slide1 l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Introduction/Overview Specific Diseases Alternative Stem Cell Transplantation Supportive Measures PowerPoint Presentation
Download Presentation
Introduction/Overview Specific Diseases Alternative Stem Cell Transplantation Supportive Measures

Loading in 2 Seconds...

play fullscreen
1 / 45

Introduction/Overview Specific Diseases Alternative Stem Cell Transplantation Supportive Measures - PowerPoint PPT Presentation


  • 158 Views
  • Uploaded on

History of BMT Definitions AML ALL Breast cancer NHL. Rationale Stem cell sources MDS Multiple Myeloma Hodgkin’s disease. Overview of Blood and Marrow Transplantation. Introduction/Overview Specific Diseases Alternative Stem Cell Transplantation Supportive Measures.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Introduction/Overview Specific Diseases Alternative Stem Cell Transplantation Supportive Measures' - andrew


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

History of BMT

Definitions

AML ALL

Breast cancer

NHL

Rationale

Stem cell sources

MDS

Multiple Myeloma

Hodgkin’s disease

Overview of Blood and Marrow Transplantation

  • Introduction/Overview
  • Specific Diseases
  • Alternative Stem Cell Transplantation
  • Supportive Measures
slide3

36

Erythrocyte

33,61

9,36,41,42,61

Platelet

Neutrophil 10

13,15,33,38

13,16,33

13,16,11b

Eosinophil

Basophil

11b,13,14,15,33,36

13,14,15,33

13,14,15,33

Monocyte

11b,16,56

NK Cell

19,20,22

9,10,19,20,24,38

10,19,24,38

B-Cell

2,3,5,7

2,3,5,7

7

2,3,5,7,38

T-Cell

Immunologic Marker Expression

In Hematopoiesis

BFU-E

CFU-E

Reticulocyte

Myeloid

SC

CFU-Mega

Megakaryocyte

Myeloblast

Promyelocyte

Myelocyte

Pluripotent

Stem Cell

Monoblast

Promonocyte

56

NK Precursor

Lymphoid

SC

Pre-B

B Progenitor

CD34+

T Progenitor

Sub Cortical

Cortical Thymocyte

Medullary

Thymocyte

history of stem cell transplantation
HISTORY OF STEM CELL TRANSPLANTATION
  • Turn of the 20th century, scientists began to formulate the idea that a small number of cells in the marrow, referred to as “stem cells”, might be responsible for the development of all blood cells.
  • Marrow injury was an important and potentially lethal side effect of exposure to the atomic bomb or to industrial accidents in the atomic weapons industry.
  • Spurred by the Atomic Energy Commission's and the military’s concern about the spread of nuclear technology and weapons, studies of bone marrow transplantation were initiated.
slide5

Lethal TBI Syndromes

  • Cerebral Syndrome
  • Intestinal Syndrome
  • Bone Marrow Syndrome

12,000-1,000,000 cGy

1,200-10,000 cGy

500-700 cGy

slide6

Effects of Spleen Shielding on Mice

After Total Body Irradiation

  • TBI Dose
  • (cGy)

Spleen

Shielding

Survival

700

700

1050

1050

1200

Yes

No

Yes

No

Yes

96.3%

0.0%

30.4%

0.0%

0.0%

slide7

Rationale for High Dose Therapy and Hematopoietic Stem Cell Transplantation

Death due to

other organ

toxicity

Increasing Dose

Death due to

Marrow toxicity

Treatment Necessary for Cure

conditioning preparative regimen
CONDITIONING (PREPARATIVE) REGIMEN
  • To suppress the patient’s immune system from rejecting the stem cells.
  • To eliminate the cancer
slide9

Stem Cell Sources

  • Bone Marrow
  • Blood
  • Umbilical Cord
  • Fetal Liver
types of stem cell transplants
TYPES OF STEM CELL TRANSPLANTS
  • AUTOLOGOUS TRANSPLANTS - Patients receive their own stem cells.
  • SYNGENEIC TRANSPLANTS - Patients receive stem cells from their identical twin.
  • ALLOGENEIC TRANSPLANTS - Patients receive stem cells from someone other than the patient or an identical twin.
slide11

Potential Stem Cell Sources

  • Autologous stem cells
  • HLA-matched related donors
  • HLA-matched unrelated donors
  • Haploidentical related donors
  • Umbilical cord blood
slide12

Autologous Bone Marrow Transplantation

Criteria

  • Tumor with dose response curve
  • Tumor sensitive to myelosuppressive agents
  • Purging techniques if marrow is contaminated
  • with tumor
  • - Preserve stem cells
  • - Eradicate tumor
  • Technique for peripheral stem cell collections
  • Minimal tumor burden
  • Marrow ablation
slide13

Host

Graft

Immunosuppression

Preparative regimen

Post-transplant Rx

Disease effects

Sensitization

Stem cell dose

T-cell dose (CD8)

Graft facilitating cells

Stromal stem cells?

Allogeneic Engraftment

With reduced immunosuppression in current NST regimen, we rely on graft cells (stem, T-

and accessories cells) to overcome rejection.

slide14

Host

Graft

Immunosuppression

Preparative regimen

Post-transplant Rx

Disease effects

Sensitization

Stem cell dose

T-cell dose (CD8)

Graft facilitating cells

Stromal stem cells?

Allogeneic Engraftment

With reduced immunosuppression in current NST regimen, we rely on graft cells (stem, T-

and accessories cells) to overcome rejection.

slide15

Host

Graft

Immunosuppression

Preparative regimen

Post-transplant Rx

Disease effects

Sensitization

Stem cell dose

T-cell dose (CD8)

Graft facilitating cells

Stromal stem cells?

Engraftment

With reduced immunosuppression in current NST regimen, we rely on graft cells (stem, T-

and accessories cells) to overcome rejection.

slide16

Graph Rejection/

GVHD

Recurrent

Disease

human leukocyte associated hla antigens
HUMAN LEUKOCYTE-ASSOCIATED (HLA) ANTIGENS
  • A set of proteins on the surface of their cells.
  • A set of HLA proteins are inherited equally from patients.
  • Chances of having a full match are ~ 1 in 3.
  • The higher the number of matching HLA antigens, the greater the chance that the patient’s body will accept the donor’s stem cells.
identification of a related allogeneic donor
IDENTIFICATION OF A RELATED ALLOGENEIC DONOR
  • Identical Twin < 1%
  • HLA-matched Sibling
  • 6 antigen 25 - 30%
  • 5 antigen 10 - 20%
  • 4 antigen 50 - 60%
  • 3 antigen > 90%
slide20

Stem Cell Source

Allogeneic

Autologous

Donor Availability

Tumor Content

GVHD/GVL

Tx-related Mortality

Limited

None

Possible

10-40%

Majority

Possible

None

0-10%

slide21

Alternatives to HLA-matched Related Donors

  • HLA-matched unrelated donors
  • Cord Blood Transplantation
  • -Related
  • -Unrelated
  • HLA-mismatched related Donors
  • (Haplo-identical)
  • (Autologous stem cell transplantation)
slide22

Allogeneic

Autologous

Majority

Possible

None

0-10%

Donor Availablity

Tumor Content

GVHD/GVL

Tx-related Mortality

Limited

None

Possible

10-40%

Stem Cell Source

slide23

Advancements in Allogeneic

Stem Cell Transplantation

  • Alternative donors
  • - Unrelated bone marrow donors
  • - Stored cord blood
  • Ganciclovir
  • Hematopoietic growth factors
  • Blood as stem cell product
  • Donor lymphocyte infusions
slide24

HLA-matched relative

Unrelated donor

Cord blood

HLA-mismatched relative

25-30%

10-40%

50%

1 Ag

2 Ag

3 Ag

10%

50%

90%

Stem Cell Donor Availability

slide25

Alternatives to HLA-matched

Related Donors

  • HLA-matched unrelated donors
  • Cord blood transplantation
  • - Related
  • - Unrelated
  • HLA-mismatched related donors
  • (Haplo-identical)
  • Autologous stem cell transplantation
slide26

The NMDP Network

98

Donor Center

(8 foreign)

Coordinating Center

Minneapolis, MN

114

Collection

Centers

(15 foreign)

112

Transplant

Centers

(23 foreign)

ASCO 1998

slide27

88

89

90

91

92

93

94

95

96

97

98

Volunteer Marrow Donors

40

Total Donors

3,134,601

30

Volunteers in Registry

(Millions)

20

Fully Typed

Donors

10

0

Year

ASCO 1998

slide28

Probability of Finding a Six-antigen HLA Matched Donor

North America Caucasian

Pool Size

Japanese

100

1000

10,000

100,000

500,000

1,000,000

0.0%

11.9%

54.2%

90.6%

99.9%

99.9%

0.0%

3.3%

20.7%

60.0%

85.7%

93.7%

slide29

Preliminary Search

54.7%

25.6%

Formal Search

DR Typing

43.5%

7.2%

Confirmatory Typing

Confirmatory Typing

20.2%

2.1%

Work-Up

Work-Up

15.8%

1.6%

Transplant

Beatty et al., 1995

slide30

Waste product of normal deliveries

Readily available

Increased availability for minorities

Decreased transmission of viruses (e.g. CMV)

One unit rescues one patient/no DLI

Theoretical risk of genetic disease transmission

Theoretical risk of maternal cell contamination (GVHD)

Efficacy in adults unknown

Cord Blood Transplantation

Advantages

Disadvantages

slide31

Nearly all patients have a donor

Share major (e.g. HLA-C) and minor hitocompatibility antigens

Immediate donor availability

HLA Barriers:

-Graft rejection

-GVHD

-Immune

dysregulation

Haplo-identical HSCT

Advantages

Disadvantages

slide32

Referral

Simultaneous Search URD, BM and UCB

Non-urgent or

Non-malignant

Diagnosis

Urgent

6/6 HLA-matched BM

Donor Available?

4-6 HLA-matched UCB(s)

Identified with Cell Dose

>1.5 x 107 NC/kg?

Yes

No

Yes

UCBT

BMT

Strategy for Donor Selection

slide33

Diagnosis

Urgency of transplant

HLA typing

Cell dose available in UC units(s)

Age

Chemo-sensitivity

Choice of Stem Cell Source

slide34

Diseases Treated by Bone Marrow Transplantation

Acute lymphocytic leukemia

Chronic myelogenous leukemia

Chronic lymphocytic leukemia

Non-Hodgkin’s lymphoma

Hodgkin’s disease

  • Aplastic anemia
  • Thalassemia
  • Sickle cell anemia
  • Immunodeficiency disorders
  • Acute myelogenous leukemia
  • Myelodysplastic syndrome
  • Multiple myeloma

Armitage, NEJM 1994

slide35

Indications for Blood and Marrow Transplantation in North America

(2000)

4,500

4,000

Allogeneic (Total N=67,000)

Autologous (Total N=11,000)

3,500

3,000

2,500

Transplants

2,000

1,500

1,000

500

0

Non-

Hodgkin

Lymphoma

AML

Hodgkin

Disease

CML

MDS/

Other

Leukemia

CLL

Multiple

Myeloma

Breast

Cancer

Other

Cancer

ALL

Non-

Malignant

Disease

Ovarian

Cancer

slide36

Annual Numbers of Blood and Marrow Transplants Worldwide

(1970-2000)

40

30

Autologous

Number of Transplants

(Thousands)

20

10

Allogeneic

0

1970

1975

1980

1985

1990

1995

2000

Year

slide37

Alternative donors

Unrelated bone marrow donors

Stored cord blood

Ganciclovir

Hematopoietic growth factors

Blood as a stem cell product

Donor lymphocyte infusions

Advancements in Allogeneic

Stem Cell Transplantation

slide38

Efficacy varies:

High incidence of GVHD (40-60%)

High correlation of GVHD and response

Optimal dose, frequency and timing remain undetermined

CML = 50-90%

AML = 25-50%

Donor Lymphocyte Infusions

slide39

Allogeneic Hematopoietic Stem Cell Transplantation

Old Paradigm

New Paradigm

The allograft is a rescue product to replace the defective stem cells following ablation with cytotoxic therapy.

Main therapeutic component of an allogeneic stem cell transplant is the “graft vs. leukemia” effect mediated by T-cells in the allograft.

slide40

Advantages:

-Decreased acute toxicity

-Application to older and/or morbid patients

-Application to broader spectrum of diseases

Disadvantages:

-Toxicity of the procedure (GVHD)

-Loss/decrease in anti-tumor activity from

cytotoxic chemotherapy/radiation

Non-myeloablative Regimens in Allo SCT

slide41

Preparative Regimen

A

Host

Donor

B

B

B

B

B

B

B

B

± DLI

HSCT

A

A

A

B

B

A

B

B

B

AL

AL

AL

A

B

B

B

A

B

Mixed

Chimera

Complete

Chimera

Recipient

Donor

Non-myeloablative Hematopoietic

Cell Transplant

slide43

Hematopoetic Stem Cell Transplantation for Auto-immune Diseases

  • Multiple Sclerosis
  • Rheumatoid Arthritis
  • Scleroderma
etib research hematopoietic stem cell transplantation
ETIB RESEARCH HEMATOPOIETIC STEM CELL TRANSPLANTATION
  • StrategyTactic
  •  Rejection Immune-depleting chemo
  • Tc2 cells
  • GVHD Th2 cells
  • GVL Tc2 cells
  • Id vaccines
  • Immune reconstitution Cytokines (IL-7)
slide45
“Diseases desperate grown
  • By disparate appliance
  • Are reliev’d,
  • Or not at all”

After Shakespeare