Blood and Marrow Transplant: The basics…what you need to know

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Blood and Marrow Transplant The basicswhat you
need to know

• Resident Education Lecture Series

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Types of Transplant

• Autologous (your own cells)
• Allogeneic
• cells from another person
• Sibling
• Unrelated Donor
• Parent or relative
• or source Umbilical cord

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Hematopoietic Progenitor Cell Sources

• Bone Marrow
• PBSC (peripheral blood stem cells)
• Umbilical Cord

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Best Allogeneic Blood/Bone Marrow Donor is a
brother or sister

• Only 25 of patients are that lucky!
• 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.

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Strategies to overcome this problem

• National registries (NMDP) to find matched
  unrelated donors have increased the pool of donor
  options. gt 5 million volunteer donors
• 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

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Bone Marrow

• Standard source of hematopoietic cells for more
  than 30 years.
• Transplant physicians may select marrow because
• Extensive clinical data are available about
  marrow transplant outcomes
• Extensive information is available about the
  marrow donation experience

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PBSC

• 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.

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Umbilical Cord Blood

• 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

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Diseases that we transplant in children

• Autologous
• Relapsed Hodgkins Disease
• Relapsed Non Hodgkins Lymphoma (NHL)
• Stage IV Neuroblastoma
• Relapsed Ewings Sarcoma
• Investigational
• Metastatic Ewings Sarcoma
• Medulloblastoma, other brain tumors
• Autoimmune Diseases (SLE)

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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

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Allotransplant for Non-Malignant Diseases

• 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

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Transplant Process (5 steps)

• (1) Conditioning,
• (2) Stem cell infusion,
• (3) Neutropenic phase,
• (4) Engraftment phase
• (5) Post-engraftment period.

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Conditioning Phase

• The conditioning period typically lasts 7-10
  days.
• The purposes are (by delivery of chemotherapy
  and/or radiation)
• 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.

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Stem cell processing and infusion

• 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.

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Stem cell processing and infusion

• 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.

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Neutropenic Phase

• 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.

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Engraftment Phase

• 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).

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Post-engraftment Phase

• 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.

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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 lt 100 days after the transplant
• Chronic gt 100 days

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• What are risk factors for GVHD?
• HLA match / mismatch
• Lymphocytes in graft
• Inadequate immune suppression
• Other???

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Acute Graft versus Host Disease of Skin
Couriel et al, Cancer 2004.
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Graft Versus Host Disease of the Skin Grade IV
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Chronic Extensive Graft versus Host Disease
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INFECTIONS POST TRANSPLANT
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Other Problems Encountered

• Hemorrhagic Cystitis
• VOD (venoocclusive disease of the liver) or SOS
  (solid organ syndrome)
• Organ Toxicity (lung, heart, kidney)
• Idiopathic Pneumonia Syndrome

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From ABP Certifying Exam Content Outline

• Immunologic problems
• Transplantation
• Understand the role of the general pediatrician
  in the care of a patient who has undergone
  transplantation

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Credits

• Slides (2)
• CIBMTR (Center for Blood and Marrow
  Transplantation Research), Milwaukee, WI
• Table
• Pediatric Hematology/Oncology/BMT Board Review
  Course, 2002
• David Margolis MDJulie An Talano MD