Study IDs Best Time for Transplant in Patients With Extramedullary AML

By Cecilia Brown - Last Updated: September 30, 2022

New research suggests that the first complete remission (CR) is the best time for allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with extramedullary acute myeloid leukemia (AML).

Aleksina Shatilova, MD, of the Personalized Medicine Centre at the Almazov National Medical Research Centre in Saint Petersburg, Russia, and colleagues conducted the research and presented their findings at the Tenth Annual Meeting of the Society of Hematologic Oncology.

Dr. Shatilova and colleagues conducted the study because the “optimal treatment strategy for patients with extramedullary [AML] is questionable, especially as applied to extramedullary tumor persistence while bone marrow response is achieved,” they wrote.

The researchers wanted to determine if venetoclax-containing regimens with intensive treatment and allogeneic HSCT could improve outcomes in patients with extramedullary AML.

The study included 27 patients with verified extramedullary AML, with slightly more patients being male (51.8%) than female. The median patient age was 40 years (range, 13-84 years). Researchers classified 55.6% of patients as adverse risk based on the 2017 European LeukemiaNet risk stratification system, while 25.9% of patients were intermediate risk, and 18.5% were favorable risk.

All patients received standard high-intensity and low-intensity chemotherapy regimens, with 37% of patients receiving venetoclax with 5-azacytidine because they had comorbidities or refractory disease. Most patients (63%) underwent allogeneic HSCT.

Patients who underwent allogeneic HSCT in their first CR had a reduced risk of early relapse (12%) compared with patients who received a transplant in their second or subsequent CR (80%; P=.015). The median overall survival was approximately 5 times longer in patients who received allogeneic HSCT in their first CR (38.85 months) than those who underwent transplant in their second or subsequent CR (7.57 months; P=.013). The median relapse-free survival was approximately 10 times longer in patients who received allogeneic HSCT in their first CR (38.85 months) than those who underwent transplant in their second or subsequent CR (3.78 months; P=.0021).

Bone marrow remission occurred in 100% of patients with favorable genetic alterations and in 44% of patients who did not have favorable genetic alterations (P=.044). However, there was no significant difference in the complete extramedullary response rate between patients with and without favorable genetic alterations (75% vs 68%; P>.05).

High-dose cytarabine “enabled eradication of extramedullary lesions in case of failure of standard and low-intensity regimens” and decreased the rate of relapse during the first year after transplant, according to the researchers.

Nearly three-quarters of patients (70%) who received venetoclax with 5-azacytidine had a response, with complete eradication of the extramedullary tumor occurring in 50% of patients. However, persistent extramedullary disease after high-dose cytarabine occurred in 3 of the 5 patients who had complete eradication of their extramedullary tumor.

“Favorable genetic aberrations do not increase the frequency of extramedullary response. Intensive treatment helps to achieve complete eradication of extramedullary tumor and reduces early relapse rate,” Dr. Shatilova and colleagues concluded. “Using [venetoclax with 5-azacytidine] is effective among patients with [extramedullary] AML, including patients who were refractory to intensive treatment, and allows complete response achievement before [allogeneic] HSCT.”

Shatilova A, Budaeva I, Motorin D, et al. Venetoclax-containing regimens improve outcomes of intensive treatment and allogeneic hematopoietic stem cell transplantation in patients with extramedullary acute myeloid leukemia. Poster AML-396. Presented at the Tenth Annual Meeting of the Society of Hematologic Oncology; September 28-October 1, 2022; Houston, TX.

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