Post on 27-May-2017
Blood and Marrow Transplant:The basics…what you need to know
Resident Education Lecture Series
Types of Transplant Autologous (your own cells) Allogeneic
cells from another person Sibling Unrelated Donor Parent or relative
or source: Umbilical cord
Hematopoietic Progenitor Cell Sources
Bone Marrow PBSC (peripheral blood stem cells) Umbilical Cord
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.
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
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
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.
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
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)
Allogeneic Transplant Indications in ChildrenMalignant 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 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) Conditioning, (2) Stem cell infusion, (3) Neutropenic phase, (4) Engraftment phase(5) Post-engraftment period.
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.
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.
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.
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.
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).
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.
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
What are risk factors for GVHD? HLA match / mismatch Lymphocytes in graft Inadequate immune suppression Other???
Couriel et al, Cancer 2004.
Acute Graft versus Host Disease of Skin
Graft Versus Host Disease of the Skin: Grade IV
Chronic Extensive Graft versus Host Disease
INFECTIONS POST TRANSPLANT
Other Problems Encountered 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 OutlineImmunologic problems Transplantation
Understand the role of the general pediatrician in the care of a patient who has undergone transplantation
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