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Autoimmune hemolytic anemia (AIHA) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with poor outcome. However, an optimal therapeutic approach is lacking. Between 2000 and 2015, 4099 allogeneic HSCT were performed in eight pediatric centers of the Grupo Español De Trasplante de Medula Osea en Niños (GETMON) and six adult centers of the Grupo Español de Trasplante Hematopoyetico (GETH). Sixty cases of AIHA were registered with a cumulative incidence of 1.5% occurring at a median of 6 months after HSCT. Patients aged less than 15 years (P=.005), and patients using cord blood (P=.005) or an HLA mismatch donor (P=.005) were more likely to develop AIHA. Most patients were lymphopenic at the time of diagnosis of AIHA, including a low number of regulatory T lymphocytes (median 3/μL). Median lines of treatment received for AIHA was 3 (range, 1-7). Almost all patients received corticosteroids (88%) and more than half received immunoglobulins or rituximab (63% and 67%, respectively). Complete resolution of AIHA was achieved in 33 of 60 cases (55%). Cumulative incidence of AIHA-related mortality was 17±6%. We found a correlation of AIHA outcome with age (better outcome in younger than 15 years, RR=1.87, P=.01) and rituximab response (higher rate of complete remission in patients responding to rituximab, RR=1.72, P=.025). We analyzed the factors involved in the response to rituximab and found a better response when there was ABO donor/receptor disparity (P=.014) and in those patients with B lymphocytes count above the median (38/μL) (P=.05).Thirty-six of 60 patients survived yielding a disease free survival of 52±8% at 40 months. In Cox analysis, age (children vs adults, HR: 8.19, CI 95%: 2.39-28.12, P=.001) and AIHA outcome (complete remission vs partial remission/non-response, HR: 4.18, CI 95%: 1.55-11.22, P=.005) were associated with a better survival. Our data suggest that patients who developed AIHA after HSCT are severely lymphopenic and have a high risk of mortality. Outcome is better in children and in patients treated with rituximab. We also propose an algorithm for treatment of AIHA after HSCT.

Context Acalabrutinib is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients with CLL. The efficacy and safety of acalabrutinib versus IdR/BR were previously reported in R/R CLL patients in a preplanned interim analysis of ASCEND ( NCT02970318 ). Objective To report final results from the ASCEND study. Design Randomized (1:1), phase 3, open-label study. Setting Multicenter clinical trial. Patients Patients with R/R CLL. Interventions Oral acalabrutinib 100 mg twice daily (BID) or investigator's choice of IdR (Id: 150 mg orally BID until progression/toxicity; R: 375 × 1 then 500 mg/m2 intravenously for 8 total infusions) or BR (B: 70 mg/m2 intravenously; R: 375 × 1 then 500 mg/m2 intravenously for 6 total cycles) until progression/toxicity. Main outcome measures Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety. Results 310 patients (acalabrutinib, n=155; IdR, n=119; BR, n=36) were enrolled (median age: 67 y; del(17p) 16%, del(11q) 27%, Rai stage 3/4 42%). At a median follow-up of 22.0 months, acalabrutinib significantly prolonged investigator-assessed PFS vs IdR/BR (median: not reached vs 16.8 months; hazard ratio: 0.27, P Conclusion Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acalabrutinib compared with standard-of-care regimens in R/R CLL patients.

Background: Acalabrutinib is a highly selective, potent inhibitor of Bruton tyrosine kinase, an essential part of the B-cell signalling pathway. Methods: ASCEND is a global, multicentre, randomised, open-label, Phase 3 study. Eligible patients, aged ≥18 years with relapsed/refractory chronic lymphocytic leukemia (CLL), were randomised 1:1 centrally via an interactive voice/web response system, and stratified by del(17p) status, Eastern Cooperative Oncology Group performance status, and prior lines of therapy, to receive oral acalabrutinib 100 mg twice daily (BID) or investigator's choice (ie, idelalisib BID plus rituximab ["I-R"] or bendamustine plus rituximab ["B-R"]). The primary endpoint was progression-free survival (PFS) assessed by an independent review committee in the intention-to-treat population. Safety was assessed in all patients who received any treatment. Findings: From February 21, 2017 to January 17, 2018, 310 patients were randomised to acalabrutinib (n=155) or investigator's choice therapy (n=155 [I-R, n=119; B-R, n=36). Patients had received a median of two prior therapies (range 1-10). After a median follow-up of 16·1 months (interquartile range 14·0-18·2), median PFS was significantly longer with acalabrutinib (not reached [95% CI 14·9-not reached]) compared with investigator's choice (16·5 months [95% CI 14·0-17·1]; HR 0·31 [95% CI 0·20-0·49]; p

ResumenObjetivosEvaluar el coste-efectividad del esquema de rituximab, fludarabina y ciclofosfamida (R-FC) en comparación con el de fludarabina y ciclofosfamida (FC) en dos tipos de pacientes con leucemia linfática crónica (LLC): no tratados previamente o bien en recidiva/resistentes al tratamiento previo.MétodosDos modelos de Markov, utilizando los resultados publicados de superviviencia libre de progresión (SLP) de pacientes con LLC tratados con R-FC o FC en primera o segunda línea, las tasas de progresión de la enfermedad y las tasas de mortalidad en España. A los estados de SLP y progresión se les asignaron utilidades obtenidas en un estudio sobre LLC. Los costes de los medicamentos y de los tratamientos de soporte, así como los años de vida ajustados por calidad (AVAC), se estimaron para un periodo de 10 años. Se efectuaron análisis de sensibilidad univariados y probabilísticos (Monte Carlo).ResultadosLa adición de rituximab a la quimioterapia con FC aumentó los años de vida ganados (AVG) y los AVAC tanto en primera como en segunda línea de tratamiento. La razón de coste-eficacia incremental fue de 20.703 € por AVG y de 19.343 € por AVAC con la primera línea de tratamiento, y de 23.183 € por AVG y 24.781 € por AVAC con la segunda línea de tratamiento.ConclusionesEn los pacientes con LLC no tratados previamente y en aquellos en recaída o resistentes al tratamiento previo, la adición de rituximab al esquema FC aumentó la esperanza de vida y los AVAC, y en ambos casos resultó ser un tratamiento coste-efectivo.AbstractObjectivesWe evaluated the cost-effectiveness of rituximab added to the chemotherapy regimen of fludarabine plus cyclophosphamide (R-FC) versus fludarabine plus cyclophosphamide (FC) for the treatment of patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL).MethodsTwo Markov models were built, using published results on progression-free survival (PFS) in patients receiving first- or second-line therapy with R-FC vs FC, rates of disease progression and mortality rates in Spain. Patient-elicited utilities were applied to PFS and progressed health states. The cost of drugs, supportive care, and quality-adjusted life years (QALY) were estimated over a 10-year period. Univariate and probabilistic (Monte Carlo) sensitivity analyses were performed.ResultsThe addition of rituximab to chemotherapy in first- and second-line therapy increased life-years gained (LYG) and QALYs compared with chemotherapy. The incremental cost per LYG and QALY gained was €20,703 and €19,343 for first-line treatment and was €23,183 and €24,781 for second-line treatment.ConclusionIn patients with previously untreated or relapsed/refractory CLL, the addition of rituximab to the FC regimen increased life expectancy and quality-adjusted life expectancy. In both types of patient, the treatment was cost-effective.

DCK catalyzes the intracellular phosphorylation of fludarabine. The promoter and coding region of the DCK gene were analyzed in 74 follicular lymphoma (FL) patients receiving a therapeutic regimen that included fludarabine. DCK mRNA expression was quantified in a cohort of healthy donors. Four previously described genotypic variants, −360C>G, −201C>T (rs2306744), C28624T (rs11544786) and c.91+37G>C (rs9997790), as well as the new variant, −12C>G, were identified. Variant C28624T showed a lower risk of lymphopenia (P = 0.04), but a higher risk of neutropenia (P = 0.04). Statistical significance was found in bivariate logistic regression between lymphopenia and infectious episodes in the induction period (odds ratio 3.85, P = 0.04).

Recently, an acute restriction of imiglucerase has occurred as a result of viral contamination and manufacturing problems. A position statement from the European Working Group for Gaucher Disease and European Gaucher Alliance established a set of key recommendations for identifying and monitoring at-risk patients. In Spain, a profile of the shortage situation was obtained through follow-up of patients with Gaucher disease (GD) and compliance with the therapy recommendations. Here we describe a group of patients, with modified doses of imiglucerase, during the shortage. Fifty adult GD1 patients (25 males/25 females), previously on ERT, were analysed before and after the 6-month shortage. The mean age was 45.3 ± 15.3 years (range: 18-84). The mean Severity Score Index at diagnosis was 8.7 ± 3.8 (range: 3-19); 20% of patients were splenectomized; and 78% had bone disease. During the shortage, 23 patients (46%) discontinued therapy; as complications in this group only one patient suffered a bone crisis and another anaemia (Hb

Fundamento y objetivo La clasificacion de los pacientes con leucemia mieloide aguda (LMA) enfuncion del cariotipo proporciona una importante informacion para la seleccion del tratamiento.Dos son los criterios mas estandarizados para la clasificacion de pacientes en grupos de riesgocitogenetico, los establecidos por el Medical Research Council, del Reino Unido (MRC), y losestablecidos por el Southwest Oncology Group, de EE.UU. (SWOG), los cuales definen tres ycuatro categorias citogeneticas, respectivamente. Los objetivos de este trabajo han sido, por unlado, definir la frecuencia de alteraciones citogeneticas en todos los pacientes diagnosticadosde LMA y, por otro, comparar los grupos de riesgo citogenetico en pacientes con LMA tratadoscon quimioterapia intensiva como guia de futuras investigaciones. Pacientes y metodo El analisis cromosomico se realizo por metodos estandar en celulas de medulaosea de 146 pacientes adultos, diagnosticados de LMA, entre enero 1995 y diciembre de 2001.Para el analisis estadistico se utilizaron los modelos de Kaplan-Meier y la regresion de Cox. Resultados Obtuvimos resultados citogeneticos en 142 pacientes. La incidencia de cariotiposcomplejos y del(5q) fue mayor entre pacientes con LMA secundaria. La clasificacion por riesgocitogenetico se llevo a cabo unicamente en los 105 pacientes tratados y fue identica segunambos modelos para 82 pacientes y distinta para 23. Los resultados del analisis univariablefueron significativos para la supervivencia libre de enfermedad (SLE) (p Conclusiones Existe relacion entre la LMA secundaria, la edad avanzada y el cariotipo adverso.Los dos modelos de clasificacion tuvieron un gran valor pronostico. En nuestra experiencia lacodificacion segun el criterios del grupo MRC se presenta mas efectiva para identificar a pacientescon alto riesgo de recaida.

16 chronic haemodialysis patients (group I), with non-microcytic anaemia (mean haemoglobin 7.2 g/dl, SD 1.0, range 5.8-9.8), moderate aluminium overload (serum aluminium 44 micrograms/l, SD 16, range 21-74), and normal or high iron stores (ferritin 800 micrograms/l SD 464, range 34-2013) were treated with intravenous desferrioxamine 1 g at the end of each dialysis for six months. 8 patients with similar characteristics served as controls (group II). After six months group I showed a rise in haemoglobin to 9.1 (SD 2.5) g/dl and a decrease in blood transfusion requirements, both significant, whereas group II showed no changes. Other significant changes observed in group I, but not group II, were a rise in reticulocytes and in red cell creatine and a fall in red cell protoporphyrin and serum ferritin. Ferritin decreased more in the patients whose anaemia improved. Minor increases in serum aluminium in group I did not differ from those in the control group. Desferrioxamine may benefit the anaemia of chronic haemodialysis patients through improvement of erythropoiesis. The effect seems not to be related to chelation of a heavy aluminium overload.