Haploidentical Hematopoietic Cell Transplantation for Children With Hematologic Malignancies and Myelodysplasia

Less than 30% of patients undergoing hematopoietic cell transplantation (HCT) will have an
HLA-matched sibling donor. There is a high likelihood of being unable to identify a perfect
HLA matched unrelated donor, and the time to procure the marrow if such a donor is available
is generally >3 months. An emerging body of literature suggests that related haploidentical
HCT with innovative graft engineering may provide equal, or possibly superior, outcomes to
conventional unrelated donors. This protocol is designed to test the hypothesis that HCT
using an αβT cell / CD19+ B cell depleted graft from partially matched related donors will
result in rapid, durable hematopoietic engraftment and rapid immune reconstitution with an
acceptably low risk of severe acute and chronic GVHD.

Inclusion Criteria:

- Patient lacks an HLA matched sibling donor and a HLA A- B- C- DR - DQ- matched
unrelated donor is not identified within 30 days of the first confirmatory typing
request.

- Meets criteria nonhematopoietic organ function according to NCH policy.

- If subjects have received a first HCT, they must be eligible for a second HCT if their
disease has recurred (see Section 3.3.1 for eligible diseases), all other restrictions
still apply.

- High resolution HLA and KIR typing

- The subject cannot have an active untreated infection. Viremia by PCR analysis is not
considered an active infection but may require immediate viral prophylaxis. Patients
with possible fungal infections must have had at least 2 weeks of appropriate anti-
fungal therapy and be asymptomatic.

- Negative pregnancy test for females ≥11 years of age or post- menarche.

- Sexually active males and females of childbearing potential must agree to use a form
of contraception considered effective and medically acceptable by the Investigator.
(Non-childbearing potential defined as pre-menarche, greater than one year
post-menopausal or surgically sterilized).

- Subjects must be ≤21 years at the time of consent.

- Signed consent by parent/guardian and assent if appropriate for subjects < 18 years of
age. Signed consent by patient/subject if ≥18 years of age.

Exclusion Criteria:

- Patient does not have a suitable donor who is willing and able (meets donor criteria).

- Patient has donor-specific anti-HLA antibodies

- Patient reports a history of allergic reactions to murine protein

Donor Eligibility:

- The donor must be ≥18 years of age at the time of the informed consent conference.

- The donor must be a parent or other related donor

- The donor will be evaluated according to the current NCH BMT SOP 04 and must meet all
criteria.

- The donor must be able and willing to undergo G-CSF mobilization and stem cell
apheresis.

- The patient does not have donor specific anti-HLA antibodies