Research publications

Found 167 publicacions matching the indicated search criteria.
Chen YB, Wang T, Hemmer MT, Brady C, Couriel DR, Alousi A, Pidala J, Urbano-Ispizua A, Choi SW, Nishihori T, Teshima T, Inamoto Y, Wirk B, Marks DI, Abdel-Azim H, Lehmann L, Yu L, Bitan M, Cairo MS, Qayed M, Salit R, Gale RP, Martino R, Jaglowski S, Bajel A, Savani B, Frangoul H, Lewis ID, Storek J, Askar M, Kharfan-Dabaja MA, Aljurf M, Ringden O, Reshef R, Olsson RF, Hashmi S, Seo S, Spitzer TR, MacMillan ML, Lazaryan A, Spellman SR, Arora M, Cutler CS

GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes.

Bone Marrow Transplant. 12 Dec 2016, . Epub 12 Dec 2016
Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.Bone Marrow Transplantation advance online publication,12 December 2016; doi:10.1038/bmt.2016.265.
More information
van Gelder M, de Wreede LC, Bornhäuser M, Niederwieser D, Karas M, Anderson NS, Gramatzki M, Dreger P, Michallet M, Petersen E, Bunjes D, Potter M, Beelen D, Cornelissen JJ, Yakoub-Agha I, Russell NH, Finke J, Schoemans H, Vitek A, Urbano-Ispízua Á, Blaise D, Volin L, Chevallier P, Caballero D, Putter H, van Biezen A, Henseler A, Schönland S, Kröger N, Schetelig J

Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation.

Bone Marrow Transplant. 12 Dec 2016, . Epub 12 Dec 2016
Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.Bone Marrow Transplantation advance online publication, 12 December 2016; doi:10.1038/bmt.2016.282.
More information
Martínez C, Millán O, Rovira M, Fernández-Avilés F, López A, Suárez-Lledó M, Carreras E, Urbano-Ispízua Á, Brunet M

Pharmacodynamics of T cell function for monitoring pharmacologic immunosuppression after allogeneic hematopoietic stem cell transplantation.

Int. J. Hematol. 23 Nov 2016, . Epub 23 Nov 2016
Information on pharmacodynamic monitoring after allogeneic hematopoietic cell transplantation (allo-SCT) to evaluate individual responses to immunosuppressive drugs is scarce. We studied the relationship between a panel of pharmacodynamic markers monitored during the first 3 months after transplant and the occurrence of graft-versus-host disease (GVHD). Lymphocyte activation assessed by intracellular ATP concentration in CD4(+) T cells, a high percentage of CD8(+) effector T cells, and a low percentage of CD4(+) regulatory T (Treg) cells correlated significantly with GVHD. A cutoff value of 0.5 for the CD8(+) effector T/Treg ratio provided the most accurate diagnosis of GVHD (sensitivity 58.8%, specificity 91%). These pharmacodynamic markers may provide an efficient complement to standard pharmacokinetic monitoring of immunosuppressive drugs after allo-SCT.
More information
Socié G, Schrezenmeier H, Muus P, Lisukov I, Röth A, Kulasekararaj A, Lee JW, Araten D, Hill A, Brodsky R, Urbano-Ispizua A, Szer J, Wilson A, Hillmen P

Changing prognosis in Paroxysmal Nocturnal Haemoglobinuria disease subcategories; an analysis of International PNH Registry.

Intern Med J 15 Jun 2016, . Epub 15 Jun 2016
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare disease. Although much progress has been made in the understanding of the pathophysiology of the disease, far less is known with respect to the clinical outcomes of the patients with PNH. Few retrospective studies provide survival estimates and even fewer have explored the clinical heterogeneity of the disease. Haemolytic and aplastic anaemia forms have been recognised as main disease categories with the haemolytic form being associated with worst prognosis by the largest studied cohort some years ago.
More information
Villegas A, Arrizabalaga B, Bonanad S, Colado E, Gaya A, González A, Jarque I, Núñez R, Ojeda E, Orfao A, Ribera JM, Vicente V, Urbano-Ispizua Á

[Spanish consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria].

Med Clin (Barc) 18 Mar 2016, 146 (6) 278.e1-7. Epub 17 Feb 2016
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of the haematopoietic progenitor cells due to a somatic mutation in theX-linked phosphatidylinositol glycan class A gene. The disease is characterized by intravascular haemolytic anaemia, propensity to thromboembolic events and bone marrow failure. Other direct complications of haemolysis include dysphagia, erectile dysfunction, abdominal pain, asthenia and chronic renal failure (65% of patients). The disease appears more often in the third decade of life and there is no sex or age preference. Detection of markers associated with glucosyl phosphatidyl inositol deficit by flow cytometry is currently used in the diagnosis of PNH. For years, transfusions have been the mainstay of therapy for PNH. A breakthrough in treatment has been the approval of the humanized monoclonal antibody eculizumab, which works by blocking the C5 complement protein, preventing its activation and therefore haemolysis. Several studies have confirmed that treatment with eculizumab avoids or decreases the need for transfusions, decreases the probability of thrombosis, improves the associated symptomatology and the quality of life in patients with PNH, showing an increase in survival. Because of rapid advances in the knowledge of the disease and its treatment, it may become necessary to adapt and standardize clinical guidelines for the management of patients with PNH.
More information
Martínez-Cibrian N, Magnano L, Gutiérrez-García G, Andrade X, Correa JG, Suárez-Lledó M, Martínez C, Rovira M, Carreras E, Rosiñol L, de Larrea CF, Cibeira MT, Gaya A, Gallego C, Hernando A, Creus N, Bladé J, Urbano-Ispizua Á, Fernández-Avilés F

At-home autologous stem cell transplantation in multiple myeloma with and without G-CSF administration: a comparative study.

Bone Marrow Transplant. 23 Nov 2015, . Epub 23 Nov 2015More information
Urbano-Ispizua A, Pavletic SZ, Flowers ME, Klein JP, Zhang MJ, Carreras J, Montoto S, Perales MA, Aljurf MD, Akpek G, Bredeson CN, Costa LJ, Dandoy C, Freytes CO, Fung HC, Gale RP, Gibson J, Hamadani M, Hayashi RJ, Inamoto Y, Inwards DJ, Lazarus HM, Maloney DG, Martino R, Munker R, Nishihori T, Olsson RF, Rizzieri DA, Reshef R, Saad A, Savani BN, Schouten HC, Smith SM, Socié G, Wirk B, Yu LC, Saber W

The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen.

Biol. Blood Marrow Transplant. Oct 2015, 21 (10) 1746-53. Epub 15 May 2015
The purpose of this study was 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, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. 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 (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .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 and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.
More information
Inamoto Y, Flowers ME, Wang T, Urbano-Ispizua A, Hemmer MT, Cutler CS, Couriel DR, Alousi AM, Antin JH, Gale RP, Gupta V, Hamilton BK, Kharfan-Dabaja MA, Marks DI, Ringdén OT, Socié G, Solh MM, Akpek G, Cairo MS, Chao NJ, Hayashi RJ, Nishihori T, Reshef R, Saad A, Shah A, Teshima T, Tallman MS, Wirk B, Spellman SR, Arora M, Martin PJ

Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia.

Biol. Blood Marrow Transplant. Oct 2015, 21 (10) 1776-82. Epub 30 May 2015
Combinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia.
More information
Rosiñol L, Jiménez R, Rovira M, Martínez C, Fernández-Avilés F, Marín P, Suárez-Lledó M, Gutiérrez-García G, Fernández de Larrea C, Carreras E, Urbano-Ispizua A, Bladé J

Allogeneic hematopoietic SCT in multiple myeloma: long-term results from a single institution.

Bone Marrow Transplant. May 2015, 50 (5) 658-62. Epub 26 Jan 2015
The role of allogeneic hematopoietic SCT (allo-HCT) in multiple myeloma (MM) remains controversial. A total of 58 patients received an allo-HCT (25 of them with myeloablative conditioning-allo-MAC-and 33 with reduced-intensity conditioning-allo-RIC) at our institution over a 28-year period. The CR rate for allo-MAC was 36%. The incidence of grade III-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) was 28% and 39%, respectively The TRM at any time was 60% and the main causes of death were aGVHD or infectious complications not directly related to GVHD. The estimated PFS and OS at 15 years were 8% and 15%, respectively. The CR rate with allo-RIC was 45%. The incidence of grade III-IV aGVHD and cGVHD were 24% and 41%, respectively. The TRM at any time was 33% and was mainly related to aGVHD. The estimated PFS and OS at 5 years were 22% and 38%, respectively. Despite its high TRM, a proportion of patients with high-risk myeloma (early relapse and newly diagnosed ultrahigh risk) may obtain long-term disease control with allo-HCT. New approaches aimed at decreasing the incidence of aGVHD, and consequently to decrease the TRM, are needed.
More information
Arora M, Hemmer MT, Ahn KW, Klein JP, Cutler CS, Urbano-Ispizua A, Couriel DR, Alousi AM, Gale RP, Inamoto Y, Weisdorf DJ, Li P, Antin JH, Bolwell BJ, Boyiadzis M, Cahn JY, Cairo MS, Isola LM, Jacobsohn DA, Jagasia M, Klumpp TR, Petersdorf EW, Santarone S, Schouten HC, Wingard JR, Spellman SR, Pavletic SZ, Lee SJ, Horowitz MM, Flowers ME

Center for International Blood and Marrow Transplant Research chronic graft-versus-host disease risk score predicts mortality in an independent validation cohort.

Biol. Blood Marrow Transplant. Apr 2015, 21 (4) 640-5. Epub 18 Dec 2014
We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10). RG3 and RG4 were combined, as RG4 accounted for only 1% of the total cohort. Cumulative incidences of nonrelapse mortality (NRM) and probability of overall survival were significantly different between each RG (all P < .01). NRM and overall survival at 5 years after CGVHD for each RG were 17% and 72% in RG1, 26% and 53% in RG2, and 44% and 25% in RG3, respectively (all P < .01). Our study validates the prognostic value of the CIBMTR CGVHD RGs for overall survival and NRM in a contemporary transplantation population. The CIBMTR CGVHD RGs can be used to predict major outcomes, tailor treatment planning, and enroll patients in clinical trials.
More information