Thrombocytopenia after allogeneic HSCT is known to be associated with increased morbidity and mortality. Although causes are not well established and seem to be multifactorial, several risk factors including HLA-mismatches, graft failure, infectious complications and their treatment, microangiopathy and GVHD have been reported. So far, platelet transfusions are the mainstay of management of post engraftment thrombocytopenia and no clear recommendations on the management are available. However, within the last years several, mostly retrospective analyses on off-label use of thrombopoietin receptor agonists (TPO-RA) with good efficacy and safety have been published.

In this retrospective analysis we aim to identify clinical and laboratory parameters associated with TPO-RA administration and systematically evaluated the patients' response to treatment. All patients receiving an allogeneic HSCT between 01/2016 and 12/2023 were included, based on the first time of TPO-RA off-label use in 2016. To define response to TPO-RA treatment criteria of the international working group (IWG) for ITP and the guidelines from the American society of hematology 2019 were used.

Within the study period a total of 595 patients (41% female, median age 53 years) received allogeneic HSCT, 27 of those (5%) were treated with a TPO-RA for primary or secondary thrombopenia (n=15, 56% vs. n=12, 44%). Eltrombopag was the most frequently used TPO-RA followed by Romiplostim and Avatrombopag in 20 (74%), 4 (15%) and 3 (11%) patients, respectively. The primary indication for TPO-RA treatment was thrombocytopenia alone in 16 patients (59%), while 11 patients had both thrombocytopenia and active bleeding (41%), including petechiae, ocular, urogenital and gastrointestinal bleeding. In 4 patients (17%) bleeding persisted after TPO-RA start. The median platelet count before TPO-RA initiation was 11 G/L (range 7-14), all patients required frequent platelet transfusions before TPO-RA start and the median time to overcome transfusion dependency was 23 days (range 10-62). Two patients developed elevated liver enzymes (7%), while no other adverse events including thromboembolic or bleeding complications occurred.

An overall response with >50 G/L platelets for 7 consecutive days was reached in 18 patients (75%), with median time of 70 days (range 53-92 days). Any response (>30 G/L and at least doubling of the platelet count) was reached within one week, one month or 6 months in 0, 11 (42%) and 17 (63%) patients, respectively. Fifteen patients were eligible for evaluation of platelet recovery at 12 months after TPO-RA start.

Of those 9 patients (60%) reached CR with platelets > 100 G/L, and 6 patients (40%) PR with platelets between 30 and 100 G/L. At 12 months 11 of 15 patients (73%) had a sustained remission after discontinuing TPO-RA treatment after a median of 114 days (range 79-145).

Lower CD34⁺ stem cell count (OR=0,750, p=0,009), GVHD prophylaxis with posttransplant cyclophosphamide (OR=2,644, p=0,016), acute GVHD (OR=2,266, p=0,043), second-line treatment for acute GVHD (OR=2,841, p=0,045), chronic GVHD (OR=5,767, p<0,001), and CMV reactivation (OR=3,565, p=0,002) are statistically significant associated with TPO-RA treatment in a univariate binary logistic regression. When tested for confounders in a multivariate binary logistic regression only chronic GVHD (OR=10,471, p<0,001), CMV reactivation (OR=5,352, p=0,002), and transplant age (OR=1,048, p=0,033) were significantly associated with increased odds of TPO-RA treatment.

We observed good response rates to TPO-RAs after allogeneic HSCT, while time to response seems quite long. Given the observed data we conclude that TPO-RA treatment after allogeneic HSCT might be a valuable option for patients with prolonged or secondary thrombocytopenia. However, prospective analyses are necessary to determine a potential difference between TPO-RA effectiveness and platelet rise in the course of delayed graft function.

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2025
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