Investigation of Epidemiological Factors and Site of Primary Tumor on the Development of AML As Second Primary Cancer after Diagnosis of Myeloid Sarcoma and the Impact of Chemotherapy on Overall Survival

Background

Myeloid sarcoma (MS), also known as extramedullary acute myeloid leukemia (AML), is an extramedullary infiltration of myeloid cells. 80-90% of MS occurs after a diagnosis of AML is previously established or after previous treatment of AML [1]. When comparing MS to AML, 3-year overall survival (OS) of MS is significantly higher than AML [2]. The current recommended treatment for MS is anti-leukemic chemotherapy due to finding that 71% of isolated MS develops into AML within 9 months compared to 41% who received treatment, however the data on the development of AML as second primary cancer (SPC) after diagnosis of MS has been limited [3] Another previous study indicated that that early chemotherapy for MS had no benefit on OS [4]. There have been no large database studies performed to investigate the risk factors for development of MS with AML as SPC or effect of chemotherapy on OS for these patients.

Methods

The SEER database was queried for all patients with MS and MS with AML as SPC from years 2000 to 2021 using the SEER Research data, 17 Registry. Myeloid sarcoma was selected by using ICD code 9930/3. Patients with SPC identified at time of death were excluded and when patients had recurrence with multiple diagnoses of MS, only the first occurrence was included. Patients with status of No/Unknown chemotherapy were counted as not having chemo. Patients with 731+ days of delay in chemo coded as 731 days.

Results

A total of 748 patients with MS, 168 patients with MS and AML as SPC, and 77,966 patients with AML were included in the study. Groups with significantly increased Relative Risk (RR) of developing AML as SPC after diagnosis of MS included Female, Age 40-59, Age 60-79, White, American Indian/Alaska Native/Asian/Pacific Islander, or with those with primary site of MS being genitourinary system, lymph node, hematopoiesis system, and digestive system. Chemotherapy was associated with an increase in median OS for MS (95% CI=9.512-16.488 versus 2.195-5.805 months) and AML (95% CI=9.835-10.165 versus 4.669-5.331) , however there was no benefit in median OS for patients with MS and AML as SPC (95% CI=9.862-20.138 versus 4.537-19.463). MS was also the only group to show decrease in months of OS for days of delay in initiation of chemotherapy (95% CI=-0.5667 to -0.075 months of OS per day of delay of initiation of chemotherapy). The Hazard Ratio (HR) for effect of chemotherapy on 12-month OS for patients with MS was increased for all of the subgroups studied other than patients age 0-19, age 80+, and those who were American Indian/Alaska Native. The HR for effect of chemotherapy on 12 month OS for patients with MS and AML as SPC was only significantly increased for Female, age 80+, white, American Indian/Alaska Native/Asian/Pacific Islander, and patients with primary site of MS including connective/soft tissue, lymph node, hematopoiesis system, or digestive system. When performing multivariate analysis for patients with MS and AML as SPC; patients with gastrointestinal as primary site for MS were more likely to be male. Age 40-59 and age 20-39 patients were more likely to be white. Age 20-39 and age 40-59 patients were more likely to receive chemotherapy than age 60-79 and age 80+ patients. Age 80+ patients were less likely to receive chemo than age 0-19, 20-39, and 40-59 patients. Black patients were more likely to have lymph node as primary site of MS compared to whites. Patients with skin as primary site of MS were less likely to receive chemotherapy compared to patients with chest/abdomen, lymph node, or hematopoiesis system as primary site.

Discussion

Our comprehensive analysis demonstrates that there is significant increased RR for specific groups of patients to develop AML after diagnosis of MS. Delay in initiation of chemotherapy for patients with MS is associated with a significant decrease in OS. After patients with MS develop AML as SPC there is no longer a significant benefit of chemotherapy on OS. There is a significantly higher HR for effect of chemotherapy on 12-month OS for MS patients compared to MS with AML as SPC patients. This is true for all groups of patients other than those who were age 80+, Asian or pacific islander, or had primary site of MS being connective/soft tissue or lymph node. These results stress the importance of early chemotherapy for MS prior to the development of AML, especially for groups of patients who are at elevated RR of developing AML as SPC or have increased HR of receiving benefit from chemotherapy.