Transcript Blood and Marrow Transplant

Blood and Marrow Transplant:
The basics…what you need to know
Resident Education Lecture Series
Types of Transplant
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Autologous (your own cells)
Allogeneic
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cells from another person
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Sibling
Unrelated Donor
Parent or relative
or source: Umbilical cord
Hematopoietic Progenitor Cell
Sources
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Bone Marrow
PBSC (peripheral blood stem cells)
Umbilical Cord
Best Allogeneic Blood/Bone Marrow
Donor is a brother or sister
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Only 25% of patients are that lucky!
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There is a 1 in 4 chance that any child will
match another child of the same parents
 the formula for knowing whether there is
a donor (1-(3/4)n)
In 1% of cases, a parent may be a donor
because of shared HLA types
Major obstacle in the treatment of
patients who would benefit from an
allogeneic transplant.
Strategies to overcome this problem
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National registries (NMDP) to find matched
unrelated donors have increased the pool of
donor options. > 5 million volunteer donors
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Approximately 70% of patients will have either a matched or
a 1-antigen mismatched donor identified through a registry
 80% for Caucasians,
 less for minorities – fewer minorities in the registry, wider
variety and ethnic variation in HLA types
Use of Umbilical Cord Blood
Partially Matched Related Donors
parent → child
Bone Marrow
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Standard source of hematopoietic cells
for more than 30 years.
Transplant physicians may select
marrow because:
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Extensive clinical data are available about
marrow transplant outcomes
Extensive information is available about
the marrow donation experience
PBSC
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Autologous transplants rely almost
exclusively on PBSC rather than marrow due
to:
Easier collection of cells
More rapid hematopoietic recovery
Decreased costs
We also use this method in certain instances
for allogeneic transplants in pediatrics.
Umbilical Cord Blood
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Physicians may consider umbilical cord blood
a good choice particularly for patients who
need an unrelated donor and have an
uncommon HLA type or are in urgent need of
a transplant.
HLA mismatch is better tolerated – even with
haploidentical donors
Available more quickly than marrow or PBSC
unrelated donors
Reduced incidence and severity of GVHD
Diseases that we transplant in
children
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Autologous
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Relapsed Hodgkins Disease
Relapsed Non Hodgkins Lymphoma (NHL)
Stage IV Neuroblastoma
Relapsed Ewings Sarcoma
Investigational
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Metastatic Ewings Sarcoma
Medulloblastoma, other brain tumors
Autoimmune Diseases (SLE)
Allogeneic Transplant
Indications in Children
Malignant Diseases
 AML CR1 – Matched Sibling
 High Risk ALL CR1 (Ph+ ALL)
 Relapsed or Refractory AML or ALL
 Chronic myelogenous leukemia
 Juvenile myelomonocytic leukemia
 Myelodysplastic syndromes
Allotransplant for Non-Malignant
Diseases
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Inherited metabolic disorders Adrenoleukodystrophy, Hurler syndrome,
metachromatic leukodystrophy, osteopetrosis, and
others
Inherited immune disorders - Severe combined
immunodeficiency, Wiskott-Aldrich syndrome, and
others
Inherited red cell disorders - Pure red cell
aplasia, sickle cell disease, beta-thalassemia, and
others
Marrow failure states - Severe aplastic anemia,
Fanconi anemia, and others
Transplant Process (5 steps)
(1)
(2)
(3)
(4)
(5)
Conditioning,
Stem cell infusion,
Neutropenic phase,
Engraftment phase
Post-engraftment period.
Conditioning Phase
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The conditioning period typically lasts 7-10
days.
The purposes are (by delivery of
chemotherapy and/or radiation)
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to eliminate malignancy
to provide immune suppression to prevent
rejection of new stem cells
create space for the new cells
Radiation and chemotherapy agents differ in
their abilities to achieve these goals.
Stem cell processing and
infusion
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Infusion - 20 minutes to an hour, varies
depending on the volume infused. The stem
cells may be processed before infusion, if
indicated. Depletion of T cells can be
performed to decrease GVHD.
Premedication with acetaminophen and
diphenhydramine to prevent reaction.
Stem cell processing and
infusion
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Infused through a CVL, much like a blood
transfusion.
Anaphylaxis, volume overload, and a
(rare) transient GVHD are the major
potential complications involved.
Stem cell products that have been
cryopreserved contain dimethyl sulfoxide
(DMSO) as a preservative and potentially can
cause renal failure, in addition to the
unpleasant smell and taste.
Neutropenic Phase
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During this period (2-4 wk), the patient
essentially has no effective immune system.
Healing is poor, and the patient is very
susceptible to infection.
Supportive care and empiric antibiotic therapy
are the mainstays of successful passage
through this phase.
Engraftment Phase
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During this period (several weeks), the
healing process begins with resolution
of mucositis and other lesions acquired.
In addition, fever begins to subside,
and infections often begin to clear. The
greatest challenges at this time are
management of GVHD and prevention
of viral infections (especially CMV).
Post-engraftment Phase
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This period lasts for months to years.
Hallmarks of this phase include the
gradual development of tolerance,
weaning off of immunosuppression,
management of chronic GVHD, and
documentation of immune
reconstitution.
Graft versus Host Disease (GVHD)
• If donor cells see the host cells as foreign,
the donor cells will attack the host.
• Skin, gut, and liver most likely to be
affected.
• Acute < 100 days after the transplant
• Chronic > 100 days
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What are risk factors for GVHD?
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HLA match / mismatch
Lymphocytes in graft
Inadequate immune suppression
Other???
Acute Graft versus Host Disease of Skin
Couriel et al, Cancer 2004.
Graft Versus Host Disease of the Skin: Grade IV
Chronic Extensive Graft versus Host Disease
INFECTIONS POST TRANSPLANT
Other Problems Encountered
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Hemorrhagic Cystitis
VOD (venoocclusive disease of the liver)
or SOS (solid organ syndrome)
Organ Toxicity (lung, heart, kidney)
Idiopathic Pneumonia Syndrome
From ABP
Certifying Exam Content Outline
Immunologic problems
 Transplantation
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Understand the role of the general
pediatrician in the care of a patient who
has undergone transplantation
Credits
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Slides (2):
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Table
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CIBMTR (Center for Blood and Marrow
Transplantation Research), Milwaukee, WI
Pediatric Hematology/Oncology/BMT
Board Review Course, 2002
David Margolis MD
Julie An Talano MD