Rodrigo Martino

Hospital de la Santa Creu i Sant Pau, Barcino, Catalonia, Spain

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Publications (119)608.4 Total impact

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    ABSTRACT: To analyze the impact of graft versus host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL), or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor HCT between 1997 and 2009 were included. Two thousand six hundred and eleven cases were included. Reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplants. In a multivariate analysis of myeloablative cases (n=970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n=1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (RR 0.51, p=0.049) and in MCL (RR 0.41, p=0.019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR 0.14, p=0.007; and RR 0.15, p=0.0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment related mortality (TRM) and overall survival (OS) in FL cases, and did not impact TRM, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in follicular and mantle cell lymphoma patients. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2015; DOI:10.1016/j.bbmt.2015.05.010 · 3.35 Impact Factor
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    ABSTRACT: We report the outcome of 30 consecutive HD patients who underwent single unit UCBT. Most (90%) patients had failed previous autologous hematopoietic stem cell transplantation. The conditioning regimens were based on combinations of thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was 90% (95% confidence interval [C.I.], 74-98%) with a median of 19 days (range, 10-48). CI of acute graft versus host disease (GvHD) grades II-IV was 30% (95% C.I., 17-44%) while the incidence of chronic GVHD was 42% (95% C.I., 23-77%). The non-relapse mortality (NRM) at 100 days and 4 years was 30% (95% C.I., 13-46%) and 47% (95% C.I., 29-65%), respectively. EBV-related post-transplant lymphoproliferative disease (EBV-PTLD) accounted for more than one third of transplant-related death, with an estimate incidence of 26% (95% C.I., 9-44). The incidence of relapse at 4 years was 25% (95% C.I., 9-42%). Four-year event-free survival (EFS) and overall survival (OS) were 28% and 30%, respectively. Despite a high NRM and a unexpected high incidence of EBV-PTLD, UCBT in heavily pre-treated HD patients is an option for patients lacking a suitable adult donor, provided the disease is not in refractory relapse. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal Of Haematology 04/2015; DOI:10.1111/ejh.12557 · 2.41 Impact Factor
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    ABSTRACT: ABSTRACT The role of allogeneic hematopoietic cell transplantation (allo-HCT) in elderly patients with acute lymphoblastic leukemia (ALL) is unclear. We conducted a study including 110 patients with ALL between 50-70 years of age prospectively and homogeneously treated. Their outcomes were analyzed by intention-to-treat in a donor-versus-no donor basis. Fifty-five patients (50%) underwent HLA typing and were considered potential allo-HCT candidates, although only 25 (23%) eventually received an allo-HCT. Among potential allo-HCT candidates, patients with (n=28) and without (n=27) an HLA-identical sibling showed similar leukemia-free survival, overall survival (OS) and relapse risk and the only variable associated with a better outcome was achievement of CR1 after induction therapy. Among the 25 patients who actually received an allo-HCT, the 4-year NRM and OS were 42% (95%C.I.31-53%) and 37% (95%C.I.27-47%), respectively. In conclusion, having an HLA-identical sibling donor was not associated with a better outcome in ALL patients aged 50 to 70 years.
    Leukemia and Lymphoma 02/2015; DOI:10.3109/10428194.2015.1014365 · 2.89 Impact Factor
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    ABSTRACT: Graft dilution and DMSO-washing prior to cord blood (CB) administration using an automated system may offer low incidence of adverse infusion events (AIE) ensuring reproducible cell yields. Hence, we analyzed the incidence and significance of immediate AIE, cellular yield and engraftment after single CB infusion. One hundred and fifty seven patients [median age, 20 years (range 1-60)] received a single CB unit for treatment of hematologic and non-hematologic malignancies with myeloablative conditioning following graft dilution and washing. The median of total nucleated cell (TNC) doses was 3.4 x 10(7) /kg (range, 2-26) and the median post-thaw recovery was 84% (range, 45-178). The cumulative incidence of neutrophil engraftment at 50 days was 84% (95%CI: 83-93). A total of 118 immediate AIE were observed in fifty-two (33%) patients. All reported AIE were transient, graded from 1 to 2 by Common Terminology Adverse Events version 4 (CTCAE v4). The most frequent toxicity was cardiovascular, but without any life-threatening reaction. Infused TNCs, recipient's weight and rate of infusion per kg were risk factors associated with cardiovascular-AIE in multivariate analysis [OR (95%CI): 1.2 (1.1-1.4), p < 0.001; 0.94 (0.9-0.97), p < 0.001, 1.5 (1.2-1.8), p < 0.001; respectively]. In summary, use of an automated method for graft washing prior to CB administration showed low incidence of AIE without compromising cell yields and engraftment. Infused TNC dose, recipient's weight and rate of infusion per kg were risk factors associated with infusion reactions. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2014; 21(4). DOI:10.1016/j.bbmt.2014.12.015 · 3.35 Impact Factor
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    ABSTRACT: Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2014; 21(2). DOI:10.1016/j.bbmt.2014.10.021 · 3.35 Impact Factor
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    ABSTRACT: We analyze the impact of cyclosporine (CsA) levels in the development of acute graft-versus-host disease (aGVHD) after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC). We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10-444), 219 (54-656), 253 (53-910) and 224 (30-699) ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2-4 aGVHD for a cumulative incidence of 45% (95% CI 34-50%) at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P = 0.02) and development of grade 2-4 aGVHD (HR: 2.5, P < 0.01), while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P = 0.06). These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting.
    Mediators of Inflammation 01/2014; 2014(4674):620682. DOI:10.1155/2014/620682 · 3.24 Impact Factor
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    ABSTRACT: Introduction: Busulfan (Bu) represents a backbone as conditioning prior to hematopoietic stem cell transplantation (HSCT). The intravenous (IV) form of Busulfan allows 100% bioavaibility and a limited inter- and intra-patient (pt) variability compared to the oral form. In Europe, IV Bu (Busilvex® fixed dose of 0.8 mg/kg x 16 doses) in combination with Cyclophosphamide (60 mg/kg/d x 2 ) is indicated prior to conventional HSCT in adults when the combination is the best available option. IV BuCy2 allows a precise delivery with 80% of adult pts within the defined therapeutic window [900 μmol/L x min-100 μmol/L x min] without dose-adjustments. Despite major advances in the risk-stratification and management of acute myelogenous leukaemia (AML) based on cytogenetics and molecular biology, the relapse rate remains high. Several published experiences suggested that Bu exposure may have an impact on the clinical outcomes after allogeneic HSCT. Study objective:The study was implemented to explore the use of a narrow range and high values of Bu exposure [4400 µmol/Lx min to 6000 µmol/Lx min] with a PK-guided dose adjustments and once-daily administration x 4 days. Methods:The study was a prospective non-randomized multicentric phase II. The eligible pts were required to have AML in first complete (CR1, cytological remission) and to be eligible allogeneic HSCT following a myeloablative regimen. On the first day of the conditioning regimen IV Bu was administered as a single dose of 3.2 mg/kg; further daily dose of IV Bu were determined based on the previous Bu AUC exposure. The graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitor, IV methotrexate post-transplant. The addition of antithymoglobulin (ATG) for unrelated donors was decided by each center based on their institutional guidelines. Pts could either receive related or unrelated bone marrow or peripheral blood stem cells. Nine centres with laboratory facilities for the pharmacokinetics analysis entered the study. Patient and transplant characteristics: Thirty AML pts in CR1 (21 males, 70%) were treated between may 2010 and may 2012, 87% of pts had de novoAML. Twenty pts (67%) had matched sibling donor, the remaining pts received allograft from an unrelated donor. The median age of the cohort was 43.5 years [19.3-55.5]. The performance status score was comprised between 90 and 100. The majority of the cohort (83%) had an intermediate or unfavorable cytogenetic risk-factors. In 3 cases (10%) the karyotyping analyses could not be performed; 1 pt (3%) did not have cytogenetic test performed. Results: Thirty pts were treated and analyzed. The expected cumulative AUC over 4 days [17600 µmol/Lxmin -24000 µmol/Lxmin ] was reached in 90% of pts. The mean dose of IV Bu administered was 3.51 mg/kg/day. The mean total cumulative dose of IV Bu over 4 days was 13.25 mg/kg [8-21.3]. All pts engrafted. For the entire cohort, the neutrophil engraftment [absolute neutrophil count (ANC) > 0.5 x 10 9/L] occured at a median time of 17.5 d (11-35). Overall, 3 episodes (10%) of sinusoidal obstruction syndrome (S.O.S) occured (one mild, two severe, all resolved) in two patients. One pt developed 2 severe episodes of S.O.S and received defibrotide. Overall, 12 pts out of 30 (40%) developed acute GVHD between day 0 and day +100 after transplant (4 pts had grade III, 6 pts had grade II and 2 pts developed grade III, no patient developed grade IV). The median follow-up was 12 months [95% CI (11.9-12.2)] After day +100, 4 pts died of non-relapse causes ; one death from pulmonary fibrosis was related to the conditioning regimen. The cumulative incidence of TRM was 13.3% [95% CI (11.1%-15.6%)]. Five pts relapsed at a median time of 3.3 months [2-5.6] and 4 pts died of relapse. The cumulative incidence of one-year survival was 73.3% [95% CI (53.7%-85.7%)]. Conclusion: The AUC intensification with once-daily IV BuCy2 is effective and yields an acceptable one year TRM for pts with high-risk AML in CR1. However, longer follow-up is needed in order to assess the impact of AUC intensification on the relapse rate and survivals.
    55th ASH Annual Meeting Exposition, New Orlean, LA; 12/2013
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    ABSTRACT: This study was conducted to determine whether the integration of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Group for Blood and Marrow Transplantation (EBMT) score would improve individual capacity for stratification of high-risk HCT candidates. A total of 442 consecutive patients receiving an allogeneic HCT after reduced-toxicity conditioning was included. Final HCT-CI and EBMT scores were calculated and validated. Then, patients were grouped into a 6-category new combination model according to the HCT-CI (0, 1 to 2, ≥3) and EBMT scores (0 to 3, 4 to 7), and the model's predictive capacity was also evaluated. Median HCT-CI and EBMT scores were 3 and 4, respectively. Increased HCT-CI was associated with higher 4-year nonrelapse mortality (NRM) and lower 4-year overall survival (OS), whereas a high EBMT score was associated with higher 4-year NRM. The HCT-CI showed a trend for a better predictive capacity than the EBMT score (c-statistic .6 versus .54, P = .1). According to the new model, patients within HCT-CI of 0 and HCT-CI of 1 to 2 groups had similar risk of NRM independently of their EBMT score. Within the HCT-CI ≥ 3 group, patients with low EBMT score showed lower NRM (25% versus 40%, P = .04) and a trend to higher OS (52% versus 36%, P = .06) than patients with a high EBMT score. Moreover, patients with HCT-CI ≥ 3 and EBMT score 0 to 3 had similar outcomes than those with HCT-CI of 1 to 2. In conclusion, the combination of HCT-CI and the EBMT score is feasible and might contribute to a better identification of high-risk patients, improving selection of best allogeneic HCT candidates.
    Biology of Blood and Marrow Transplantation 10/2013; 20(1). DOI:10.1016/j.bbmt.2013.10.011 · 3.35 Impact Factor
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    ABSTRACT: Allogeneic stem cell transplantation (ASCT) from related or unrelated donors may cure patients with myelodysplastic syndromes (MDS), a heterogeneous group of clonal stem cell disorders. We analysed 384 elderly patients (55-69 years) with advanced MDS who received either ASCT (n=247) and were reported to The European Group for Blood and Marrow Transplantation (EBMT) or a non -transplant approach (n=137) reported to the Düsseldorf registry. Besides an attempt to answer the question of "comparison", the purpose of this work is to explain the difficulties in comparing a non-transplant with a transplant cohort, when death before transplant is likely but unknown and the selection of patients for transplant is based on assumptions. It shows which methods are almost always biased and that even the most sophisticated approaches crucially rely on clinical assumptions. Using the most appropriate model for our data, we derive an overall univariate non-significant survival disadvantage for the transplant cohort (HR: 1.29, p = 0.11). We show that such an "average" hazard ratio is however misleading due to non-proportionality of the hazards reflecting early treatment related mortality, the occurring of which is logically correlated with the interval between diagnosis and transplant creating a disproportional drop in the (reconstructed) survival curve of the transplanted patients. Also in multivariate analysis (correcting for age > 60 (HR: 1.4, p = 0.02) and abnormal cytogenetics (HR: 1.46, p = 0.01)), transplantation seems to be worse (HR: 1.39, p = 0.05) but only in the (incorrect but commonly applied) model without time varying covariates. The long term (time depending) hazard ratio is shown to be virtually 1 and overall survival is virtually identical in both groups. Nonetheless no conclusion can be reached from a clinical point of view without assumptions which are by their very nature untestable unless all patients would be followed from diagnosis.
    PLoS ONE 10/2013; 8(10):e74368. DOI:10.1371/journal.pone.0074368 · 3.23 Impact Factor
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    ABSTRACT: There are scarce disease-specific studies focusing on outcomes of umbilical cord blood transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. We report the outcome of 45 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia underwent myeloablative single unit cord blood transplantation from unrelated donors within the GETH/GITMO cooperative group. Conditioning regimens were based on combinations of thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin. At the time of transplantation, 35 patients (78%) were in first complete remission, 4 (8%) in second complete remision and 6 (14%) in second or subsequent response. The cumulative incidence of myeloid engraftment was 96% at a median time of 20 days and significantly better for patients receiving higher doses of CD34+ cells. The incidence of acute graft-versus-host disease grade II-IV and overall chronic graft-versus-host disease was 31% and 53%, respectively. Treatment-related mortality was 17% at day +100 and 31% at 5 years. The 5-year relapse, event-free survival and overall survival were 31%, 36% and 44%, respectively. Although patients without BCR/ABL transcripts detectable at time of transplant had a better event-free and overall survivals compared with those positive detection of BCR/ABL (46% vs 24% and 60% vs 30%, respectively) these differences were not statistically significant in the univariate analysis (p = 0.07, respectively). These results demonstrate that umbilical cord blood transplantation from unrelated donors can be a curative treatment for a substantial number of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
    Haematologica 10/2013; 99(2). DOI:10.3324/haematol.2013.091009 · 5.87 Impact Factor
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    ABSTRACT: Bacteremia is the most frequent infectious complication during neutropenia in patients receiving autologous hematopoietic stem cell transplantation (ASCT). The objective of this study was to analyze the incidence, characteristics, risk factors, and outcome of bacteremia during the early period after ASCT. A total of 720 patients undergoing ASCT in two observational prospective consecutive multicenter studies of the Programa Español para el Tratamiento de las Hemopatías group were analyzed. Bacteremia occurred in 20 % of patients. Coagulase-negative Staphylococcus was the most frequent (66 %) among the gram-positive agents and Escherichia coli (49 %) among the gram-negative agents. Multivariate analysis showed that the length of neutropenia <1 × 10(9)/L (more than 9 days) [relative risk (RR) of 2.6, p < 0.001] was the sole risk factor for overall bacteremia. We identified the length of neutropenia <1 × 10(9)/L (more than 9 days) (RR 4.98, p < 0.001) and the use of prophylactic fluoroquinolones (RR 0.46, p < 0.01) as specific risk factors for gram-negative bacteremia. Risk factors for gram-positive bacteremia were the use of total parenteral nutrition (RR 1.92, p < 0.01) and deep neutropenia (<0.1 × 10(9)/L), with duration over 5 days (RR 1.67, p < 0.027). Bacteremia showed an increased morbidity with no impact on neither overall nor infectious related mortality. The identification of such risk factors may be helpful to implement prophylactic and therapeutic risk-adapted strategies to reduce the incidence of bacteremia in ASCT.
    Annals of Hematology 09/2013; 93(2). DOI:10.1007/s00277-013-1872-4 · 2.40 Impact Factor
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    ABSTRACT: Strongyloides stercoralis is an intestinal nematode that causes strongyloidiasis, which affects 30 to 100 million people worldwide. Risk factors for hyperinfection and disseminated disease include immunosuppressive drug therapy, human T-lymphotropic virus-1 (HTLV-1) infection, solid organ and bone marrow transplantation, hematologic malignant diseases, hypogammaglobulinemia, and severe malnutrition and associated conditions. The diagnosis can be difficult because a single stool examination fails to detect larvae in up to 70% of the cases, and the symptoms are nonspecific. Although eosinophilia is a common finding in patients with chronic Strongyloides infection, it is an unreliable predictor of hyperinfection. Furthermore, the lack of eosinophilia while receiving immunosuppressive therapy cannot reliably exclude the underlying chronic Strongyloides infection. We report here a fatal Strongyloides hyperinfection in a patient receiving allogeneic stem cell transplantation; risk factors and outcome in this clinical setting are discussed.
    07/2013; 2013:860976. DOI:10.1155/2013/860976
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    ABSTRACT: The current study was designed to assess the safety and efficacy of bortezomib in combination with fludarabine and melphalan as reduced intensity conditioning before allogeneic stem cell transplantation in patients with high risk multiple myeloma. Sixteen patients were evaluable. The median number of previous line of treatment was 3; all patients had relapsed following a prior autograft and 13 had previously received bortezomib. Fifteen of them either remained stable or improved disease status at day +100 post-transplant, including 11 patients with active disease. More specifically, nine patients (56%) and five patients (31%) reached complete remission and partial response, respectively. 25% developed grade III acute graft-versus-host disease. The cumulative incidence of non-relapse mortality, relapse and overall survival were 25%, 54% and 41%, respectively, at 3 years. Regarding the non-haematological toxicity (grade>2), two patients developed peripheral neuropathy, two patients liver toxicity and 1 pulmonary toxicity early post-transplant. The haematological toxicity was only observed during the first three cycles mostly related to low haemoglobin and platelet levels. The current trial is the first one evaluating the safety and efficacy of bortezomib as part of a reduced intensity conditioning regimen among patients with high risk multiple myeloma.
    British Journal of Haematology 06/2013; 162(4). DOI:10.1111/bjh.12410 · 4.96 Impact Factor
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    ABSTRACT: Background. The objective of this analysis was to investigate prognostic factors that influence the outcome of EBV-related post-transplant lymphoproliferative disorders (PTLD) after a rituximab-based treatment in the allo-HSCT setting. Methods. 4466 allo-HSCTs performed between 1999-2011 in 19 EBMT centres have been retrospectively analysed for PTLD, either biopsy-proven or probable disease. Results. 144 PTLD cases were identified, indicating an overall EBV-PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donor, and 11.24% in mismatched unrelated donor recipients. EBV-PTLD occurred at a median of 2 months (range, 0.5-53) after HSCT and was proven by biospy in 59.7% cases with the remaining 40.3% being considered probable cases. 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extra-lymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2 or 3 factors being associated with mortality of 7%, 37% and 72%, respectively (p<0.0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%) and a decrease of EBV-DNA-emia in peripheral blood during therapy was predictive of better survival. Conclusions. Over two-thirds of patients with EBV-PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome while older age, extra-nodal disease, and acute GVHD predicted poor outcome.
    Clinical Infectious Diseases 06/2013; 57(6). DOI:10.1093/cid/cit391 · 9.42 Impact Factor
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    ABSTRACT: The survival of relapsed acute myeloid leukemia (AML) after autologous hematopoietic stem cell transplantation (Autologous HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (Allo-HCT) from an unrelated donor (URD) using either myeloablative (n=242) or reduced-intensity conditioning regimens (RIC, n=60) reported to CIBMTR. After a median follow-up of 58 months (range 2-160), the probability of treatment-related mortality (TRM) was 44% (95%CI 38-50) at 1-year. The 5-year incidence of relapse and overall survival (OS) was 32% (95%CI 27-38) and 22% (95%CI 18-27), respectively. In multivariate analysis significantly better OS was observed with RIC regimens (Hazard Ratio (HR) 0.51, 95%CI 0.35-0.75, p<0.001), with Karnofsky performance status (KPS) ≥90% (HR 0.62, 95%CI 0.47-0.82, p=0.001) and in CMV-negative recipients (HR 0.64, 95%CI 0.44-0.94, p=0.022). Longer interval (>18 months) from Autologous HCT to URD Allo-HCT was associated with significantly lower Relapse risk (HR 0.19, 95%CI 0.09-0.38, p<0.001) and improved LFS (HR 0.53, 95%CI 0.34-0.84, p=0.006). URD Allo-HCT after Autologous HCT relapse results in 20% long-term leukemia-free survival, with best results with longer interval to secondary URD transplantation, KPS ≥90%, in complete remission, and using RIC regimens. Further efforts to reduce TRM and relapse are still needed.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2013; 19(7). DOI:10.1016/j.bbmt.2013.04.022 · 3.35 Impact Factor
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    ABSTRACT: Background: Busilvex® (Bu) followed by Cyclophosphamide (Cy) is a standard conditioning therapy used prior to Allogeneic HSCT. Moreover, relapse rate in AML CR1 patients remains a matter of concern, being as high as 25%. Therefore, we hypothesized that Area Under the Curve (AUC) intensification may reduce the relapse incidence for high-risk patients. Primary objective: To target the upper range of the Bu therapeutic window (i.e.: AUC = 4400 - 6000 µmol/L.min) from a once daily BuCy2 regimen. Methods and patients: This prospective phase II study included 30 (9 females, 21 males) CR1 AML patients (26 de novo AML, 4 secondary AML). All patients received a once-daily 3.2 mg/kg dose of Busilvex® on day 1 of conditioning, with dose adjustment from day 2 to day 4 in order to target the middle of the defined therapeutic area (AUC = 5200 µmol/L.min). The total dose of Cy was 120 mg/kg. GVHD prophylaxis included ciclosporine, methotrexate, and ATG in case of unrelated donors. Median age: 43.5 years (19.3-55.5). Median time interval from the diagnosis to HSCT: 5.6 months (2.5-9); 20 patients were transplanted with a matched sibling donor and 10 with MUD; 13 patients received BM and 17 PBSC. Results: The median observed AUC was 4837 µmol/L.min at day 1 and 5297, 5709, 5395 µmol/L.min for the following adjusted doses. The inter-individual coefficient of variation of AUCs decreased from 29% at day 1 to 16%, 18% and 21% at days 2, 3 and 4, respectively. Based on the cumulated AUC over the 4 days, 27 out of 30 patients (90%) achieved the targeted therapeutic window. The median follow-up was 7.65 months (3.4-12.05). All patients engrafted: the median time to reach neutrophil and platelet engraftment was 17.5 (11-35) and 14 (8-49) days, respectively. The median duration of hospitalization post-HSCT was 25.5 days (14-75). At day +100, 2 cases of VOD occurred, one mild, one severe, both resolved. No death from organ toxicities occurred at 3 months. Overall, 25 patients were alive at last follow up. Two patients died of relapse and 3 of non-relapse. The cumulative incidence of relapse at one year was 16.9% [95% CI 14-20]. Conclusions: This study confirms that once-daily IV BuCy2 with AUC intensification is feasible, without major safety concerns, and is potentially an effective regimen in high risk AML.
    39th Annual Meeting of the European Group for Blood and Marrow transplantation, London, UK; 04/2013
  • Salut Brunet · Rodrigo Martino · Jorge Sierra
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    ABSTRACT: Patients with acute myeloid leukemia (AML) traditionally classified as having an intermediate cytogenetic risk [mostly cytogenetically normal AML (CN-AML)] really include a significant proportion of cases with a poor outcome. This is based on the molecular findings at diagnosis, mainly the presence of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3/ITD). Optimal postremission therapy for these high-risk molecular cases is not well established; as the prognosis is adverse hematopoietic cell transplantation (HCT), mainly allogeneic HCT (allo-HCT), is the most widely accepted strategy. As a rule, patients with FLT3/ITD have a poor outcome with conventional chemotherapy alone. Only patients with an associated nucleophosmin 1 (NPM1) mutation and those with a low mutated-to-wild-type allelic ratio of FLT3/ITD have less unfavorable outcome. Most studies show an advantage of allo-HCT in first complete remission (CR1), with higher 3-5 year disease-free survival and lower relapse risk than with chemotherapy or autologous transplantation (auto-HCT). Regarding allo-HCT proceeding early after reaching CR1 seems to improve survival, rather than after several courses of consolidation chemotherapy. Patients with intermediate-risk cytogenetics AML and FLT3/ITD, especially NPM1-wild cases and those NPM1 mutated with a high allelic ratio, should proceed to allo-HCT if possible early after achieving CR1.
    Current opinion in oncology 03/2013; 25(2):195-204. DOI:10.1097/CCO.0b013e32835ec91f · 3.76 Impact Factor
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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; 19(4). DOI:10.1016/j.bbmt.2012.12.018 · 3.35 Impact Factor
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    ABSTRACT: Refractory acute graft-versus-host disease (aGVHD) remains an important cause of mortality after allogeneic stem cell transplantation. No standard therapy exists once steroids fail to obtain a good response. In 2006, our group published a series of patients who received inolimomab, an anti-interleukin-2 receptor monoclonal antibody, as salvage therapy with initial encouraging results. In this update, we have analysed a larger group of patients with prolonged follow-up. Ninety-two consecutive patients were treated with inolimomab in our center between April 1999 and December 2011. Overall response rate was 42% (complete response [CR] in 14%) on day +30. Predictors of failure to respond in the multivariate analysis were overall aGVHD grade IV, instauration of inolimomab before day 15 of aGVHD diagnosis and severe lymphopenia. Patients without gastrointestinal (GI) involvement appeared to do better, with a 70% response rate compared with 39% in patients with GI involvement (p=0.06). However, the 2-year overall survival (OS) was 18% (95% CI 10-26%) for the entire cohort and 33% (95% CI 25-40%) for day-30 responders. Acute GVHD was the main cause of death (49%) followed by opportunistic infections (27%). In conclusion, results of this update show that although inolimomab is a well tolerated drug with a moderate number of short term responses, it is associated with long-term survival in only one third of responding patients. These data highlight the need of investigating new rescue treatments with sustained effect and theimportance of reportinglong-term outcomesin GVHD studies.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2012; 19(3). DOI:10.1016/j.bbmt.2012.11.012 · 3.35 Impact Factor

Publication Stats

4k Citations
608.40 Total Impact Points

Institutions

  • 1994–2015
    • Hospital de la Santa Creu i Sant Pau
      • Hematology Clinic Services
      Barcino, Catalonia, Spain
  • 2013
    • University of Rome Tor Vergata
      Roma, Latium, Italy
  • 2005–2012
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2008
    • Carl Gustav Carus-Institut
      Pforzheim, Baden-Württemberg, Germany
    • Hospital Clínic de Barcelona
      • Servicio de Hematología
      Barcino, Catalonia, Spain
  • 2003
    • University of Chicago
      • Section of Hematology/Oncology
      Chicago, Illinois, United States
    • Universidad de Salamanca
      Helmantica, Castille and León, Spain
  • 2002
    • Hospital Universitario de Salamanca
      Helmantica, Castille and León, Spain