Understanding BMT: Before, During,

and After Transplant

(BMT 101)

Corey Cutler, MD MPH FRCP(C)

Associate Professor of MedicineHarvard Medical School

Dana-Farber Cancer Institute

Boston, MA

Definitions

• Stem Cell Transplantation (aka BMT)

– The transfer of Hematopoietic Stem Cells from Donor

to Recipient

• What is a Stem Cell?

– Stem cells are defined by two characteristics:

• They can make copies of themselves, or self-renew

• They can differentiate, or develop, into more

specialized cells

Definitions• Are there different types of Stem Cells?

– Embryonic / Pluripotent Stem Cells

– Tissue Specific Stem Cells

• Hematopoietic Stem Cells – A stem cell capable of

giving rise to ALL cells in the blood and immune system

4

Rationale for Transplantation

• Elimination AND Replacement of:

– Diseased marrow

– Poorly functioning marrow

– Immune compromised marrow

– Metabolically compromised marrow

• Protection against ultra-high doses of chemoradiotherapy

• Establish immunologic platform for immunotherapy

5

Types of Transplantation

Autologous – High doses of chemotherapy and/or radiation

– Designed to kill tumor; overcome resistance with dose intensity

– Requires stem cell rescue

– Not really a transplant

Allogeneic – 2 mechanisms to cure:

• Immunologic: Donor vs. Host (Graft vs. Tumor)

• Chemotherapy and/or radiation

Decision to use autologous/allogeneic marrow source is disease, stage and patient specific

Indications for Transplantation

• Autologous

– Multiple Myeloma in remission

• Prolongation of remission

– Diffuse Large B Cell NHL in 2nd remission

– Hodgkin Disease in remission

– Mantle Cell NHL

– Some Germ Cell Tumors

– AML, in very rare circumstances

Curative Intent

Indications for Transplantation -

Allogeneic

2,000

1,500

500

0

1,000

2,500

Num

ber

of

Tra

nspla

nts

MultipleMyeloma

NHLAML HDALL MDS/

MPD

AplasticAnemia

CML OtherLeuk

OtherCancer

Non-MaligDisease

Related Donor (Total N=3,282)

Unrelated Donor (Total N=3,389)

8

Stem Cell Transplant Decision Tree

Type of Transplant Autologous Allogeneic

Conditioning

Intensity

• High (Myeloablative) • High (Myeloablative)

• Reduced Intensity

9

Conditioning Regimen

• Determined by:

– Primary tumor type

– Stage of disease at transplantation

– Graft vs. tumor effect in that disease

– Performance status/comorbidity of recipient

• Large variety of regimens exist

• Differ in intensity and toxicity

– Ablative is Hard; RIC is pretty easy

• We have “Recipes” for these regimens

9

0 2 61 3 4 5

Reduced-intensity conditioning, HLA-identical sibling

(N=232)

0

20

40

60

80

100

10

30

50

70

90

0

20

40

60

80

100

10

30

50

70

90

Myeloablative, HLA-identical sibling (N=318)

Years

Pro

bability o

f Surv

ival

CIBMTR, Age >50, 1998–2006

What is Better? Myeloablative or RIC?

BMT CTN 0901

Advanced MDS /AML< 5% blasts

18 Month Overall Survival

Randomize

RIC regimensBu/Flu

Flu/Mel

MAC RegimensBu/Flu

Bu/CyCy/TBI

GVHD

Prophylaxis per

Institutional

practice

Centers will choose one myeloablative and one reduced intensity regimen for each patient at time of randomization

Overall Survival by Treatment Arm

12

9.7% difference (95% CI: -0.9%, 20.3%) MAC vs. RIC

P=0.07 (18 month pointwise)

RIC 67.7%

MAC 27 25 25 23 22 22 21

RIC 27 26 26 25 23 22 20

108 105 101 91 87 77 68

110 103 91 77 73 67 62

Su

rviv

al

Pro

ba

bilit

y

Months Months

Su

rviv

al

Pro

ba

bilit

y

Overall Survival by Disease Group

13

RIC 85.2%

RIC 63%

14

Stem Cell Transplant Decision Tree

Type of Transplant Autologous Allogeneic

Conditioning

Intensity

• High (Myeloablative) • High (Myeloablative)

• Reduced Intensity

Donor Type • Self • Related

• Unrelated

Degree of Match • Perfect • Matched

• Mismatched

• Highly Mismatched

Finding a Donor

• Goal is to MATCH donor-recipient pairs

– Not a problem in Autologous transplantation

– Identical Twins (Syngeneic Transplantation) not

commonly found nor used

• Matching performed for HLA (Human Leukocyte

Antigen) molecules, encoded by MHC complex

(Major Histocompatibility Complex)

• Matching at non-HLA loci also important, but not

done (yet).

The HLA System

Klein and Sato, NEJM 2000

Histocompatibility Histocompatibility – Unrelated Donors

HLA-A -B -C -DR -DP -DQ

2132 2798 1672 1196 179 158

HLA-A -B -C -DR -DP -DQ

2132 2798 1672 1196 179 158

Nearly Infinite Possible Combinations!!!

19

Courtesy Martin Maiers, NMDP Bioinformatics

“Perfect” Match Rates in the Adult

Donor Registry

20Courtesy Martin Maiers, NMDP Bioinformatics

“Perfect” and “Pretty Good” Match

Rates in the Adult Donor Registry

Does the Degree of Match Matter?

Weisdorf, BBMT 2008 22

Stem Cell Transplant Decision Tree

Type of Transplant Autologous Allogeneic

Conditioning

Intensity

• High (Myeloablative) • High (Myeloablative)

• Reduced Intensity

Donor Type • Self • Related

• Unrelated

Degree of Match

• Bone Marrow

• PBSC

• Bone Marrow

• PBSC

• Umbilical Cord Blood

Stem Cell Source

• Perfect • Matched

• Mismatched

• Highly Mismatched

Stem Cell Source

Bone MarrowPeripheral Blood

Stem Cells

Umbilical Cord

Blood

Ease of Collection Hard Easy Very Easy

Engraftment 18-21 days 12-15 days 21-40 days

Immune

ReconstitutionGood Better Very Poor

GVHD Rates Average Perhaps Higher Low

Graft-vs.Tumor Average Perhaps Higher ??

Umbilical Cord Blood – A New Alternative

• Medical waste – Procured at the time of delivery

• Contains hematopoietic stem cells – Can be

used for transplantation

• Immunologically “immature” – Can be used with

less stringent matching

25Courtesy Martin Maiers, NMDP Bioinformatics

“Perfect”, “Pretty Good” and UCB Match

Rates in the Adult Donor RegistryHaploidentical Transplantation

A B C D

A E D F

E F B D

A F

B CA D A CXNIMA mmNIPA mm

Preparing for Transplantation

• Pre-Transplant Testing

– Blood tests: Kidney, Liver function, Infectious disease

– Functional tests: Heart, Lung

– Psychosocial interviews

– Financials

• Pre-Transplant Teaching

– Restrictions / Safety

– Nutrition

– Medication

27

Preparing for Transplantation

• Consent Session

– Should be VERY thorough

– At least an hour

– Ask a lot of questions

– Be prepared to be offered participation in Research

studies

28

Other Things To Do Pre-Transplant

• Go see a bunch of movies

• Go out to eat

• Gain some weight

• Have a party

29

Grand Overview of Transplantation

30

Conditioning

Transplantation

Engraftment

Recovery

Complications

Transplantation Timeline

AdmissionLine Placement

ConditioningChemotherapy, Radiation

-7 -1 0

Transplantation

Await EngraftmentInfection

Mucositis

Bad Complications

10-18

DischargeRecovery

GVHD

Infection

Post-Transplantation

• A lot of ‘alone’ time

– Designed to PROTECT you

• Frequent visits to the clinic (big social outing of

the week)

• Lots of medications

• Complication time

• You won’t feel great. Yet.

GVHD - Background

• After disease relapse, GVHD is the most

common cause of treatment failure after

transplantation.

• 2 syndromes:

– Acute GVHD

– Chronic GVHD

• Previously defined by temporal relationship to time of

transplantation

• Now defined by clinical features

• Differences in pathobiology

GVHD

• Caused by the interaction between the

transplanted immune system (Graft) and recipient

tissues (Host)

Transplanted Organ Immune System

Transplanted Organ

Rejection

GVHD

Target Tissues

Graft-vs.-Leukemia

0 12 24 30 48 60 72

MONTHS

0.0

0.2

0.4

0.6

0.8

1.0

No GVHD (N=433)

T Cell Depletion (N=401)

Twins (N=70)

PR

OB

AB

ILIT

Y O

F R

ELA

PS

E

Acute GVHD only (N=738)

Chronic GVHD only (N=127)

Both Acute and Chronic GVHD

(N=485)

Horowitz et al, Blood 1990

*

5

4

3

2

1

2

3

4

5

P=.02P=.009P=.04 P=.02

P=.04

P=.0001

FO

LD

DE

CR

EA

SE

OR

IN

CR

EA

SE

IN

RIS

K

INC

RE

AS

ED

EC

RE

AS

E

TREATMENT

FAILURERELAPSE

*

I III II III IV

III IV

Double-Edged SwordDouble-Edged Sword

Horowitz et al, Blood 1990

GVHD Grade

GVHD Grade

Acute GVHD

Incidence:

– 35% after Related Donor Transplantation

– 50% after Unrelated Donor Transplantation

Despite prophylaxis

– Current Standard: Tacrolimus/Cyclosporine and

Methotrexate

Risk Factors for Acute GVHDFactor Condition That ↑ Risk of Acute GVHD

Donor-Recipient Factors

Major HLA Disparity (HLA Class I, II) HLA Mismatched donor > Matched Donor

Minor HLA Disparity (mHA) Unrelated Donor > Related Donor

Sex Matching Mismatch > Match

Donor Parity Multiparity > Nulliparity

Donor Age Older donor > Younger Donor

ABO type ABO Mismatch > ABO Match

Donor CMV Serostatus CMV positive > CMV Negative

Cytokine Gene Polymorphisms Numerous Associated with Acute GVHD

Stem Cell Graft Factors

Stem Cell Source PBSC > BM > UCB

Graft composition Higher CD34+ count > Lower CD34+ cell count*

Higher T cell dose > Lower T cell dose*

Transplantation Factors

Conditioning Intensity Myeloablative > Reduced-intensity Regimens

Acute GVHD

• Clinicopathologic syndrome

– Skin

Erythematous rash Bullae Desquamation

– Liver

Hyperbilirubinemia Hepatic failure

– Gut

Secretory diarrhea Ileus

Days after allogeneic HSCT

Marrow infusion

0 50 100 365

days

Host

Defense

Deficit

Bacterial

Fungal

Viral

Engraftment

CMV

Neutropenia

Mucositis

Acute GVHD + Rx Chronic GVHD + Rx

Gram Negative Rods

Low Risk High Risk

Pneumocystis jirovecii pneumonia

VZV

CMV

BK Virus HHV 6

Aspergillus

Respiratory and Enteric viruses - Epidemic

Candida sp

HSV / Resistant HSV

Gram Positive Cocci

Central Venous Catheters

Encapsulated Bacteria/Listeria/Salmonella/Nocardia

Aspergillus/Vasculotrophic Molds

Prophylaxis/preemptive/empiric

Infection

Post-Transplantation – Beyond 100 Days

• 2 Main issues

– Middle Term Complications

– Late Effects and Survivorship

Chronic GVHD - Background

• >50% of Related and Unrelated Recipients – Incidence increasing as early transplant outcomes

improve

• Important cause of morbidity in the later post-transplant period– Most have more than 1 organ system involved

• Median 2-3 years of treatment

• Associated with Quality of Life and functional deficits

Wt loss Diarrhea Lung Esophagus Joint

IBMTR-1 IBMTR-2 NMDP

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Cutaneous Oral Liver Eye

Organ Involvement

Adapted from Lee et al, 2002

Chronic GVHD – Organ Involvement

SYSTEM SIGNS SYMPTOMS

SKIN AND RELATED

STRUCTURES

Skin: Hyper/hypopigmentation,

lichenoid, sclerodermal,

papulosquamous, ichthyosiform and

psoriasiform changes. Atrophy,

poikiloderma and ulcers. Nails:

dystrophy, longitudinal ridging,

onycholysis, pterygium, destruction.

Scalp: scaling, fibrosis, scarring and

non-scarring alopecia, papulosquamous

changes.

Pruritus, dryness, pain,

infection, rigidity,

decreased range of motion,

photosensitivity.

Nail and hair loss.

MOUTH Lichenoid changes, erythema, ulcers,

xerostomia, fibrosis, leukoplakia. Dental

caries.

Pain, odinophagia,

dysphagia, dysgeusia,

dryness, sensitivity to food.

EYES Keratoconjunctivis sicca, corneal

ulcerations.

Pain, dryness photophobia.

MUSCULOSKELETAL Polymyositis, muscle weakness,

myalgias, arthritis, arthralgias, fasciitis.

Weakness, arthralgias,

myalgias, decrease ROM

GI TRACT Upper: Abnormal motility, esophageal

fibrosis, ulcerations, strictures.

Lower: Mucosal

abnormalities/malabsorption,

submucosal fibrosis

Odynophagia and lower

dysphagia, pain, heartburn,

nausea, anorexia, vomiting,

abdominal pain,

diarrhea/malabsorption,

dehydration, weight loss

SYSTEM SIGNS SYMPTOMS

LIVER Hyperbilirrubinemia, elevated Alk P,

elevated ALT/AST, fibrosis.

Fatigue, jaundice, pruritus.

LUNG Obstructive (BO/BOOP) or restrictive

(scleroderma of the chest) dysfunction.

Air trapping, bronchiectasis,

pneumothorax, pneumomediastinum,

subcutaneous emphysema. Microbial

colonization or pneumonia.

Dyspnea, wheezing, productive or

non productive cough.

NEUROLOGIC Neuropathy, myasthenic syndromes. Pain, burning, dysesthesias,

paresthesias, muscle weakness

VAGINAL

MUCOSA

Erythema, lichenoid changes, dryness,

ulcers, strictures/stenosis.

Pain, burning, dryness,

Dyspareunia

SEROSAL Serositis, pericardial, pleural and

peritoneal effusions.

Dyspnea, chest pain, pleuritic

pain, abdominal pain, ascites.

HEMATOPOIETIC Isolated or combined cytopenias,

eosinophilia, hemolysis.

Fatigue, fever, infection, bleeding.

IMMUNOLOGIC Repeated infections of various

etiologies, lymphopenia,

Hyper/hypogammaglobulinemia

Increased susceptibility to

infection.

Treatment Strategy

• Local Symptoms Local Rx

– Early identification crucial

– Supportive vs. Local immunosuppressive

– National Institutes of Health Consensus

Development Project on Criteria for Clinical Trials

inChronic Graft-versus-Host Disease: The 2014

Ancillary Therapy and Supportive Care Working

Group Report.

Biology of Blood and Marrow Transplantation, 2015

• Can be accessed through ASBMT Website:

http://www.asbmt.org/?page=GuidelineStatements

Treatment Strategy

• Systemic Symptoms / Multiple Local Sites Systemic Rx

• Initial Rx:

– Prednisone 1 mg/kg/day

– Tacrolimus: 5-10 ng/ml or

– Cyclosporine: 200-400 µg/L

• Complete Response Rate: 50-55%

• Median Time to Discontinue Immune Therapy:

1.6 – 2.2 years!!

• Multiple Clinical Trials available – You should participate!!!

– www.clinicaltrials.gov

Post-Transplant Transitions

• You will experience a number of transitions post transplant– Gaining more independence and freedom - welcomed yet

very stressful

– Relationships with family/friends/loved ones-going through a time of adjustment

– Financial pressures – Going/not going back to work

• Acknowledge the enormity of your experience– The reality of your diagnosis

– The trauma inherent in transplant

– The loss of who you were and the security you previously felt

– Seek help if you are stuck

Psychosocial Effects of BMT

• BMT survivors generally experience a high global quality of life

• Some problems may be persistent– Low energy, sleep problems

• Emotional or psychological distress can be common

• Depression– Frequently observed

– Exact prevalence rates unknown

– Depression before and after transplant can affect morbidity and mortality

– Treatment is important

– Women more likely to have current depression (75% v 25%, p=.007)

– Women more likely to receive antidepressants (92% v 50%, p=.02)

– People with treated depression are similar to those without depressionDeMarinis et al., European J of Cancer Care

Changing Emotions

• Recovery is a slow process

• Emotions some experience after transplant:

– Frustration: Lack of energy to do what you once did

– Anger: Why do I have GVHD? Why can't I just feel

normal?

– Guilt: Being a burden to caregiver/family/loved ones

– Mood Changes: "up and down"--caused by

medications (steroids)

– Depression/Anxiety

Quality of Life

• Fatigue: Patients give up being as they were

• Work: full-time, part-time, permanent disability

• Recreation: This can change too. Figure out

what you CAN do.

• Relationships: Transplant can take a toll

• Chronic Graft vs. Host Disease Physical

Psychological

Spiritual Social

Cognitive Changes

• Clinical evaluation for neurologic dysfunction is warranted• Neuropsychological testing

• Additional tests may be indicated

• What we know– Pre HSCT deficits are common

– Post HSCT deficits are even more common

• Complication rates– Allogeneic (Unrelated > Related) >> Autologous

• Types of complications

– Late CNS infections

– Cerebrovascular complications

– 20% will report impaired memory, attention span, verbal fluency

Sexuality after Transplant• Important QoL issue

• Sexual dysfunction is a common, enduring consequence of systemic cancer treatment

• Changes in body image, decline in perceived attractiveness

• Infertility for both men and women

• Majority of survivors say they were not prepared for changes in sex life– Women: Ovarian failure low estrogen levels and vaginal GVHD

stenosis, mucosal changes pain, irritation and sensitivity

– By 2 yrs, there is improvement compared to 6 months, but quantity and quality still not what it was even 5 yrs later

– Men: Gonadal and cavernosal insufficiency ED and lower libido

– Rates of sexual activity improve by 1 year, but takes 2 years to see improvement in quality and quantity. At 5 years still lower function compared to no BMT group

Coping Strategies

• Recognize the impact has been physical, emotional, psychological and spiritual

• Go at your OWN pace, not an 'expected' pace

• Your situation, coping style may be different from others - that's OK!

• Be open, be honest about your feelings and needs

• Try to process what you are experiencing with a loved one or a professional

• Ask what would be most helpful to me now?– Support group

– One on one counseling

– Reading

Taking care of yourself

• Take your medications

• Make your appointments

• Respect your altered immune function

• Mind your emotional well being

• Get enough sleep

• Pay attention, keep lists, make associations

• Consider cognitive rehabilitation services

• Keep your perspective

– Do not over-generalize

– Time heals all?

• Nutrition

• Exercise

Dietary Challenges after Transplant

• Weight gain or loss

• Appetite changes– Small, frequent meals

– Avoid eating snacks too close to meal times

– Choose nutrient dense foods

– Fortify foods to boost calories

– Try new recipes

• Lack of interest in food

• Taste alterations / Dry Mouth– Drink plenty of fluids, at least 8 cups per day

– Moisten foods with gravies, sauces, or broth

– Limit caffeine

– Artificial saliva products

• Steroids, GVHD

Post-Transplant Diet• Eat 5-10 servings fruits & veggies each day

– 1 serving = 1/2 cup cut, cooked or sliced; 1 piece medium fruit; 1 cup leafy greens

• Re-shape your plate– 1/2 veggies, 1/4 protein, 1/4 whole grains

• Emphasis on variety• Look for richly colored plant foods• Emphasize whole grains

– Reduce risk for certain cancers, diabetes and heart disease

– Keep weight off

– Lower cholesterol levels

– Promote digestive health

• Reduce consumption of saturated and trans- fats, increase monounsaturated and omega-3 Fats

Focus on Physical Activity

Physical Activity + Proper Diet = Healthy Weight• Create an individualized fitness plan

– Always talk with your doctor first

– Schedule time for activity each day, remember every bit counts

– Ensure intensity appropriate

– Choose activities you enjoy

– Find a workout “buddy”

• Incorporate key components

– Cardiovascular exercise, strength, flexibility and relaxation

Returning to Work• Up to 89% of BMT patients return to work or school within 5 years

after treatment.

• Influences that impact the ability to return to work are:– Age– Gender– Education– Personal values– Perceived advantages of work

• Influences that impact the INability to return to work:– Physical demands

– Job Lock

– Employer accommodation

– Fear of disclosure

– Perceived discrimination

• Data suggests BONE MARROW recipients more likely to return to work than PBSC recipients (Lee, ASH 2015)

Employer Accommodation

Accommodation: Aiding an employee to perform

their job by providing modifications.

“Reasonable” accommodations

– Change in duties

– Change in work hours

– Flexible work hours

– Periodic rest breaks

– Allow employees to work from home

– Modify dress code

Caregivers• Acknowledge the long haul of BMT caregiving

– Physical demands

– Feelings of loss, anger, fatigue, resentment, hope

• Change has been difficult, you have HAD to adapt to the change-shift in roles

• Sometimes paddling in the same direction as your loved one is difficult

• Every relationship/family functions differently

• As a caregiver, must adapt to what works best for you

• Make time for yourself

• Rely upon others (transportation, child care, meals)

• Say NO to non-essential needs – Prioritize!

Survivorship in BMT

After 1998

Before 1998

• Donor-recipient matching• GVHD prophylaxis anfd treatment• Supportive care

Survivorship in BMT

• 2 components:

– Surviving Malignancy

– Surviving Transplantation

• Different sets of risks and complications need

to be considered

Medical Monitoring after BMT

Majhail et al. Recommended screening and

preventive practices for long-term survivors after

hematopoietic cell transplantation.

Biology of Blood and Marrow Transplantation, 2012

Antin JH. Long term care after hematopoietic –cell

transplantation in adults.

New England Journal of Medicine, 2002

Medical MonitoringOrgan Risk Outcome What To Do?

Mouth Radiation, cGVHD Dryness, Caries Regular dental exams

Monitor for oral cancers

Eyes Radiation, cGVHD,

steroids

Dryness, Cataracts Regular eye exams

Schirmer test for dryness

Bones Radiation, steroids,

low estrogen/testost.

Osteoporosis, fracture Bone Densitometry

Calcium/Vitamin D

Hormone replacement

Lungs Radiation, Immune

suppression

Pneumonitis Quit smoking

Regular lung function test

Endocrine Radiation, Chemo,

steroids

Hypothyroidism

Hypoadrenalism

Hypogonadism

Screening

Slow steroid tapers

Hormone replacement

Medical MonitoringOutcome Risk What To Do?

Infection cGVHD, Immune Suppression Prophylaxis

Second Cancers Radiation, Chemotherapy,

cGVHD, Immune Suppression

Screening exams

Cardiovascular Steroids, Hypogonadal state,

Medications, Glucose

Intolerance

Routine BP monitoring

Routine Glucose monitory

General Health Survivorship See your PCP !

Allogeneic BMT Survivorship Clinic

• Target population– Allogeneic recipients of high-dose myeloablative

conditioning

– Alive, without malignancy, 12 months after transplantation

– May have evidence of chronic GVHD

– Total treatment considered• Chemotherapy to treat malignancy

• Focal radiotherapy to treat malignancy

• High-dose chemotherapy for transplant prep

• Total body irradiation for transplant prep

Allogeneic BMT Survivorship Clinic

• Multidisciplinary clinic– 1x/month, capture all patients (voluntary) for a one

time consultative visit

• Goals of the clinic– Develop wellness plan to address the needs of this

high risk group

– Develop an individualized follow up plan to address the non-GVHD related risks of transplant survivors

Allogeneic BMT Survivorship Clinic

• Providers– BMT Specialists: MD and NP – Endocrine,

cardiovascular, respiratory, bone, sexuality, cancer screening

– Dermatology– Oral Medicine– Ophthalmology– Exercise Physiology– Nutrition– Psychosocial Counselor

• Patients will be followed annually by NP for their survivorship needs, outlined in the wellness plan

• Research Agenda

Treatment summary

Diagnostic tests performed and results

Tumor characteristics (e.g. site, stage, grade, markers)

Dates of treatment initiation and completion Surgery, radiotherapy, chemotherapy, including agents used

Treatment regimen, total dosage, clinical trials (if any), and toxicities experienced during treatment

Psychosocial, nutritional, and other supportive services

Contact information on treating institutions and providers Identification of a key coordinator of continuing care

More Resources in BMT

• National Marrow Donor Program

– www.bethematch.org

– Smartphone app (excellent)

• BMT InfoNet

– www.bmtinfonet.org

• nbmtLink

– www.nbmtlink.org

• Questions?

72

Transplant for MDS and AA

HSCT Outcomes - MDS2001-2011

Timing of HCT for MDS

Figure 1

MDS

RIC Transplantation

Non-transplant

Therapies

Dead

Alive Post Transplantation

Alive

When?

Not too early, but not too late

Probably no single formula to fit all patients

Markov Models useful since there is NO randomized

data

Summary of Decision Models

Low Risk IPSS Int-1 Risk IPSS Int-2 Risk IPSS High Risk IPSS

Myeloablative, Sibling

Donor Cutler 2004

RIC, Sibling or Matched, Unrelated Donor Koreth 2013

RIC or Ablative, Sibling or Matched, Unrelated

Donor Allesandrino 2013

Non-Transplant

Transplant

p < 0.001

Age and Comorbidity

McClune et al, J Clin Onc 2009 Sorror et al, J Clin Onc 2014

Donor Availability

Pro

ba

bili

ty o

f S

urv

iva

l, %

Months

0 6 12 362418

100

0

20

40

60

80

90

10

30

50

70

0

100

20

40

60

80

90

10

30

50

70

30

Sib (N=176)

8/8 MUD (N=413)

7/8 MUD (N=112)

Relative Risk (95% CI):8/8 MUD vs. Sib 1.12 (0.89-1.39) 7/8 MUD vs. Sib 1.43 (1.08-1.91) 7/8 MUD vs. 8/8 MUD 1.29 (1.00-1.65)

Saber et al, Blood 2013

Donor Availability

100

0

20

40

60

80

0

100

20

40

60

80

Pro

ba

bili

ty,

%

Years

0 2 94

Cord Blood (N=153)

861 3 75

Haploidentical donor (N=95)

Partially-matched UD (N=289)

Mismatched UD (N=65)

Log Rank p-value = 0.24

Courtesy W. Saber

HSCT Outcomes - SAA

>20 y, Unrelated Donor, (N = 114)

< 20 y, Unrelated Donor, (N = 244)

> 20y, Sibling Donor (N = 845)

>20 y, Sibling Donor (N = 844)

1994-19992001-2011

HCT for SAA

• This is an HCT EMERGENCY

• HLA type IMMEDIATELY

– Serologic family typing available often in 1-2 business

days

• Avoid Transfusion if possible

– Permissive anemia

– Permissive thrombocytopenia

Doney, Ann Intern Med 1997