Transcript HAPLOIDENTICAL STEM CELL TRANSPLANT

HAPLOIDENTICAL STEM CELL
TRANSPLANT
Zeina Al-Mansour, MD
Assistant Professor
Hematology/Bone Marrow Transplant
Loyola University Medical Center
May 21st, 2016
S
OUTLINE
S Introduction
S HLA Antigens & HLA
Matching
S Donor Options,
Selection & Eligibility
S How Haplo-SCT Works
S Advantages of this
approach
S Outcomes
S Who Should Consider
Haplo-SCT
S Summary
INTRODUCTION
S Allogeneic Stem Cell Transplant (Allo-SCT) is a potentially
curative therapy for a wide variety of malignant and nonmalignant hematologic disorder.
S Stem cell: mother of all types of blood cells, divides and
differentiates to give rise to all types of blood cells.
S Obtained from the bone marrow or peripheral blood of a related or
unrelated donor
HLA Antigens
S HLAs are proteins — or markers —
found on most cells in the body.
S The immune system
uses these
markers to recognize cells that
belong in the body versus those that
do not.
HLA Matching
Role of HLA Matching
S Increases the likelihood of a successful transplant
S Improves engraftment—when the donated cells start to
grow and make new blood cells in you.
S Reduces the risk of complications after transplant, especially
graft-versus-host disease (GVHD).
S
GVHD is a potentially serious complication.
S
Occurs when the immune cells, which are part of the donated
marrow or cord blood, attack your body.
DONOR OPTIONS
S Matched sibling donor
S Matched unrelated donor
S Alternative options:
S Half-matched related donor  HAPLOIDENTICAL
S Cord blood transplant
DONOR SELECTION
S Normally, we look for a donor who matches a patient's tissue type,
specifically their human leukocyte antigen (HLA) tissue type.
S The closer the match between a patient's HLA markers and the
donor’s, the better for the patient.
S The chances that each full sibling is a donor is only 1 in 4 (or 25%)
S Given the small family sizes in developed nations, an HLA-
matched sibling can be found for only approximately 1/3 of
patients.
DONOR ELIGIBILITY
S Criteria to consider in selecting the optimal donor include:
HAPLOIDENTICAL SCT
S Requires just a half-match of the HLA antigens.
S Potential HLA-haploidentical donors include biological
parents, biological children, and full or half siblings
S With this option, we estimate that nearly all patients who
need allo-SCT have potential matches.
HOW HAPLO-SCT WORKS
S 3 days after transplant, a patient is given a high dose of a drug
called cyclophosphamide, which “re-boots” the immune system.
S The cyclophosphamide spares the donor's stem cells and allows
them to establish new blood cells and a new immune system.
S The budding immune system is re-trained to see the patient's
body as friend, preventing the patient from rejecting the
transplanted bone marrow.
ADVANTAGES OF
HAPLO-SCT
S Near universal availability of highly motivated donors
S Patients have an average of 2.7 potential HLA-haploidentical
donors among first degree relatives
S Rapid availability
S Ability to collect adequate doses of stem cells compared to
cord blood
ADVANTAGES OF
HAPLO-SCT
S Availability of the donor for repeated donations
S Needed to treat relapse or if the patient needs a stem cell boost
S Potentially lower chances of disease relapse
S With a higher level of mismatch between the donor and
recipient, the immune system reacts more strongly against the
cancer cells and lowers the chance of relapse- Graft-vs-Tumor Effect
OUTCOMES
• 6-months survival 85%
• 1-year cancer-free
survival 50%
• 1-year overall survival
62%
Brunstein C, et al. Blood. 2011
OUTCOMES
• The rate of grade II-IV
acute GVHD at day
100 is 32%
Brunstein C, et al. Blood. 2011
OUTCOMES
• The rate of chronic
GVHD at 1 year is
13%
Brunstein C, et al. Blood. 2011
OUTCOMES
• 1-year non-relapse
mortality 7%
• 1-year risk of relapse 45%
• The most frequent cause
of death is relapse
Brunstein C, et al. Blood. 2011
WHO SHOULD CONSIDER
HAPLO-SCT
S Patient with a type of blood cancer that needs allo-SCT
S No available HLA-matched sibling to donate
S Suitably matched unrelated donor CANNOT be found in
the donor registry
S OR if donor cannot have stem cell collection in a reasonable
time frame.
SUMMARY
S Haploidentical donor is a half-matched donor
S Potential donors are biological parents, biological children and
full and half siblings
S Most patients have >1 first degree relative willing & able to donate
S Advantages: rapid & universal availability, adequate doses of stem
cells and availability of donor for repeated donations
S The major challenge is the risk of GVHD
S Outcomes are very encouraging with the use of post-transplant
cyclophosphamide as part of the immune suppression regimen.
THANK YOU