Martinez C.,Institute of Hematology and Oncology |
Canals C.,Hospital de la Santa Creu i Sant Pau |
Sarina B.,Istituto Clinico Humanitas |
Alessandrino E.P.,Centro Trapianti Of Midollo Osseo |
And 20 more authors.
Annals of Oncology | Year: 2013
Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. Methods: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. Results: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. Conclusion(s): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Boyiadzis M.,University of Pittsburgh |
Arora M.,University of Minnesota |
Klein J.P.,Medical College of Wisconsin |
Hassebroek A.,Center for International Blood and Marrow Transplant Research |
And 24 more authors.
Clinical Cancer Research | Year: 2015
Purpose: Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse, it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year after transplant at the time when acute GVHD is still active. Experimental Design: This study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7,489 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndromes (MDS), who were leukemia free at 12 months after myeloablative allogeneic HCT. Results: Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on late relapse was present only in patients with CML [RR, 0.47; 95% confidence interval (CI), 0.37-0.59; P < 0.0001). cGVHD was significantly associated with higher risk of treatment-related mortality (TRM; RR, 2.43; 95% CI, 2.09-2.82; P < 0.0001) and inferior overall survival (RR, 1.56; 95% CI, 1.41-1.73; P < 0.0001) for all diseases. In patients with CML, all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse. Conclusions: These results indicate that clinically relevant antileukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL, or MDS. Chronic GVHD in patients who are 1-year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival. © 2015 American Association for Cancer Research.
do Pazo-Oubina F.,Hospital Clinic |
Creus-Baro N.,Hospital Clinic |
Martinez-Munoz C.,Institute of Hematology and Oncology |
Rovira-Tarrats M.,Institute of Hematology and Oncology
European Journal of Oncology | Year: 2013
Aim: Acute graft-versus-host disease is a major complication of allogeneic hematopoietic stem cell transplantation. First-line treatment is with corticosteroids, but there is no standard second-line treatment, although etanercept is an option. In this case series, we present the efficacy and safety profile of etanercept in the second-line treatment of acute graft-versus-host disease. Patients and Methods: Ten patients received at least 1 dose of etanercept for treatment of acute graft-versus-host disease between January 2009 and February 2011.We assessed response to treatment and associated toxicity. Results: Diagnosis of acute graft-versushost disease was histologically confirmed in all but 1 patient. A clinical response was obtained in 3 patients (2 complete responses and 1 partial response).Etanercept was well tolerated, and no cases of associated secondary toxicity were observed. Conclusions: The efficacy results of this study were slightly worse than those reported in the literature. The poorer response obtained may be explained by the more severe acute graft-versus-host disease at diagnosis: all the patients had intestinal grade ≥ II (7 with grade IV disease). © Mattioli 1885.
Diaz T.,University of Barcelona |
Navarro A.,University of Barcelona |
Ferrer G.,Institute of Hematology and Oncology |
Gel B.,Polytechnic University of Catalonia |
And 7 more authors.
PLoS ONE | Year: 2011
Standard cytotoxic chemotherapy for Hodgkin Lymphoma (HL) has changed little in 30 years; the treatment for patients with relapsed or refractory disease remains challenging and novel agents are under development. JAK/STAT constitutive activation plays an important role in the pathogenesis of HL. Lestaurtinib is an orally bioavailable multikinase inhibitor that has recently been shown to inhibit JAK2 in myeloproliferative disorders. The potential role of Lestaurtinib in HL therapy is unknown. We have analyzed the effect of Lestaurtinib treatment in five HL cell lines from refractory patients, L-428, L-1236, L-540, HDML-2 and HD-MY-Z. At 48 h, a dose-dependent cell growth inhibition (23%-66% at 300 nM) and apoptotic increment (10%-64% at 300 nM) were observed. Moreover, Lestaurtinib inhibited JAK2, STAT5 and STAT3 phosphorylation and reduced the mRNA expression of its downstream antiapoptotic target Bcl-xL. In addition, we have analyzed the effect of Lestaurtinib treatment in lymph nodes from four classic HL patients. We observed a decrease in cell viability at 24 hours of treatment in three patients (mean decrease of 27% at 300 nM). Our findings provide, for the first time, a molecular rationale for testing JAK2 inhibitors, specifically Lestaurtinib, in HL patients. © 2011 Diaz et al.
Rocha V.,EUROCORD ED |
Rocha V.,Institut Universitaire de France |
Rocha V.,University of Oxford |
Labopin M.,University Pierre and Marie Curie |
And 17 more authors.
Transplantation | Year: 2013
BACKGROUND: Unrelated cord blood transplantation (UCBT) is associated with delayed hematopoietic recovery. Intrabone injection of cord blood cells (IB-UCBT) and double-UCBT (dUCBT) are designed to circumvent this problem. METHODS: In a retrospective registry-based analysis, we compared outcomes of 87 IB-UCBT with 149 dUCBT recipients, after myeloablative conditioning regimen adjusting for the differences between the two groups. Median-infused total nucleated cells were 2.5×107/kg for IB-UCBT and 3.9×107/kg for dUCBT (P<0.001). RESULTS: At day +30, cumulative incidence (CI) of neutrophil recovery was 76% and 62% (P=0.014) with a median time to engraftment of 23 and 28 days (P=0.001), after IB-UCBT and dUCBT, respectively. At day +180, CI of platelets recovery was 74% after IB-UCBT, and 64%, after dUCBT (P=0.003). In multivariate analysis, IB-UCBT was associated with neutrophil and platelets recovery and lower acute graft versus host disease (II-IV) (P<0.01). At 2 years, CI of nonrelapse mortality and relapse incidence were 30% and 25% after IB-UCBT and 34% and 29% after dUCBT, and disease-free survival was 45% and 37%, respectively. However, after landmark analysis at 4.7 months from transplantation, in multivariate analysis, relapse incidence was reduced (P=0.03), and there was a trend for better disease-free survival after IB-UCBT (P=0.09). CONCLUSION: Both approaches expand the possibility of offering UCBT to patients with hematopoietic malignancies; IB-UCBT is associated with faster myeloid and platelet recovery and lower acute graft versus host disease and may reduce the total cost. However, studies on cost effectiveness are needed to compare both strategies. Copyright © 2013 by Lippincott Williams & Wilkins.