Influence of TP53 Gene Mutations and its Allelic Status in Myelodysplastic Syndromes with Isolated 5q Deletion.

Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twenty-four percent of TP53-mutated patients exhibited multihit alterations, while the remaining patients displayed monoallelic mutations. TP53 multihit alterations were predictive of an increased risk of leukemic transformation. The impact of monoallelic alterations was dependent on the variant allele frequency (VAF); patients with TP53 monoallelic mutations and VAF <20% exhibited behavior similar to TP53 wild type, and those with TP53 monoallelic mutations and VAF ≥20% presented outcomes equivalent to TP53 multihit patients. This study underscores the importance of considering TP53 allelic state and VAF in the risk stratification and treatment decision-making process for patients with MDS-del(5q).

DNA methylation profiling of myelodysplastic syndromes and clinical response to azacitidine: A multicentre retrospective study.

Real-world data have revealed that a substantial portion of patients with myelodysplastic syndromes (MDS) does not respond to epigenetic therapy with hypomethylating agents (HMAs). The cellular and molecular reasons for this resistance to the demethylating agent and biomarkers that would be able to predict the treatment refractoriness are largely unknown. In this study, we shed light on this enigma by characterizing the epigenomic profiles of patients with MDS treated with azacitidine. Our approach provides a comprehensive view of the evolving DNA methylation architecture of the disease and holds great potential for advancing our understanding of MDS treatment responses to HMAs.

Germline assessment for alloHSCT candidates over 50 years: A 'Fast-Track' screening in myeloid neoplasms.

Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations.

Validation of the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes in chronic myelomonocytic leukaemia: A novel approach for improved risk stratification.

Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS-MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS-MDS accurately predicted overall survival (OS) and leukaemia-free survival (LFS), outperforming the Revised-IPSS score. Similarly, in the Taiwanese cohort, the AIPSS-MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS-MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision-making in CMML enables clinicians to identify high-risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS-MDS to further refine risk stratification in CMML and improve patient outcomes.

Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy.

Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy in myeloid malignancies. Hypomethylating agents (HMA), such as azacitidine, have become standard-of-care therapy to treat myelodysplastic syndromes (MDS), myeloid neoplasms that can evolve into acute myeloid leukemia. However, our capacity to identify who will respond to HMAs, and the duration of response, remains limited. To shed light on this question, we have leveraged the unprecedented analytic power of single-cell technologies to simultaneously map the genome and immunoproteome of MDS samples throughout clinical evolution. We were able to chart the architecture and evolution of molecular clones in precious paired bone marrow MDS samples at diagnosis and posttreatment to show that a combined imbalance of specific cell lineages with diverse mutational profiles is associated with the clinical response of patients with MDS to hypomethylating therapy. SIGNIFICANCE: MDS are myeloid clonal hemopathies with a low 5-year survival rate, and approximately half of the cases do not respond to standard HMA therapy. Our innovative single-cell multiomics approach offers valuable biological insights and potential biomarkers associated with the demethylating agent efficacy. It also identifies vulnerabilities that can be targeted using personalized combinations of small drugs and antibodies.

Ofatumumab as part of reduced intensity conditioning in high risk B-cell lymphoma patients: final long-term analysis from a prospective multicenter Phase-II Trial.

Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.

Post-transplant cyclophosphamide compared to sirolimus/tacrolimus in reduced intensity conditioning transplants for patients with lymphoid malignancies.

Despite novel cellular and immunomodulatory therapies, allogeneic hematopoietic stem cell transplantation (HSCT) remains a treatment option for lymphoid malignancies. Post-transplant cyclophosphamide (PTCY) is increasingly employed for graft vs. host disease (GVHD) prophylaxis. This study aims to evaluate the safety and efficacy of PTCY in reduce intensity (RIC) HSCT for patients with lymphoid neoplasms compared to sirolimus with tacrolimus (SIR/TAC). The primary endpoint was to compare grade III-IV acute GVHD, severe chronic GVHD, and relapse-free survival (GRFS) between the two GVHD prophylaxis strategies. This study, conducted from January 2012 to December 2020, included 171 consecutive patients (82 in the PTCY and 89 in the SIR/TAC group). Results revealed a significantly decreased incidence of moderate and severe forms of chronic GVHD in PTCY cohort (5.8% [95% CI, 1.8 to 13.1]) versus the SIR/TAC cohort (39.6% [95% CI, 29.3 to 49.7] (p < 0.001)). Other outcomes, including GRFS (PTCY [45.9% (95% CI, 35.8-58.7)] and SIR/TAC groups [36.8% (95% CI, 28-48.4)], (p = 0.72)), non-relapse mortality (NRM), relapse and overall survival (OS) were similar in both groups. Interestingly, the failure to achieve GRFS was mainly attributed to GVHD in the SIR/TAC group, while disease relapse was the primary reason in the PTCY cohort.

Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial.

BACKGROUND: The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial. METHODS: COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting). FINDINGS: Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis. INTERPRETATION: Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups. FUNDING: Celgene and Acceleron Pharma.

Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide.

While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS.

Immune-monitoring of myelodysplastic neoplasms: Recommendations from the i4MDS consortium.

Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing "immune classes" among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune "risk factors." By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.

Use of micafungin as antifungal prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Spain (GETH-MIC) / Profilaxis antifúngica con micafungina en pacientes que reciben un trasplante alogénico de progenitores hematopoyéticos (alo-TPH) en España (GETH-MIC)

INTRODUCTION: The fungal infections remain an important problem in the allogeneic stem cell trasnsplantation (allo-SCT) setting and thus, anti-fungal prophylaxis is commonly used. The antifungal drug should offer activity, at least against Candida and Aspergillus spp., a good safety profile and low probability interactions. Micafungin could theoretically fulfill these requisites. The aim of the study was to describe the experience with micafungin as primary prophylaxis in patients undergoing allo-SCT in a cohort of Spanish centres, and to evaluate its efficacy and tolerability in this population. MATERIAL AND METHODS: Retrospective multicentre observational study including all consecutive adult patients admitted for allo-SCT in participating centres of the Grupo Español de Trasplante Hematopoyético (GETH), from January 2010 to December 2013, who received micafungin as primary prophylaxis during the neutropenic period. RESULTS: A total of 240 patients from 13 centres were identified and 159 patients were included for the analysis. Most patients (95.6%) received 50 mg/day of micafungin. During the follow-up, 7 (4.4%) patients developed breakthrough invasive fungal disease, 1 proven and 6 probable; one patient discontinued the drug because of serious drug interactions. Prophylaxis with micafungin was considered effective in 151 (94.9%) patiens. CONCLUSIONS: According to our experience, micafungin is an appropriate alternative for antifungal prophylaxis in patients undergoing an allo-HSCT, because its efficacy, its low profile of drug interactions and side-effects

INTRODUCCIÓN: Las infecciones fúngicas siguen representando un problema en el trasplante alogénico de progenitores hematopoyéticos (alo-TPH) por lo que es habitual el uso de profilaxis antifúngica en estos PACIENTES: El tratamiento antifúngico debe presentar al menos actividad frente a Candida y Aspergillus spp, un buen perfil de seguridad y baja probabilidad de infecciones, siendo micafungina una de las opciones que podría cumplir todos estos requisitos. El objetivo del estudio fue describir la experiencia con micafungina como profilaxis primaria en pacientes sometidos a alo-TPH en una cohorte de hospitales españoles, y evaluar su eficacia y seguridad en esta población. MATERIAL Y MÉTODOS: Estudio retrospectivo multicéntrico observacional consecutivo de todos los pacientes adultos ingresados para alo-TPH en los centros del Grupo Español de Trasplante Hematopoyético (GETH) desde enero de 2010 a diciembre de 2013 y que recibieron micafungina como profilaxis primaria durante el periodo de neutropenia. RESULTADOS: Se identificaron 240 pacientes de 13 hospitales y 159 fueron incluidos para el análisis. La mayoría (95.6%) de ellos recibieron dosis de 50mg/día de micafungina. Durante el seguimiento, 7 (4.4%) pacientes desarrollaron infecciones de brecha, 1 probada y 6 probables; en un paciente se suspendió el tratamiento por interacciones medicamentosas graves. La profilaxis con micafungina se consideró efectiva en el 94,9% de los pacientes (151 de 159). CONCLUSIONES: En base a nuestros resultados, consideramos que micafungina es una buena alternativa como profilaxis antifúngica en pacientes sometidos a alo-TPH, por su eficacia, el bajo riesgo de interacciones y de efectos adversos

Bacteriemia e infección del catéter vascular en el ámbito hematológico: posicionamiento y actitudes de manejo basados en el método Delphi / Bacteraemia and infection of the vascular catheter in the haematology patient: positioning and management based on the Delphi method

Introducción. Las complicaciones infecciosas son una causa importante de morbi-mortalidad en los pacientes hematológicos con neutropenia febril. El objetivo del presente trabajo fue desarrollar un documento de recomendaciones consensuado para optimizar el manejo del paciente hematológico con neutropenia febril o infecciones por catéteres vasculares en áreas en las que no se dispone de una sólida evidencia científica. Material y métodos. Tras la revisión de las evidencias científico-médicas, un comité científico formado por especialistas expertos en hematología y enfermedades infecciosas elaboró una encuesta con 55 aseveraciones. Para el consenso se utilizó un método Delphi modificado con dos rondas de evaluación. Resultados. La encuesta fue respondida online por 52 especialistas en hematología y en enfermedades infecciosas. Tras las dos rondas de evaluación fue posible el consenso en 43 de los 55 ítems planteados (un 78,2%): 40 en el acuerdo y 3 en el desacuerdo. Con ello, se proporcionan una serie de recomendaciones relativas al tratamiento antibiótico empírico del paciente con neutropenia febril, a cuestiones relacionadas con mecanismos de acción, toxicidad y sinergia de los antibióticos en este contexto, a las modificaciones del tratamiento antibiótico en el curso de la neutropenia febril y al manejo de las infecciones de catéter vascular central en el ámbito hematológico. Conclusiones. Existe un alto grado de acuerdo entre los expertos consultados sobre algunos aspectos controvertidos relativos al manejo de la neutropenia febril y la infección por catéter en pacientes hematológicos. Este acuerdo se ha traducido en unas recomendaciones que pueden ser de utilidad en la práctica clínica (AU)

Introduction. Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. Materials and Methods. After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. Results. The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. Conclusions. There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice (AU)

Uso de ruxolitinib como tratamiento puente al trasplante alogénico de progenitores hematopoyéticos en un paciente con mielofibrosis idiopática / Ruxolitinib as a bridge to allogeneic hematopoietic cell transplantation in a patient with idiopathic myelofibrosis

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Coste por paciente con respuesta a romiplostim y rituximab en el tratamiento de la trombocitopenia inmune primaria en España / Cost-per-responder analysis comparing romiplostim to rituximab in the treatment of adult primary immune thrombocytopenia in Spain

Fundamento y objetivo: Romiplostim, agonista del receptor de la trombopoyetina, está aprobado para el tratamiento de segunda línea en pacientes con trombocitopenia inmune primaria (PTI). El tratamiento con rituximab no es infrecuente, aunque esta indicación no esté recogida en la ficha técnica. Este análisis compara el coste por paciente respondedor a romiplostim frente a rituximab en España. Materiales y método: Se ha diseñado un modelo para estimar el coste de 6 meses de tratamiento por paciente que responde (recuento plaquetario ≥ 50 × 109/l). Este modelo toma las referencias conforme a los datos publicados más sólidos. Los pacientes tratados con romiplostim recibieron inyecciones semanales; los pacientes tratados con rituximab recibieron 4 infusiones intravenosas semanales. Los precios se obtuvieron de las listas de reembolso españolas. Los pacientes sin respuesta incurrieron en gastos por el tratamiento de episodios relacionados con sangrado (ERS), tal como se notificó en los ensayos clínicos. La utilización de recursos médicos y la práctica clínica se basaron en las guías de tratamiento españolas y fueron validadas por expertos locales. Resultados: Las tasas de respuesta para romiplostim y rituximab fueron del 83 y 62,5%, y el coste medio por paciente fue de 16.289 Euros y 13.459 Euros, respectivamente. Con rituximab el coste por paciente respondedor fue un 10% superior (21.535 Euros) comparado con romiplostim (19.625 Euros). Romiplostim redujo el coste de administración de fármacos, el uso de inmunoglobulina intravenosa y los costes relacionados con ERS comparado con rituximab. Conclusiones: Romiplostim representaría una opción terapéutica eficiente en comparación con rituximab para el tratamiento de pacientes adultos con PTI crónica en el Sistema Nacional de Salud español (AU)

Background and objective: Romiplostim, a thrombopoietin-receptor agonist, is approved for second-line use in idiopathic thrombocytopenic purpura (ITP) patients where surgery is contraindicated. Anti-CD20 rituximab, an immunosuppressant, is currently used off-label. This analysis compared the cost per responder for romiplostim versus rituximab in Spain. Materials and method: A decision analytic model was constructed to estimate the 6-month cost per responding patient (achieving a platelet count ≥ 50 × 109/l) according to the most robust published data. A systematic literature review was performed to extract response rates from phase 3 randomized controlled trials. Romiplostim patients received weekly injections; rituximab patients received 4 weekly intravenous infusions. Medical resource costs were obtained from Spanish reimbursement lists. Treatment non-responders incurred bleeding-related event (BRE) management costs as reported in clinical trials. Medical resource utilization and clinical practice were based on Spanish treatment guidelines and validated by local clinical experts. Results: The literature review identified phase 3 romiplostim trials with a response rate of 83%. Due to a lack of phase 3 controlled rituximab trials, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. The mean cost per patient for romiplostim was 16,289 Euros and 13,459 Euros for rituximab. Rituximab resulted in a 10% higher cost per responder (21,535 Euros versus 19,625 Euros for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related costs compared to rituximab. Conclusions: Due to its high level of efficacy leading to lower BRE costs, romiplostim represents an efficient use of resources for adult ITP patients in the Spanish Healthcare System (AU)

Diagnóstico, tratamiento y seguimiento de la trombocitopenia inmune primaria / Guidelines for diagnosis, treatment and monitoring of primary immune thrombocytopenia

El documento de consenso sobre el diagnóstico, tratamiento y seguimiento de la trombocitopenia inmune primaria fue elaborado en 2010 por especialistas con reconocida experiencia en esta enfermedad bajo el auspicio de la Sociedad Española de Hematología y Hemoterapia y la Sociedad Española de Hematología y Oncología Pediátricas, con el fin de adaptar a España las recomendaciones de los documentos de consenso internacional recientemente publicados. La decisión de iniciar tratamiento se basa en las manifestaciones hemorrágicas y en la cifra de plaquetas (<20×109/L). El tratamiento de primera línea son los glucocorticoides, aunque durante un plazo limitado de 4-6 semanas, reservándose la adición de inmunoglobulinas intravenosas para pacientes con hemorragia grave. La esplenectomía es el tratamiento de segunda línea más eficaz. Para los pacientes refractarios a la esplenectomía y para aquellos con contraindicación o rechazo, los nuevos agentes trombopoyéticos son los fármacos de elección por su eficacia y excelente perfil de seguridad. El resto de las opciones terapéuticas presentan tasa de respuesta y duración muy variables, y carecen de estudios controlados que permitan establecer recomendaciones claras. El seguimiento debe individualizarse, aunque, como mínimo, en pacientes sin tratamiento activo, se recomienda un hemograma cada 3-6 meses, y programas de educación al paciente para que consulte en caso de hemorragia, cirugía o procedimiento invasor y gestación. En una considerable proporción de la población pediátrica la enfermedad tiene tendencia a la remisión espontánea. Los glucocorticoides a altas dosis en pauta corta y las inmunoglobulinas intravenosas son el tratamiento de elección. Los tratamientos de segunda línea y los posteriores deben controlarse en centros especializados

The consensus document on the diagnosis, treatment and monitoring of primary immune thrombocytopenia was developed in 2010 by specialists with recognized expertise in this disease under the auspices of the Spanish Society of Hematology and Hemotherapy and the Spanish Society of Pediatric Hematology and Oncology, with the aim to adapt to Spain the recommendations of the recently published international consensus documents. The decision to start treatment is based on bleeding manifestations and platelet count (<20×109/L). The first-line treatment is corticosteroids, albeit for a limited period of 4-6 weeks. The addition of intravenous immunoglobulin is reserved to patients with severe bleeding. Splenectomy is the most effective second-line treatment. For patients refractory to splenectomy and those with contraindications or patient refusal, the new thrombopoietic agents are the drugs of choice due to their efficacy and excellent safety profile. The other treatment options have highly variable response rates, and the absence of controlled studies does not allow to establish clear recommendations. Monitoring should be individualized. In patients without active treatment, blood counts are recommended every 3-6 months, and the patient should be instructed to consult in case of bleeding, surgery or invasive procedure and pregnancy. In most of the pediatric population, the disease tends to spontaneous remission. High-dose corticosteroids in short course and intravenous immunoglobulin are the treatment of choice. Second- and further-line treatments should be monitored in specialized centers (AU)