A Look Inside Cell Therapy and Bone Marrow Transplant Program at Texas Children’s

For Physicians

Below is an interview that was conducted with the Chief and Associate Chief of the Cell Therapy and Bone Marrow Transplant Program featuring (L-R) Drs. Caridad (Cary) Martinez and David Steffin, at Texas Children’s Cancer and Hematology Center.

What does your program do? What are cell therapies and bone marrow transplants?

Caridad A. Martinez, MD

Dr. Martinez: Cell therapies are used to treat a variety of conditions. They save lives, can cure serious disorders and give patients a fighting chance against cancer. Around half of our patients receive therapy for cancer. The other half are treated for other disorders—including those that affect the blood, immune system or how we ‘metabolize’ and use food energy.

While there are many different cell therapies, they all have one aim: to fix certain cells in the body that are either malfunctioning or unable to do their job. Cell therapies can greatly improve the lives of the individuals suffering from these conditions, so it is a very rewarding job.

When all the cells of a patient’s immune system are replaced using this approach, we call this a bone marrow transplant. As one of the largest of these programs in the United States, we do about 140 bone marrow transplants a year, in which we either reintroduce the patients’ own—autologous—cells or those of a matched donor—an allogeneic transplant.

Photos of the clinical spaces at Texas Children’s Cancer and Hematology Center, which are vital to delivering care to patients in need of cell and transplant therapies.

What sets you apart from other cell therapy and bone marrow transplant programs?

Dr. Martinez: Being situated in a big city and state within the world’s largest medical center—the Texas Medical Center (TMC)—provides many unique benefits.

First, because of our size and location within the TMC, we have a wealth of expertise.

From when the program first launched in 1997, we have been lucky to be able to treat a wide range of conditions and do so in a way that is tailored to each patient. Our physicians, which have extensive subspecialty expertise, can treat cancers, blood disorders like sickle cell disease and thalassemia, as well as immune and metabolism disorders. Annually we conduct around 140 cell therapy transplants.

To provide the best care, we take a multidisciplinary approach. Our core expertise in hematology and oncology is complemented by specialists in cardiology, dermatology, gastroenterology and infectious disease. All this know-how comes into play when tailoring treatments to individual patients—especially those with complex health conditions.

We also have a very multicultural group of physicians—many of whom speak different languages and who come from a wide variety of religious and cultural backgrounds. This is important for serving such a diverse city and state.

Second, the sizable population right here in Texas makes it possible for us to build lasting relationships with patients. Because of this we have one of the largest long-term survivorship bone marrow transplant clinics in the United States.

Through this program, rather than just seeing patients when they receive therapy, we can touch base with individuals over longer periods of time—years and decades in some cases. This added dimension provides much richer data and insights that are essential to advancing the field—something that benefits all patients.

Third, we offer an array of therapies, which rely on the cutting-edge clinical-grade facilities.

Our in-house diagnostics and cell therapy manufacturing facilities provide us with the ability to offer the most cutting-edge treatments. These include the ability to use stem cells from cord blood libraries for transplant, and the ability to do successful haploidentical transplants from donors who are only a ‘half match’. We are also experts at delivering immunotherapies, which are tailored to each individual patient.

Because we are situated in the world’s largest medical complex, we have a wealth of unique resources. For example, we have access to a cord blood library in the TMC. Our researchers also collaborate with the Center for Cell and Gene Therapy at Baylor College of Medicine, which shares our goal of moving foundational discoveries from the lab into clinic to help patients.

The Center for Cell and Gene Therapy is located in-house. This world-class facility meets rigorous good manufacturing process (GMP) standards and is a joint effort between Texas Children’s, Baylor College of Medicine and Houston Methodist

Fourth, we have specialized clinics that provide customized care—so that no matter what situation our patients are in, we can provide them with the best care possible across their entire treatment journey. These clinics are listed below:

  • Long-term Survivor (LTS) BMT Clinic – long-term and follow-up care for patients who have received a hematopoietic stem cell transplant.
  • Graft-Versus-Host Disease (GVHD) Multidisciplinary Clinic – specialized care for graft versus host disease – a complication that sometimes arises after stem cell or bone marrow transplants.
  • Metabolic Genetics Clinic - comprehensive, quality medical and dietary therapy for children and adults with inborn errors of metabolism.
  • BMT/Infectious Disease Clinic – Diagnosis, treatment and follow-up care for cell therapy and bone marrow transplant patients with infectious diseases.

Taken together, these unique capabilities enable the team to treat every patient and provide the most advanced and life-changing care regardless of the circumstance. 

A full list of conditions that are treated and treatments offered are listed below:

Conditions We Treat

Blood Cancers

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Histiocytic Disorders

Solid Cancers

  • Solid Cancers
  • Brain Cancers
  • Rare Cancers

Blood Disorders

  • Hematopoietic Blood Disorders (E.G., Aplastic Anemia)
  • Hemoglobinopathies (E.G., Sickle Cell Disease, Thalassemia)
  • Thrombocytopenia

Immune Disorders

  • Severe Combined Immunodeficiency (SCID)
  • Chronic Granulomatous Disease (CGD)
  • Leukocyte Adhesion Defect/Deficiency (LAD)
  • Wiskott Aldrich Syndrome (WAS)
  • T Cell Disorders
  • Primary Immune Regulatory Disorders (PIRDs)
Metabolic Disorders
  • Adrenoleukodystrophy (ALD)
  • Beta-Glucoronidase Deficiency (VII)
  • Gaucher Disease
  • Glucorage Storage Disease
  • Mucopolysaccharidoses (MPS)
  • Hurler Syndrome (MPS1)
  • Hunter Disease
  • I Cell Disease
  • Leukodystrophies (e.g., Krabbe Disease) 
  • Neimann-Pick
  • Osteopetrosis (IMD)
  • Sanfilippo (III)

Bone Marrow Transplant Complications

  • Graft-Versus-Host-Disease (GVHD)

Treatment Approaches

  • Immune Cell Therapy (Immunotherapy; experimental as part of Phase 1 Clinical Trials)
  • Stem Cell Transplant (Autologous, Allogenic)
  • Gene Therapy (currently experimental for Sickle Cell Disease and not widely available)


How is the Cell Therapy and Bone Marrow Transplant program organized?

Dr. Martinez: In addition to David and I, we have around 10 clinical pediatric hematologist/oncologist clinicians who are specialized in bone marrow transplantation on rotation. Each of these physicians see their own patients and follow them throughout their entire patient journey. Various other experts work closely with these doctors, including nurse practitioners and physician assistants.

We also have several non-clinical researchers that lead their own laboratories. Their research is essential for expanding our understanding of heath and disease and staying at the cutting edge. Along with our clinical doctors, they also contribute to our clinical trials, which push the envelope forward and are essential for developing new, more effective therapies. The close connection that we have between the clinic and the laboratory is key for improving care.

Other staff include those that run our highly specialized cell manufacturing facilities. It is here where the living cell-based therapies are prepared. Close to 30 specialized staff and technical experts run these facilities 24 hours, seven days a week. They conduct a myriad of tests on patient samples so that we can follow progress and determine whether patients are eligible clinical trials.

Photos of some of the spaces and specialized research equipment available at the Center for Cell and Gene Therapy.

Other team members include pharmacy staff, nutritionists, art therapists, social workers, and psychology consultants, who address emotional dimensions of what patients are going through.

Third party organizations also provide support to patients in the form of housing, transportation, food and laundry services. When it comes to taking care of patients, the African adage "it takes a village" holds true!

Can you give an example of how your program has improved the standard of care for children?

Dr. Martinez: One of the biggest challenges in the transplantation field is finding compatible donors on a tight timeline. This is particularly true for treating a very common condition called severe combined immune deficiency. Babies born with this condition do not have an immune system and need a bone marrow transplant within four weeks of birth. When we can’t find a good match, there is no consensus on what the best approach is.

To address this issue, we conducted a clinical trial that explored using stem cells from donated umbilical cord blood, which is widely available. In the clinical trial we treated children using either matched donors or umbilical cord stem cells. Our findings revealed that there was no difference in outcome between the two groups, showing that umbilical cord stem cells are a great option for patients that don’t have matched donors.

We now use umbilical cord stem cells as our standard approach. This means we can help more kids—especially visible minorities, who are currently not well represented in donor registries—and treat them faster, so that we can avoid complications.

Our findings were published in the blood advances journal and can be found here: https://pubmed.ncbi.nlm.nih.gov/36453638/.

What’s on the horizon? What gets you excited about the future of the program?

Dr. Martinez: We’re working very hard on improving access to our services—especially for those living in rural Texas.

Part of this is increasing our capacity so that we can treat every patient in need. Another part of this is developing ways to reach out to underserved areas.

As we treat more patients outside of our immediate area, we are also working on expanding telehealth capabilities and exploring the possibility of opening outreach clinics. These will be essential for us to maintain long-term relationships with patients, provide them with follow-up care and continue to learn as much as we can so that we can continually improve care.

Can you provide an example of a cutting-edge clinical trial that is being led by the program?

David H. Steffin, MD

Dr. Steffin: Sure, one of phase 1 clinical trials that we’re working on is focused on finding a new way to help children with treatment-resistant solid tumors.

The study is known as AGAR and is being led by myself and Andras Heczey. In it, we’re exploring whether T-cell based immunotherapy can help kids who have recurrent cancer. They have been through standard treatments, and their cancers have returned and their tumors no longer respond to existing therapies.

We began the study with a focus on liver tumors and have since been expanded the scope to include any solid tumors that have a specific protein marker called Glypican-3.

How does this experimental therapy work? How are the therapeutic cells prepared?

Dr. Steffin: The therapy involves removing some of the patient’s immune cells—known as T cells—from the blood, training them to target the marker found on cancer cells, then returning them to the body, where they then target and kill cancer cells.

It’s important to note that the marker Glypican-3 is not normally present in the body after birth. Because of this, after we ‘arm’ the T cells to target and kill cancer cells with this marker, normal tissue remains unharmed, minimizing unwanted side effects.

What is the most exciting thing about this trial for you?

Dr. Steffin: The most exciting thing for me is that we’ve been able to give kids and their families renewed hope—and we’ve been able to enroll patients from all over the world.

Our patients include those from other nearby institutions such as MD Anderson, other cities such as San Antonio, states such as California and New York, and countries as far away as New Zealand and Singapore.

Part of the success of this trial is that we can prepare the therapeutic cells without having patients travel back and forth between our center and their home. To minimize inconveniencing patients, we can arrange to have their local hospital can draw blood and ship it to us overnight. Once we receive it, we reprogram and ‘arm’ patient’s own T cells in our in-house facility—a process that takes around two weeks. Then, when the cell therapy is ready, patients only need to make one trip. And when they arrive, they can receive treatment right away without waiting.

Why is research important for providing the best care possible?

Dr. Steffin: Having a robust clinical research program is key to pushing the dial towards new and better therapies that improve quality of life.

Physicians rely on clinical protocols and guidelines. These protocols are established through collaborative and evidence-based research.

Without research, a single physician can help only so many patients in a day. With research, you unlock endless potential. By studying new therapies, including those that are better tailored to patients, you gain a superpower: you can improve the standard of care. So, you’re able to help not just the patients enrolled in clinical trials, but all future patients that will benefit from your discoveries. You can truly have global impact. Being able to tap into this potential is exciting.

What is the hardest part of your job and what keeps you going?

Dr. Steffin: Because of the inherent uncertainty in developing new therapies through phase 1 clinical trials, we can’t be certain that patients will respond or that these new treatments will help to control the cancer.

The hardest part is having to communicate this to kids and families. But it’s essential that we are realistic about limitations.

The thing that keeps me going is also related to this uncertainty. Like a double-edged sword, uncertainty, in some circumstances, enables us to push past current limitations. And, yes, we have seen so many patients with very poor outcomes—young children and adolescents—who experience amazingly positive responses.

Without clinical trials, we would have never made the progress that we have. For example, through clinical trials, we’ve pushed overall survival of children with leukemia from less than 20% in the 1970s to greater than 90% survival today. Ultimately, that keeps us going—we know that by working together, with patients and families as partners, we can make real, life-changing improvements to care. It’s an honor to be part of this work and to do so as part of a supportive team at Texas Children’s Cancer and Hematology Center.

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