ABSTRACT
A single-center retrospective study was performed with consecutive patients who received salvage therapy using ponatinib for the aim of allogeneic hematopoietic cell transplantation (HCT) for relapsed or refractory Ph-leukemia between January 2017 and July 2018. A total of ten patients-seven with Ph-acute lymphoblastic leukemia (ALL) and three with chronic phase (CP)/accelerated phase chronic myeloid leukemia (CML)-were eligible. Eight patients had a history of a single tyrosine kinase inhibitor (TKI) use prior to ponatinib. Any mutation of the tyrosine kinase domain was detected in eight patients, including seven of T315I. The median dose of ponatinib was 15 mg with a median duration of 7 weeks (range 4-23 weeks). The median duration from the start of ponatinib to HCT was 54 days (range 35-175 days). Hematological remission was obtained in five Ph-ALL patients. Maintenance therapy of ponatinib was applied to five patients. No vascular occlusion event has occurred over this series of treatments. Salvage therapy with low-dose ponatinib appears to be safe and effective in patients with relapsed or refractory Ph-leukemia, which may immediately bridge to HCT.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Imidazoles/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Pyridazines/administration & dosage , Salvage Therapy/methods , Adult , Aged , Allografts , Female , Humans , Imidazoles/therapeutic use , Induction Chemotherapy/methods , Maintenance Chemotherapy/methods , Male , Middle Aged , Philadelphia Chromosome , Protein Kinase Inhibitors/therapeutic use , Pyridazines/therapeutic use , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: A multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML). METHODS: The study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients. RESULTS: The median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003). CONCLUSION: Elevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group.
Subject(s)
Biomarkers, Tumor/blood , Ferritins/blood , Leukemia, Myeloid, Acute/mortality , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Prognosis , Remission Induction/methods , Retrospective Studies , Tumor Burden , Young AdultABSTRACT
Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3-year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB.
