Procedures

Haploidentical or “Half-matched” Blood Stem Cell Transplantation

Historically, children in need of a blood stem cell transplant required a human leukocyte antigen (HLA) identical or “fully matched” bone marrow donor. HLAs are proteins found on most cells in the body; the immune system uses these markers to recognize cells that belong in the body versus those that do not.

It used to be that the closer the match between a patient’s and donor’s HLA markers, the  better the outcome. The best matched donor is usually a sibling, but only about 25 percent of children in need of a transplant will have a “fully matched” sibling donor. In addition, only approximately 30 percent of patients can find a perfectly matched unrelated donor in the national bone marrow and cord blood registries; however, this percentage is much lower for people of color, especially for African Americans, Native Americans and Latino Americans, who have a less than 10 percent chance of finding a “fully matched” unrelated donor because these groups are underrepresented in the stem cell registries.

Johns Hopkins clinicians have developed a unique method of using “half-matched” donors to ensure that every patient needing a bone marrow transplant has a donor that can be rapidly identified. Children inherit half of their bone marrow from their mother and half from their father, so in almost every situation a parent can be the bone marrow donor. Half of siblings are “half-matched,” too. This dramatically increases the number of patients who can successfully be transplanted. The “half-matched” bone marrow transplant regimen we have pioneered includes giving a standard chemotherapy drug called cyclophosphamide to the patient after the new bone marrow is infused. This method has made “half-matched” transplants as safe as transplants from perfectly matched donors.

Read more about the procedure, called haploidentical transplant.

Listen to Dr. Heather Symons discuss bone marrow transplant:

High-dose Cyclophosphamide

In another novel treatment  approach, physician-scientists at Johns Hopkins use  the chemotherapy drug cyclophosphamide (trade name: cytoxan) without giving new bone marrow , to “re-boot” the immune system and achieve long-lasting, complete remissions in many patients with severe aplastic anemia, multiple sclerosis, autoimmune enteropathy, ROHAAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and  autonomic dysregulation) syndrome, and other severe autoimmune disorders.

BMT for non-malignant disorders

The Pediatric BMT Program at Johns Hopkins also uses blood stem cell transplantation from suitably matched donors to treat patients with non-malignant disorders of the blood, and of immune and metabolic systems. When possible, our clinicians use less intense methods to prepare the body for transplantation. These “reduced intensity” regimens minimize both short- and long-term side effects from chemotherapy and radiation therapy. In the case that a “fully matched” donor is identified, they employ protocols to minimize the amount of and time needed to take the immunosuppressive drugs that are needed after bone marrow transplant. This approach allows patients to come off of their medication sooner and helps the immune system recover faster. 

Non-malignant disorders treated at Johns Hopkins include, but are not limited to:

• Immune system disorders – such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), Hyper-IgM syndrome, common variable immunodeficiency (CVID), and hemophagocytic lymphohistiocytosis (HLH).
• Acquired and inherited bone marrow failure syndromes – such as severe aplastic anemia (SAA), Fanconi anemia (FA), dyskeratosis congenita (DKC), and Diamond-Blackfan anemia (DBA)
• Metabolic disorders – such as Hunter syndrome and Hurler syndrome
• Leukodystrophies – such as adrenoleukodystrophy (ALD) and metachromatic leukodystrophy (MLD)
• Hemoglobinopathies- such as sickle cell disease (SSD) and thalassemia.

The Johns Hopkins BMT Program has done pioneering work in adults using haploidentical donors and reduced intensity conditioning to cure many patients with SSD. We are currently using this approach to treat pediatric patients with SSD and thalassemia.

Patients with non-malignant disorders are co-managed by members of the Pediatric BMT Program and pediatric specialists --- including immunologists, hematologists, endocrinologists, geneticists and neurologists --- with expertise in the diseases being treated.