Abstract
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative procedure for several hematological malignancies. Haploidentical HSCT (haplo-HSCT) using high-dose post-transplantation cyclophosphamide (PTCy) makes transplantation possible for patients with no HLA-matched sibling donor. However, this treatment can cause complications, mainly infection, graft-vs.-host disease (GVHD), and conditioning-related toxicity. In recent years, different biomarkers in the form of tissue-specific proteins have been investigated; these may help us to predict complications of allo-HSCT. In this study we explored two such biomarkers, suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (REG3α), in the largest series reported of T cell–replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed. ST2 and REG3α levels at day +15 were not associated with post-transplant complications. ST2 levels at day +30 were higher in patients with grade II-IV acute GVHD, mainly those who received reduced intensity conditioning (RIC; median 2,503 vs. 1,830 ng/ml; p = 0.04). Of note, patients with higher plasma ST2 levels at day +30 also presented a higher incidence of non-relapse mortality (HR, 7.9; p = 0.004) and lower 2-year overall survival (25 vs. 44 months; p = 0.02) than patients with lower levels. Patients with REG3α levels higher than 1,989 pg/ml at day +30 presented a higher incidence of acute gastrointestinal GVHD in the whole cohort (HR, 8.37; p = 0.003) and in the RIC cohort (HR 6.59; p = 0.01). These data suggest that measurement of ST2 and REG3α might be useful for the prognosis and prediction of complications in patients undergoing haplo-HSCT with PTCy.
Highlights
Post-transplant high-dose cyclophosphamide (PTCy) provides effective prophylaxis against graft-vs.-host disease (GVHD) in patients undergoing unmanipulated haploidentical stem cell transplantation
We found that only plasma suppression of tumorigenicity 2 (ST2) levels >1,882 ng/ml on day +30 were associated with death both in the whole cohort (HR, 5.49; p = 0.01) and in the reduced intensity conditioning (RIC) cohort (HR, 3.47; p = 0.05) (Table 4)
Interest in plasma biomarkers for prediction, diagnosis, and prognosis of post-transplant complications has grown in recent years
Summary
Post-transplant high-dose cyclophosphamide (PTCy) provides effective prophylaxis against graft-vs.-host disease (GVHD) in patients undergoing unmanipulated haploidentical stem cell transplantation (haplo-HSCT). In the last few years, various biomarkers have been studied to enable the prediction, diagnosis, and prognosis of NRM and GVHD [15,16,17] Such biomarkers could potentially guide treatment decisions, leading to intensive clinical surveillance of patients at high risk of developing complications. ST2, on the other hand, is a member of the interleukin-1 receptor family and has been directly related to the risk of treatmentresistant aGVHD and 6-month NRM after onset of aGVHD independently of clinical severity [23,24,25] Most of these studies are performed in identical HLA or umbilical cord–based alloHSCT. Our objective was to analyze plasma levels of REG3α and ST2 at days +15 and +30 after transplant and to correlate them with complications in a large cohort of patients who underwent unmanipulated haplo-HSCT with high-dose PTCy
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