Eltrombopag may induce bone marrow fibrosis in allogeneic hematopoietic stem cell transplant recipients with prolonged thrombocytopenia.

Poor graft function (PGF) and secondary failure of platelet recovery (SFPR) are significant causes of transplant related morbidity and mortality. Although thrombopoietin receptor agonists (TPO-RA), particularly Eltrombopag (EPAG), have been reported to be efficacious in the treatment of prolonged thrombocytopenia, potential long term adverse effects remain to be elucidated. This retrospective study was performed to determine the efficacy and toxicity profile of TPO-RAs in allogeneic hematopoietic stem cell transplant (alloHCT) recipients. Medical records of 27 patients [median age: 55(21-73) years; male/female: 15/12] who received posttransplant EPAG for SFPR or PGF were analysed. Eltrombopag was started on day 110(33-670) after transplant. Median initial dose was 25(25-50) mg/day which was properly escalated to a maximum dose of 75(50-100) mg/day. Duration of the treatment was median 120(31-377) days. Overall response rate (ORR) was 59.3% in the study population. Time-to-treatment response was 42(3-170) days. Mild-to-moderate bone marrow fibrosis was detected in the posttreatment biopsies of 12/22 patients (54.5%), 9 of whom did not represent any grade of myelofibrosis in their inital biopsies. The grade of posttreatment fibrosis was significantly increased when time-to-treatment response was longer (p = 0.008). Long term use of TPO-RAs may be considered as a potential cause of myelofibrosis in alloHCT recipients.

Hematopoietic Cell Transplant-Composite Risk (HCT-CR): A Novel Predictor of Prognosis in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curable treatment modality for hematologic disorders. Transplant-related mortality remains high despite prominent scientific and technologic improvements. In consideration with the potential impact of patient- and disease-related factors on transplant outcome, this retrospective study was performed to investigate the predictive role of pretransplant HCT-composite risk (HCT-CR) score in allo-HCT recipients. METHODS: A total of 313 patients with acute leukemia (male/female: 192/121; median age, 36 [18-71] years) were included in this study. The study cohort was divided into 2 subgroups based on pretransplant HCT-CR categories. The HCT-CRlo group included low-risk patients, and the HCT-CRint-hi group consisted of intermediate-, high-, and very high-risk patients. RESULTS: In the whole cohort, overall survival (OS) and 5-year OS were found to be 32.2% and 45.1%, respectively. Probability of OS was significantly better in the HCT-CRlo group compared with the HCT-CRint-hi group (P < .001). Leukemia-free survival (LFS) and 3-year LFS were 59.5% and 65.1%, respectively. Probability of LFS was better in the HCT-CRlo group compared with the HCT-CRint-hi group (P = .001). Nonrelapse mortality (NRM) and 3-year NRM were estimated to be 38.1% and 27.5%, respectively. Probability of NRM was significantly higher in the HCT-CRint-hi group compared with the HCT-CRlo group (P = .012). In multivariate analysis, HCT-CR was shown to have significant prognostic impact in acute lymphoblastic leukemia patients (P = .023; hazard ratio, 2.613; 95% CI, 1.142-5.982). CONCLUSION: Pretransplant evaluation of patient- and disease-related factors is essential for the accurate prediction of posttransplant survival. Further efforts to evolve current criteria for pretransplant risk assessment would eventuate in better transplant outcomes.

Comparison of post-remission strategies in acute myeloid leukemia: Autologous hematopoietic stem cell transplantation versus consolidation chemotherapy.

Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT) has become a therapeutic option for first-line consolidation in Acute Myeloid Leukemia (AML) patients with favorable and intermediate risk features. A total of 101 AML patients in first complete remission, who were not eligible for allogeneic HSCT, were randomized to receive intensive cytarabine-based chemotherapy or to undergo auto-HSCT. The probability of LFS was significantly better in auto-HSCT recipients compared to chemotherapy arm (43% vs 4.8%, p=0.008). At the end of 915 (30-4470) days of followup, the probability of overall survival was better in auto-HSCT group compared to chemotherapy, without statistical significance (79.2% vs 38.8%, p=0.054). Multivariate analysis revealed a significant predictive impact of cytogenetic risk status on OS (p=0.002, HR: 2.824, 95% CI: 1.445-5.521). Auto-HSCT is considered as an effective consolidation approach in favorable and intermadiate risk AML patients.