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HAPLOIDENTICAL STEM CELL TRANSPLANT

HAPLOIDENTICAL STEM CELL TRANSPLANT. Zeina Al-Mansour, MD Assistant Professor Hematology/Bone Marrow Transplant Loyola University Medical Center May 21 st , 2016. OUTLINE. Advantages of this approach Outcomes Who Should Consider Haplo-SCT Summary. Introduction

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HAPLOIDENTICAL STEM CELL TRANSPLANT

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  1. HAPLOIDENTICAL STEM CELL TRANSPLANT Zeina Al-Mansour, MD Assistant Professor Hematology/Bone Marrow Transplant Loyola University Medical Center May 21st, 2016

  2. OUTLINE • Advantages of this approach • Outcomes • Who Should Consider Haplo-SCT • Summary • Introduction • HLA Antigens & HLA Matching • Donor Options, Selection & Eligibility • How Haplo-SCT Works

  3. INTRODUCTION • Allogeneic Stem Cell Transplant (Allo-SCT) is a potentially curative therapy for a wide variety of malignant and non-malignant hematologic disorder. • Stem cell: mother of all types of blood cells, divides and differentiates to give rise to all types of blood cells. • Obtained from the bone marrow or peripheral blood of a related or unrelated donor

  4. HLA Antigens • HLAs are proteins — or markers — 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.

  5. HLA Matching

  6. Role of HLA Matching • Increases the likelihood of a successful transplant • Improves engraftment—when the donated cells start to grow and make new blood cells in you. • Reduces the risk of complications after transplant, especially graft-versus-host disease (GVHD). • GVHD is a potentially serious complication. • Occurs when the immune cells, which are part of the donated marrow or cord blood, attack your body.

  7. DONOR OPTIONS • Matched sibling donor • Matched unrelated donor • Alternative options: • Half-matched related donor  HAPLOIDENTICAL • Cord blood transplant

  8. DONOR SELECTION • Normally, we look for a donor who matches a patient's tissue type, specifically their human leukocyte antigen (HLA) tissue type. • The closer the match between a patient's HLA markers and the donor’s, the better for the patient. • The chances that each full sibling is a donor is only 1 in 4 (or 25%) • Given the small family sizes in developed nations, an HLA-matched sibling can be found for only approximately 1/3 of patients.

  9. DONOR ELIGIBILITY • Criteria to consider in selecting the optimal donor include: Donor Health Age Gender Blood type HLA Mismatch Relation to patient

  10. HAPLOIDENTICAL SCT • Requires just a half-matchof the HLA antigens. • Potential HLA-haploidentical donors include biological parents, biological children, and full or half siblings • With this option, we estimate that nearly all patients who need allo-SCT have potential matches.

  11. HOW HAPLO-SCT WORKS • 3 days after transplant, a patient is given a high dose of a drug called cyclophosphamide, which “re-boots” the immune system. • The cyclophosphamide spares the donor's stem cells and allows them to establish new blood cells and a new immune system. • The budding immune system is re-trained to see the patient's body as friend, preventing the patient from rejecting the transplanted bone marrow.

  12. ADVANTAGES OF HAPLO-SCT • Near universal availability of highly motivated donors • Patients have an average of 2.7 potential HLA-haploidentical donors among first degree relatives • Rapid availability • Ability to collect adequate doses of stem cells compared to cord blood

  13. ADVANTAGES OF HAPLO-SCT • Availability of the donor for repeated donations • Needed to treat relapse or if the patient needs a stem cell boost • Potentially lower chances of disease relapse • 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

  14. OUTCOMES • 6-months survival 85% • 1-year cancer-free survival 50% • 1-year overall survival 62% Brunstein C, et al. Blood. 2011

  15. OUTCOMES • The rate of grade II-IV acute GVHD at day 100 is 32% Brunstein C, et al. Blood. 2011

  16. OUTCOMES • The rate of chronic GVHD at 1 year is 13% Brunstein C, et al. Blood. 2011

  17. 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

  18. WHO SHOULD CONSIDER HAPLO-SCT • Patient with a type of blood cancer that needs allo-SCT • No available HLA-matched sibling to donate • Suitably matched unrelated donor CANNOT be found in the donor registry • OR if donor cannot have stem cell collection in a reasonable time frame.

  19. SUMMARY • Haploidentical donor is a half-matched donor • Potential donors are biological parents, biological children and full and half siblings • Most patients have >1 first degree relative willing & able to donate • Advantages: rapid & universal availability, adequate doses of stem cells and availability of donor for repeated donations • The major challenge is the risk of GVHD • Outcomes are very encouraging with the use of post-transplant cyclophosphamide as part of the immune suppression regimen.

  20. THANK YOU

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