ABSTRACT
Patients with classic Hodgkin lymphoma (cHL) who relapse after autologous hematopoietic cell transplantation (auto-HCT) historically have had poor outcomes. We hypothesized that, post-auto-HCT relapse, overall survival (PR-OS) has improved in recent years as a result of more widespread use of novel therapies and allogeneic HCT (allo-HCT). We conducted a retrospective study in 4 US academic centers, evaluating 215 patients who underwent auto-HCT from 2005 to 2016 and relapsed thereafter. Patients were divided into 2 cohorts based on timing of auto-HCT, 2005 through 2010 (cohort 1; n = 118) and 2011 to 2016 (cohort 2; n = 97), to compare differences in clinical outcomes. The median age and disease status at auto-HCT were similar in cohorts 1 and 2. The proportions of patients who received brentuximab vedotin (Bv; 55% vs 69%; P = .07), checkpoint inhibitors (CPIs; 3% vs 36%; P ≤ .001), and allogeneic-HCT (22% vs 35%, P = .03) were significantly different between cohorts 1 and 2, respectively. At the 5-year follow-up after auto relapse, 32% and 50% of patients were alive in cohorts 1 and 2, respectively (P = .01). In multivariate analysis for PR-OS, cohort 1 vs 2 (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.14-4.60; P = .01), age at auto-HCT (HR, 1.48; 95% CI, 1.18-1.87; P ≤ .001), and time to relapse from auto-HCT (HR, 0.59; 95% CI, 0.47-74; P ≤ .0001), retained independent prognostic significance for PR-OS. Our study supports the hypothesis that survival of cHL patients after auto-HCT failure has significantly improved in recent years, most likely because of incorporation of novel therapies and more widespread use of allo-HCT.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Hodgkin Disease/drug therapy , Humans , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation, AutologousABSTRACT
Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1). At discontinuation, 14 were still in CP, three had progressed to AP and two to blast phase (BP). Three CP patients improved their cytogenetic response (CyR) to complete CyR (CCyR), two after SCT and one on omacetaxine. None of the 12 patients, without a major cytogenetic response at ponatinib discontinuation, including all patients treated with subsequent TKIs, responded to therapy. Seventeen AP patients, stopped ponatinib due to resistance (n = 15) or intolerance (n = 2). At discontinuation, 14 were still in AP and three had progressed to BP. Four patients were treated with SCT and one achieved major molecular response. None of the 12 patients treated with non-SCT approaches responded to subsequent therapy. Median survival for all patients was 16.6 months after ponatinib discontinuation (31, 9 and 13 months for patients in CP, AP and BP, respectively). Median survival was 60 months for patients who discontinued ponatinib for toxicity and 11 months for those who discontinued for resistance. Long-term outcome of patients with ponatinib failure are poor with estimated one-year OS and EFS rates of 54% and 40%, respectively. New treatment options are required for this subset of patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Imidazoles/therapeutic use , Leukemia, Myeloid, Accelerated Phase/drug therapy , Leukemia, Myeloid, Chronic-Phase/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyridazines/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Imidazoles/administration & dosage , Imidazoles/adverse effects , Leukemia, Myeloid, Accelerated Phase/genetics , Leukemia, Myeloid, Accelerated Phase/mortality , Leukemia, Myeloid, Accelerated Phase/pathology , Leukemia, Myeloid, Chronic-Phase/genetics , Leukemia, Myeloid, Chronic-Phase/mortality , Leukemia, Myeloid, Chronic-Phase/pathology , Middle Aged , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyridazines/administration & dosage , Pyridazines/adverse effects , Salvage Therapy , Survival Analysis , Treatment Failure , Treatment Outcome , Young AdultABSTRACT
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe immune activation with macrophage and T-cell infiltration resulting in, multi organ damage. HLH may be primary or secondary in etiology. A high index of suspicion is essential for early diagnosis and treatment. Diagnostic criteria need to be refined and newer treatment options to be explored in order to improve survival especially in adult HLH and malignancy-associated HLH (M-HLH). We report a case of malignancy associated HLH (M-HLH) in adult treated on one of the only FDA-approved protocols for adult HLH to highlight the diagnostic and therapeutic challenges of this disease entity.
