1. Blood and Marrow Transplant: The basics…what you need to know
Resident Education Lecture Series

2. Types of Transplant Autologous (your own cells) Allogeneic
cells from another person
Sibling
Unrelated Donor
Parent or relative
or source: Umbilical cord

3. Hematopoietic Progenitor Cell Sources
Bone Marrow
PBSC (peripheral blood stem cells)
Umbilical Cord

4. 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.

5. Strategies to overcome this problem
National registries (NMDP) to find matched unrelated donors have increased the pool of donor options. > 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

6. 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

7. 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.

9. 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

11. 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)

12. 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

13. 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

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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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).

20. 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.

21. 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

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

23. Acute Graft versus Host Disease of Skin
Couriel et al, Cancer 2004.

24. Graft Versus Host Disease of the Skin: Grade IV

25. Chronic Extensive Graft versus Host Disease

26. INFECTIONS POST TRANSPLANT

27. Other Problems Encountered
Hemorrhagic Cystitis
VOD (venoocclusive disease of the liver) or SOS (solid organ syndrome)
Organ Toxicity (lung, heart, kidney)
Idiopathic Pneumonia Syndrome
(do you want a slide per problem?)
Do you want a separate slide per problem, or is this sufficient?

29. 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

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