sick children,Toronto,Canada and National institutes of health(NIH),USA. At the hospital for sick children I learned and developed stem cell assays and invivo models of human hematopoiesis that were critical in understanding of stem cell biology and its clinical applications. At the NIH I spent Two years with Drs. Nienhuis and Cynthia Dunbar and developed gene transfer assays in Hematopoietic cells. At the NIH I also worked on developing the mammalian models for in vivo gene tranfer in hematopoietic cells.During this time we also published our work on chronic myeloid leukemia addressing the role of interaction of stromal cells with hematopoietic cells in the bone marrow.This publication defined conditions to favor the growth of benign hematopoietic cells in patients with chronic myeloid leukemia.
At CHMC,Cincinnati,I established the stem cell biology laboratory to furthur investigate the field of Hematopoietic stem cells specifically involving the umbilical cord blood.I started the clinical Umbilical cord blood transplant program at CHMC.Through my research efforts we were able to develop a sterile system for collection and use of cord blood cells. This endeavor later contributed in establishing methods to collect and store cord blood for clinical use.In the laboratory we were able to set up the assays to identify and collect highly purified hematopoietic cells from the cord blood. The engraftment and expansion potential of the cord blood derived hematopoietic cells was studied in the immune deficient mice.Also these models were then used to develop assays for gene tranfer in Fanconi Anemia.Currently, at Stanford my focus is to develop clinical research protocols to reduce toxicity from high doses of chemotherapy and radiation therapy,graft manipulation to reduce complications from graft vs. host disease and study late complications of transplant.
Thoughout my academic career,I have maintained my interest and committment in providing not only excellent patient care but to provide basic research data which can be utilized to improve patient care at the end.

Clinical Trials

  • Long Term Effects On Recipients of Hematopoietic Stem Cell Transplantation Recruiting

    This project allows for the systematic collection and analysis of long-term follow-up clinical parameters in children who have received a stem cell transplant. The data collected will assist in determining appropriate intervention and treatment plans for patients enrolled on this study. In addition, future patients may benefit by having the ability to anticipate problems and develop methods of prevention or early intervention.

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  • Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes Recruiting

    This randomized phase II trial studies how well donor umbilical cord blood transplant with or without ex-vivo expanded cord blood progenitor cells works in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy stem cells and ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded cord blood progenitor cells is more effective than giving a donor umbilical cord blood transplant alone.

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  • Haploid Allogeneic Transplant Using the CliniMACS System Not Recruiting

    To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant. To assess the incidence of acute GvHD during the first 100 days after transplantation.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • A Study of Safety and Pharmacokinetics of Repeated Dose of Micafungin as Antifungal Prophylaxis in Children and Adolescents Who Undergo Hematopoietic Stem Cell Transplant Not Recruiting

    The study will evaluate PK and safety of two dose levels of Micafungin (FK463) as Antifungal prophylaxis in children and adolescents undergoing HSCT

    Stanford is currently not accepting patients for this trial. For more information, please contact Laila Craveiro, (650) 724 - 9179.

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  • Phase I/II MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell Recruiting

    For patients with hematologic malignancies undergoing allogeneic myeloablative (MA) HCT with a T cell depleted graft, the infusion of naturally occurring regulatory T cells with conventional T cells (T cell addback) in pre-defined doses and ratios will reduce the incidence of acute graft vs host disease while augmenting the graft vs leukemia effect and improving immune reconstitution.

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  • A Phase II Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease Not Recruiting

    We hypothesize the addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, and enable a more rapid and effective steroid taper.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • Sirolimus and Mycophenolate Mofetil in Preventing GVHD in Patients With Hematologic Malignancies Undergoing HSCT Recruiting

    This pilot phase I/II trial studies the side effects and how well sirolimus and mycophenolate mofetil work in preventing graft versus host disease (GvHD) in patients with hematologic malignancies undergoing hematopoietic stem cell transplant (HSCT). Biological therapies, such as sirolimus and mycophenolate mofetil, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Giving sirolimus and mycophenolate mofetil after hematopoietic stem cell transplant may be better in preventing graft-versus-host disease.

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  • Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study Not Recruiting

    Single arm, open-label study to provide Defibrotide to patients diagnosed with VOD. Defibrotide is no longer available though the Emergency Use IND mechanism (also known as compassionate use, or single patient named use). This protocol is the only mechanism by which Defibrotide can be made available to patients in the U.S.

    Stanford is currently not accepting patients for this trial. For more information, please contact Physician Referrals, 650-723-0822.

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  • Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients Not Recruiting

    The purpose of this study is to (1) demonstrate the efficacy and safety (toxicity) of 25 mg/kg/day of Defibrotide in patients with severe veno-occlusive disease (sVOD) and (2) evaluate serum and endothelial markers of VOD through the analysis of blood samples.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • The Adv Halt Trial Not Recruiting

    The primary objective of this study is to evaluate the safety and efficacy of preemptive treatment with CMX001 versus placebo for the prevention of AdV disease in recipients of HSCT with asymptomatic AdV viremia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Julia Buckingham, (650) 736 - 1556.

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  • Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT Not Recruiting

    GVHD prophylaxis of sirolimus and mycophenolate mofetil for patients undergoing matched related allogeneic transplant for acute and chronic leukemia, MDS, high risk NHL and HL

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by dsDNA Viruses Not Recruiting

    CMX001 is an orally administered lipid conjugate of the synthetic nucleotide analog cidofovir (CDV). The conjugate is believed to be absorbed in the small intestine then delivered to target organs throughout the body where it crosses cell membranes by facilitated and passive diffusion. Inside the cell, CMX001 is cleaved by intracellular phospholipases to release CDV which is converted to the active antiviral agent, CDV-diphosphate (CDV-PP), by intracellular anabolic kinases. Adults and adolescents, regardless of viral infection/disease, will have a maximum weekly dose of 200 mg i.e., 200 mg once weekly OR 100 mg twice weekly; not to exceed 4mg/kg total weekly dose. Pediatric subjects (< 12 years), regardless of viral infection/disease, will have a maximum weekly dose of 4 mg/kg i.e., 4 mg/kg once weekly OR 2 mg/kg twice weekly.

    Stanford is currently not accepting patients for this trial. For more information, please contact Julia Buckingham, (650) 736 - 1556.

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  • Peripheral Blood Stem Cell Transplant vs Bone Marrow Transplant in Individuals With Hematologic Cancers (BMT CTN 0201) Not Recruiting

    The study is designed as a Phase III, randomized, open label, multicenter, prospective, comparative trial of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) versus marrow from unrelated donors for transplantation in patients with hematologic malignancies. Recipients will be stratified by transplant center and disease risk and will be randomized to either the PBSC or marrow arm in a 1:1 ratio.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kate Tierney, (650) 725 - 7063.

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  • Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease Not Recruiting

    To study the effectiveness of an immunosuppressive drug, sirolimus in the treatment of chronic graft versus host disease in combination with prednisone.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402) Not Recruiting

    The study is designed as a phase III, randomized, open label, multicenter, prospective, comparative trial of sirolimus and tacrolimus versus tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis after human leukocyte antigen (HLA)-matched, related, peripheral blood stem cell transplantation in individuals with hematologic cancer. Participants will be stratified by transplant center and will be randomly assigned to the sirolimus/tacrolimus or tacrolimus/methotrexate arms at a 1:1 ratio.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant Not Recruiting

    This phase II trial is studying how well etanercept works in treating young patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant. Etanercept may be effective in treating patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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2016-17 Courses


All Publications

  • A Pediatric Case of T-Cell Prolymphocytic Leukemia PEDIATRIC BLOOD & CANCER Mitton, B., Coutre, S., Willert, J., Schlis, K., Porteus, M., Kharbanda, S., Agarwal-Hashmi, R. 2015; 62 (6): 1061-1062


    T-cell Prolymphocytic Leukemia (T-PLL) is a rare entity, and to date has never been reported in children. Here, we describe the first pediatric case of T-PLL in a 16-year old male and review his clinical course through treatment. He underwent therapy with alemtuzumab and pentostatin, which was successful in inducing initial remission. He then underwent an allogeneic matched sibling stem cell transplant following a myeloablative conditioning regimen and remains disease-free 1.5 years after diagnosis. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/pbc.25336

    View details for Web of Science ID 000353231500025

    View details for PubMedID 25417638

  • A Reduced-Toxicity Regimen Is Associated with Durable Engraftment and Clinical Cure of Nonmalignant Genetic Diseases among Children Undergoing Blood and Marrow Transplantation with an HLA-Matched Related Donor BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Mahadeo, K. M., Weinberg, K. I., Abdel-Azim, H., Miklos, D. B., Killen, R., Kohn, D., Crooks, G. M., Shah, A. J., Kharbanda, S., Agarwal, R., Kapoor, N. 2015; 21 (3): 440-444


    Blood and marrow transplantation (BMT) is a standard curative therapy for patients with nonmalignant genetic diseases. Myeloablative conditioning has been associated with significant regimen-related toxicity (RRT), whereas reduced-intensity conditioning regimens have been associated with graft failure. In this prospective pilot trial conducted at 2 centers between 2006 and 2013, we report the outcome of 22 patients with nonmalignant genetic diseases who were conditioned with a novel reduced-toxicity regimen: i.v. busulfan (16 mg/kg), alemtuzumab (52 mg/m(2)), fludarabine (140 mg/m(2)), and cyclophosphamide (105 mg/kg). The median age of the study population was 3.5 years (range, 5 months to 26 years). No cases of sinusoidal obstruction syndrome, severe or chronic graft-versus-host disease (GVHD), or primary graft failure were reported. Median time to neutrophil engraftment (>500 cells/?L) and platelet engraftment (>20K cells/?L) were 19 (range, 12 to 50) and 23.5 (range, 14 to 134) days, respectively. The median length of follow-up was 3 years (range, .2 to 6.3). The overall survival rates were 95% at 100 days (95% confidence interval, .72 to .99) and 90% at 6 years (95% confidence interval, .68 to .98). RRT and chronic GVHD are significant barriers to BMT for patients with nonmalignant genetic diseases. This alemtuzumab-based reduced-toxicity regimen appears to be promising with durable engraftment, effective cure of clinical disease, low rates of RRT, and no observed chronic GVHD.

    View details for DOI 10.1016/j.bbmt.2014.11.005

    View details for Web of Science ID 000350009500009

    View details for PubMedID 25459642

  • Improved Outcomes after Autologous Bone Marrow Transplantation for Children with Relapsed or Refractory Hodgkin Lymphoma: Twenty Years Experience at a Single Institution BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Garfin, P. M., Link, M. P., Donaldson, S. S., Advani, R. H., Luna-Fineman, S., Kharbanda, S., Porteus, M., Weinberg, K. I., Agarwal-Hashmi, R. 2015; 21 (2): 326-334


    The purpose of this study is to evaluate the survival of pediatric patients undergoing autologous bone marrow transplantation (auBMT) for relapsed or refractory Hodgkin lymphoma (rrHL) and to identify factors that might contribute to their outcome. We reviewed the records and clinical course of 89 consecutive rrHL patients ? 21 years old who underwent auBMT at Stanford Hospitals and Clinics and the Lucile Packard Children's Hospital, Stanford between 1989 and 2012. We investigated, by multiple analyses, patient, disease, and treatment characteristics associated with outcome. Endpoints were 5-year overall and event-free survival. Our findings include that cyclophosphamide, carmustine, and etoposide (CBV) as a conditioning regimen for auBMT is effective for most patients ? 21 years old with rrHL (5-year overall survival, 71%). Transplantation after the year 2001 was associated with significantly improved overall survival compared with our earlier experience (80% compared with 65%). Patients with multiply relapsed disease or with disease not responsive to initial therapy fared less well compared with those with response to initial therapy or after first relapse. Administration of post-auBMT consolidative radiotherapy (cRT) also appears to contribute to improved survival. We are able to conclude that high-dose chemotherapy with CBV followed by auBMT is effective for the treatment of rrHL in children and adolescents. Survival for patients who undergo auBMT for rrHL has improved significantly. This improvement may be because of patient selection and improvements in utilization of radiotherapy rather than improvements in chemotherapy. Further investigation is needed to describe the role of auBMT across the entire spectrum of patients with rrHL and to identify the most appropriate preparative regimen with or without cRT therapy in the treatment of rrHL in young patients.

    View details for DOI 10.1016/j.bbmt.2014.10.020

    View details for Web of Science ID 000348632700018

  • Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hiniker, S. M., Agarwal, R., Modlin, L. A., Gray, C. C., Harris, J. P., Million, L., Kiamanesh, E. F., Donaldson, S. S. 2014; 89 (1): 67-74


    To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen.Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes.All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college.The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.

    View details for DOI 10.1016/j.ijrobp.2014.01.056

    View details for Web of Science ID 000334590500011

    View details for PubMedID 24725690

  • Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies Using a Reduced-Intensity Conditioning Regimen and Third-Party Mesenchymal Stromal Cells BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Kharbanda, S., Smith, A. R., Hutchinson, S. K., McKenna, D. H., Ball, J. B., Lamb, L. S., Agarwal, R., Weinberg, K. I., Wagner, J. E. 2014; 20 (4): 581-586


    Allogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). Six patients were enrolled, including 4 with high-risk sickle cell disease (SCD) and 2 with transfusion-dependent thalassemia major. Conditioning consisted of fludarabine (150 mg/m(2)), melphalan (140 mg/m(2)), and alemtuzumab (60 mg for patients weighing > 30 kg and .9 mg/kg for patients weighing <30 kg). Two patients received HLA 7/8 allele matched bone marrow and 4 received 4-5/6 HLA matched umbilical cord blood as the source of HSCs. MSCs were of bone marrow origin and derived from a parent in 1 patient and from an unrelated third-party donor in the remaining 5 patients. GVHD prophylaxis consisted of cyclosporine A and mycophenolate mofetil. One patient had neutropenic graft failure, 2 had autologous hematopoietic recovery, and 3 had hematopoietic recovery with complete chimerism. The 2 SCD patients with autologous hematopoietic recovery are alive. The remaining 4 died either from opportunistic infection, GVHD, or intracranial hemorrhage. Although no infusion-related toxicity was seen, the cotransplantation of MSCs was not sufficient for reliable engraftment in patients with advanced hemoglobinopathy. Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated. Further investigations into understanding the mechanisms of graft resistance and development of strategies to overcome this barrier are needed to move this field forward.

    View details for DOI 10.1016/j.bbmt.2013.12.564

    View details for Web of Science ID 000333322400022

  • Cytokine and Chemokine Patterns Across 100 Days after Hematopoietic Stem Cell Transplantation in Children BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION DiCarlo, J., Agarwal-Hashmi, R., Shah, A., Kim, P., Craveiro, L., Killen, R., Rosenberg-Hasson, Y., Maecker, H. 2014; 20 (3): 361-369


    We mapped the cytokine response to hematopoietic stem cell transplantation (HSCT) by assaying 51 cytokines and chemokines each week for 100 days in 51 children receiving allogeneic (n = 44) or autologous HSCT (n = 7). Assay values were reported as mean fluorescence intensity (MFI). Log transformation converted MFI to clinically relevant measures (ie, pg/mL). We searched for potential markers of transplant complications by using mixed treatment by subject analysis of variance. Global cytokine secretion in HSCT recipients was significantly lower than in concurrent control patients (n = 11). Coincident with the nadir in WBC count, the concentration of many cytokines declined further by the second and third week. All analytes (except monokine induced by gamma interferon [MIG]) subsequently rebounded by week 4 (coincident with engraftment and recovery of WBC count) but often still remained well below control levels. Concurrent with the collective nadir of multiple cytokines, monocyte chemoattractant protein 1 (MCP-1), growth-regulated oncogene alpha (GRO-a), and leptin surged during weeks 2 to 4. High levels of leptin persisted throughout the 100 post-transplant days. Also during weeks 2 to 4, hepatocyte growth factor (HGF) and IL-6 surged in children with complications but not in those without complications. The peak in HGF was more pronounced in veno-occlusive disease (VOD). HGF and IL-6 secretion rose at least 2 weeks before the clinical diagnosis of VOD or graft-versus-host disease (GVHD). From week 4 onward in all groups, the MFI of the cytokine resistin increased to 5 to 15 times above concurrent control. HGF has now emerged in 3 or more biomarker discovery efforts for GVHD (and in our population for VOD as well). HGF (with or without IL-6) should be investigated as a potential predictive biomarker of VOD or GVHD. Alternatively, the hyperinflammatory "signature" provided by a multicytokine assay may be predictive.

    View details for DOI 10.1016/j.bbmt.2013.11.026

    View details for Web of Science ID 000332816700011

  • Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: Results of the first 2 years JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Kwan, A., Church, J. A., Cowan, M. J., Agarwal, R., Kapoor, N., Kohn, D. B., Lewis, D. B., McGhee, S. A., Moore, T. B., Stiehm, E. R., Porteus, M., Aznar, C. P., Currier, R., Lorey, F., Puck, J. M. 2013; 132 (1): 140-U245


    Assay of T-cell receptor excision circles (TRECs) in dried blood spots obtained at birth permits population-based newborn screening (NBS) for severe combined immunodeficiency (SCID).We sought to report the first 2 years of TREC NBS in California.Since August 2010, California has conducted SCID NBS. A high-throughput TREC quantitative PCR assay with DNA isolated from routine dried blood spots was developed. Samples with initial low TREC numbers had repeat DNA isolation with quantitative PCR for TRECs and a genomic control, and immunophenotyping was performed within the screening program for infants with incomplete or abnormal results. Outcomes were tracked.Of 993,724 infants screened, 50 (1/19,900 [0.005%]) had significant T-cell lymphopenia. Fifteen (1/66,250) required hematopoietic cell or thymus transplantation or gene therapy; these infants had typical SCID (n = 11), leaky SCID or Omenn syndrome (n = 3), or complete DiGeorge syndrome (n = 1). Survival to date in this group is 93%. Other T-cell lymphopenic infants had variant SCID or combined immunodeficiency (n = 6), genetic syndromes associated with T-cell impairment (n = 12), secondary T-cell lymphopenia (n = 9), or preterm birth (n = 8). All T-cell lymphopenic infants avoided live vaccines and received appropriate interventions to prevent infections. TREC test specificity was excellent: only 0.08% of infants required a second test, and 0.016% required lymphocyte phenotyping by using flow cytometry.TREC NBS in California has achieved early diagnosis of SCID and other conditions with T-cell lymphopenia, facilitating management and optimizing outcomes. Furthermore, NBS has revealed the incidence, causes, and follow-up of T-cell lymphopenia in a large diverse population.

    View details for DOI 10.1016/j.jaci.2013.04.024

    View details for Web of Science ID 000321052300019

    View details for PubMedID 23810098

  • Pathological evidence of Wolman's disease following hematopoietic stem cell transplantation despite correction of lysosomal acid lipase activity BONE MARROW TRANSPLANTATION Gramatges, M. M., Dvorak, C. C., Regula, D. P., Enns, G. M., Weinberg, K., Agarwal, R. 2009; 44 (7): 449-450

    View details for DOI 10.1038/bmt.2009.57

    View details for Web of Science ID 000270933000007

    View details for PubMedID 19308038

  • Nontuberculous Mycobacteria Infections in Immunocompromised Patients Single Institution Experience JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Wei, M. C., Banaei, N., Yakrus, M. A., Stoll, T., Gutierrez, K. M., Agarwal, R. 2009; 31 (8): 556-560


    Disseminated infection due to nontuberculous Mycobacterium (NTM) species is rare in pediatrics. Here we report 6 infections affecting 5 patients at a single institution in an immunocompromised population of pediatric oncology and stem cell transplant recipients. The patients presented within a 1-year period with catheter-associated bacteremia. New pulmonary nodules were noted in 4 of the 5 patients. All of the infections were due to rapidly growing NTM. Patients were successfully treated with removal of the infected catheter and combination antibiotic therapy. There are currently no consensus guidelines for treatment of NTM infections in this population, and a therapeutic approach is presented here.

    View details for Web of Science ID 000268815000006

    View details for PubMedID 19641470

  • High-dose chemotherapy followed by stem cell rescue for high-risk germ cell tumors: the Stanford experience BONE MARROW TRANSPLANTATION Agarwal, R., Dvorak, C. C., Stockerl-Goldstein, K. E., Johnston, L., Srinivas, S. 2009; 43 (7): 547-552


    Germ cell tumors carry an excellent prognosis with platinum-based therapy upfront. The patients who either relapse or demonstrate refractoriness to platinum pose a challenge. There exist many reports in the literature on the use of high-dose chemotherapy and stem cell rescue improving the outcome in patients with relapsed germ cell tumors. However, the reports have great variability in the patient selection, prior treatments, the choice of the conditioning regimen and variability of the doses within the same regimen. In this report, we present 37 patients who underwent a uniform protocol of high-dose chemotherapy with stem cell rescue. Stem cell mobilization was performed with high-dose CY (4 g per m(2)) and we were able to collect adequate cells for marrow rescue in all patients. Patients received a high-dose regimen with etoposide (800 mg/m(2) per day) days -6, -5 and -4 as a continuous infusion, carboplatin (667 mg/m(2) per day) on days -6, -5 and -4 as a 1 h infusion, and CY (60 mg/kg per day) on days -3 and -2. In this high-risk group of patients, high-dose chemotherapy with autologous stem cell rescue led to a 3-year overall survival of 57% and a 3-year event-free survival of 49%. The results are reflective of a single procedure. No tandem transplants were performed. The treatment-related mortality was low at 3% in this heavily pretreated group.

    View details for DOI 10.1038/bmt.2008.364

    View details for Web of Science ID 000265005800005

    View details for PubMedID 18997833

  • Hematopoietic stem cell transplant for pediatric acute promyelocytic leukemia BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Dvorak, C. C., Agarwal, R., Dahl, G. V., Gregory, J. J., Feusner, J. H. 2008; 14 (7): 824-830


    The optimal form of treatment for children with relapsed or refractory acute promyelocytic leukemia (APL) is unclear. We retrospectively analyzed the results of 32 (11 autologous, 21 allogeneic) hematopoietic stem cell transplants (HSCT) performed for children originally treated on either the Eastern Cooperative Group E2491 Trial or the Cancer and Leukemia Group B C9710 Trial and subsequently diagnosed with relapsed or refractory APL. For autologous HSCT, the incidence of treatment-related mortality (TRM) and relapse was 0% (95% confidence interval [CI], 0%-30%) and 27% (95% CI, 9%-57%), respectively. The 5-year event-free survival (EFS) and overall survival (OS) following autologous HSCT was 73% (95% CI, 43%-91%) and 82% (95% CI, 51%-96%), respectively. For allogeneic HSCT, the incidence of TRM and relapse was 19% (95% CI, 7%-41%) and 10% (95% CI, 2%-30%), respectively. The 5-year EFS and OS following allogeneic HSCT was 71% (95% CI, 50%-86%) and 76% (95% CI, 55%-90%), respectively. There was no significant difference in EFS or OS between autologous and allogeneic HSCT. This data demonstrates that autologous and allogeneic HSCT are both effective therapies for treatment of children with relapsed or refractory APL. Autologous HSCT is associated with a low incidence of TRM, whereas allogeneic HSCT is associated with a low incidence of relapse, suggesting a strong GVL effect against residual APL.

    View details for DOI 10.1016/j.bbmt.2008.04.015

    View details for Web of Science ID 000256971000013

    View details for PubMedID 18541203

  • SAFETY OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN LESS THAN THREE YEARS OF AGE PEDIATRIC HEMATOLOGY AND ONCOLOGY Dvorak, C. C., Wright, N. B., Wong, W. B., Kristovich, K. M., Matthews, E. W., Weinberg, K. I., Amylon, M. D., Agarwal, R. 2008; 25 (8): 705-722


    Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment for a variety of hematologic conditions. However, very young children may experience different complications of HSCT compared to older patients. The authors retrospectively analyzed the results of 51 transplants performed on children less than 3 years of age between June 1987 and October 2005. Donors were matched-related (n = 21), partially mismatched related (n = 3), and unrelated (n = 27). The majority of patients had one or more grade III organ toxicities, but all nonrelapse deaths were attributable to infection. Perineal dermatitis was found in a large number (73%) of recipients of cyclophosphamide-based conditioning regimens. The 1-year transplant-related mortality (TRM) was 14%, but significantly declined in the more modern period. Grades II-IV acute graft-versus-host-disease (GvHD) was seen in 22% of patients, while chronic extensive GvHD developed in only 7% of patients. Relapse was seen in 40% of transplants performed for a malignant condition, most commonly in those patients not in remission at time of HSCT. The 5-year event-free survival (EFS) and overall survival (OS) were 53 and 64%, respectively. Recipients of fractionated total body irradiation (fTBI) were more likely to have at least one long-term sequelae than patients who received chemotherapy-based regimens (p = .014). These data demonstrate that HSCT can be performed safely in very young children, especially as supportive-care techniques improve. Cyclophosphamide-related perineal dermatitis is a unique complication in very young children. Finally, the incidence of acute and chronic GvHD in this population is low.

    View details for DOI 10.1080/08880010802243524

    View details for Web of Science ID 000261504200001

    View details for PubMedID 19065437

  • Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy BLOOD Deeg, H. J., O'Donnell, M., Tolar, J., Agarwal, R., Harris, R. E., Feig, S. A., Territo, M. C., Collins, R. H., McSweeney, P. A., Copelan, E. A., Khan, S. P., Woolfrey, A., Storer, B. 2006; 108 (5): 1485-1491


    In 87 patients with aplastic anemia who failed to respond to immunosuppressive treatment, we determined the minimal dose of total body irradiation (TBI) required when added to antithymocyte globulin (ATG, 30 mg/kg x 3) plus cyclophosphamide (CY, 50 mg/kg x 4) to achieve engraftment of unrelated donor marrow. TBI was started at 3 x 200 cGy, to be escalated or deescalated in steps of 200 cGy depending on graft failure or toxicity. Patients were aged 1.3 to 53.5 years (median, 18.6 years). The interval from diagnosis to transplantation was 3 to 328 months (median, 14.6 months). Donors were HLA-A, -B, -C, -DR, and -DQ identical for 62 patients, and nonidentical for 1 to 3 HLA loci at the antigen or allele level for 25. The dose-limiting toxicity was diffuse pulmonary injury. The optimum TBI dose was 1 x 200 cGy. Nine patients did not tolerate ATG and were prepared with CY + TBI. Graft failure occurred in 5% of patients. With a median follow-up of 7 years, 38 (61%) of 62 HLA-identical, and 10 (40%) of 25 HLA-nonidentical transplant recipients are surviving. The highest survival rate with HLA-identical transplants was observed at 200 cGy TBI. Thus, low-dose TBI + CY + ATG conditioning resulted in excellent outcome of unrelated transplants in patients with aplastic anemia who had received multiple transfusions.

    View details for DOI 10.1182/blood-2006-03-005041

    View details for Web of Science ID 000240271500016

    View details for PubMedID 16684959

  • Use of intravenous mycophenolate mofetil for graft-versus-host disease prophylaxis in an allogeneic hematopoietic stem cell transplant recipient with an allergic reaction to cyclosporine and tacrolimus BONE MARROW TRANSPLANTATION Dvorak, C. C., Callard, E., Agarwal, R. 2006; 38 (3): 253-254

    View details for DOI 10.1038/sj.bmt.1705422

    View details for Web of Science ID 000239118600014

    View details for PubMedID 16785867

  • Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation BONE MARROW TRANSPLANTATION Dvorak, C. C., Steinbach, W. J., Brown, J. M., Agarwal, R. 2005; 36 (7): 621-629


    Invasive fungal infections (IFI) are the leading cause of infectious mortality in adult patients undergoing hematopoietic cell transplantation (HCT) after myeloablative conditioning, but the extent of this problem in the pediatric population is unclear. We retrospectively examined risk factors for IFI among 120 consecutive pediatric patients undergoing allogeneic HCT at a single center. The incidence of proven or probable IFI in pediatric patients during the first year after allogeneic HCT was 13%, comparable to the rate reported in adult patients; however, unlike IFI in adult patients, the majority of IFI in children occurred within the first month after transplantation. The primary risk factors for IFI were duration of neutropenia, age greater than 10 years, transplant for severe aplastic anemia or Fanconi anemia, and high-dose corticosteroid administration for 10 days or longer. IFI were more likely to be successfully treated (42%, 5/12 patients) in pediatric HCT recipients when compared to previous reports of adult recipients. Nonrelapse mortality was estimated at 17% (20/120 patients) after allogeneic HCT, of which 35% (seven patients) were directly attributed to IFI. Thus, IFI is a significant cause of nonrelapse mortality in children undergoing allogeneic HCT and more effective strategies are needed to prevent and treat IFI.

    View details for DOI 10.1038/sj.bmt.1705113

    View details for Web of Science ID 000231877200009

    View details for PubMedID 16044133

  • High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin's disease: Results and prognostic indices JOURNAL OF CLINICAL ONCOLOGY Lieskovsky, Y. E., Donaldson, S. S., Torres, M. A., Wong, R. M., Amylon, M. D., Link, M. P., Agarwal, R. 2004; 22 (22): 4532-4540


    To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT).From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS).At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation).More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.

    View details for DOI 10.1200/JCO.2004.02.121

    View details for Web of Science ID 000225175600015

    View details for PubMedID 15542804

  • Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY DiCarlo, J. V., Alexander, S. R., Agarwal, R., Schiffman, J. D. 2003; 25 (10): 801-805


    Acute respiratory distress syndrome (ARDS) may result from immunologic activity triggered by irradiation and/or chemotherapy. Hemofiltration removes plasma water and soluble components below 25 kilodaltons. The authors hypothesized that early hemofiltration might attenuate the inflammatory component of ARDS, resulting in increased survival in immunocompromised children and young adults.Ten children (6 bone marrow transplantation, 3 chemotherapy, 1 lymphoma/hemophagocytosis) with ARDS (Pao2/Fio2 94 +/- 37 torr) received early continuous veno-venous hemodiafiltration as adjunctive therapy for respiratory failure, regardless of renal function. Six children had normal urine output and initial serum creatinine (range 0.1-1.2 mg/dL); four had renal insufficiency (initial creatinine 1.7-2.4 mg/dL). Hemofiltration was instituted coincident with intubation. Respiratory failure was precipitated by Enterobacter sepsis in two patients and by Aspergillus in one.Hemodiafiltration was performed for 13 +/- 9 days. A high rate of clearance was achieved (52 +/- 17 mL/min/1.73 m2). Duration of mechanical ventilation was 14 +/- 9 days. Nine of the 10 children were successfully extubated; 8 survived.Early hemofiltration may improve survival from ARDS following bone marrow transplantation or chemotherapy. Possible mechanisms include strict fluid balance, immunomodulation through filtration of inflammatory constituents, and immunomodulation through intensive extracellular water exchange that delivers biochemicals to organs of metabolism as well as the hemofilter.

    View details for Web of Science ID 000185790000010

    View details for PubMedID 14528104

  • Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation BONE MARROW TRANSPLANTATION Morris, J. D., Harris, R. E., Hashmi, R., SAMBRANO, J. E., Gruppo, R. A., Becker, A. T., Morris, C. L. 1997; 20 (10): 871-878


    A hypercoaguable state has been shown to follow high-dose chemotherapy for bone marrow transplantation (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S correlate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dysfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platelet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction of severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatening organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control group receiving the same preparative regimen (P = 0.047 and P = 0.034, respectively). Significant improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.

    View details for Web of Science ID A1997YG89600010

    View details for PubMedID 9404929

  • Retroviral transduction of CD34-enriched hematopoietic progenitor cells under serum-free conditions HUMAN GENE THERAPY Sekhar, M., Kotani, H., Doren, S., Agarwal, R., McGarrity, G., DUNBAR, C. E. 1996; 7 (1): 33-38


    The use of defined or serum-free culture conditions during retroviral transduction of hematopoietic cells would be desirable for standardization and safety reasons, as well as potentially allowing greater expansion of progenitor cells. Retroviral vector supernatants were concentrated and purified via tangential flow filtration polyethylene glycol (PEG)-precipitation, and ultracentrifugation, allowing serum-free transductions at standard multiplicities of infection (moi). Protein content of transductions using these concentrated vectors was 5-6 logs lower than in standard transductions. Transduction efficiencies of these concentrated vector preparations added back to serum-free or serum-containing media were equivalent to standard retroviral supernatant transductions of CD34-enriched progenitors. Absolute progenitor (CFU-C) numbers at the end of transduction were higher in serum-free + concentrated virus transductions, as opposed to transductions in standard vector supernatants containing fetal calf serum.

    View details for Web of Science ID A1996UA84500004

    View details for PubMedID 8825866



    Long-term culture of marrow from patients with chronic myelogenous leukemia (CML) has been reported to favor the outgrowth of bcr/abl- progenitor cells in some patients. We examined the effect of the presence of soluble or transmembrane forms of stem cell factor (SCF) in long-term cultures of CML marrow. CD34-enriched cells from CML patients in advanced chronic phase or accelerated phase were plated on immortalized fetal liver stromal cells from homozygous SCF-deficient SI/SI mice (SI/SI4) with or without the addition of soluble human SCF, SI/SI4 cells expressing high levels of the transmembrane form of human SCF (SI/SIh220), or primary human allogeneic stroma. Cells were removed from cultures and plated weekly in colony assays. The clonagenic cell output from cultures completely lacking SCF was lower over the first 2 to 3 weeks, but by 5 weeks was similar to the clonagenic cell output from the other culture conditions. Analysis of bcr/abl transcripts from individual colonies showed a lower percentage of malignant progenitors present in long-term cultures completely deficient in SCF than under the other culture conditions, particularly compared with primary human stroma-containing long-term cultures. SCF may specifically favor malignant versus benign progenitor cells present in the marrow of CML patients, and an abnormal proliferative response to SCF in very primitive cells may be an underlying defect in the pathophysiology of this disease.

    View details for Web of Science ID A1995QJ43500021

    View details for PubMedID 7532038


    View details for Web of Science ID A1992GW60800014

    View details for PubMedID 1727362

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