Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial

Abstract

Refractory prolonged isolated thrombocytopenia (RPIT) is an intractable complication after allogeneic hematopoietic cell transplantation (HCT), which often leads to poor prognosis. A clinical study was designed to validate the efficacy and safety of low-dose decitabine for RPIT after HCT and explore the related underlying mechanisms. Eligible patients were randomly allocated to receive 1 of 3 interventions: arm A, low-dose decitabine (15 mg/m2 daily IV for 3 consecutive days [days 1-3]) plus recombinant human thrombopoietin (300 U/kg daily); arm B, decitabine alone; or arm C, conventional treatment. The primary end point was the response rate of platelet recovery at day 28 after treatment. Secondary end points included megakaryocyte count 28 days after treatment and survival during additional follow-up of 24 weeks. Among the 91 evaluable patients, response rates were 66.7%, 73.3%, and 19.4% for the 3 arms, respectively (P < .001). One-year survival rates in arms A (64.4% ± 9.1%) and B (73.4% ± 8.8%) were similar (P = .662), and both were superior to that in arm C (41.0% ± 9.8%; P = .025). Megakaryocytes, endothelial cells (ECs), and cytokines relating to megakaryocyte migration and EC damage were improved in patients responding to decitabine. This study showed low-dose decitabine improved platelet recovery as well as overall survival in RPIT patients after transplantation. This trial was registered at www.clinicaltrials.gov as #NCT02487563.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

CONSORT diagram for the study. A total of 97 patients were enrolled in the trial, and 91 patients were evaluated. aPlatelet count <30 × 109/L. bNeutrophil count <1.0 × 109/L and/or red blood cells transfusion dependent.

Figure 2.

Significantly improved platelet and megakaryocyte (MK) counts were observed in patients receiving decitabine treatment. (A) Platelet counts increased significantly in arms A and B during third week after decitabine administration. (B) Total MKs (per cm2), platelet-shedding MKs (per cm2), and MK polyploidy (%) in patients in arms A and B increased remarkably after treatment compared with those in arm C. (C) Representative microscopic images (Wright-Giemsa staining) of bone marrow biopsy in case 29 in arm A at week 0 (left) and week 4 (right) after treatment. Arrows indicate MKs. *P < .05. ns, not significant.

Figure 3.

Decitabine treatment is associated with better overall survival. (A) One-year overall survival rates in arms A, B, and C were 64.4% ± 9.1%, 73.4% ± 8.8%, and 41.0% ± 9.8%, respectively (P = .025). (B) One-year overall survival rates for patients in arms A and B (decitabine ± rhTPO; 68.2% ± 6.4%) were higher than those for patients in arm C (conventional treatment; 41.0% ± 9.8%; P = .008).