Bone Marrow Failure Flashcards
What is pancytopenia
it includes low rbc wbc and plts.
what is bone marrow failure definition
pancytopenia due to failulre of bm to produce blood cells.
what are thee symptoms of bm failure
anemia, difficulty breathing, chest pain and fatigue
what are symtpoms of leukopenia/neutropenia
fever, infxn, mouth sores
what are symtpoms of thrombocytopenia
bleeding
what are things that may lead to hypercellular marrow?
hematologic malignancies, leukemias,myeloma, lymphoma, carcinoma, storage disoreders, myelodysplastic syndromes, b12 or folate deficiency
what are things leadings to hypocellular marrow
congential (fanconis anemia)
acquired (idiopathic, myelodysplastic syndrome, drugs radiation,viruses)
what is aplastic anemia?
sever, life-threatening syndrome in which production of rbcs, wbcs and plts has failed. may occur in all age groups
charaxterized by peripheral pancytopenia and accompanied by a hypocellular bone marrow
what is the pathophysiology of aplastic anemia?
primary defect is reduction in or depletion of hematopoeitic precursor stem cells. this is what leads to peripheral pancytopenia.
what three problems can lead to aplastic anemia in terms of pathways?
failure of self-renewal, proliferation or differentiation, or no cytokines and gf from environment
what is fanconi’s anemia
usually symptomatic around age 5 and has progressive bm hypoplasia. congenital defects such as skin hyperpigmentation and small stature are also seen in affected individuals
what is familial aplastic anemia
a subset of fanconi’s in which congenital defects are absent
what are viral infxns that can lead to aplastic anemia?
mononucleosis, infxs hepatitis, parvovirus, and cytomegalovirus infxns as well as tuberculosis
what are lab findings of aplastic anemia?
severe pancytopenia with relative lymphocytosis, normochromic rbcs, mild to moderate anisocytosis and poikilocytosis, decreased retic count, hypocellular bone marrow with more than 70% yellow marrow
how do you treat aplastic anemia?
withdrawal of offending agent
transfusions, antibiotics
immunosuppressive regimns
hsct
what is pure red cell aplasia?
pure red cell aplasia is characterized by a selective decrease in erythroid precursor cells in bm. wbcs and plts are unaffected.
what are myelodysplastic syndromes?
primary, neopalstic stem cell disorders that ten to terminate in acute leukemia. normally bm is normocellualar or hyperceull. with evidnce of qualitiative abnormaliites in one or more cell lines resutling in ineffective erythropoiesis
what is a common histo sighting in mds?
ringed sideroblasts
When do myelodysplastic syndromes become Acute Myelogenous Leukemia?
when the blast count rises about 20% for who and 30% for fba
What are the goals of treatment of mds?
control symptoms, improve quality of life, improve overall survival, and decrease progression to acute myelogenous leukemia
what is the mainstay of treatment of myelodysplastic syndromes?
supportive care with blood products and hematopoeitic growth factors (epo)
what chemotherapy agent is used with myelodysplastic syndromes?
methylating agent 5-azacytidine and decitabine (they decrease the need for blood transfusions and retard the progression of mds to aml and increase survival)
what was approved in 2005 for the treatment of mds with the 5q syndrome?
lenalidomide
what in general can be down for mds patients that are younger and more severely affected patients?
hsct
What is autologous stem cell transplant?
It is when stem cells are collected from the patient, stored in a freezer, and reused within that patient later following a high dose of chemotherapy.
what are the advantages of allogeneic stem cell transplant?
they can be used when recipient’s bone marrow fails such as in aplastic anemia and myelodysplastic syndrome. when recipient has a certain disease such as leukemia and lymphoma, the donor cells can attack these tumor cells via graft versus disease effect to prevent relapse of the tumor.
What are disadvantages of hsct?
higher risk of chemotherapy related complications
higher risk of infxn compared to auto sct
risk of gvhd
what is myeloablative hsct?
bm is ablated with dose-levels of chemo that cause minimal injury to other tissues. the chemo or irradiation given immediately prior to a translant is called the condition of preparative regimen, prior to infusion of hsc.
what is non-myeloablative hsct?
newer tx approach using lowerdoses of chemotherapy and radiation which are too low to eradicate all of the bm of a recipient. goal is to prevent donor cells from being rejected by recipient. also called reduced intensity allogeneic transplant.
why would you use non-myeloablative hsct?
- it is less intense, so there are less complications associated with typical chemotherapy.
- leaving some of your original stem cells can lead to the beneficial effect of graft vs disease.
what are the complications of infxns due to hsct?
bm transplant usually requires destruction of your own cells, leading to low numbers of immune cells to fight infxn
immunosuppressive agents employed in allogeneic transplants for the prevention of tx of gvhd further increase risk of infxn
patient must be revaccinated because they lose their acquired immunity.
what are additional complications due to hsct?
veno-occlusive disease
mucositis
gvhd (acute and chronic)
how do you treat gvhd?
prevent of acute with cyclosporine and methotrexate to supress immune response
tx with high dose of steroids
when is graft versus tumor disease beneficial?
when it’s a slowly progressing tumor, chronic leukemia, low-grade lymphoma, and some cases multiple myeloma. less effectve in rapidly growing acute leukemias.
