ABSTRACT
A retrospective cohort study was conducted to assess differences in efficacy and tolerability between a busulfan AUC target of 16.4 mg × Hr/L per day (FluBu4K) and a conventional RIC regimen (FluBu2). Adult patients with a diagnosis of AML or MDS who received fludarabine + busulfan conditioning with or without antithymocyte globulin between 2015 and 2018 were included. The primary outcome was relapse free survival. Overall, 74 patients received conditioning with either FluBu4K or FluBu2. At 18 months, relapse-free survival was not significantly different, at 63.9% with FluBu4k compared to 57.5% with FluBu2 (p = 0.49). There was a statistically significant difference in the cumulative incidence of relapse at 18 months in favor of the FluBu4K regimen, at 12.0% vs 32.5% (p = 0.047). The results of this study indicate that for select patients, there may be benefit in choosing targeted FluBu4K over FluBu2. Adverse effects other than mucositis were not significantly different.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Area Under Curve , Busulfan , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/therapy , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation Conditioning , Transplantation, Homologous , Vidarabine/analogs & derivativesABSTRACT
Acute graft-versus-host-disease (aGVHD) is a complication after allogeneic stem cell transplant. After the failure of treatment with high dose corticosteroids, steroid-refractory aGVHD (SR aGVHD) is associated with high rates of mortality. Tocilizumab has evidence of activity in SR aGVHD. For patients ineligible for trials, the OSU James Comprehensive Cancer Center has been utilizing tocilizumab as first-line therapy for SR aGVHD. We retrospectively report on 15 patients who received tocilizumab. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 49 years. Median time to tocilizumab administration was 9 days (range, 3-16). Six patients had complete responses (40%) with a resolution of aGVHD. From the last contact, median overall survival for responders was not yet reached vs. 31 days for non-responders (p = .0002). Patients with skin and/or GI aGVHD demonstrated the greatest benefit. Patients with liver aGVHD did not respond. Future studies are needed to evaluate tocilizumab prior to steroid failure.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Glucocorticoids/pharmacology , Graft vs Host Disease/drug therapy , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Immunosuppressive Agents/administration & dosage , Acute Disease/mortality , Acute Disease/therapy , Adult , Aged , Allografts/drug effects , Allografts/immunology , Antibodies, Monoclonal, Humanized/adverse effects , Disease Progression , Drug Resistance , Female , Glucocorticoids/therapeutic use , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Humans , Immunosuppressive Agents/adverse effects , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , Transplantation, Homologous/adverse effects , Treatment Outcome , Young AdultABSTRACT
Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.
Subject(s)
Aminocaproic Acid/adverse effects , Antifibrinolytic Agents/adverse effects , Hematologic Neoplasms/complications , Hemorrhage/drug therapy , Thrombocytopenia/drug therapy , Thromboembolism/epidemiology , Adult , Aged , Catheterization, Central Venous/adverse effects , Catheters, Indwelling/adverse effects , Female , Hemorrhage/etiology , Hemorrhage/prevention & control , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Thrombocytopenia/etiology , Thrombocytopenia/prevention & control , Thromboembolism/chemically induced , Treatment OutcomeABSTRACT
Acute graft-versus-host-disease (aGVHD) is a frequent and often lethal complication of allogeneic hematopoietic stem cell transplant despite prophylaxis. Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody that has evidence of activity in patients with steroid refractory (SR) GVHD. We retrospectively report on nine patients with grade 3 or 4 SR aGVHD who received tocilizumab. Eight mg/kg of tocilizumab was administered intravenously every 3-4 weeks. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 48 years. Five patients had alternate donor sources. Median time from aGVHD onset to tocilizumab administration was 44 days. Two patients had complete responses and two had partial responses. Median survival from start of tocilizumab was 26 days (range 13-1054). Our limited experience demonstrated an overall response rate of 44% (CR + PR); however, this response was not durable. Further studies are needed to determine the optimal time for tocilizumab initiation.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Drug Resistance , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Adult , Antibodies, Monoclonal, Humanized/pharmacology , Female , Graft vs Host Disease/diagnosis , Hematopoietic Stem Cell Transplantation , Humans , Infections/diagnosis , Infections/etiology , Male , Middle Aged , Receptors, Interleukin-6/antagonists & inhibitors , Steroids/therapeutic use , Transplantation Conditioning , Transplantation, Homologous , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate whether the incidence of thromboembolic events (venous and arterial) increases when bevacizumab-based chemotherapy and erythropoietin stimulating agents (ESAs) are used in combination versus alone. METHODS: A retrospective, pilot study of 79 colorectal cancer patients treated with chemotherapy were divided into 3 groups: bevacizumab (n = 28), ESA (n = 21), and bevacizumab plus ESA (n = 28). The primary end point was the incidence of thromboembolic events. Secondary endpoints included median time-to-event; effect of anticoagulation; and association with concurrent chemotherapy, baseline risk factors, hemoglobin, and performance status. RESULTS: The incidence of thromboembolic events was 11% in the bevacizumab group, 23.8% in the ESA group, and 30% in the combination group (P = 0.194). The median time-to-event was 7.5, 3.5, and 2.5 months, respectively (P = 0.060). The 5 month difference in time-to-event between the bevacizumab group and combination group was significant (P = 0.045). When combining all patients, ESA treatment, prior venous thromboembolic event (VTE), obesity, cardiac disease, and use of exogenous hormones were strong predictors for thromboembolic events. Prior VTE was a strong predictor in those patients in the combination group. CONCLUSION: The incidence of thromboembolic events was increased with the combination of bevacizumab plus ESA compared with either agent alone with chemotherapy. Median time-to-event in the combination group was significantly shorter compared with the bevacizumab group. Prior VTE, cardiac disease, obesity, and exogenous hormone use should be taken in consideration when using the combination of bevacizumab and ESAs.
