Programs

The Pediatric Hematopoietic Stem Cell Transplantation (HSCT) Program of the Stanford School of Medicine is housed in a discrete 12 bed unit in the Lucille Packard Childrens Hospital.  The Program has performed more than 850 transplants for the treatment of children and young adults with cancer and non-malignant diseases. The Program performs conventional transplants using allogeneic HSC from a variety of sources including bone marrow, mobilized peripheral blood and umbilical cord blood.  Autologous HSCT is used to treat some patients with cancer.  In addition to the conventional HSCT, the Program is engaged a series of Phase1/Proof of Concept clinical trials to evaluate antibody-based conditioning instead of chemotherapy, T regulatory type 1 (Tr1) T lymphocytes to prevent graft versus host disease and the gene transfer/gene editing of autologous HSC for the treatment of genetic diseases including immune deficiencies, hemoglobinopathies and in born errors of metabolism.

Dr. Agarwal-Hashmi is the Clinical Director of Pediatric Stem Cell Transplantation Program and leads the development of the innovative clinical research trials.  Dr. Agarwal-Hashmi received her MD from Indore University in 1983 and completed her fellowship in pediatric hematology/oncology at Cincinnati Children's Hospital Medical Center in 1995.  She joined the faculty of the Stanford University School of Medicine in 2001.

Allogeneic HSCT is associated with several complications and risk factors, including graft versus host disease (GVHD).  Since alpha-beta T lymphocytes are the primary mediators of GVHD, depleting them from the HSCT graft should reduce the risk of GVHD. The Program aims to understand how gamma-delta T lymphocytes support immune reconstitution after alpha-beta T-cell depleted HSCT and their impact on the outcome of children treated for both malignant and non-malignant diseases. Gamma-delta T lymphocytes combine the features of conventional adaptive immunity with rapid, innate-like responses. In addition, gamma-delta T lymphocytes recognize tumor cells irrespective of the classical major histocompatibility complex presentation. For this reason, they are the ideal cellular mechanism for immunotherapy.

Dr. Bertaina received her MD degree from the University of Pavia in 2000, obtained her PhD degree in Immunology and Biotechnology from Tor Vergata University in 2013, and completed her fellowship in HSCT at the Bambino Gesù Children’s Hospital in 2005, and she joined the faculty of the Stanford University School of Medicine in 2017.

The Center for Definitive and Curative Medicine (CDCM) is a joint initiative of the Stanford University School of Medicine, Stanford Health Care and Stanford Children’s Health. It is co-directed by Drs. Maria Grazia Roncarolo, Anthony Oro, and Matthew Porteus.

The CDCM provides the know-how, organizational and physical infrastructure to support investigator-initiated clinical translational studies on cell and gene therapy (CGT) from initial discovery through completion of clinical proof-of-concept trials. Stanford Medicine’s clinical enterprise provides an exemplary clinical environment in which to deploy cures. The CDCM will support the development of life-changing and curative treatments for patients who come to Stanford to receive the highest level of care.

For more information about the center, or for information about trials associated with the center, please visit the CDCM website

More information coming soon.

Genome editing involves the targeted and engineered insertion, deletion, modification or replacement of DNA in the genome of a living organism. In 2011, Nature Methods selected genome editing as the 2011 Method of the Year. The Program is focused on developing genome editing as the safest and most robust approach to cure genetic diseases, particularly sickle cell disease, thalassemia, primary immunodeficiencies including severe combined immunodeficiency and hemophilia and ultimately other organ systems as well. Genome editing offers the precise modification of the target gene of interest by homologous recombination while leaving the rest of genome unperturbed.  Engineered nucleases make a specific DNA double-strand break in the gene of interest.  By simultaneously providing a piece of “donor” DNA, the cell’s endogenous homologous recombination machinery repairs the induced double-strand break using the donor DNA as a template.  In this way, precise sequence changes can be introduced into the gene.  The Program has made important discoveries in advancing the field of genome editing including the first use of genome editing using engineered nucleases in human cells and optimizing the use of the CRISPR/Cas9 system in primary human stem cells. The Program is planning an IND submission for the treatment of patients with sickle cell disease by the transplantation of their autologous HSC, which have been genetically modified to produce normal hemoglobin.  

Matthew Porteus received his MD and PhD degrees from Stanford University in 1994 and completed a fellowship in pediatric hematology/oncology at Boston Children’s Hospital/Dana Farber Cancer Institute in 1999. He joined the faculty of the Stanford University School of Medicine in 2010.

The hemoglobinopathies are genetic diseases of hemoglobin metabolism. With approximately 7% of the worldwide population being carriers, hemoglobinopathies are the most common monogenic diseases and are one of the world’s major health problems.  The Program specializes in the treatment of patients with hemoglobinopathies, specifically β -thalassemia and Sickle Cell Disease (SCD).  β-thalassemia syndromes are due to insufficient (β⁺) or absent (β⁰) production of β-globin chains. In patients with SCD, at least the defective hemoglobin S. replaces one of the β-globin subunits of the hemoglobin molecule. The molecular basis for both β-thalassemia and Sickle Cell Disease are β-globin gene mutations. The only curative therapy for the hemoglobinopathies is allogeneic HSCT; however, appropriate donors can be identified for only 30% of patients.  The Program in conjunction with alpha beta T cell depletion Program has developed a haploidentical HSCT clinical trial.  In addition, the Program is collaborating in a gene editing approach in which SCD patients will have their autologous HSC corrected and transplanted following myeloablative conditioning.

Immunodeficiency diseases are characterized by abnormalities in specific components of the immune system that can lead to an increased susceptibility to infection. In some patients, these abnormalities can also result in immune dysregulation, resulting in an immune response that is not properly regulated.  The Program is investigating the molecular basis of both immunodeficiency and immune dysregulation syndromes. By exploring the genetic and immunological basis of diseases with autoimmunity or immune dysregulation in children, the Program is developing in depth mechanistic understanding of pediatric autoimmune diseases. The Program has a particular interest in how mutations of key immune tolerance genes affect regulatory T cell (Treg) and effector T cell (Teff) functions. Mutation of one gene, FOXP3, which causes the IPEX syndrome, results in the prototypic pathology of a clinical Treg defect. The Program is currently testing the feasibility and safety of two different gene therapy approaches to treat IPEX patients: one based on lentivirus mediated conversion of Teff cells into Treg cells, and the other based on gene editing of the autologous HSC. A long-term goal is to facilitate gene correction for patients with IPEX syndrome and other genetic diseases of immune dysregulation.

Dr. Bacchetta received her MD degree from the University of Turin in 1987 and completed her fellowship in pediatric immunology at the University of Turin in 1991. She joined the faculty of Stanford University School of Medicine in 2014.

Management of the late effects after HSCT is important for the growing number of long-term HSCT survivors. Many studies have shown that HSCT survivors can suffer from significant late effects that adversely affect morbidity, mortality, working status and quality of life. The Program supports a Survivorship Program, which empowers survivors to take charge of their renewed health and teaches them how to educate their family members and healthcare team regarding their needs.

Dr. Shah received her MD degree from the University of North Carolina in 1990 and completed her fellowship in pediatric hematology/oncology at Children’s Hospital Los Angeles in 1996. She joined the faculty of the faculty of the Stanford University School of Medicine in 2015.

Understanding how HSC interact with their microenvironment and the principles controlling HSC engraftment is central to a successful HSCT.  The Program has done pioneering work highlighting that host HSC limit donor HSC engraftment and has developed novel antibody-based conditioning regimens to overcome this limitation, the most advanced of which is being presently tested in clinical trials at Stanford in immunodeficiency patients undergoing HSCT.  The Program’s current research is aimed at modulating how HSC interact with their microenvironment to ultimately improve HSCT. The focus is to study the cell surface receptors on HSC and bone marrow stromal cells to learn how to manipulate so that their cell fate can be altered.

Dr. Czechowicz received her MD and PhD degrees from Stanford University School of Medicine in 2011 and completed her fellowship in pediatric hematology/oncology at the Boston Children’s Hospital/Dana Farber Cancer Institute in 2017.  She returned to the faculty of the Stanford University School of Medicine in 2017.

Lysosomal storage diseases are inherited metabolic diseases, which are characterized by the abnormal build-up of toxic materials in the body's cells because of genetic mutations leading to enzyme deficiencies.  Current research is directed at developing safer, more effective therapies for lysosomal storage disorders with a special focus on those diseases with neurological involvement. For mucopolysaccharidosis type I lysosomal storage disease, present treatments include enzyme replacement therapy and allogeneic HSCT. Both methods are limited in efficacy and at best can slow disease progression. A safer, more effective approach would be to genetically engineer the patient’s own HSC to secrete high levels of enzyme following the transplantation of the genetically modified autologous HSC. The Program in conjunction with the Gene Editing Program has developed an efficient genome editing strategy to target α-L-iduronidase into the C-C chemokine receptor type 5, a “safe harbor locus”, in human CD34+ HSC.

Dr. Gomez-Ospina received her MD and PhD degrees from Stanford University School of Medicine in 2010 and fellowship in medical genetics in 2015.

Patients with primary immune deficiencies have defects in their immune system that places them at an increased risk of infection. The identification of their primary genetic defect has provided insights into the functioning of the normal human immune system.  The Program’s research efforts are directed at identifying new genetic defects that result in either an increased rate of infection and/or immune dysregulation.  The Program clinically is investigating approaches to improve allogeneic HSCT using an antibody-conditioning regimen and the transplantation of autologous HSC, which have been genetically modified.

Dr. Weinberg received his MD degree from the Stanford University School of Medicine in 1978 and completed his fellowship in pediatric hematology/oncology at the Childrens Hospital Los Angeles in 1985.  He joined the faculty of Stanford University School of Medicine in 2004.