Falling Splenectomy Rates in ITP Raise Questions Over Role

Liam Davenport

May 11, 2020

Patients with immune thrombocytopenia (ITP) are undergoing fewer and fewer splenectomies later and later in the disease course, which is resulting in lower gains from the procedure, say UK researchers, who question its ongoing role.

The research was published as an abstract from the British Society for Haematology 60th Annual Scientific Meeting, which was cancelled due to the COVID-19 pandemic. 

Role of Splenectomy 'Unclear'

Dr Sophie Todd, Royal London Hospital, Barts Health NHS Trust, London, and colleagues studied more than 3800 ITP patients diagnosed in the UK from the early 1950s.

The results, which are an update of findings presented at the 24th European Heart Association Congress in June 2019, show that around a third of patients underwent splenectomy in the 1990s, falling to less than 4% since 2009.

This has corresponded to an increase in the use of medical therapies, with the procedure consequently performed later on in the treatment course.

This move has seen the median duration of response (DOR) fall from more than 10 years in the 1990s to less than 2 years today.

The team writes that, with medical therapies now having "large amounts" of efficacy and safety data, "the role of splenectomy is unclear and needs further analysis of markers of response".

Moved Down the Treatment Pathway

Approached for comment, Dr Quentin Hill, Department of Haematology, St James's University Hospital, Leeds, told Medscape News UK that there are "several reasons" why splenectomy has moved down the treatment pathway.

This is not least in part because patients "often" want to try medical treatments before undergoing surgery, "so I think patient choice is a big part of this, and in the UK we generally are quite consensual about deciding on treatment options".

He also pointed out that the 2010 International consensus report on the investigation and management of primary immune thrombocytopenia recommended deferring splenectomy for 6 months, where possible.

By the time the Updated international consensus report on the investigation and management of primary immune thrombocytopenia was released in mid-2019, that recommendation had been pushed out to 1 year.

This, Dr Hill noted, was "in recognition of the fact that individuals with ITP sometimes will achieve full remission after first-line steroids, or have a platelet count elevated sufficiently that they don't require treatment", in addition to which patients may have "spontaneous remissions".

During that period, there was also an increase in the availability of medical treatments, which is another "driver for patients to be a little bit more thoughtful" over whether or not to opt for surgery, he said.

Study Details

To examine splenectomy trends, Dr Todd and colleagues collated data from the UK Adult ITP Registry, including cases from 2007, when the national database was set up, to December 2018.

They studied a total of 3824 registered patients diagnosed with ITP between 1953 and 2018.

Splenectomy was performed in 351 (9.2%) patients, of whom 37.9% were male. The median age at splenectomy was 40 years, and 86.3% were aged <65 years.

The median follow-up was 8.2 years, giving an overall follow-up across the whole cohort of 2511 years. Seventy-nine patients were excluded due to incomplete data.

The team reports that splenectomy use decreased over time, from 34.3% in 1989–1998 to 16.2% in 1999–2008 and 3.87% in 2009–2018.

The median time from ITP diagnosis to splenectomy being performed was 1.5 years, increasing from 1.17 years in 1989–1998 to 1.67 years in 2009–2018.

There was a corresponding increase in the median number of treatments given prior to splenectomy, from a median of two in 1989–1998 to three in 2009–2018, and splenectomy went from being used as a median third-line treatment in 1989–1998 to a fourth-line treatment in 2009–2018.

The most commonly used treatments prior to splenectomy were prednisolone, in 92% of patients, intravenous immunoglobulin (50%), azathioprine (27%), rituximab (21%), dexamethasone (12%), mycophenolate (10%) and romiplostin (10%).

Results

Complete responses with splenectomy were seen in 64.4% of patients at one month, 54.4% at 6 months, 46.2% at 12 months and 35.4% at 24 months, with rates lower in patients aged 65 years and over than in younger patients.

The median DOR after splenectomy was 3.0 years, falling from 10.3 years in 1989–1998 to 3.8 years in 1999–2008 and 1.7 in 2009–2018.

Among patients aged <65 years, the median DOR was 3.3 years, but only 0.83 years in patients aged 65 years and older.

When splenectomy was used as a second-line treatment, the median DOR was 2.7 years, falling to 2.2 years when used as a fourth-line treatment, and 1.5 years at sixth-line.

The median time to next treatment following relapse after splenectomy was 2.2 years.

Infections were reported in 12.9% of patients following splenectomy, while thromboses were reported in 15.2%. Among twelve (3.5%) deaths, one was attributed to splenectomy.

Pros and Cons

Dr Hill suggested that the better responses to splenectomy at the start of the study period "may reflect some patients who 'didn't need it'".

"In other words, if you splectomise everybody at 6 months, then within that long-term follow-up data you encapsulate some of those patients whose platelet count would have gotten better or gotten to a point that they didn't require treatment with splenectomy."

He also believes that, in the future, the trend for fewer splenectomies will "probably continue".

The procedure will nevertheless continue to have a role as a "rescue therapy" in patients with severe thrombocytopenia refractory to multiple lines of treatment, and as an "acute intervention" in patients with, for example, life-threatening bleeding that is not controlled with medical therapy.

For some patients, splenectomy "has the attraction of relatively low burden of frequent hospital visits", Dr Hill added, "and in those small numbers of patients in whom we have carried out splenectomy and it's worked well, their quality of life has been pretty good".

He underlined that there are "pros and cons" to splenectomy and clinicians should "chew these over" with their patients, although "they are voting, generally speaking, for the option of medical treatments first".

The authors acknowledge unrestricted educational grants from Rigel Pharmaceuticals, Amgen and Novartis.

No conflicts of interest declared.

BSH 2020: Abstract BSH2020-OR-009

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