Transcript No Slide Title

The University of Kansas Hospital
Blood & Marrow Transplant Program
Joseph McGuirk, D.O.
Clinical Program Director
Rationale for High-Dose Therapy
100%
Dose
Lethal Bone
Marrow Toxicity
Lethal Toxicity
to Other Organs
Allogeneic vs Autologous
Stem Cell Support
Allogeneic
Autologous
Age limits
40 - 55 (conventional)
up to 70 (mini-transplant)
60 - 75
Pros
Tumor free stem cells
Untreated stem cells
Graft vs Tumor
No GVHD
No rejection
Cons
GVHD
Graft rejection
Age & match restricted
Tumor contamination
Treatment damage
Relapse of disease
Recovery of Neutrophils Following Transplant
Days to Reach 500 Neutrophils/uL
120
100
Auto blood
80
60
Auto marrow
Allo marrow
40
20
0
0
10
20
Days Post Transplantation
30
40
Autologous Stem Cell Sources
1995 - 1998
Bon e Marrow (BM)
Perip h eral Blood (PB)
BM + PB
100
80
60
40
20
0
1995
1996
1997
1998
IBMTR/ABMTR 2000
Umbilical Cord BloodHypothesis
1) Superior proliferative
capacity will compensate
for low cell dose
2) Naïve immune system
reduced GVHD 
extension of donor pool
3) Unlimited supply, rapid
availability
Courtesy of Dan Weisdorf, M.D.
Allogeneic Course of BMT
•
•
•
•
•
•
•
Conditioning therapy
Transplantation
Immediate post-BMT period
Engraftment
Graft versus host disease
Disease-free survival
Long term effects
Conditioning Therapy
• Myelo-ablative therapy
* Irradiation: TBI, TLI
* High dose chemotherapy: Cytoxan, VP-16,
Busulfan, BCNU
• Immuno-ablative therapy
* Irradiation
* Chemotherapy - Cytoxan, Fludarabine
* Immunosuppressant: steroids, ATG
Allogeneic Course of BMT
•
•
•
•
•
•
•
Conditioning therapy
Transplantation
Immediate post-BMT period
Engraftment
Graft versus host disease
Disease-free survival
Long term effects
Allogeneic Course of BMT
•
•
•
•
•
•
•
Conditioning therapy
Transplantation
Immediate post-BMT period
Engraftment
Graft versus host disease
Disease-free survival
Long term effects
Immediate post-BMT Period
• High risk of infection
* Neutrophil/T-cell/B-cell/NK-cell/dendritic and
macrophage dysfunction or absence
* Mucositis
• High risk of bleed
* Low platelet count
• Chemo-radio therapy side effects
* Diarrhea and vomiting
* Liver problems - VOD
* Damage to other organs
Host immune
system defect
Phase I, Pre-engraftment,
< 30 days
Phase II, Post-engraftment,
30 - 100 days
Neutropenia,
mucositis and aGvHD
Neutropenia,
mucositis and aGvHD
and cGvHD
Impaired cellular and
humoral immunity
and cGvHD
(continuous risk)
Central line
Device risk
Phase III, Late phase,
> 100 days
Respiratory and enteric viruses
Allogeneic
patients
Herpes simplex virus
Cytomegalovirus
Varicella-zoster virus
Facultative Gram-neg. bacilli
Epstein-Barr virus lymphoproliferative ds
Staphlococcus epidermidis
Encapsulated bacteria
(eg., pneumococcus)
GI tract Streptococci species
All Candida species
Aspergillus species
KEY:
Aspergillus species
High incidence
Pneumocystis carinii
Low incidence
Toxoplasma gondii
Episodic
0
Strongyloides stercoralis
30
Days after transplant
100
360
Single-Organism Bacteremia In
EORTC-IATCG Trials
I
1973-78
Gram-negative
Bacteremia (%)
103 (71)
E. Coli
46
P. aeruginosa
18
Gram-positive
Bacteremia (%)
42 (29)
S. aureus
28
Coag-neg staph
5
S. pneumoniae
5
Other streptococci
0
Other gram-positive
4
III
1980-83
V
1986-88
IX
1992-94
85 (59)
38
23
76 (37)
45
14
53 (33)
22
10
58 (41)
14
24
4
14
2
135 (63)
20
49
4
46
16
108 (67)
10
53
0
40
5
CMV in BMT Patients
•
•
•
•
•
•
CMV interstitial pneumonitis
Mononucleosis syndrome
Hepatitis
Enteritis
Retinitis
Encephalitis
Aspergillosis and Other Molds After HCT:
Clinical Syndromes and Mortality
Syndromes
Aspergillus only:
Pneumonia
Brain
Oral invasive
Multiple organ
Other syndrome
Total
Other molds:
Mucomycosis
Rhizopus
Fusarium
Petrielidiem
Total
Total
# Patients
% Mortality
21
1
2
17
2
43
62
100
0
100
50
74
1
2
2
1
6
49
100
50
100
100
83
84
Causes of Death Following
Conventional Allogeneic Transplant
GvHD
Disease
IPn
Infection
Other
GvHD and IPn
Number of Different Respiratory Viruses per
Month During a Typical Season (1991-1992)
at Fred Hutchinson Cancer Research Center
F lu A
Para 1
Rh in o
RSV
Para 3
4
3
2
1
0
O ct
Nov
1991
Dec
Jan
F eb
Mar
Ap r
1992
May
Allogeneic Course of BMT
•
•
•
•
•
•
•
Conditioning therapy
Transplantation
Immediate post-BMT period
Engraftment
Graft versus host disease
Disease-free survival
Long term effects
Engraftment
CBC with manual differential on an allogeneic
PBSCT patient day + 11:
CBC
Manual differential
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDW
0.7 K/uL
2.57 M/uL
8.2 g/dL
23.8 %
92.7 fL
31.9 Pg
34.5 g/dL
15.0 %
PLT
28 K/uL
SEG
BAND
LYMP
MONO
VAR LYM
7%
4%
27 %
45 %
17 %
Absolute Neutrophil Count 77
Allogeneic Course of BMT
•
•
•
•
•
•
•
Conditioning therapy
Transplantation
Immediate post-BMT period
Engraftment
Graft versus host disease
Disease-free survival
Long term effects
Causes of Death Following
Conventional Allogeneic Transplant
GvHD
Disease
IPn
Infection
Other
GvHD and IPn
Risk Factors for GvHD
•
•
•
•
HLA mis-match or unrelated donor
Non-T cell depleted marrow
Older age
Female donors (?)
Graft versus Host Disease
• Skin rash
• Gastrointestinal - diarrhea, vomiting
• Liver - high bilirubin
Approach to GvHD
• Prevention
• Prevention
• Prevention
• Prevention
Prophylaxis for GvHD
• Pre-transplant
* T-cell depletion of the graft / ATG
• Post transplant (most commonly used)
* Cyclosporine
* Tacrolimus
* Steroids
* Methotrexate
* Anti-thymocyte globulin
* Monoclonal antibodies
* Mycophenolate mofetil (Cellcept)
Allogeneic Course of BMT
•
•
•
•
•
•
•
Conditioning therapy
Transplantation
Immediate post-BMT period
Engraftment
Graft versus host disease
Disease-free survival
Long term effects
Transplants for AML with Myeloablative Conditioning, 1998-2004
sease Status -
100
Probability, %
80
Early (N=3,174)
60
Intermediate (N=785)
40
20
Advanced (N=1,278)
P < 0.001
0
0
1
2
3
Years
CIBMTR data 2005
4
5
6
bling Transplants for ALL, Age >20 Years, 1998-2004
sease Status -
100
Probability, %
80
60
Early (N=879)
40
Intermediate (N=323)
20
Advanced (N=360)
P < 0.001
0
0
1
2
3
Years
CIBMTR data 2005
4
5
6
-identical Sibling Transplants for CML
us and Transplant Year -
100
Probability, %
80
CP, 2000-04 (N=2,344)
60
CP, 1996-99 (N=3,391)
AP, 2000-04 (N=278)
40
AP, 1996-99 (N=598)
20
P < 0.001
0
0
1
2
3
Years
CIBMTR data 2005
4
5
6
ling Transplants for Follicular Lymphoma, 1998-2004
and Conditioning Regimen -
100
Probability, %
80
Chemo-sensitive, RIC (N=195)
60
Chemo-sensitive, Myeloablative
(N=267)
Chemo-resistant, RIC (N=37)
40
Chemo-resistant, Myeloablative
(N=60)
20
P = 0.0258
0
0
1
2
3
Years
CIBMTR data 2005
4
5
6
RIC = Reduced Intensity
Conditioning
rvival after Transplants
stic Anemia, 1998-2004
r Type and Age 100
HLA-id sib, 20y (N=915)
Probability, %
80
HLA-id sib, >20y (N=822)
60
Unrelated, 20y (N=388)
40
Unrelated, >20y (N=212)
20
P < 0.001
0
0
1
2
3
Years
CIBMTR data 2005
4
5
6
Allogeneic Course of BMT
•
•
•
•
•
•
•
Conditioning therapy
Transplantation
Immediate post-BMT period
Engraftment
Graft versus host disease
Disease-free survival
Long term effects
Transplant Related Complications
Late
• Chronic GVHD
• Immune dysfunction
• Pulmonary complications
• Endocrine function
• Ocular
• Secondary malignancies
• Psychosocial issues
Challenges
 Lack of donors
 Advanced age/comorbidities
 Graft versus Host Disease (GvHD)
ALTERNATIVE DONOR AVAILABILITY
Related
Unrelated
5-6/6
4/6
3/6
Genetic Haploidentity
6/6 (Serology)*
Phenotypic Identity
100
75
50
25
0
All patients
Donor found
Caucasian
Transplant available
Non-caucasian
Transplant available
Range
Umbilical Cord BloodHypothesis
1) Superior proliferative
capacity will compensate
for low cell dose
2) Naïve immune system
reduced GVHD 
extension of donor pool
3) Unlimited supply, rapid
availability
Courtesy of Dan Weisdorf, M.D.
Rate per 100,000 Population
AML
ALL
CML
CLL
MDS
40
30
20
10
0
<20 20- 25- 30- 35- 40- 4524 29 34 39 44 49
50- 55- 60- 65- 70- 75- 80- 85+
54 59 64 69 74 79 84
Ages
Efferent Phase
Afferent Phase
Pathophysiology of GVHD
APC
Conditioning
Regimen
1. Antigen presentation
Interleukin-1
Interleukin-2
T cell
Interleukin-2
receptor
2. Activation of
individual T cells
3. Clonal proliferation
Lymphokine dysregulation
Target cell
death
CTL
NK cell
Macrophage
Ferrara and Deeg, NEJM, 1991
BMT Staff
Physicians:
Dr. Abhyankar
Dr. Bodensteiner
Dr. Deauna
Dr. Ganguly
Dr. McGuirk
Dr. Skikne
Nurse Practitioners:
Teresa Hoffman
Jan Lewis
Julie Wilhauk
Transplant Coordinators:
Beth Harvey
Ellen Maxwell
Janet Sherman
Cell Processing Lab:
Shaun DeJarnette
Anne Hirner
Dean Merkel
Khai Trieu
Supportive Staff:
Jennifer Bunch
Meredith Foster
Kathy Curran
Tiffany Guinnip
Kelly Vandiver
Denise Ishmael
Clint Divine
PharmD:
Tanya Folker
Casey Williams
Administration:
Mary Perrin
Jeff Wright
Inpatient and
Outpatient
Nursing Staff
Alternative Donor Sources:
Matched Unrelated Donors
Potential limitations:
1. Certain ethnic groups under-represented
2. Time associated obtaining graft
3. Availability of donor cells for posttransplant immunotherapy
4. Cost
5. Serologic vs. molecular match
Umbilical Cord BloodHypothesis
1) Superior proliferative
capacity will compensate
for low cell dose
2) Naïve immune system
reduced GVHD 
extension of donor pool
3) Unlimited supply, rapid
availability
Courtesy of Dan Weisdorf, M.D.
Survival after partial matched UCBT
vs. 6/6 URD BMT in Children
0.8
Proportion Surviving
1.0
Proportion Surviving
1.0
0.8
0.6
UCBT
0.4
BMT-MTX
53%
41%
BMT-TCD
0.6
56%
UCBT 52%
0.4
0.2
0.2
p = 0.40
0.0
0
6
12
Months
18
24
p > 0.80
0.0
0
6
12
18
Months
24
UCBT is now a standard option for pediatric leukemia
Barker et al, Blood, 2001: 97, 2957
CUMULATIVE INCIDENCE, %
URD UCB vs. BMT in Adults with Leukemia:
Neutrophil Recovery
100
BM, matched (n = 365)
BM, 1 Ag MM (n = 83)
80
UCB, 1 Ag MM (n = 166)
60
40
Median dose: 2.2 x 107/kg
20
0
0
20
40
60
80
100
DAYS
Laughlin et al, NYBC / IBMTR: Blood, 2003: 102, 244a
Solution: Use 2
Courtesy of Dan Weisdorf, M.D.
Cumulative Incidence
Neutrophil Engraftment (n = 21)
100%
1.0
0.8
0.6
Median: 23 days
(range 15-41)
0.4
0.2
I
0.0
I
0
7
14
21
Days
28
35
42
Disease-Free Survival
1.0
Tx in Remission (n = 15):
72% (95% CI: 49-95)
Probability
I
0.8
I
I
I
I
I
0.6
I
I
Tx in Relapse (n = 8):
25% (95% CI: 0-64)
0.4
I
0.2
p = 0.04
0.0
0
2
4
6
Months
8
10
12
Overview
Advantages:
 UCB advantages of speed, HLA mismatch
Disadvantages:
 Adult UCBT limited by dose
 High TRM independent of cell dose
 Delayed immune reconstitution
 Lack of cells for post-tx immunotherapy
 GvHD
Mismatch Family Donor
Transplant (Haplo-identical)
 Most everyone has a readily
available donor
Haploidentical
Transplantation
Strategies to improve results:
1. Graft failure
increase intensity of conditioning regimen
increase immunosuppression
increase progenitor cell dose
2. GVHD
TCD
increase immunosuppression
NK cell effect
Haploidentical
Transplantation
Strategies to improve results (cont’d):
3. Leukemia relapse
 Increase intensity of conditioning regimen
 Post-transplant immunotherapy for MRD (DLI)
 Donor selection - KIR mismatch
4. Delayed immuno-reconstitution
 Adult patient with compromised thymic function
 Post-transplant immunotherapy
 Growth factor post transplant
 Cytokine administration
 DLI
Haplo - identical Transplant Protocol
Patient
Thiotepa
10mg/kg
Day - 7
-6
T-cell depleted
PBSC infusion
ATG 2.5mg/kg/d
-5
-4
-3
-2
-1
0 +1 +2
TBI 8cGy
Fludarabine 40 mg/m2/d
single fraction
w/lung shield to 4cGy
Donor
Day - 5
-4
-3
-2
G-CSF 8mcg/kg BID
-1
0 +1 +2
T- cell deplete
T- cell deplete
Miltenyi
Device
HLA-haplotype-mismatched Transplants With and Without
KIR Ligand Incompatibility in the GVH Direction
KIR ligand incompatibility in GVH direction
Number of transplants
No
58
Yes
34
Donors displaying antirecipient NK clones
Disease
ALL
AML
Transplantation outcomes
Rejection
Acute GVHD, > grade II
Probability of relapse at 5 years
ALL
AML
1/58
34/34*
21
37
14
20
* p < 0.01; **p < 0.0008 (22)
15.5%
13.7%
0%*
0%*
90%
75%
85%
0%**
Ruggeri, Science 2002
Background
 NK alloreactivity
Haplo Donor – Advantages
and Disadvantages
 Almost all SCT pts will have immediate
access to a donor
 Stronger graft vs tumor effect due to
HLA disparity and NK alloreactivity
 Increased Rejection
 Increased GvHD
 Delayed Immune Reconstitution
 Leukemia relapse
Challenge # 2
 Advanced age
 Comorbidities
Rate per 100,000 Population
AML
ALL
CML
CLL
MDS
40
30
20
10
0
<20 20- 25- 30- 35- 40- 4524 29 34 39 44 49
50- 55- 60- 65- 70- 75- 80- 85+
54 59 64 69 74 79 84
Ages
Rationale for High-Dose Therapy
100%
Dose
Lethal Bone
Marrow Toxicity
Lethal Toxicity
to Other Organs
Effect of T-Cell Depletion and GVHD on
Probability of Relapse in Leukemia
Probability of Relapse
1.0
0.8
Twins
0.6
T depletion
0.4
No GVHD
Acute GVHD only
Chronic GVHD only
0.2
Acute+Chronic GVHD
0.0
0
12
24
36
48
60
72
Months
Adapted from: Horowitz M et al., Blood 1990; 75; 55-62.
Probability of Relapse in Leukemia Patients
No T-cell Depletion Vs. T-cell Depletion
Probability of Relapse
1.0
No t T -cell d ep leted
T -cell d ep leted
0.8
0.6
172
0.4
89
159
0.2
260
560
452
0.0
AL L
AM L
Disease
CM L
Donor Leukocytes for CML
Ref
Pts
Cell Dose
8
x10 /kg
Kolb
3
4.4-7.4
3/3
2/3
0/3
Bar
6
0.34-5.2
5/6
5/5
2/5
Helg
3
3.8-12.3
3/3
3/3
3/3
Hertenstein
8
3.0-5.5
6/8
5/6
6/6
Drobyski
8
2.5-5.0
7/8
7/7
4/7
Porter
11
0.9-7.9
7/11
7/7
7/7
Van Rhee
14
0.6-10.1
10/14
8/10
2/10
Total
53
0.34-12.3
41/53
37/41
24/41
REM
GVHD/CR
Aplasia
Disease Sensitivity to GVM Effects
Sensitive
-CML
-low-grade
lymphoma
-Mantle cell
lymphoma
-CLL
Intermediate
Insensitive
-AML
-ALL
-intermediate-high-grade
grade lymphoma
lymphoma
-Multiple myeloma
-Hodgkin’s disease
Mini - Allogeneic Transplant Protocol
Fludarabine 40 mg/m2/d
Day - 6
-5
Busulfan
8mg/kg
total dose
-4
-3
-2
ATG 1.5mg/kg/d
Donor
PBSC
-1
0
+1
*Mini-dose MTX
(d +1,+3,+6)
*Tacrolimus 0.03mg/kg/d
* Tacrolimus and MTX = GVHD prophylaxis
Engraftment Profile
aGVHD
Disease regression
% Donor chimerism
100
Taper CSA
80
Donor T-cell
engraftment
60
40
Donor myeloid
engraftment
20
0
0
10
30
40
50
60
70
80
90
100
Days post transplant
120
130
150
170
190
Mini-transplant
Future applications:
 Older patients
 Younger patients with end-stage
organ dysfunction
 Relapse s/p autologous
transplant
 Indolent diseases
A Continuuum of non-Myeloablative and
Reduced Intesity Conditionin Regimens
Immunosuppression
Cy+ATG+Thymic XRT
Genetic disparity
Haplo/
T-cell depl.
TBI+Cy
TBI+F+TT
F+TBI
2Gy
MUD
FM
F+Cy
Bu8+F+ATG
Bu16+Cy
Matched
sibling
TBI-2Gy
Flag-Ida
BEAM
Myelsuppression
CLL/
LGL
CML
LCL
MM
Aggressiveness of malignancy
AML
Challenge # 3
 Graft versus Host Disease
Causes of Death Following
Conventional Allogeneic Transplant
GvHD
Disease
IPn
Infection
Other
GvHD and IPn
Efferent Phase
Afferent Phase
Pathophysiology of GVHD
APC
Conditioning
Regimen
1. Antigen presentation
Interleukin-1
Interleukin-2
T cell
Interleukin-2
receptor
2. Activation of
individual T cells
3. Clonal proliferation
Lymphokine dysregulation
Target cell
death
CTL
NK cell
Macrophage
Ferrara and Deeg, NEJM, 1991
Haptoglobin
PLASMA PROTEIN SYTHESIZED IN LIVER AND
NEUTROPHILS
 Binds free hemaglobin


clearance by macrophages
- Antioxidant
- Bacteriostatic (Fe++ enhances bacterial growth and virulence)
 Re-establishment of homeostasis after local or systemic infection
 Broad range of anti-inflammatory activities
Theilgaard-Monch Blood 2006, Vol. 108 #1
Arredonani Immunology 2005 114
Arredonani Immunology 2003 108
Haptoglobin
 Two variants of HP gene (Hp 1 and Hp2)
 Gene duplication a chain
 Common b-chain
 Results + 3 major phenotypes
Hp1-1, Hp2-2, Hp 2-1
 Hp1-1 biologically most effective binding Hb
 Hp 2-2 biologically least active
Clinical characteristics of the
allo-HSCT patients
Sex/
Age
GVHD
Grade
Organ involvement
Conditioning
Regimen
Skin eye oral
Liver
Skin eyes oral gut
Skin eye oral
Skin oral eye liver
Skin eye oral
Skin Gut
Skin Gut
Skin
Eye oral gut
Skin, oral
Skin eye
Oral
Skin, lung
Cy/TBI/ATG
Bu/Cy
Bu/Cy
Cy/TBI
Bu/Cy
Cy/TBI
Cy/TBI
Cy/TBI
Cy/TBI
Bu/Cy
Cy/TBI/ATG
Cy/TBI
BEAC
Cy/TBI/ATG
Tac
Tac
Tac
Tac
Tac
Tac
CSA
CSA
CSA
Tac
Tac
Tac
Tac
Tac
/
/
/
/
/
/
/
/
/
/
/
/
/
/
Skin gut liver
Skin
Skin Gut
Gut
Bu/Flu/ATG
Cy/TBI/ATG
Vp-16/TBI
Cy/TBI/ATG
Tac
Tac
Tac
Tac
-
Cy/TBI
Cy/TBI/ATG
Cy/TBI/ATG
Cy/TBI/ATG
Bu/Cy/ATG
Cy/TBI/ATG
Tac
Tac
Tac
Tac
Tac
Tac
Diagno
sis
1.*^
2.*^
3.^
4.*^
5.*^
6.^
7.*^
8.*^
9.*^
10.*^
11.*^
12.*^
13.^
14.*^
F/40
M/28
M/48
F/42
F/42
M/49
F/29
F/58
F/45
M/38
F/54
M/54
M/54
M/50
AML
CML
AML
AML
IMF
CLL
CML
AML
AML
CML
SAA
NHL
NHL
NHL
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Chronic
Extensive
Extensive
Extensive
Extensive
Extensive
Limited
Extensive
Extensive
Extensive
Extensive
Limited
Extensive
Limited
Extensive
15.*^
16.
17.^
18.*^
M/46
M/47
F/39
F/20
MM
CLL
ALL
AML
Acute
Acute
Acute
Acute
Grade
Grade
Grade
Grade
19.^
20.*^
21.^
22.*^
23.*^
24.*^
F/58
M/38
M/23
F/49
M/31
F/54
MDS
AML
AML
AML
CML
NHL
No
No
No
No
No
No
GVHD
GVHD
GVHD
GVHD
GVHD
GVHD
-
IV
II
II
II
GVHD
Prophylaxis
Infections
Outcome
MTX
MTX
MTX
MTX
MTX
MTX
MTX
MTX
MTX
MTX
MTX
MTX
MTX
MTX
None
None
None
None
None
None
CMV
None
CMV
None
None
None
None
None
Alive, no active GVHD
Alive, no active GVHD
Alive, active GVHD
Dead, AML relapse
Alive, active GVHD
Dead, GVHD
Dead, CMV pneumonia
Dead, unknown causes
Dead, CMV/organ
failure
Alive, active GVHD
Alive, no active GVHD
Alive, active GVHD
Alive, no active GVHD
Dead, GVHD
/
/
/
/
MTX
MTX
MTX
MTX
None
None
None
None
/
/
/
/
/
/
MTX
MTX
MTX
MTX
MTX
MTX
None
None
None
None
None
None
Dead, GVHD/sepsis
Dead, pulmonary
failure
Dead, CMV pneumonia
Alive, no active GVHD
Dead, AML/MDS relapsed
Dead, relapsed
Alive CR
Relapsed
Alive CR
Dead, heart failure
AML: acute myelogenous leukemia; CML: chronic myelogenous leukemia; IMF: idiopathic myelofibrosis; CLL: chronic lymphocyte leukemia: SAA: severe aplastic anemia; NHL: NonHodgkin's Lymphoma; ALL: acute lymphoblastic leukemia; MM: multiple myeloma; MDS: myelodysplastic syndrome; * done of 2-DE gel assay; ^ done of Hp Elisa assay.
Serum Hp polymorphism in the
patients and normal controls
Patients
Chronic GVHD n= 14
Acute GVHD
n= 4
no GVHD
n= 6
Normal Donor n= 12
Hp phenotype
1-1
2-1
2-2
2(14.3%)
0
1(16.7%)
0
5(35.7%)
3
5(83.3%)
10(83.3%)
7(50%)
1
0
2(16.7%)
Hp characterized by molecular heterogeneity
 3 major phenotypes: Hp 1-1, Hp2-2, Hp 2-1
- differing biologic activities
Hp1-1 anti-oxidation
Hb binding
.OH
Protective in D.M.
Hp 2-2 macrophoge activation
Myocardial damage in acute MI
Independent risk of MI
Over represented in Autoimmmune disorders
eg RA, SLE
Chaperle New England Journal of Med. 1987 307
Levy New England Journal of Med 200 343
Rantapaa Hum Hered 1985 35
Rantapaa Hum Hered 1988 38
 Serum Hp levels may be related to
cGVHD development
 Specific Hp polymorphisms may be
associated with cGVHD development.
BMT Staff
Physicians:
Dr. Abhyankar
Dr. Bodensteiner
Dr. Deauna
Dr. Ganguly
Dr. McGuirk
Dr. Skikne
Nurse Practitioners:
Teresa Hoffman
Jan Lewis
Julie Wilhauk
Transplant Coordinators:
Beth Harvey
Ellen Maxwell
Janet Sherman
Cell Processing Lab:
Shaun DeJarnette
Anne Hirner
Dean Merkel
Khai Trieu
Supportive Staff:
Jennifer Bunch
Meredith Foster
Kathy Curran
Tiffany Guinnip
Kelly Vandiver
Denise Ishmael
Clint Divine
PharmD:
Tanya Folker
Casey Williams
Administration:
Mary Perrin
Jeff Wright
Inpatient and
Outpatient
Nursing Staff