Research That Leads to Innovation

The Bone Marrow Transplantation doctors and researchers at Cincinnati Children’s conduct numerous clinical and laboratory-based research projects in hopes of improving the lives and prognosis for children receiving transplantation for cancer, immune deficiencies, bone marrow failure syndromes, hemoglobinapathies and other rarer diseases.

Some of these projects work to:

  • Understand the biology and genetics of blood stem cells and the bone marrow microenvironment which may contribute to diseases like leukemia and failure
  • Improve bone marrow transplant regimens and donor screening processes to decrease the unwanted effects and improve outcomes 
  • Identify new biomarkers to predict damage to vital organs after a bone marrow transplant
  • Learn more about clinical, biological and genetic changes of bone marrow failure syndromes
  • Develop novel therapies for patients with hemophagocytic lymphohistiocytosis (HLH)
  • Develop new diagnostic and genetic tests for patients with rare immune deficiencies 
  • Treat sickle cell disease by using gene therapy to treat a patient’s own hematopoietic (blood-making) stem cells
  • Identify novel diagnostics for early detection of transplant-related complications such as graft-versus-host disease and thrombotic microangiopathy
  • Offer new cellular therapies that prevent and treat infections after transplantation
  • Provide new cellular therapies that attack cancer cells
  • Develop intervention strategies to improve quality of life for children who have received transplants
  • Develop long-term surveillance and intervention strategies for children growing up after transplantation

Examples of Novel Approaches Developed Through Research

Cytotoxic T lymphocytes (or CTLs) are specialized immune T cells with the ability to protect you from infections and cancer. After a hematopoietic stem cell transplant, a donor’s T cells must grow and expand in your body before they become CTLs that can provide suitable protection. This may take many months to occur.

BMT researchers and clinicians have developed manufacturing platforms that train CTLs in a laboratory facility to attack certain viruses before they can cause damage. Before the transplant process begins, blood can be collected from your donor and this manufacturing process can be started so that CTLs are ready. These can then be provided to you in the first weeks after receiving the stem cell transplant.

Chimeric antigen receptor (CAR) engineered T cell technology is one of the most exciting areas of emerging treatment for cancer. Special immune cells called T cells can be harvested from a patient’s peripheral blood. These can then be manipulated in a laboratory to express CARs on their surface, rendering the CAR-positive T cell highly effective at attacking leukemia. Our team and other members of the Cancer and Blood Diseases Institute have partnered with industry to provide additional options to some of our patients with hard-to-treat leukemia. A variety of treatment platforms are either currently available or actively in development.

Vitamins are an important part of maintaining a healthy physiology and metabolism. They also serve essential roles in a balanced and controlled immune system. Stella Davies, MBBS, PhD, and other members of the Bone Marrow Transplantation team are currently exploring the role of vitamins A and D in patients who have received a hematopoietic stem cell transplant. These vitamins may provide protection against graft-versus-host disease and infections within the intestine after a transplant. Patients’ levels are monitored closely during the transplant process to ensure adequate vitamin levels. Ongoing research exploring the interplay between your body’s vitamins and transplant success is currently under way. 

Blood vessels are an important organ system of the human body. They can also be affected by the administration of a hematopoietic stem cell transplant. Sonata Jodele, MD, and other members of the Bone Marrow Transplantation team have explored many aspects of TA-TMA including the role of a group of blood proteins called complement. She has pioneered the use of complement-blocker medications that can be used to reverse the effects of this transplant-related complication. As such, her work is highly referenced, and our center has been internationally recognized as establishing new standards of care for this entity. Learn more.

Our research has succeeded in the development of reduced intensity conditioning (RIC) regimens, a transplant procedure that offers lower doses of chemotherapy, which can offer improved outcomes by decreasing the unwanted effects of a transplant. We have pioneered the application of this RIC approach to diseases such as hemophagocytic lymphohistiocytosis (HLH), a pro-inflammatory condition that carries significant life-threatening risks.

Your bone marrow transplant attending doctor will determine if you are eligible to participate in any of our current research studies.

Chemotherapy and other medications used in hematopoietic stem cell transplant have potential unwanted secondary effects. Bone Marrow Transplantation team members Rebecca Marsh, MD, Sharat Chandra, MD, and Parinda Mehta, MD, are actively researching existing and emerging technologies that can monitor drug levels in real time. These new techniques will allow for the most accurate administration of medication while minimizing toxicity wherever possible. 

Graft-versus-host disease (GVHD) is a significant risk of allogeneic (a donor) HSCT. GVHD is caused when the immune cells from the donor (graft) recognize your body (host) as foreign and cause a reaction. This can cause damage to tissues or organs in your body that can range in severity from mild to life-threatening. Rebecca Marsh, MD, and Pooja Khandelwal, MD, have been working hard to delineate the importance of certain cell populations that emerge early in the post-transplant period as possible GVHD markers. They utilize flow cytometry, a laboratory technique that characterizes immune cell populations, to detect the presence of cell-surface proteins like CD38. Additionally, Khandelwal is studying methods that can detect subtle signs of graft-related inflammation in the skin using sensitive patches. Lastly, their work has also assisted in clarifying the role of novel approaches to treat refractory GVHD.

HSCT can be a challenging process, and our team continues to improve the patient experience. Christopher Dandoy, MD, is a clinician scientist with a research niche that utilizes a number of quality control and improvement measures. He works hard with our nursing and ancillary staff to create initiatives that address patient safety, comfort and satisfaction. Some of these endeavors include trials that:

  • Evaluate sleep
  • Minimize unnecessary vital sign checks
  • Decrease the incidence of bacterial infections
  • Improve cleanliness and hygiene

Your bone marrow transplant attending doctor will determine if you are eligible to participate in any of these research trials.