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

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Presentation on theme: "Blood and Marrow Transplant: The basics…what you need to know Resident Education Lecture Series."— Presentation transcript:

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.

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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

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

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

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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): 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


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