What is the relationship between Sarcoma and Acute Myeloid Leukemia (AML) and potential health concerns?

From the Guidelines

Patients with sarcoma should be closely monitored for the development of acute myeloid leukemia (AML) as a potential secondary malignancy, particularly if they have received chemotherapy or radiation therapy, as this can increase their risk of developing therapy-related AML, as noted in the 2019 NCCN clinical practice guidelines in oncology 1. The relationship between sarcoma and AML is complex, with both cancers having distinct pathologies but potentially shared risk factors. Sarcomas are solid tumors that arise from connective tissues, while AML is a hematologic malignancy characterized by the clonal expansion of myeloid blasts in the bone marrow, peripheral blood, and/or other tissues, as described in the 2019 guidelines 1. Key health concerns for patients with either diagnosis include:

• Monitoring for secondary malignancies, particularly therapy-related AML in patients who have received chemotherapy or radiation therapy for sarcoma
• Managing treatment side effects, such as myelosuppression and increased risk of infections
• Genetic counseling if hereditary cancer syndromes, such as Li-Fraumeni syndrome, are suspected Regular follow-up with oncologists, blood tests to monitor bone marrow function, and awareness of symptoms like unexplained fatigue, bruising, or bone pain are crucial for early detection of secondary cancers. The underlying biological connection between sarcoma and AML involves DNA damage from cancer treatments or inherited genetic mutations affecting DNA repair mechanisms and cell cycle regulation, highlighting the importance of careful monitoring and management of patients with a history of either cancer.

From the FDA Drug Label

Secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) has been reported in patients treated with anthracyclines, including doxorubicin The occurrence of refractory secondary AML or MDS is more common when anthracyclines are given in combination with DNA-damaging anti-neoplastic agents or radiotherapy, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated The rate of developing secondary AML or MDS has been estimated in an analysis of 8,563 patients with early breast cancer treated in 6 studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), including NSABP B-15 Among 4,483 such patients who received conventional doses of AC, 11 cases of AML or MDS were identified, for an incidence of 0.32 cases per 1,000 patient years (95% Cl, 0.16 to 0. 57) and a cumulative incidence at 5 years of 0.21% (95% Cl, 0.11 to 0.41%).

The relationship between sarcoma and AML is not directly addressed in the provided drug label. However, the label does mention that secondary acute myelogenous leukemia (AML) can occur in patients treated with doxorubicin, particularly when used in combination with other DNA-damaging agents or radiotherapy.

• The incidence of AML is estimated to be around 0.32 cases per 1,000 patient years.
• Pediatric patients are at increased risk for developing delayed cardiotoxicity and secondary AML.
• The label does not provide information on the relationship between sarcoma and AML, but it does highlight the potential health concerns associated with doxorubicin treatment, including cardiac toxicity and secondary AML 2.

From the Research

Sarcoma and AML Relationship

• Sarcoma and Acute Myeloid Leukemia (AML) are two distinct types of cancer, with sarcoma being a type of cancer that originates in the bones or soft tissues, and AML being a type of blood cancer 3.
• There is a potential relationship between the two, as some studies have shown that patients with sarcoma may be at increased risk of developing secondary AML, particularly after receiving chemotherapy or radiation therapy 4, 5.

Potential Health Concerns

• Patients with sarcoma who develop secondary AML may face poor prognosis and limited treatment options 3.
• The use of certain chemotherapy agents, such as doxorubicin and ifosfamide, may increase the risk of developing secondary AML in patients with sarcoma 5, 6.
• The treatment of advanced soft tissue sarcomas with doxorubicin and olaratumab versus doxorubicin, ifosfamide, and mesna has shown similar outcomes in terms of overall survival and progression-free survival, but with different toxicity profiles 7.

Treatment Options

• The treatment of sarcoma and AML often involves a combination of chemotherapy, radiation therapy, and surgery 4, 5, 6.
• The use of novel therapies, such as CPX-351, a liposomal co-encapsulation of cytarabine and daunorubicin, has shown improved outcomes in older patients with high-risk secondary AML 3.
• The optimal diagnosis and treatment of patients with sarcoma and AML requires a multidisciplinary approach and further research to improve outcomes in this high-risk population 3, 4, 5.