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)
  • Associate chief, Pediaric hematology/oncology/stem cell transplantation (2010 - 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

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details


2015-16 Courses


All Publications

  • 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