Mannose-binding lectin gene variants and infections in patients receiving autologous stem cell transplantation

BACKGROUND: Serious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections. METHODS: Prospective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression. RESULTS: A statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria. CONCLUSIONS: Low-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection

Clinical and Sociodemographic Characteristics of Patients With Relapsed and/or Refractory Multiple Myeloma and Their influence on Treatment in the Real-World Setting in Spain: The CharisMMa Study

Introduction: Treatment of relapsed and/or refractory multiple myeloma (RRMM) should be established based on multiple factors, including previous treatment and the sociodemographic/clinical characteristics of the patients. However, patients enrolled in randomized-controlled trials often do not mirror the scenario encountered in real-world practice, thus challenging therapeutic decisions in day-to-day practice. Patients and methods: This observational, cross-sectional, multicenter study aimed to investigate the sociodemographic and clinical characteristics of patients with RRMM treated in routine practice in Spain and their influence on treatment regimens. Results: The study included 276 RRMM patients (median age 69 years; no gender predominance). Seventy-four percent of patients had CRAB features at the time of study inclusion, 65.9% bone lesions, 28.7% high-risk cytogenetics, and 27.0% were at ISS stage III; 65.1% were retired and lived in urban areas (75.7%) with their relatives (85.8%); 28.7% had some dependence degree. Patients had experienced their last relapse in a median of 1.61 months before enrollment and had received a median of 2 treatment lines (range 1-10). Second-and third-line therapies were mostly based on immunomodulatory drugs, followed by proteasome inhibitors (PIs), whereas monoclonal antibodies prevailed in later treatment lines. The presence of extramedullary plasmacytomas, the absence of osteopenia, and being in the second or third treatment line (vs. later lines) significantly increased the odds of receiving PIs. Conclusions: RRMM treatment in the real-world setting is highly heterogeneous and is primarily influenced by the number of previous lines. The consideration of patients' clinical and sociodemographic characteristics may support clinicians in making therapeutic decisions

Long term survival in patients with acute myeloid leukemia treated with hematopoietic stem cell transplantation. Analysis of risk factors.

RESUMEN: La leucemia mieloblástica aguda (LMA) es un grupo heterogéneo de leucemias con perfiles biológicos y clínicos singulares y diferente pronóstico, englobando desde la Leucemia Promielocítica Aguda que responde a ácido retinoico en combinación con quimioterapia, hasta casos que solo pueden curarse con un procedimiento tan agresivo como es el trasplante alogénico (Alo-TPH). El trasplante autólogo (Auto-TPH) tiene un papel intermedio, con resultados discretamente mejores que la quimioterapia en pacientes de bajo riesgo, pero aplicable también en pacientes de alto riesgo en los que no es factible un Alo-TPH. La diferencia entre ambos radica en el efecto inmune denominado “injerto contra leucemia” asociado en general a la Enfermedad Injerto Contra Huésped (EICH) que se desarrolla tras el Alo-TPH. Se trata de un estudio retrospectivo de los 274 adultos diagnosticados de LMA y sometidos a Trasplante de Precursores Hematopoyéticos en el Hospital Universitario Marqués de Valdecilla de Santander desde Marzo de 1982, en que se puso en marcha dicho procedimiento en nuestro centro, hasta Diciembre de 2011. Se ha analizado todo el material genético almacenado en el Banco de Sangre y Tejidos de Cantabria para completar el perfil biológico, mediante FISH y Biología Molecular, de los pacientes con LMA transplantados en nuestro centro, que no fueron estudiados al diagnóstico, pero de los que disponíamos de células criopreservadas de aquel momento. El objetivo principal es analizar la supervivencia global, la toxicidad y las recaídas en los 112 pacientes autotrasplantados y en los 162 pacientes, así como su calidad de vida a largo plazo. El objetivo secundario es analizar mediante un modelo explicativo la verdadera magnitud de efecto que tiene cada uno de los factores pronósticos (características clínicas y biológicas relacionadas con el paciente, con la enfermedad y su tratamiento previo o con el procedimiento) sobre la Incidencia Acumulada de Recaída y sobre la Supervivencia Global, evitando el efecto de confusión que podrían ejercer el resto de variables analizadas.ABSTRACT: Acute myeloid leukemia (AML) is a heterogeneous group of leukemias with unique biological and clinical profile and different prognosis, which goes from acute promyelocytic leukemia treated with retinoic acid and chemotherapy, to high risk leukemias which can only be cured with allogeneic transplantation (allo-HSCT). Autologous transplantation (auto-HSCT) has an intermediate role, slightly better than chemotherapy in low risk patients, but also an option in high-risk patients with no suitable donor. The difference is the immune effect called "graft versus leukemia", generally associated with the graft versus host disease (GVHD), both developed after allo-HSCT. This is a retrospective study of 274 adults diagnosed of AML who underwent Hematopoietic Stem Cell Transplantation (HSCT) in Marqués de Valdecilla University Hospital in Santander from March 1982 to December 2011. We analyzed all the genetic samples stored in the Blood and Tissues Bank of Cantabria to complete the biological profile, by FISH and Molecular Biology, of all patients which were not studied at the diagnosis but have available cryopreserved cells from that time. The main objective is to analyze the overall survival, toxicity and relapse in 112 autotransplanted and 162 allotransplanted patients, and also their quality of life with such long-term follow-up. The secondary objective is to analyze the true effect of each prognostic factor (clinical and biological characteristics related to the patient, the disease and its treatment or the procedure) on the cumulative incidence of relapse and the overall survival, with an explaining model which could avoid the confounding effect of the other analyzed variables

How to Manage Patients with Lenalidomide-Refractory Multiple Myeloma

Although lenalidomide-based combinations, such as lenalidomide plus a proteasome inhibitor or an anti-CD38 monoclonal antibody, improve the overall response rate, progression-free survival, and overall survival of patients with relapsed/refractory multiple myeloma (RRMM), there is a tendency to use these regimens as a frontline treatment. This strategy has led to the development of refractoriness early in the disease course, usually after the patient’s first treatment. Since lenalidomide-free regimens have so far shown limited efficacy in lenalidomide-refractory patients, there is an unmet need for other treatment options. In this review, we discuss the therapeutic options available to treat the general population of lenalidomide-refractory patients (mono, double and triple refractory) and the subpopulation of patients with other high-risk features such as renal failure, extramedullary disease, and high-risk cytogenetics. Moreover, new promising individual therapies and the possible impact of immunotherapy in RRMM patients are debated

Clinical and Sociodemographic Characteristics of Patients With Relapsed and/or Refractory Multiple Myeloma and Their influence on Treatment in the Real-World Setting in Spain : The CharisMMa Study

The authors would like to thank to AEAL (Asociación de pacientes con Linfoma, Mieloma, Leucemia y Síndromes Mieloproliferativos [Spanish Association of Patients with Lymphoma, Myeloma, Leukemia and Myeloproliferative Disorders]) and all the researchers of the CharisMMa study group: Luis Palomera Bernal (Hospital Lozano Blesa), Antonia Sampol Mayol (H. Son Espases), Carmen Couto Caro (H. Valme), Fernando Escalante Barrigón (H. Universitario de León), Cristina Encinas (H. Universitario Gregorio Marañón), Marta Sonia González Pérez (C.H.U. Santiago), Miguel Teodoro Hernández (C.H.U. Canarias), Esperanza Lavilla Rubira (H. Lucus Agusti,), Francisco Javier Capote (H. Puerta del Mar), Joan Bargay Lleonart (H. Son Llátzer), Josep Sarrá Escarre (H.U. Joan XXIII, María Casanova Espinosa (H. Costa Sol), Juan Nicolás Rodríguez Rodríguez (H. Juan Ramon Jiménez,), Juan José Lahuerta (H. Doce de Octubre), Felipe Casado Montero (C.H. Toledo). Josep Puig and Gerard Carot-Sans provided statistical and medical writing support, respectively, on behalf of BioClever, 2005, S.L.U. (both funded by Takeda Farmacéutica España). The study was sponsored and funded by Takeda Farmacéutica España.Introduction: Treatment of relapsed and/or refractory multiple myeloma (RRMM) should be established based on multiple factors, including previous treatment and the sociodemographic/clinical characteristics of the patients. However, patients enrolled in randomized-controlled trials often do not mirror the scenario encountered in real-world practice, thus challenging therapeutic decisions in day-to-day practice. Patients and methods: This observational, cross-sectional, multicenter study aimed to investigate the sociodemographic and clinical characteristics of patients with RRMM treated in routine practice in Spain and their influence on treatment regimens. Results: The study included 276 RRMM patients (median age 69 years; no gender predominance). Seventy-four percent of patients had CRAB features at the time of study inclusion, 65.9% bone lesions, 28.7% high-risk cytogenetics, and 27.0% were at ISS stage III; 65.1% were retired and lived in urban areas (75.7%) with their relatives (85.8%); 28.7% had some dependence degree. Patients had experienced their last relapse in a median of 1.61 months before enrollment and had received a median of 2 treatment lines (range 1-10). Second-and third-line therapies were mostly based on immunomodulatory drugs, followed by proteasome inhibitors (PIs), whereas monoclonal antibodies prevailed in later treatment lines. The presence of extramedullary plasmacytomas, the absence of osteopenia, and being in the second or third treatment line (vs. later lines) significantly increased the odds of receiving PIs. Conclusions: RRMM treatment in the real-world setting is highly heterogeneous and is primarily influenced by the number of previous lines. The consideration of patients' clinical and sociodemographic characteristics may support clinicians in making therapeutic decisions