10/27/2017

1

An Introduction to Bone Marrow Transplant

Rushang Patel, MD, PhD, FACP

Florida Hospital Medical Group

Introduction to Blood Cancers

Gran

Lym

S

PltMy

B

T,N

K

RBC Polycythemia Vera

AML, CML, MDS

Essential ThrombocythemiaMDS

/ MPN

AML

maturation

T,N

K

How is SCT/BMT different from other transplants

Difference between …..

solid organ and stem cell

transplant

Where does SCT fit in the treatment of blood cancers?

• Almost never done as a first step

• Is not offered instead of chemotherapy

• First, control the cancer with few cycles of chemotherapy

• Then, perform SCT

time

Chemotherapy

Transplant

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Types of Stem Cell Transplants

Autologous

• Stem cells obtained from the patient

• Stem cells frozen in lab before conditioning chemotherapy

• Rejection is never a problem

• Fast recovery

• For Myeloma and Lymphoma

Allogeneic

• Stem cells from a donor

• Donor must ‘match’ (what do we mean by a match?)

• Rejection can occur in both directions (?)

• Takes longer for immune system to recover

• For other blood cancers like AML, ALL, MDS, etc.

Autologous

Stem Cell Transplant

From ‘auto’ – one’s own

Autologous (Self) SCT Autologous (Self) SCT

Risk Period

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Allogeneic

Stem Cell Transplant

From a DONOR

Allogeneic (Donor) SCT

Allogeneic (Donor) SCT

• ‘Complicated one’

• Trying to treat with a ‘double attack’• Chemotherapy• Immunotherapy (donor immune system fighting patient cancer)

• Cannot be done successfully without a great team

Compliant Patient

+ Supportive Caregiver(s)

+ BMT providers

=

Great Team

Donor and Source

• Donor • Related

• Unrelated (volunteer, cord blood)

• Source• Bone marrow (requires going to the OR)

• Peripheral blood (collected by apheresis after giving G-CSF e.g. Neupogen®)

Marrow

Peripheral Blood

Related

UnRelated

Matched (10/10)

MisMatched(8 or 9/10)

Haplo (5/10)

SOURCE MATCH DONOR

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… a MATCH !!! ...

• What do we mean when we say that someone is a ‘match’• Not blood type match

• Match means at HLA loci

• 6 main HLA loci – A, B, C, DP, DQ, DR on each set of chromosome – total 12

• 5 of 6 (total 10) are important

• So;• 10/10 = full match

• 8 or 9/10 = mismatch

• 5/10 = half match (haplo)

Matched Sibling Donor

MOM DAD

The Transplant Journey

Eval

uat

ion

–N

eed

fo

r tr

ansp

lan

t ?

(Dis

ease

Ris

k St

rati

fica

tio

n)

1st visit

• General principles: • Do it if benefit >> risk

• Autologous SCT• Myeloma – upfront • Lymphoma – at relapse OR refractory (exception – MCL)

• Allogeneic SCT • Acute leukemia - risk stratify

• Low risk AML, ALL … at relapse• Other AML, ALL ... Upfront (AFTER induction)

• Chronic leukemia – ONLY if refractory OR high risk gene abnormality predictive of aggressive behavior OR blast phase

• CML – T315I mutation• CLL – p53 involvement

• AA/MDS/MF/MPN – high‘er’ risk categories

Benign hematologic conditions – Sickle, Thal

Non-hematologic conditions – breast CA, GCT, rheumatologic disorders

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The Transplant Journey

Eval

uat

ion

–N

eed

fo

r tr

ansp

lan

t ?

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1st visit 2w – 2m

Be the match!!

The Transplant Journey

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Conditioning Chemotherapy

• Different from the chemotherapy given at time of diagnosis

• Given right before the stem cell transplant

• Purpose is to:• Remove any leftover disease

• ‘Make room’ for the donor cells

• Suppress host (patient) immune system

• Confusing classification• Myeloablative

• Non-myeloablative

• Reduced IntensityToxicity

Inte

nsi

ty

Worst

Best

Not So Useful

Useful but risky

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The Transplant Journey

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1st visit 2w – 2m 3-4 wk First 3 months

The Transplant Journey

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1st visit 2w – 2m 3-4 wk Beyond 3 months …First 3 months

The Dream Transplant

Good Stuff (Desire it) Bad Stuff (Avoid it)

• Engraft • Graft Failure (TRM)

• Immune Reconstitution • Infection (TRM)

• Immune Tolerance • GVHD (TRM)

• GvT (Tumor Free Survival) • Relapse

GVHD vs GVT (the holy grail of transplant)

V

BF

P

DONOR body

PATIENT body

DONOR immune system

DONOR immune system

InPATIENT body

GVT

GVHD

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Variables of the ‘Transplant Equation’

• Indication (hematologic malignancy)

• State of the disease • CR

• MRD / active disease

• Donor • Auto

• Allo• related (full, haplo),

• unrelated (10/10, 9/10, cord blood)

• Source • BM – less T-cells

• PB – more T-cells

• Conditioning regimen• MA

• NMA / RIC

• GVHD prophylaxis • what, when, how much

• ID prophylaxis• anti-microbials – what, when,

how much

How do I answer “What are my chances?”

Complications of Allogeneic SCT

• Rejection• Donor stem cells never really ‘take’ in the patient’s body

• Infections• Bacterila• Fungal• Viral

• Graft vs Host Disease (GVHD)• Donor cells thrive in patient’s body but reject (‘don’t like being in

there’) and fight with patient’s normal cells.• Skin• Liver• GI• Lungs• Eyes

Hmm … sounds really complicated! Can it be done safely? YES

0

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>= 50 years

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SUM12_27.ppt

* Transplants for AML, ALL, NHL, Hodgkin Disease, Multiple Myeloma Slide 7

Tra

nspla

nts

, %

Allogeneic Transplants Autologous Transplants

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What’s new?

• New and widely available:• Haplo-identical transplant

• New and experimental:• Graft engineering

• Off the shelf donor cells

• Stem Cell Expansion

• Better anti-biotics

• Antigen-specific T-cells for infection control

• Better GVHD medications

Donor Availability for Transplantation

• Only 20-25% of patients will have a matched related donor (10/10 allele match) for transplantation

• Probability of finding a matched unrelated donor (MUD) in the world wide registries varies with race/ethnicity of the recipient:• 50% Caucasians

• 30% Hispanics

• 10% or less for African-Americans or Asians

• The likelihood of finding an unrelated donor - highest within their own race/ethnic group

• Time to transplantation with a MUD donor is up to 2-4 months

Haploidentical Transplantation

• Advantages of using a half matched related donor:

• Almost universal donor availability; >95% of patients will have a half matched donor in the immediate family (children, parents, siblings)

• Fast procurement of stem cells – transplant possible within 2 weeks (when patient is in remission or at the time of maximum reduction of tumor burden)

• Donor remains available to collect other cells for cellular therapy, if needed

Haplo-identical Donor

MOM DAD

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Questions ?