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Processing Marrow

from the AABB publication, "Processing of Bone Marrow for Transplantation," 1990

What is the difference between allogeneic and syngeneic? syngeneic = genetically identical, has to be from an identical twin; allogeneic = genetically different
In autologous therapy, what cells need to be concentrated and what cells need to be cleared in the patient during ablation? mononuclear cells = concentrated; potentially contaminating malignant cells = cleared
clearing malignant cells during ablation is also called: bone marrow tumor cell purging
In 1990 a rapidly expanding development in the field was: bone marrow stem cell harvesting and its potential for in vitro bone marrow culture and re-infusion
bone marrow transplantation is within the reach of those countries in which: a reasonably developed second generation stage of supportive clinical and diagnostic services has been established
a network of supportive services includes: 1. tissue typing and compatibility testing lab 2. micro lab to support selective decontamination programs and infection prevention regimes 3. radiotherapy dep't. 4. pharmacology department to provide pharmacotoxicological support 5. blood transfusion serv
roles for the blood transfusion service 1.provide hemotherapy during preparation, tissue preservation, and the immunocompromised stage/deliberate aplasia
chemotherapy plus radiation therapy is called chemoradiotherapy
What led to the development of autologous bone marrow transplantation programs? the options for more successful chemoradiotherapy in solid tumors necessitated autologous BMT programs to rescue pt. from deep hematopoietic aplasia
what is the solution for a variety of hematological disorders? transplantation of allogeneic pluripotent stem cells (i.e., as in thallasemia)
Bone marrow transplantation is being used as: replacement therapy or rescue from bone marrow failure, whether acquired, from congenital disposition, ablation, or iatrogenic marrow suppression
iatrogenic = induced inadvertently by a physician or surgeon or by medical treatment or diagnostic procedures
ANLL acute nonlymphoblastic (nonlymphocytic) leukemia
How is new information in the BMT field lost to the larger scientific community? When a large medical center considers BMT profitable and doesn't refer pt. elsewhere; their results never get published (BMT is still experimental)
acquired malignancies treated by BMT ANLL, ALL, CML, CLL, Non-Hodgkin's lymphoma, Hodgkin's, MM, preleukemia, hairy cell leukemia, hypereosinophilic syndrome, some solid tumors
acquired nonmalignancies treated by BMT aplastic anemia, PNH, myelofibrosis, AIDS
congenital diseases treated by BMT as of 1990 Immunodeficiencies, hematological defects (i.e., thalassemia, sickle cell disease), osteoporosis, Mucopolysaccharidoses, mucolipidoses, and lysosomal diseases (page 3 for complete list)
ALL acute lymphoblastic leukemia, ALSO acute lymphocytic leukemia
CML chronic myelocytic leukemia; *chronic myelogenous leukemia;* chronic myeloid leukemia
CLL chronic lymphocytic leukemia
Which disease has served as a model for BMT? severe aplastic anemia
prep for ablation includes: cyclophosphamide (CY) (sometimes with irradiation)
How is irradiation administered? total body (TBI) or modified total lymphoid irradiation (TLI)
What makes the failure of engraftment more likely? allosensitization from transfusion (failure jumps from 5-10% to 30-60%; but donor leukocyte infusions post BMT, TBI and TLI has lowered failure to 5-15%)
In 1990, the failure rate for HLA nonidentical bone marrow transplants was: 30 - 45%, and GVHD was a huge problem
How many patients have an HLA identical sibling? 1/3
CR = complete remission
What happens to the probability of relapse AND survival as the disease is not stopped after the first CR? probability of relapse goes up, and probability of survival drops
PBSC = peripheral blood stem cells
monozygotic = derived from a single egg <monozygotic twins>
allogeneic encompasses: HLA genotypically identical sibling; HLA phenotypically identical donor (family member or unrelated); HLA-nonidentical donor
xenogeneic different species
Do HLA genotypically identical donors (NOT an identically twin) still present problems? Yes; GVHD can still occur.
Steps taken to decide between a transplant vs. a non-transplant decision 1. HLA typing of recipient. 2. HLA typing of siblings (stop here if a match -- not always the best option, though). 3.autologous/HLA-identical-unrelated/HLA-nonidentical donors (in that order)
Does bone marrow involvement of the disease affect the outcome and how well BMT will work? yes
What options need to be weighed if trying to achieve the "graft-vs-leukemia" effect? "Conversely, since a graft-vs-leukemia effect may be mediated by allogeneic cells, the benefit from this effect may outweigh the risk of GVHD even with a partially HLA-identical related or a phenotypically matched unrelated donor."
What are the two situations where autologous stem cells are not an option? 1. congenital disorders 2. severe aplastic anemia (HAVE TO USE BMT FROM AN HLA-NONIDENTICAL, UNRELATED DONOR)
What changed in 1990? BMT only if an HLA gentotypically identical sibling was available
What were the major problems with BMT in 1990? 1. GVHD 2. Failure of engraftment 3. Recurrent leukemia 4. Infections, such as CMV 5. Delayed complications
What percent of BMT patients develop clinically relevant, acute GVHD? In 1990, 10-20% of patients given HLA-identical and 40-90% of those given HLA-nonidentical transplants.
In 1990, what was being administered to GVHD patients with concurrently developing infections? IV and oral immunoglobulin. But 30-50% of these still went on to develop chronic GVHD.
Created by: alanh1954
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