Research publications

Found 170 publicacions matching the indicated search criteria.
McCurdy SR, Zhang MJ, St Martin A, Al Malki MM, Bashey A, Gaballa S, Keesler DA, Hamadani M, Norkin M, Perales MA, Reshef R, Rocha V, Romee R, Solh M, Urbano-Ispizua A, Waller EK, Fuchs EJ, Eapen M

Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide.

Blood Adv 13 Feb 2018, 2 (3) 299-307.
We studied the association between non-HLA donor characteristics (age, sex, donor-recipient relationship, blood group [ABO] match, and cytomegalovirus [CMV] serostatus) and transplant outcomes after T-cell-replete HLA-haploidentical transplantation using posttransplantation cyclophosphamide (PT-Cy) in 928 adults with hematologic malignancy transplanted between 2008 and 2015. Siblings (n = 358) and offspring (n = 450) were the predominant donors, with only 120 patients having received grafts from parents. Although mortality risks were higher with donors aged 30 years or older (hazard ratio, 1.39;
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Martín-Antonio B, Suñe G, Perez-Amill L, Castella M, Urbano-Ispizua A

Natural Killer Cells: Angels and Devils for Immunotherapy.

Int J Mol Sci 29 Aug 2017, 18 (9) . Epub 29 Aug 2017
In recent years, the relevance of the immune system to fight cancer has led to the development of immunotherapy, including the adoptive cell transfer of immune cells, such as natural killer (NK) cells and chimeric antigen receptors (CAR)-modified T cells. The discovery of donor NK cells' anti-tumor activity in acute myeloid leukemia patients receiving allogeneic stem cell transplantation (allo-SCT) was the trigger to conduct many clinical trials infusing NK cells. Surprisingly, many of these studies did not obtain optimal results, suggesting that many different NK cell parameters combined with the best clinical protocol need to be optimized. Various parameters including the high array of activating receptors that NK cells have, the source of NK cells selected to treat patients, different cytotoxic mechanisms that NK cells activate depending on the target cell and tumor cell survival mechanisms need to be considered before choosing the best immunotherapeutic strategy using NK cells. In this review, we will discuss these parameters to help improve current strategies using NK cells in cancer therapy. Moreover, the chimeric antigen receptor (CAR) modification, which has revolutionized the concept of immunotherapy, will be discussed in the context of NK cells. Lastly, the dark side of NK cells and their involvement in inflammation will also be discussed.
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Urbano-Ispizua Á, Muus P, Schrezenmeier H, Almeida AM, Wilson A, Ware RE

Different clinical characteristics of paroxysmal nocturnal hemoglobinuria in pediatric and adult patients.

Haematologica Mar 2017, 102 (3) e76-e79. Epub 24 Nov 2016More information
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.
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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.
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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.
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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.
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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.
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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.
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