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Jordina Rovira,
Joan Cid,
Gonzalo Gutiérrez-García,
Arturo Pereira,
Francesc Fernández-Avilés,
Laura Rosiñol,
Carmen Martínez, Enric Carreras,
Alvaro Urbano,
Montserrat Rovira,
Miguel Lozano
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ABSTRACT: Immune hemolytic anemia is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). There are 4 possible causes for this complication. First, antibodies present in the recipient destroy donor cells. Second, donor red cell antibodies at the time of stem cell infusion are transferred to the recipient. Third, sometimes, engrafted donor lymphocytes cause active production of red cell antibodies. Fourth, another cause of hemolysis after allogeneic HSCT is autoimmune hemolytic anemia (AIHA). It is thought to be due to antibodies produced by the donor's immune system against antigens on red cells of donor origin. Autoimmune hemolytic anemia after allogeneic HSCT is rare, it is still not well characterized, and it represents a life-threatening situation. We describe 2 patients with acute myeloid leukemia treated with intensive chemotherapy and umbilical cord blood stem cell transplantation (UCBT). One patient developed AIHA at day +182 and the other at day +212 after receiving UCBT. Patients received 5 and 7 line treatment options, respectively, including continuous corticosteroids, intravenous immunoglobulin, splenectomy, cyclophosphamide, plasma exchange, rituximab, bortezomib, and eculizumab. However, both patients died because of massive hemolysis after 85 and 106 days of intensive treatment, respectively. These cases reflect the extreme difficulty in the therapeutic management of patients with AIHA following UCBT. After an extensive review of the literature, the exact physiopathologic mechanisms of AIHA after allogeneic HSCT in general, and after UCBT in particular, and therefore an effective treatment remain unknown.
Transfusion medicine reviews 04/2013; · 3.61 Impact Factor
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Pere Barba,
David Valcárcel,
José Antonio Pérez-Simón,
Francesc Fernández-Avilés,
José Luis Piñana,
Rodrigo Martino,
Lucía López-Anglada,
Montserrat Rovira,
Irene Garcia-Cadenas,
Silvana Novelli, Enric Carreras,
Lucía López Corral,
Jorge Sierra
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ABSTRACT: Hyperferritinemia has been associated with adverse outcome after allogeneic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning. However, its characteristics and impact on the outcome in the reduced-intensity conditioning (RIC) and in the lymphoid malignancies settings are far from clear. The study includes 201 adult patients undergoing allo-HCT with RIC (allo-RIC) for lymphoid malignancies with a median follow-up for survivors of 52 months (range 3-123). Median serum ferritin level at allo-RIC was 379 ng/ml (range 4-10790). In the multivariate analysis, patients with hyperferritinemia at transplant (>399ng/ml) showed lower 4-year overall survival (HR 1.8 [95%CI 1.2-2.8], p=0.008), higher NRM (HR 1.8 [95%CI 1.1-3.2], p=0.03) and higher infection related mortality (HR 2.3 [95%CI 1.1- 4.8], p=0.02) than patients without hyperferritinemia. Neutrophil and platelet engraftment and 100-days NRM were similar between both groups. The adverse outcome associated with hyperferritinemia seemed higher in patients without major comorbidities and it was not influenced by the elevation of acute phase reactants. Our results indicate that high ferritin levels at HCT are associated with an adverse outcome after allo-RIC in patients with lymphoid malignancies.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2013; · 3.15 Impact Factor
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Damien Roos-Weil,
Sascha Dietrich,
Ariane Boumendil,
Emmanuelle Polge,
Dominique Bron, Enric Carreras,
Arturo Iriondo Atienza,
William Arcese,
Dietrich W Beelen,
Jan J Cornelissen,
Nicolaus Kröger,
Giuseppe Milone,
Giuseppe Rossi,
Fabrice Jardin,
Christina Peters,
Vanderson Rocha,
Anna Sureda,
Mohamad Mohty,
Peter Dreger
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ABSTRACT: Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have a poor prognosis with conventional chemotherapy. We retrospectively analyzed the outcome of patients with BPDCN who underwent allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (auto-SCT). A total of 39 patients (allo-SCT 34, auto-SCT 5) were identified in the European Group for Blood and Marrow Transplantation registry. The 34 allo-SCT patients had a median age of 41 years (range, 10-70) and were transplanted from sibling (n=11) or unrelated donors (n=23) between 2003 and 2009. Myeloablative conditioning (MAC) was applied in 74%. Nineteen allo-SCT patients (56%) were transplanted in first complete remission. Three-year cumulative incidence of relapse, disease-free survival and overall survival was 32%, 33% and 41%, respectively. By univariate comparison, being in first remission at allo-SCT favorably influenced survival, whilst age, donor source and chronic graft-versus-host disease had no significant impact. High-dose therapy followed by allo-SCT from related or unrelated donors can provide durable remission even in elderly patients with BPDCN. It remains to be shown, however, if graft-versus-malignancy effects can contribute significantly to BPDCN control after allo-SCT.
Blood 11/2012; · 9.90 Impact Factor
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American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 06/2012; 69(11):917-22; author reply 922. · 2.10 Impact Factor
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ABSTRACT: We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole) for the prevention of invasive fungal infections (IFI) and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML) or myelodysplastic syndromes (MDS). The perspective was that of the Spanish National Health Service (NHS).
A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS), total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS) over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values) which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS) was performed.
Posaconazole was associated with fewer IFI (0.05 versus 0.11), increased LYS (2.52 versus 2.43), and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928) per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain.
Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy) compared with fluconazole or itraconazole in high-risk neutropenic patients.
BMC Infectious Diseases 04/2012; 12:83. · 3.12 Impact Factor
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Rafael Rojas,
José R Molina,
Isidro Jarque,
Carmen Montes,
Josefina Serrano,
Jaime Sanz,
Juan Besalduch, Enric Carreras,
José F Tomas,
Luis Madero,
Daniel Rubio,
Eulogio Conde,
Miguel A Sanz,
Antonio Torres
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ABSTRACT: Invasive mold infection (IMI) remains a major cause of mortality in high-risk hematological patients. The aim of this multicenter retrospective, observational study was to evaluate antifungal combination therapy (ACT) for proven and probable IMI in hematological patients. We analyzed 61 consecutive cases of proven (n=25) and probable (n=36) IMI treated with ACT collected from eight Spanish hospitals from January 2005 to December 2009. Causal pathogens were: Aspergillus spp (n=49), Zygomycetes (n=6), Fusarium spp (n=3), and Scedosporium spp (n=3). Patients were classified in three groups according to the antifungal combination employed: Group A, liposomal amphotericin B (L-AmB) plus caspofungin (n=20); Group B, LAmB plus a triazole (n=20), and Group C, voriconazole plus a candin (n=21). ACT was well tolerated with minimal adverse effects. Thirty-eight patients (62%) achieved a favorable response (35 complete). End of treatment and 12-week survival rates were 62% and 57% respectively, without statistical differences among groups. Granulocyte recovery was significantly related to favorable response and survival (p<0.001) in multivariate analysis. Our results suggest that comparable outcomes can be achieved with ACT in high risk hematological patients with proven or probable IMI, whatever the combination of antifungal agents used.
Mediterranean Journal of Hematology and Infectious Diseases 01/2012; 4(1):e2012011.
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ABSTRACT: The evolution of the incidence, morbidity, and mortality of veno-occlusive disease (VOD) was analyzed in 845 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) performed over 24 years. A total of 117 patients and 73 patients developed VOD following the Seattle and the Baltimore diagnostic criteria, respectively (cumulative incidence 13.8% and 8.8%). The cumulative incidence was significantly higher in the period 1985 to 1996 than in 1997 to 2008 (11.5% vs 6.5%; P = .01). This decline was because of the low incidence of VOD among reduced-intensity conditioning-HSCT (RIC-HSCT) (2.1%) and the reduction among those receiving myeloablative-HSCT from unrelated donors (32.7% vs 10.5%, P = .001). A total of 35 patients had severe VOD (26 with multiorgan failure [MOF]), and 20 died by VOD (cumulative mortality rate 17.3%, Seattle, or 22.5%, Baltimore). The mortality declined since 1997 (from 22% to 9%; P = .06, Seattle, and from 36% to 14%; P = .04, Baltimore), with the introduction of defibrotide being the only relevant change in the management of patients. This occurred even though the severity of VOD was similar in both periods. Among those with MOF, only 2 of 8 (25%) receiving defibrotide died versus 14 of 18 (78%) receiving other treatments (P = .007). Myeloablative conditioning, previous liver disease, poor performance status, and alternative donors were the variables with higher impact on VOD development. In summary, although VOD remains a dreaded early complication of HSCT, technical and therapeutic progress in recent decades have notably reduced its incidence and improved the outcome.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2011; 17(11):1713-20. · 3.15 Impact Factor
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Enric Carreras
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ABSTRACT: Hematopoietic stem cell transplantation is currently the main cause of hepatic veno-occlusive disease, which is the early complication of this procedure with the highest short-term morbidity and mortality. Given that mortality from severe hepatic veno-occlusive disease can be nearly 100%, the search for measures to prevent of treat this complication is essential. Several risk factors for this complication have been identified and the triggering event that leads to sinusoidal obstruction has been shown to be sinusoidal endothelial cell injury. The present review analyzes measures to avoid or modify the casual risk factors for this complication, as well as the pharmacological agents that can prevent or modify the initial endothelial dysfunction or the resulting sinusoidal occlusion.
Gastroenterología y Hepatología 05/2011; 34(9):635-40. · 0.73 Impact Factor
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Pere Barba,
José Luis Piñana,
Francesc Fernández-Avilés,
Jose Antonio Perez-Simón,
Rodrigo Martino,
Eva López-Guerrero,
David Valcárcel,
Montserrat Rovira,
Silvana Novelli,
Isabel Campos-Varela,
Lucía López-Anglada,
Xavier Vidal,
Lucía López Corral, Enric Carreras,
Jorge Sierra
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ABSTRACT: Liver dysfunction is frequent before allogeneic stem cell transplantation (allo-SCT). However, its characteristics and impact on transplantation outcomes are uncertain, especially in the reduced-intensity conditioning (RIC) setting. We analyzed 455 patients receiving an allo-SCT in 3 Spanish centers. Pretransplantation aspartate aminotransferase (AST), alanine aminotransaminase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), total bilirubin, and international normalized ratio were analyzed. Pretransplantation liver function test abnormalities were found in 94 (22%) patients. The most frequent cause of pretransplantation liver dysfunction was isolated elevation of GGT/AP (n = 49, 53%). Patients with high bilirubin levels before allo-SCT showed higher 4-year nonrelapse mortality (4y-NRM) (hazard ratio [HR] 2 [95% confidence interval [CI] 1.1-3.8] P = .02) and patients with high GGT levels showed higher 100-day NRM and lower 4-year overall survival (OS) (HR 3.4 [95% CI 1.8-6.7] P < .001, and HR 2 [95% CI 1.4-3], P = .001), respectively. High levels of transaminases did not influence on survival or mortality. In conclusion, hepatic dysfunction before allo-SCT is frequent and has an impact on transplantation outcomes. The best indicator of liver dysfunction still has to be determined.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2011; 17(11):1653-61. · 3.15 Impact Factor
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Carlos Cervera,
Francesc Fernández-Avilés,
Oscar de la Calle-Martin,
Xavier Bosch,
Montserrat Rovira,
Montse Plana,
Asunción Moreno,
Felipe García,
Jose M Miró,
Antonio Martínez,
Teresa Gallart, Enric Carreras,
Joan Blade,
Jose M Gatell
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ABSTRACT: A 40-year-old man with severe chronic idiopathic CD4+ lymphocytopenia complicated with opportunistic infections was successfully treated with non-myeloablative allogeneic hematopoietic stem cell transplantation. After conditioning with fludarabine plus low dose of total-body irradiation, CD34+ peripheral blood stem cells obtained by leukapheresis from his HLA-identical sister were infused. T cell and myeloid complete chimerism was achieved at day +28 and remained stable during the follow-up period. The patient did not develop infectious complications during the procedure. At 35 months of follow-up, his CD4+ T cell count was 1019 cells per microliter. Non-myeloablative allogeneic hematopoietic stem cell transplantation should be considered a treatment option for patients with severe forms of idiopathic CD4+ lymphocytopenia.
European Journal Of Haematology 03/2011; 87(1):87-91. · 2.61 Impact Factor
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ABSTRACT: The present article is an update of the literature on fungemia in onco-hematologic patients. A multidisciplinary group of Spanish physicians with an interest in this field selected the most important papers published lately. Papers from the fields of epidemiology, risk factors, pathogenesis, diagnosis, outcome, prevention and treatment are discussed. Important aspects of these studies include the assessment of different strategies in the management of fever in neutropenic patients. Moreover, early identification of patients at risk of fungal infections, as well as identification of patients at risk for fluconazole-resistant strains are topics of increasing interest.
Enfermedades Infecciosas y Microbiología Clínica 03/2011; 29 Suppl 4:42-7. · 1.49 Impact Factor
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ABSTRACT: In the time since the first allogeneic hematopoietic stem cell transplantation (HSCT) was performed over 40 years ago, this life-saving procedure has been used increasingly for patients with hematologic, metabolic, and malignant diseases. Despite major advances in our understanding of the immunologic processes (both beneficial and injurious) that are associated with HSCT and improvements in supportive and critical care medicine, successful outcomes are still limited by several serious complications. As such, the establishment of effective therapeutic strategies for these complications will be crucial as increasing numbers of high-risk transplants are performed each year. The development of such approaches is fundamentally dependent upon a basic understanding of pathophysiologic mechanisms of disease and also on our ability to successfully translate these insights back to the bedside. This brief review will highlight breakthroughs in translational research endeavors that have paved the way for the development of novel strategies intended to change the standard of care and optimize outcomes for patients in whom allogeneic HSCT offers the only hope for a cure.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2011; 17(1 Suppl):S101-8. · 3.15 Impact Factor
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ABSTRACT: Endothelial activation and damage occur in association with autologous hematopoietic stem cell transplantation (HSCT). Several of the early complications associated with HSCT seem to have a microvascular location. Through the present study, we have characterized the activation and damage of endothelial cells of both macro (HUVEC) and microvascular (HMEC) origin, occurring early after autologous HSCT, and the potential protective effect of defibrotide (DF). Sera samples from patients were collected before conditioning (Pre), at the time of transplantation (day 0), and at days 7, 14, and 21 after autologous HSCT. Changes in the expression of endothelial cell receptors at the surface, presence and reactivity of extracellular adhesive proteins, and the signaling pathways involved were analyzed. The expression of ICAM-1 at the cell surface increased progressively in both HUVEC and HMEC. However, a more prothrombotic profile was denoted for HMEC, in particular at the time of transplantation (day 0), reflecting the deleterious effect of the conditioning treatment on the endothelium, especially at a microvascular location. Interestingly, this observation correlated with a higher increase in the expression of both tissue factor and von Willebrand factor on the extracellular matrix, together with activation of intracellular p38 MAPK and Akt. Previous exposure and continuous incubation of cells with DF prevented the signs of activation and damage induced by the autologous sera. These observations corroborate that conditioning treatment in autologous HSCT induces a proinflammatory and a prothrombotic phenotype, especially at a microvascular location, and indicate that DF has protective antiinflammatory and antithrombotic effects in this setting.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2010; 17(4):497-506. · 3.15 Impact Factor
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ABSTRACT: Autologous stem cell transplantation (ASCT) is considered the gold standard in the frontline therapy of younger patients with multiple myeloma because it results in higher complete remission (CR) rates and longer event-free survival than conventional chemotherapy. The greatest benefit from ASCT is obtained in patients achieving CR after transplantation, the likelihood of CR being associated with the M-protein size at the time of transplantation. The incorporation of novel agents results in higher pre- and posttransplantation CR rates. Induction with bortezomib-containing regimens is encouraging in patients with poor-risk cytogenetics. However, longer follow-up is required to assess the impact of this increased CR on long-term survival. The results of posttransplantation consolidation/maintenance with new drugs are encouraging. All this indicates that, in the era of novel agents, high-dose therapy should be optimized rather than replaced. Because of its high transplantation-related mortality, myeloablative allografting has been generally replaced by reduced-intensity conditioning (reduced intensity conditioning allogeneic transplantation). The best results are achieved after a debulky ASCT, with a progression-free survival plateau of 25% to 30% beyond 6 years from reduced intensity conditioning allogeneic transplantation. The development of novel reduced-intensity preparative regimens and peri- and posttransplantation strategies aimed at minimizing graft-versus-host disease, and enhancing the graft-versus-myeloma effect are key issues.
Blood 03/2010; 115(18):3655-63. · 9.90 Impact Factor
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Medicina Clínica 02/2010; 134(5):222-33. · 1.38 Impact Factor
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Christelle Ferrá,
Jaime Sanz,
Rafael de la Cámara,
Guillermo Sanz,
Arancha Bermúdez,
David Valcárcel,
Montserrat Rovira,
David Serrano,
Dolores Caballero,
Ildefonso Espigado, [......],
Carlos Solano,
Rafael Duarte,
Cristina Barrenetxea,
Ana García-Noblejas,
José L Díez-Martin,
Arturo Iriondo, Enric Carreras,
Jordi Sierra,
Miguel-Angel Sanz,
Josep-Maria Ribera
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ABSTRACT: Adults with high-risk acute lymphoblastic leukemia (HR-ALL) have a poor outcome with standard chemotherapy and usually undergo unrelated stem cell transplantation (SCT) if a matched sibling donor is not available. We analyzed the outcome of adult patients with unrelated SCT for HR-ALL and studied the possible effect of the hematopoietic stem cell source of the transplant. A total of 149 adult patients (median age, 29 years, range, 15-59 years) with HR-ALL underwent unrelated SCT in 13 Spanish institutions between 2000 and 2007. Patients in first complete remission (CR1) at transplantation had at least one adverse prognostic factor (advanced age, adverse cytogenetics, hyperleukocytosis, or slow response to induction therapy). ALL was in CR1 in 81 patients (54%), in second CR (CR2) in 37 patients (25%), in third CR (CR3) in 11 patients (7%), and with overt disease in 20 patients (13%). The hematopoietic source was unrelated cord blood (UCB) in 62 patients and an unrelated donor (UD) in 87 patients. The patients undergoing UCB-SCT and UD-SCT were comparable in terms of the main clinical and biological features of ALL, except for a higher frequency of patients with more overt disease in the UCB-SCT group. There was no statistically significant difference in overall survival (OS) or disease-free survival (DFS) at 5 years between the 2 groups. Treatment-related mortality (TRM) was significantly lower in the UCB-SCT group (P = .021). The probability of relapse at 1 year was 17% (95% confidence interval [CI], 7%-27%) for the UD-SCT group and 27% (95% CI, 14%-40%) for the UCB-SCT group (P = .088), respectively. Only disease status at transplantation (CR1, 41% [95% CI, 18%-64%] vs CR2, 51% [95% CI, 17%-85%] vs advanced disease, 66% [95% CI, 46%-86%]; P = .001) and the absence of chronic graft-versus-host disease (74% [95% CI, 46%-100%] vs 33% [95% CI, 17%-49%]; P = .034) were significant factors for relapse. All unrelated transplantation modalities were associated with high treatment-related mortality for adult HR-ALL patients without a sibling donor. UCB-SCT and UD-SCT were found to be equivalent options. Disease status at transplantation and chronic GVHD were the main factors influencing relapse in both transplantation modalities.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2010; 16(7):957-66. · 3.15 Impact Factor
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ABSTRACT: There is endothelial activation and damage in hematopoietic stem cell transplantation (HSCT). The impact of the conditioning and type of HSCT on endothelial dysfunction in the early phases of HSCT has been evaluated. Plasma samples were obtained before and at different times after autologous and allogeneic HSCT with and without early complications. Changes in soluble markers of endothelial damage (VWF, ADAMTS-13, sVCAM-1, sICAM-1, and sTNFRI) were measured. There were changes in all markers evaluated that followed different patterns in auto and allo settings. For VWF and sTNRI, progressive increases from day Pre to day 14 and to day 21 were observed in the auto and the allo group, respectively. ADAMTS-13 activity correlated inversely with VWF levels. Levels of sVCAM-1 decreased until day 7, and raised significantly to day 14 and to day 21 in the auto and the allo HSCT, respectively. No significant changes were detected for sICAM-1. Our results confirm that there is endothelial damage at the early phases of HSCT, apparently induced by the consecutive effects of the conditioning, the proinflammatory agents used during transplantation, the translocation of endotoxins across the damaged gastrointestinal tract, and the engraftment. However, the comparative analysis between patients with and without complications suggests that none of these markers has diagnostic or prognostic value.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2010; 16(7):985-93. · 3.15 Impact Factor
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David Gallardo,
Rafael de la Cámara,
Jose B Nieto,
Ildefonso Espigado,
Arturo Iriondo,
Antonio Jiménez-Velasco,
Carlos Vallejo,
Carmen Martín,
Dolores Caballero,
Salut Brunet,
David Serrano,
Carlos Solano,
Josep M Ribera,
Javier de la Rubia, Enric Carreras
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ABSTRACT: Granulocyte colony-stimulating factor mobilized peripheral blood stem cells are increasingly used instead of bone marrow as a stem cell source for transplantation. Whereas this change is almost complete for autologous transplantation, there are some concerns when considering allogeneic transplants.
We performed a retrospective case-control study including 820 adult patients who had received an allogeneic stem cell transplant from an HLA-identical sibling donor. Quality of life (QoL) was assessed in 150 patients using the EORTC Quality of Life Questionnaire C30 (QLQ-C30).
There were no statistically significant differences in overall survival at ten years (bone marrow: 48.9% vs. peripheral blood stem cells: 39.8%; p=0.621), transplant-related mortality (bone marrow: 28.9% vs. peripheral blood stem cells: 34.4%; p=0.682) or relapse incidence at 9 years (29.4% vs. 35.2%, respectively; p=0.688). Similar outcomes were maintained independently of the phase of the disease. However, multivariate analysis identified a higher incidence of acute graft-versus-host disease grades II-IV (p: 0.023; Hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.05-1.89) and grades III-IV (p: 0.006; HR: 1.89; 95% CI: 1.20-2.98), in the peripheral blood stem cells-stem cell transplant group. As previously described, extensive chronic graft-versus-host disease was also more frequent in the peripheral blood stem cells group (28% vs. 15.6%; p<0.001). Patients transplanted with peripheral blood stem cells had significant impairment of role and social functioning.
Although overall survival was not affected by the stem cell source, peripheral blood stem cell transplants were associated with a higher risk of both acute and chronic GvHD. Global quality of life was similar in both groups, but patients transplanted with peripheral blood stem cells showed worse role and social functioning scores, probably related to the increased incidence of chronic graft-versus-host disease.
Haematologica 10/2009; 94(9):1282-8. · 6.42 Impact Factor
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ABSTRACT: This study evaluated the relative impact of the intensity of the conditioning regimen and the alloreactivity in the endothelial dysfunction occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It involved a comparative analysis of the effect of incubating human umbilical vein endothelial cells (ECs) with serum samples from patients receiving autologous HSCT (auto-HSCT) or unrelated donor allo-HSCT. In both groups, blood samples were collected through a central line before conditioning (Pre), before transplantation (day 0), and at days 7, 14, and 21 after transplantation. Changes in the expression of EC receptors and adhesion proteins, adhesion of leukocytes and platelets under flow, and signaling pathways were analyzed. Endothelial activation and damage were observed in both groups, but with differing patterns. All markers of endothelial dysfunction demonstrated a progressive increase from day Pre to day 14 in the auto-HSCT group and exhibited 2 peaks of maximal expression (at days 0 and 21) in the allo-HSCT group. Both treatments induced a proinflammatory state (ie, expression of adhesion receptors, leukocyte adhesion, and p38 MAPK activation) and cell proliferation (ie, morphology and activation of ErK42/44). Prothrombotic changes (ie, von Willebrand factor expression and platelet adhesion) predominated after allo-HSCT, and a proapoptotic tendency (ie, activation of SAPK/JNK) was seen only in this group. These findings indicate that endothelial activation and damage after HSCT also occur in the autologous setting and affect macrovascular ECs. After the initial damage induced by the conditioning regimen, other factors, such as granulocyte colony-stimulating factor (G-CSF) toxicity, engraftment, and alloreactivity, may contribute to the endothelial damage seen during HSCT. Further studies are needed to explore the association between this endothelial damage and the vascular complications associated with HSCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2009; 15(5):537-46. · 3.15 Impact Factor
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Medicina Clínica 05/2009; 132(13):507-21. · 1.38 Impact Factor
