MDS Flashcards
(27 cards)
Abnormalities of which chromosome are the most common abnormality in MDS?
Abnormalities of which chromosome are the most common abnormality in MDS? 5
Which mutation in MDS has been associated with a more favorable diagnosis?
SF3B1
Previous exposure to what agents increases the risk of MDS?
- Alkylating agents
- Topoisomerase II inhibitors
- Ionizing radiation
Alkylating agent-related MDS characteristically causes mutations of chromosome(s) ____ with a median onset of ____ after therapy.
- chromosomes 5 and 7
- 5-7 years after therapy
Topoisomerase inhibitor-related MDS typically causes mutations of chromosome(s) ____ with a median onset of ____ after therapy.
- chromosome 11q23
- 2-3 years after therapy
There is risk for developing ____ from antecedent MDS.
Secondary AML
MDS is classified as AML if ____.
Presence of any of the following muations (regardless of blasts or other features):
* t(15:17)
* t(8:21)
* inv16
or greater than 20% blasts
Current therapy recommendations for MDS are based on what stratification categories?
Current therapy recommendations divide patients into lower-risk and higher-risk groups.
____ is the only curative therapy forMDS.
Allogeneic hematopoietic cell transplantation (HCT)
Patients with lower-risk MDS may benefit from ____.
- Hematopoietic growth factors (ie: ESA and luspatercept)
- DNA hypomethylating agents
- Immunosuppressive therapy
- Immunomodulating agents (ie: lenalidomide)
Patients with higher-risk MDS are more likely to progress to AML and may benefit from ____.
- DNA hypomethylating agents
- Intensive chemotherapy
- Allogeneic HCT
When do you decide to treat or deploy therapy in lower-risk MDS?
When the patient becomes transfusion dependent. Patients that are transfusion independent are typically just observed until then.
Describe the role of hematopoietic growth factors in the treatement of MDS.
Haven’t been shown to change the natural history of the disease and, in contrast to some solid tumors, have not been reported to have detrimental effects on
overall survival or progression.
When do you use ESA in MDS?
- Lower-risk disease
- Transfusion dependent but low pretreatment RBC requirement (<2 units per month).
- EPO level <500 units/L
How is ESA dosed in MDS?
Common dose is epoetin alpha (or epoetin alfa-epbx) 300 units/kg subQ 3x/week - titrate to achieve a hemoglobin level of 10-12 g/dL.
Describe the role of thrombopoiesis stimulating agents in MDS.
- Not fully known at this time.
- Concern regarding complications related to disease transformation and marrow fibrosis.
- Can consider eltrombopag or romiplostim in patients with severe or refractory thrombocytopenia.
Chemotherapy options in MDS include ____.
- Hypomethylating agents (Azacitadine, Decitabine, or the comination Decitabine/Cedazuridine)
- Intensive therapy with regimens used for induction therapy in AML.
Which hypomethylating agent is preferred in MDS and why?
Azacitadine because it has shown to improve overall survival especially in patients with progressing or high-risk disease
Describe the role of hypomethylating agents in MDS
- Primarily used in higher-risk disease as they have shown to decrease risk of leukemic transformation in these patients. Considered the standard of care in this subgroup.
- Less utility in lower-risk MDS as they have not shown to modify the natural history of disease in these patients but they are an appropriate option for lower-risk patients with symptomatic anemia and elevated epoetin levels who are not expected to respond to other treatment options.
- Indicators for use are:
1. Higher-risk MDS
2. Not a candidate for high-intensity therapy
3. Potential candidate for allogeneic HCT, but in which a delay is anticipated. These agents may be used as “bridging therapy” prior to transplant.
4. Relapse after allogeneic HCT.
Describe the role of lenalidomide in MDS
This is an immunomodulating agent with demonstrated activity in lower-risk MDS - particularly beneficial in patients with del(5q) as the sole chromosomal abnormality. This subtype confers a favorable prognosis.
Describe the role of luspatercept in MDS
- Luspatercept – is a first in class recombinant fusion protein that inhibits the transforming growth factor dependent stages of erythroid maturation.
- Luspatercept can be used without regard to EPO levels unlike ESAs or lenalidomide in non-del-5q).
- Luspatercept does not provide disease modifying effects, thus is unlikely to reduce the risk of progression to AML (importantly it also does not lead to an increased risk of progression to AML).
- The primary indictor for use are lower-risk MDS with ring sideroblasts.
How is luspatercept dosed in MDS?
1 mg/kg subQ q3weeks - titrate based on hemoglobin levels.
Describe the role of immunosuppressive therapy in MDS
Immunosuppression with anti-thymocyte globulin (ATG), steroids, cyclosporine, and can be used to treat the cytopenias associated with lower-risk MDS. The following pretreatment characteristics are predictive of response to immunosuppressive therapy:
* Younger age (≤60 years old)
* Shorter duration of red cell transfusion dependence (RCTD)
* Overrepresentation of the class II histocompatibility antigen DR15 (HLA-DR15)
* Bone marrow hypoplasia (<5% blasts)
* Normal cytogenetics
Describe the overall treatment principles/draw the treatment algorithm for lower-risk MDS.
