SCIDBMT: Bone Marrow Transplant for Infants with Severe Combined Immunodeficiency (SCID)

Brief Summary

Matched sibling donor hematopoietic cell transplantation (HCT) is the standard therapy for children with severe combined immunodeficiency (SCID), an immune system disorder also known as “bubble boy” disease. When a sibling match is not available, unmanipulated matched unrelated donor (MUD) or T-cell depleted haploidentical transplantation from a relative may be appropriate.

Immune reconstitution after HCT is one of the most important determinants of successful treatment for SCID patients. Given the major human leukocyte antigen (HLA) donor-recipient disparities in the haploidentical setting and some disparities in MUD, innovative approaches are needed to prevent the occurrence of complications, such as graft-vs-host-disease (GvHD) or difficulties with engraftment.

This protocol will investigate recovery of immune system, using a peripheral blood manipulation method that removes potentially GVHD-inducing α/β and CD45RA+ T cells while still providing potentially beneficial donor γδ and memory T cells to provide immunity and viral protection.

Primary Objectives

• To evaluate the safety of a TCRα/β/CD19-depleted graft with CD45RA-depleted DLI in infants with SCID
• To estimate overall survival at 1 year after transplantation

Eligibility Criteria

Transplant recipient

Inclusion criteria include:

• Infant at least 2 months old
• Diagnosis of severe combined immunodeficiency (SCID) with proven mutation as defined by direct sequencing of patient DNA
• Has suitable matched sibling donor or matched unrelated donor or a single haplotype matched family member donor
• Lansky performance score ≥50

Exclusion criteria include:

• Positive for HIV infection by genome PCR
• Active malignancy

Matched sibling donor and haplocompatible donor

Inclusion criteria include:

• Fully matched sibling donor (8/8) or matched unrelated donor (8/8) or at least single haplotype matched (≥3 of 6) family member
• At least 1 year old (matched sibling donor)
• At least 18 years old (matched unrelated or haploidentical donor)

Study Sites

St. Jude Children’s Research Hospital, Memphis, Tennessee

About this study

Severe combined immunodeficiency  (SCID) is a disease that affects the immune system. It is commonly known as “bubble boy” disease. Children with SCID are more likely to get infections because their immune systems do not work properly.

Hematopoietic cell transplant  (HCT) is a common procedure used to treat SCID and other diseases. HCT is also known as stem cell transplant or bone marrow transplant.

HCT begins with anti-cancer medicine called chemotherapy. This medicine damages or kills the bone marrow to make space within the bones for new blood cells. Next, doctors give your child healthy blood-making cells from a donor. These cells travel through the blood to the bone marrow space, where they begin to grow and make new blood cells.

The best donor for a bone marrow transplant is a brother or sister who is a “match” for your child’s immune type. If your child does not have a sibling match, someone who is a close or partial match may donate blood cells. This donor might be another family member or an unrelated volunteer.

In this study, doctors will give your child immune cells from an unrelated donor or family member to provide some immune protection before your child can make his/her own immune cells. If your child has a matched sibling, no additional immune cells will be given.

Purpose of this clinical trial

The main goal of this study is to learn more about the good and bad effects of this procedure. The study will look at how bone marrow transplant affects your child’s disease and overall survival.

Eligibility overview

• Infant at least 2 months old with SCID diagnosis
• Has a suitable matched sibling donor or matched unrelated donor, or a single haplotype matched family member donor