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 Advantages of this

approach
S HLA Antigens & HLA
Matching S Outcomes

S Donor Options, S Who Should Consider

Selection & Eligibility Haplo-SCT

S How Haplo-SCT Works S Summary

 INTRODUCTION

S Allogeneic Stem Cell Transplant (Allo-SCT) is a potentially

curative therapy for a wide variety of malignant and non-
malignant 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