SM_267b: Stem Cell Transplantation Flashcards
Stem cell transplant is ___
Stem cell transplant is use of hematopoietic progenitor cells to restore qualitative or quantitative marrow function (bone marrow rescue) AND / OR create long-term alloreactivity against a malignancy (graft vs tumor effect)
Autologous stem cell transplant is ___
Autologous stem cell transplant is when patients receive their own stem cells
- Allows for high dose chemo for specific blood cancers (myeloma and lymphoma)
Allogeneic stem cell transplant is ___
Allogeneic stem cell transplant is when patients receive stem cells from someone other than themselves
Describe manipulated cell therapy
Manipulated cell therapy
- Selection and / or engineering of specific types of hematopoietic cells: allogeneic SCT with T cells removed, allogeneic SCT with only ZCD34+ cells
- Chimeric angien receptor T cells
- Many types of SCTs are investigational: some types of chimeric antigen receptor T cells, mesenchymal stem cells
Describe rationale for hematopoietic stem call transplant in non-malignant conditions
Rationale for hematopoietic stem call transplant in non-malignant conditions
- Reconstitute some / all of patient’s hematopoietic tissue
- Erythroid; severe aplastic anemia, thalassemia, sickle cell
- Immune: severe combined immunodeficiency
- Enzymatic: Gaucher’s disease
Describe rationale for hematopoietic stem call transplant in malignant conditions
Rationale for hematopoietic stem call transplant in malignant conditions
- Permit treatment with high dose chemo / radiotherapy: myeloablative (permanent cytopenia) versus near or non-myeloablative (temporary cytopenia)
- Graft vs tumor
Describe indications for allogeneic and autologous stem cell transplant
Allogeneic and autologous stem cell transplant
- Pediatric: neuroblastoma, Ewing’s sarcoma, Wilms tumor, and autoimmune diseases
- Adult / pediatric: germ cell tumors, lymphomas, multiple myeloma
Autologous HSCT may be beneficial for ___
Autologous HSCT may be beneficial for multiple myeloma
Allogeneic HCST may be useful for ___
Allogeneic HCST may be useful for AML
Risk factors for HCST are ___, ___, ___, and ___
Risk factors for HCST are age, comorbidities, donor availability, and status of disease at the time of HCST
- More comorbidities -> worse outcomes
Describe general preferences for a stem cell source
General preferences for a stem cell source
- Fully matched sibling donor
- Fully matched unrelated donor
- Alterative donor: umbilical cord blood, haploidentical related donor, mismatched unrelated donor
HLA match
Describe histocompatability antigens
Histocompatability antigens
- HLA: engage T cells for immune recognition, inherited as co-dominant alleles from patients, important for matching donor or recipient
- Non-HLA antigens: minor, killer inhibitory receptor and HLA-I
Describe histocompatability matching
Histocompatability matching
- Matching bone marrow / peripheral blood
- 10/10 allele level match preferred
- HLA class I antigens: HLA - A, B, C
- HLA class II antigens: HLA - DR > DQ > DP
Describe HLA inheritance
HLA inheritance
- 25% chance of having a match to a full sibling
- 50% chance of having a half match to a full sibling
Describe alternative stem cell sources
Alternative stem cell sources
- Cord blood: less match required (4/6 or 5/6 acceptable)
- HLA mismatched donors: 9/10 or 8/10, haploidentical (5/10)
Describe process of stem cell transplant
Stem cell transplant
- Stem cells removed from donor
- Recipient conditioned
- Recipient receives stem cells
Conditioning is requires prior to stem cell transplant to ___
Conditioning is requires prior to stem cell transplant to prevent rejection
Post-HSCT phases are ___, ___, and ___
Post-HSCT phases are pre-engraftment, early post-engraftment, and late post-engraftment
Describe pathogens in post-HSCT phases
Pathogens in post-HSCT phases
Discuss recipient risk factors in post-HSCT phases
Recipient risk factors in post-HSCT phases
Describe common acute complications of HSCT
Common acute complications of HSCT
- Relapse of disease
- Infection / sepsis
- Toxicity from chemo or medications
- Acute and chronic graft vs host disease
- Sinusoidal obstructive syndrome of liver
- Engraftment syndrome
Describe common chronic complications of HSCT
Common chronic complications of HSCT
- Adults / pediatric: relapse of disease, infection, chronic graft vs host disease, secondary malignancies, and psychological disorders
- Pediatric: growth retardation, learning disabilities
Describe acute graft vs host disease
Acute graft vs host disease
- Primarily occurs in skin, liver, or gut
- Caused by activation of donor T cells in setting of inflammation from pre-SCT conditioning regimen (chemotherapy and/or radiation)
- Incidence as high as 30%
- Symptoms usually present within 100 days
- 50% response rate to steroids
Describe chronic graft vs host disease
Chronic graft vs host disease
- Multi-organ disorder characterized by immune dysregulation, inflammation, fibrosis, and impaired organ function
- Incidence as high as 70%
- Symptoms usually present within 1-3 years after HSCT and associated with high morbidity
- Associated with decreased incidence of relapse but increased risk of non-relapse mortality -> overall worse survival
___ is used for refractory B cell malignancy
CAR T-cell therapy is used for refractory B cell malignancy
- Transgenic autologous T cells with Ag specific CARs
____ is a form of CAR T-cell therapy used to treat B cell precursor acute lymphoblastic leukemia
Tisagenlecleucel is a form of CAR T-cell therapy used to treat B cell precursor acute lymphoblastic leukemia
____ is a CAR-T cell therapy used for large B cell lymphoma
Axicabtagene ciloleucel is a CAR-T cell therapy used for large B cell lymphoma
Describe adverse effects of CAR T cell therapy
Adverse effects of CAR T cell therapy
- Insertional mutagenesis
- Myelosuppression: anemia, leukopenia / neutropenia / lymphopenia, thrombocytopenia
- Cytokine release syndrome: high fevers, flu-like symptoms, life-threatening hypotension, capillary leak syndrome, nephrotoxicity, CNS toxicity (seizures, altered mental status)
