Higher Spleen Volume at HSCT Associated With Worse Outcomes in AML

A study evaluating the predictive value of spleen volume among patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) suggests higher spleen volume may be linked to adverse outcomes, including worse overall survival (OS). The findings were published in the journal Annals of Hematology.

Allogeneic HSCT is an effective treatment option for AML that has led to increased survival among patients with AML over time, the authors noted. But HSCT also carries a risk of severe complications, especially infections and graft versus host disease (GVHD) related to immunosuppression, and rates of nonrelapse mortality (NRM) have risen. The identification of risk factors for NRM aside from infections is a key area of research, the authors added.

“In patients with myelofibrosis undergoing allogeneic HSCT, splenomegaly has been linked to primary graft failure and poor outcome,” the authors wrote. “However, little is known on the association of spleen volume and outcome after HSCT in patients with AML.”

The study retrospectively explored pretransplant spleen volume in relation to OS, NRM, cumulative incidence of relapse (CIR), and hematological recovery among patients with AML who underwent HSCT. The predictive value of spleen enlargement in regard to engraftment kinetics after HSCT was also examined.

“While the leading hypothesis is that an enlarged spleen in AML patients who receive HCST is indicative of poor clinical outcome, it remains controversial whether spleen volume is independently associated with outcome in those patients,” the researchers wrote.

A total of 402 patients were included in the study, all of whom underwent initial HSCT between January 2012 and March 2019. Median follow-up was 33.7 months (95% CI, 28.9-37.4), and patients were categorized as either having small spleen volume (SSV) or large spleen volume (LSV), with a median spleen volume of 238.0 cm³ as the cutoff.

The cohort of patients with LSV at HSCT had an OS rate of 55.7% at 2 years of follow-up vs 66.6% among patients with SSV (P = .009). Those with LSV at HSCT also experienced a higher cumulative incidence of NRM at 28.8% compared with 20.2% in those with SSV (P = .048), and the adjusted HR for NRM in those with LSV was 1.55 (95% CI, 1.03-2.34).

The SSV and LSV groups showed similar time to neutrophil or platelet engraftment and rates of acute or chronic GVHD.

The study was limited in its retrospective nature, as well as its single-center design, which may cause patient bias. Another limitation was the inability to rule out myelodysplastic syndrome or myeloproliferative neoplasm overlap syndrome in addition to AML diagnosis, which could be a cause of spleen enlargement. Transfusions and therapeutic agents could also affect spleen volume, the authors noted.

Despite the limitations, the findings suggest spleen volume could be an independent risk factor for adverse outcomes among patients undergoing HSCT for AML, particularly due to higher NRM rates in the cohort of patients with larger spleens in the study.

“Our results highlight the importance of considering spleen volume as a measure to assess the outcome of AML patients after HSCT in the future,” the authors concluded. “However, before reducing spleen size (eg, by radiotherapy) can be considered a therapeutic option to positively influence outcome in posttransplant AML, the pathophysiological mechanisms underlying the observed associations need to be clarified.”

Reference

Pohlmann A, Bentgens E, Schülke C, et al. Pretransplant spleen volume and outcome after hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML). Ann Hematol. Published online July 10, 2023. doi:10.1007/s00277-023-05353-9