Splenectomy Before Stem Cell Transplant May Help Certain Patients With MF

Splenectomy before allogeneic hematopoietic stem cell transplantation (alloHSCT) might be a promising option in patients with myelofibrosis (MF) who failed to achieve significant spleen response after ruxolitinib therapy, according to results from a recently published study.

The aim of the study was to evaluate the safety of splenectomy before alloHSCT, the only treatment option with curative potential in patients with myelofibrosis if they fail to achieve significant spleen response after ruxolitinib. Ruxolitinib, a tyrosine kinase inhibitor (TKI) that inhibits Janus kinase (JAK) 1/2, is approved for use in intermediate- to high-risk patients. AlloHSCT is indicated in these patients if they are younger than 65 years. Most of the transplant candidates have significant tumor burden.

Massive spleen enlargement (>15 cm under left costal margin) is documented in 53% to 77% of cases and might be associated with worse outcomes. While therapy with JAK1 and JAK2 inhibitors significantly reduces spleen volume in at least 50% of patients with MF, 30% of patients do not achieve adequate spleen response and massive splenomegaly is still present at the time of alloHSCT. While the broad use of splenectomy before alloHSCT is limited due to perioperative morbidity and mortality, it might be an option for some patients who do not have a superior spleen response after ruxolitinib.

In this study, splenectomy was performed for alloHSCT in 12 patients with MF—primary MF (6 patients), post—polycythemia vera MF (3 patients), or post–essential thrombocythemia MF (3 patients)—between 2016 and 2018. The patients were prospectively included in the study if persistence of splenomegaly of 25 cm or greater was documented after at least 3 months of ruxolitinib. In 8 patients, subsequent alloHSCT was performed.

Median length of hospital stay was 11 (8-30) days and median follow-up after splenectomy was 20 (0.6-31.1) months. Three patients experienced portal vein thrombosis and 1 experienced splenic vein thrombosis. One patient developed pancreonecrosis and subdiaphragmatic abscess.

Mean (SD) leukocyte count was significantly higher 1 month after splenectomy than before, 10.7 (1.7) versus 6.9 (2.3) × 10⁹/L (P = .03). Platelet rate significantly elevated starting Day + 7 after splenectomy (P  = .01). Median time between splenectomy and alloHSCT was 2.6 (0.17-4.5) months. All patients achieved engraftment.

In early posttransplant period no cases of severe sepsis, intraabdominal infections were documented.

One patient died after alloHSCT due to thrombotic microangiopathy; 7 patients are alive in disease complete remission. No relapses after alloHSCT were observed, and the 2-year overall survival in the whole group is 90%.

The researchers said this is the first report regarding the use of splenectomy as a bridge to alloHSCT in patients with MF who failed to achieve spleen response after JAK1 and JAK2 inhibitor therapy and that larger studies are needed to confirm their findings.

They note that a previous study found that the risk of primary graft failure was dependent on spleen status and presence of splenomegaly. Large splenomegaly is linked with poor prognosis and higher risk of poor graft function, possibly because there might be a pooling of donor cells in the enlarged spleen. Splenectomies might be an option to reduce tumor burden before alloHSCT and improve transplant outcomes.

Reference

BarabanshikovaaIgor MV, Vjacheslav NZ, Savrasovb M, et al. Splenectomy following JAK1/JAK2 inhibitor therapy in patients with myelofibrosis undergoing allogeneic stem cell transplantation [published online April 6, 2019]. Hematol Oncol Stem Cell Ther. doi: 10.1016/j.hemonc.2019.03.001.