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Hematopoietic Stem Cell Transplantation Lynn Savoie September 30, 2006.

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Presentation on theme: "Hematopoietic Stem Cell Transplantation Lynn Savoie September 30, 2006."— Presentation transcript:

1 Hematopoietic Stem Cell Transplantation Lynn Savoie September 30, 2006

2  Hematopoietic stem cell transplantation is potentially life-saving therapy in patients with SAA or MDS  Generally done when benefits thought to outweigh risks  Only allogeneic stem cell transplantation considered for these diseases therefore need a donor  Recipient and donor factors considered when assessing risk

3 General Concept  Blood cell production and immune system very closely linked and ultimately derived from bone marrow  Goal of high dose chemotherapy is to kill “defective” marrow – MDS or malfunctioning immune system – SAA  Replace with healthy marrow/immune system – Unfortunately not straightforward – mostly due to the new immune system

4 Risks  Infections –Potentially life or organ threatening  Due to neutropenia then immunosupression  Graft versus host disease –New immune system attacking recipient organs –Acute and chronic  Can affect many different organs –Potentially life or organ threatening –Potentially life altering  Graft failure –Rare but potentially fatal  Increased risk in aplastic anemia

5 Types of transplants 3 main factors

6  Type of donor –Related –Unrelated  Source of stem cell –Bone marrow –Peripheral blood –Cord blood  Conditioning Regimens –Myeloablative –Non-myeloablative –TBI containing

7 Type of donor Related vs. Unrelated

8 HLA Matching

9  HLA antigens –Proteins that help the immune system identify self vs. non-self –Genetically inherited together on chromosome 6 –Most important determinant of compatibility between donor and recipient –Each sibling pair has a 25% chance of inheriting the same HLA antigens –Approximately 30% of patients will have an HLA matched sibling

10 MOTHERFATHER M1M2 F1F2 CHILDCHILD M1F1 M2F1 CHILDCHILD M2F2 M1F2

11  Statistically unlikely for an extended family member to have 2 similar HLA groupings to patient just by chance  Able to find a unrelated donor in 70% of cases that is fully matched but not likely “identical”  Search can take time  More difficult in some ethnic groups due to genetic diversity  Generally increased and more severe graft versus host disease than with related donor

12 Other important factors in donor selection  Age –Younger generally better  Sex –Males generally better  Number of pregnancies –Few the better  Blood group –Same is better  CMV status –Negative donor is best if patient is negative  Health –Some health conditions preclude donation from a recipient perspective and some from a donor perspective

13 Source of Stem Cell Bone marrow vs. peripheral blood vs. cord blood

14  Still unclear whether bone marrow or peripheral blood stem cells better for recipients – studies ongoing –Currently using bone marrow in SAA and peripheral blood in MDS  Faster count recovery with peripheral blood stem cells but increase chronic graft versus host disease that may or may not translate into decreased relapse  Peripheral blood collection generally felt to be easier for donor but long term effects of G-CSF not known

15 Cord Blood Stem Cells  Rapidly available  Can accept a lesser match  Less graft versus host disease –Immune cells naive  Cell doses often a concern in adults –Because based on weight  Longer time to count recovery –can increase risk of infection due to prolonged neutropenia  Combinations or expansion being investigated

16 Conditioning Regimens Myeloablative vs. Non- myeloablative vs. TBI containing

17  Myeloablative –Generally used for SAA or MDS –Calgary regimens somewhat less myeloablative than other regimens…..but not technically non- myeloablative  Non-myeloablative –Unclear if really safer – generally more graft vs. host disease, particularly chronic due to mixture of cells present –Unclear if really a role in these disorders since don’t need much graft vs. leukemia effect-under investigation  TBI containing –Used in acute leukemia and at times in MDS if transforming – felt to decrease relapse

18 IBMTR, MDS, Sib HSCT

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20 EBMT, SAA

21 IBMTR, SAA, Sib HSCT

22 Calgary – FLUBUP +/- TBI  From 05/99 to 05/05  Matched related donor (MRD) –201 pts, survival 60%  Mismatched related donor (MMRD) –22 pts, survival 58%  Matched unrelated donor (MUD) –81 pts, survival 57%  Mismatched unrelated donor (MMUD) –40 pts, survival 38%

23 Calgary  MDS –MRD – 15 pts  Survival 79% –Alt – 10 pts  Survival 38%  SAA –MRD -20 pts  survival 90%, 100% in last 13 yrs –Alt – 10 pts  survival 38%

24 Indications

25  Myelodysplasia –Patients < 65 yrs of age –Before transfusion dependence and/or clinically significant neutropenia –Before transformation to acute leukemia  Severe aplastic anemia –If pt < 40 y.o. with sib match –If >60 y.o. pt > 40 y.o. with sib match trial after failure of immunosupression –No sib match – Failure of immunosupression X 2, consider after 1 if pt is young

26 Donor Search  Type sibling at presentation if HSCT at all a consideration now or later  Can identify an unrelated donor when HSCT strongly under consideration –Costs –Can only “hold” a donor for 3 months

27 UBMDR  Established in 1989  Administered by Canadian Blood Services  potential volunteer donors  If no Canadian donor can search the world

28 NMDP  United States  6 million donors  cord blood units

29 Bone Marrow Donors Worldwide  As of August 22, 2006 – donors and cord blood units  58 stem cell donor registries from 43 countries  38 cord blood banks from 21 countries  571 users from 420 organizations

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