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Objectives This work aims to describe the proportion of patients with polycythemia vera (PV) or essential thrombocythemia (ET) and thrombosis prior to the diagnosis who had erythrocytosis or thrombocytosis prior to the thrombosis. Patients and methods This is a retrospective review of 63 patients with PV and 130 with ET. Results In regard to PV, we found prior erythrocytosis in 7 (11.1%) of the 17 cases (27%) with thrombosis prior to diagnosis. In ET, we found prior thrombocytosis in 10 (7.7%) of the 25 cases (19.2%) with thrombosis prior to diagnosis. The median time between the laboratory finding and thrombosis was 8.2 months and 11.8 months for PV and TE, respectively. In both entities, patients with thrombosis prior to diagnosis had significantly lower survival. Conclusion A significant proportion of patients with thrombosis prior to the diagnosis of PV and ET present with erythrocytosis or thrombocytosis prior to the episode of thrombosis. This could allow for anticipating diagnosis and treatment.

Resumen Objetivos Describir la proporcion de pacientes con policitemia vera (PV) o trombocitemia esencial (TE) y trombosis previa al diagnostico que presentaban eritrocitosis o trombocitosis antes de la trombosis. Pacientes y metodos Revision retrospectiva de 63 pacientes con PV y 130 con TE. Resultados En PV, encontramos eritrocitosis previa en 7 (11,1%) de los 17 casos (27%) con trombosis previa al diagnostico. En TE, encontramos trombocitosis previa en 10 (7,7%) de los 25 casos (19,2%) con trombosis previa al diagnostico. La mediana de tiempo entre el hallazgo analitico y la trombosis fue de 8,2 meses y 11,8 meses para PV y TE, respectivamente. En ambas entidades, los pacientes con trombosis previa al diagnostico tenian una supervivencia significativamente menor. Conclusion Una proporcion significativa de pacientes con trombosis previa al diagnostico de PV y TE presenta eritrocitosis o trombocitosis previa al episodio de trombosis, lo que permitiria anticipar el diagnostico y el tratamiento.

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to

Objective/Background: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era—that is, in patients treated in induction and rescued only with chemotherapy. Methods: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). Results: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of

Resumen Fundamento y objetivo Comparar la biopsia de medula osea (BMO) y la PET/CT en la deteccion de la afectacion medular en el linfoma de Hodgkin. Material y metodos Analisis retrospectivo de 65 pacientes con realizacion de ambas pruebas en la estadificacion inicial o en recaida con especial atencion al patron de la PET/CT. Resultados En 3 pacientes (4,6%) la BMO mostro afectacion medular, siendo la PET/CT positiva en todos ellos: 2 con patron difuso + multifocal y uno solo difuso. En 11 pacientes mas (total 14/65, 21%) se estimo que habia afectacion medular osea por PET/CT al tener un consumo de medula osea superior al hepatico. El patron fue focal unico en 2 casos, multifocal en 5, difuso en 3 casos y difuso + multifocal en uno. En estos ultimos 4 casos la BMO mostro una mielopatia inespecifica. Conclusiones La PET/CT detecta todos los casos con BMO afectada y muchos que se escapan a la biopsia; sin embargo, cuando el patron de captacion es difuso puede ser por afectacion o por hiperplasia reactiva y en esos casos deberia mantenerse la BMO.

Background and objectives To compare bone marrow biopsy (BMB) and PET/CT in detecting bone marrow involvement in Hodgkin's lymphoma. Material and methods Retrospective analysis of 65 patients with both tests in the initial staging or in relapse with special attention to the PET/CT uptake pattern. Results In 3 patients (4.6%), the BMB showed bone marrow involvement with the PET/CT being positive in them all: 2 with diffuse + multifocal pattern and one diffuse only. In 11 additional patients (total 14/65, 21%), bone marrow involvement was diagnosed by PET/CT because bone marrow uptake was above hepatic one. The pattern was focal only in 2 cases, multifocal in 5, diffuse in 3 and diffuse + multifocal in one. In these last 4 cases the BMB showed an unspecific myelopathy. Conclusions PET/CT detects all cases with BMB affected and many that escape to biopsy, however when the uptake pattern is diffuse it could be by involvement or reactive hyperplasia and in those cases the BMB should be done.

To compare bone marrow biopsy (BMB) and PET/CT in detecting bone marrow involvement in Hodgkin's lymphoma MATERIAL AND METHODS: Retrospective analysis of 65 patients with both tests in the initial staging or in relapse with special attention to the PET/CT uptake pattern.In 3 patients (4.6%), the BMB showed bone marrow involvement with the PET/CT being positive in them all: 2 with diffuse+multifocal pattern and one diffuse only. In 11 additional patients (total 14/65, 21%), bone marrow involvement was diagnosed by PET/CT because bone marrow uptake was above hepatic one. The pattern was focal only in 2 cases, multifocal in 5, diffuse in 3 and diffuse+multifocal in one. In these last 4 cases the BMB showed an unspecific myelopathy.PET/CT detects all cases with BMB affected and many that escape to biopsy, however when the uptake pattern is diffuse it could be by involvement or reactive hyperplasia and in those cases the BMB should be done.

High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Espafiol de Linfomas y Trasplantes de Medula Osea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease = 2 or PR >= 2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL. (C) 2017 American Society for Blood and Marrow Transplantation.

Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P=0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P=0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

Introduction:SMM is an asymptomatic and heterogeneous plasma cell disorder. The Spanish Myeloma Group demonstrated that patients at high risk of progression benefit from early treatment with Rd. In addition, our preliminary results of the curative approach (GEM-CESAR) showed encouraging results (Mateos ASH 2017). Aim: The primary end-point was to evaluate the Minimal Residual Disease negative (MRD-ve) rate by next generation flow (NGF) after induction and ASCT and the sustained MRD-ve rate at 3 and 5 yrs after ASCT as secondary end-points. Our aim was to increase the MRD -ve rate from 34% (reported in NDMM patients after VTD and ASCT) to 50%. As all patients have completed induction and ASCT, we report the results of the primary end point, efficacy and safety after induction and ASCT. Methods: In this phase II single arm trial, 90 SMM patients at high-risk of progression (>50% at 2 yrs), younger than 70 yrs and transplant candidates were included. The high risk was defined by the presence of both ≥PC 10% and MC ≥3g/dL (Mayo criteria) or ifonly one criterion was present, patients must have a proportionof aberrant PCs within the total PCsBM compartment by immunophenotypingof 95% plus immunoparesis (Spanish criteria). Asymptomatic MM patients with any of the three biomarkers recently included into the definition of active MM were allowed to be included. Induction therapy consisted on six 4-weeks cycles of KRd in which K was given at dose of 36 mg/m2twice per week plus R at dose of 25 mg on days 1-21 and dexamethasone at dose of 40 mg weekly. Melphalan at dose of 200 mg/m2followed by ASCT was given as intensification therapy and three months later, patients received two KRd consolidation cycles followed by maintenance with R at dose of 10 mg on days 1-21 plus dex at dose of 20 mg weekly for up to 2 yrs Results: Between June 2015 and June 2017, the 90 SMM patients at high risk of progression were recruited. Twenty-eight pts (32%) shared at least one of the new biomarkers predicting imminent risk of progression to MM. The primary end point of the trial was met, since 55% of the patients who completed induction and ASCT achieved MRD -ve by NGF (sensitivity 3 x 10-6). Upon analyzing the results after induction, 88 patients completed the 6 induction cycles and were evaluable for response (two patients early discontinued): the ORR was 98% including 41% of ≥CR (32% sCR and 9% CR) and 41% of VGPR rate. Two patients were mobilization failures and one patient rejected ASCT. Two additional patients experienced biological progression before ASCT and went off the study. Eighty-three patients, therefore, proceeded to HDT-ASCT and were evaluable at day +100: the ORR was 100% including ≥CR in 63% of the patients (51% sCR and 12% CR) and VGPR rate in 23%. The MRD-ve rate increased from 31% after induction to 55% with the ASCT. No differences in outcome have been observed according neither to the definition of high risk (Mayo or Spanish model) nor ultra high risk SMM. Concerning toxicity, during induction, G3-4 neutropenia and thrombocytopenia were reported in 5 (6%) and 10 pts (11%), respectively. G3-4 infections were the most frequent non-hematological AE observed in 16 pts (18%), followed by skin rash in 8 pts (9%). One patient reported G1 atrial fibrillation and another cardiac failure secondary to respiratory infection. Three patients reported hypertension (G2 in two and G3 in one). Thirteen patients required lenalidomide dose reduction whilst carfilzomib was not reduced in any patient. In four patients, dexamethasone was reduced. In all but two of the pts, PBSC collection was successful with a median of 4.10 x 106/Kg CD34 cells collected. All patients engrafted. Consolidation and maintenance phases are ongoing. After a median follow-up of 17 months (5-36), 94% of patients remain alive and free of progression and 97% of them alive. Three patients experienced biological progression and discontinued the study: one of them was refractory to the rescue therapies and died and the other two are receiving rescue therapies. One additional patient died early during induction due to a massive ischemic stroke unrelated to the treatment. Conclusions: Although longer follow-up is required, this "curative strategy for high risk SMM" continues being encouraging with an acceptable toxicity profile. The study has met its primary endpoint. The depth of response improved over the treatment: 63% of patients who completed induction and ASCT achieved ≥CR with a MRD-ve rate of 55%. Disclosures Mateos: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees. Rodriguez Otero:Takeda: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Bristol Myers Squibb: Research Funding; Clínica Universidad de Navarra: Employment. Ocio:AbbVie: Consultancy; Pharmamar: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS: Consultancy; Takeda: Consultancy, Honoraria; Sanofi: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Mundipharma: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Array Pharmaceuticals: Research Funding. Oriol:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rios:Amgen, Celgene, Janssen, and Takeda: Consultancy. Rosinol:Janssen, Celgene, Amgen, Takeda: Honoraria. Alegre:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Puig:Janssen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Takeda: Consultancy, Honoraria. De La Rubia:Ablynx: Consultancy, Other: Member of Advisory Board. García Mateo:Binding Site: Research Funding; Amgen: Honoraria; Celgene: Honoraria. Bladé:Janssen: Honoraria. Lahuerta:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. San-Miguel:Novartis: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Roche: Honoraria.

A histomorphometric analysis of the length of reticulin fibres per area of haemopoietic bone marrow was performed on 59 trephine iliac crest biopsies. The values obtained were found to correlate with the degree of fibrosis as determined by a simple optical method based on the degree of microscopic magnification required for recognition of the presence of reticulin fibres. The mean length of fibre (microns/10,000 micron2) for the three degrees of fibrosis defined by the optical method were: 241.8 +/- 16.6 for grade I, 713 +/- 85.6 for grade II, and 1827.9 +/- 230.4 for grade III (P < 0.001). In a series of 67 biopsies, the overall interobserver agreement of the optical method was found to be good (Spearman's r = 0.99; P < 0.001) and there was good individual agreement for each of the three degrees of fibrosis (improved kappa test). There was a small amount of overlap between the extreme values of adjacent optical degrees. These results suggest that the optical method described here can be recommended as a practical technique for the routine evaluation of myelofibrosis.

Fundamento y objetivo El ictus constituye una causa importante de mortalidad y discapacidad. El objetivo del presente estudio es identificar los factores predictores de infeccion nosocomial en la fase aguda del ictus y como esta influye en la morbimortalidad de esta enfermedad. Pacientes y metodo Se ha realizado un estudio prospectivo, observacional y longitudinal de cohortes de pacientes con ictus agudo. El ictus se diagnostico segun la definicion de la Organizacion Mundial de la Salud, actualizada por la Sociedad Espanola de Neurologia. La infeccion nosocomial se definio por los criterios de los Centers for Disease Control y los de la Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. Resultados Se incluyo a 258 pacientes con ictus agudo. De estos, 102 (39,5%) presentaron, al menos, una infeccion nosocomial -un 45,5% de mujeres; edad media (desviacion estandar) de 78,2 (9,7) anos-. La estancia media hospitalaria fue significativamente mayor en los pacientes infectados: 14,9 (8,4) frente a 8,4 (5,6) dias en los no infectados (p Conclusiones La disfagia, la afectacion motriz crural, la incontinencia urinaria y la diabetes mellitus son las variables clinicas que se identifican como factores de riesgo independientes para la infeccion nosocomial en la fase aguda del ictus. Esta complicacion medica, sobre todo la infeccion respiratoria, aumenta significativamente la probabilidad de muerte de esta enfermedad.

High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m2 melphalan (MEL200), 127 patients with 140 mg/m2 melphalan plus total body irradiation (MEL140 + TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P = 0.003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26-68] compared with 43% (CI 31-54) for MEL140 + TBI and 37% (CI: 18-56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 + TBI groups respectively. These differences were non-significant (P = 0.2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 + TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P = 0.01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.

Fundamento Algunos pacientes con aparente neutropenia cronica benigna presentan trastornos de la distribucion de los granulocitos entre los distintos compartimientos fisiologicos, situacion que puede ponerse de manifiesto mediante diversas pruebas de movilizacion. La administracion de hidrocortiso-na intravenosa es la mas conocida, pero su realizacion e interpretacion se encuentran poco estandarizadas. Se presentan los resultados de una serie de 19 pacientes con neutropenia periferica cronica idiopatica a quienes se realizo la mencionada prueba de acuerdo con criterios homogeneos. Pacientes y metodo Se realizo un hemograma basal, seguido de una inyeccion intravenosa de 200 mg de hidrocortisona, y otro hemograma a las 4 h de la inyeccion. Se recogieron en cada caso los siguientes datos: recuento basal de neutrofilos en sangre (RBN), recuento final de neutrofilos (RFN), diferencia entre RFN y RBN o incremento (INCR), y el cociente 60% de INCR/2,0 (x 10 9 /l ) - RBN, al cual denominamos indice de desmarginalizacion (ID). Resultados Se observaron tres patrones de respuesta (tres grupos de pacientes): patron I, con RFN normal e ID superior o igual a 1 (compatible con seudoneutropenia con componente de hipermarginaliza-cion); patron II, con RFN normal e ID inferior a 1 (seudoneutropenia por mecanismos distintos a hiper-marginalizacion), y patron III, con RFN subnormal e ID inferior a 1 (neutropenia verdadera). Al comparar los grupos I y II, no existen diferencias significativas en los RBN ni en los INCR, pero si en los RFN (p = 0,026) y en el ID (p = 0,026). La comparacion entre los grupos I y III arroja significacion estadistica en los cuatro parametros (RBN, p = 0,07; RFN, p Conclusiones La prueba de movilizacion granulocitaria con 200 mg de hidrocortisona intravenosa, es-tableciendo 4 h de separacion entre el hemograma basal y el final, permite diferenciar la seudoneu-tropenia con componente de hipermarginalizacion de la neutropenia verdadera.

Objective: To discern if factors such as organic pathology, sex, duration and/or intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with poor food and drink consumption, or disturbance of social and familial networks, are related to an impaired nutritional status in hospitalized drug addicts. Design: Cross-sectional prospective study. Setting: Detoxication unit and internal medicine unit of a university hospital. Patients: 140 drug addicts without acute organic pathology and 18 with acute organic pathology related to drug addiction. The immunological study was compared with a control group composed of 50 healthy and well-nourished individuals (26 women and 24 men), age-matched with our patients. Results: Drug addicts without organic pathology were under-nourished: 92.4% weighed under the mean weight for the population and 55.7% had had a weight loss above 5%. The distribution of mid-upper arm circumference (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA) compared with the percentiles for the population showed a shift towards lower values. We found a high percentage of patients with a high lymphocyte count (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean calorific intake was 978 ± 89 kcal/day in females and 1265 ± 64 kcal/day in males. However, in most cases, malnutrition (usually marasmus-like malnutrition) was not very severe; only 30% of the drug addicts weighed less than 80% of the mean weight for the population, or admitted to a weight loss above 10%, and by subjective nutritional assessment, only 18% were deeply malnourished. Otherwise, the nutritional status was very poor in drug addicts with acute organic pathology. We also found a worse nutritional status in our patients related to female sex, intensity of drug addiction, anorexia with poor food and drink consumption, and disturbance of the social and familial networks. Conclusions: Many drug addicts suffer from calorie and protein malnutrition. This malnutrition is related to female sex, intensity of drug addiction, anorexia and poor food and drink consumption, and disturbance of the social and familial links. Acute organic pathology leads to a significant worsening of the nutritional status of drug addicts.

Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (>= 25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease.

27 páginas, 3 figuras, 2 tablas.-- et al., Background The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m2 and melphalan 200 mg/m2 as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study. Design and Methods The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m2; because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m2. Results Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m2 resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m2 group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m2 (58%; P=0.01). Conclusions Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m2 but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma patients., This research was supported by grant PI051284 from the Fondo de Investigación Sanitaria (FIS), Instituto Carlos III, Ministerio de Sanidad, by the Cooperative Research Thematic Network (G03/136 and RD06/0020/0006), and by the Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (PI060339 and 02/0905).

To analyze the relationship between the subjective assessment of nutritional status and anthropometric parameters, as well as the prognostic value of the subjective evaluation, the nutritional status of 280 patients was evaluated as follows on admission to a semi-intensive care unit: temporal muscle atrophy, Bichat's fat atrophy, upper and lower extremities muscle atrophy and subcutaneous fat atrophy. Each parameter was categorized into three degrees of severity and a nutritional score (NS) was obtained. We have also determined the mid-upper arm circumference (MUAC), the triceps skinfold (TSF), the mid-arm muscle area (MAMA), serum albumin and transferrin. During the hospital admission 88 patients died. We found a good concordance (82%) between subjective and objective (anthropometric data, fifth percentile criteria) assessments. Those patients who died showed significant lower values of MUAC, MAMA, TSF, serum albumin and transferrin; and higher neutrophil count, alpha-1-antitrypsin, ferritin, BUN and als...

Purpose Complete response (CR) is considered an important goal in most hematologic malignancies. However, in multiple myeloma (MM), there is no consensus regarding whether immunofixation (IF)-negative CR, IF-positive near-CR (nCR), and partial response (PR) are associated with different survivals. We evaluated the prognostic influence on event-free survival (EFS) and overall survival (OS) of these responses pre- and post-transplantation in newly diagnosed patients with MM. Patients and Methods We analyzed 632 patients from the prospective Grupo Español de Mieloma 2000 protocol who were uniformly treated with vincristine, carmustine, cyclophosphamide, melphalan, and predisone/vincristine, carmustine, adryamcine, and dexamethasone induction followed by high-dose therapy and autologous stem-cell transplantation. Results Post-transplantation response markedly influenced outcomes. Patients achieving CR had significantly longer EFS (median, 61 v 40 months; P < 10−5) and OS (medians not reached; P = .01) versus patients achieving nCR, who likewise had somewhat better outcomes compared with patients achieving PR (median EFS, 34 months, P = .07 v nCR; median OS, 61 months, P = .04). EFS and OS and influence of response were similar among older (age 65 to 70 years) and younger (age < 65 years) patients. Similar findings were observed with pretransplantation response, with trends toward EFS (P = .1; P = .05) and OS (P = .1; P = .07) benefit in patients achieving CR versus nCR and PR, respectively. Post-transplantation response was markedly influenced by pretransplantation response; improvements in response were associated with prolonged survival. Conclusion Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.

Although alkylating agents are clearly beneficial in multiple myeloma (MM), their deleterious effect on bone marrow hematopoietic progenitor cells usually precludes their use as front-line therapy in patients scheduled to undergo autologous stem cell transplantation (ASCT). We analyzed the impact of first-line chemotherapy with alkylating agents on stem cell collection in MM patients.Seven hundred and eighty-nine patients included in the Spanish multicenter protocol GEM-2000 underwent mobilization therapy after four courses of alternating VBMCP/VBAD chemotherapy.The mobilization regimens consisted of standard or high-dose granulocyte colony-stimulating factor (G-CSF) in 551 (70%) patients, and chemotherapy and G-CSF in 206 (26%) patients. The CD34+ cell yield was lower than 4x10(6)/kg in 388 patients (49%), and equal or greater than 4x10(6)/kg in 401 patients (51%). Multivariate analysis indicated that advanced age (p0.0001) and longer interval between diagnosis and mobilization (p=0.012) were the two variables associated with a lower CD34+ cell yield. Significant differences in CD34+ cell yield were not observed between the mobilization regimens. Of the 789 patients included in the protocol, 726 (92%) underwent the planned ASCT, whereas 25 (3%) patients did not because of the low number of CD34+ cells collected. Following ASCT, 0.5x10(9) neutrophils/L could be recovered after 11 days (median time; range, 5-71 days) and 20x10(9) platelets/L could be recovered after 12 days (median time; range, 6-69 days).A short-course of therapy with alkylating agents according to the GEM-2000 protocol was associated with an appropriate CD34+ cell collection, and allowed the planned ASCT to be performed in the majority of MM patients.

Objective: To assess the nutritional status of drug addicts without acute organic pathology, in order to determine the prevalence of malnutrition and to discern if early HIV infection is associated with a poor nutritional status in this group of patients. Design: Prospective study. Setting: Detoxication unit of a university hospital. Patients: 140 drug addicts without acute organic pathology. 31 patients were HIV+. No one fulfilled the definition of AIDS. Results: We found that drug addicts were undernourished: 92.4% weighed under the mean populational weight and 55.7% had a weight loss above 5%. The distribution of mid upper arm circumference (MUAC), triceps skinfold (TSF) and mid arm muscle area (MAMA) was lower than a reference normal population. Food intakes were poor; 66.4% of our patients complained of anorexia on admission. The mean caloric intake was 978 ± 89 kcal/day in females and 1265 ± 64 kcal/day in males. The mean protein intakes were 39.3 ± 3.3 g/day in females (0.76 ± 0.07 g/kg/day) and 49.7 ± 2.7 g/day in males (0.77 ± 0.04 g/kg/day). When we compared nutritional parameters between HIV+ and HIV- patients we found no differences. Conclusions: Nutritional impairment in drugs abusers with early stages of HIV infection should be attributed to drug abuse rather than to HIV infection.

Bone marrow biopsy (BMB) is generally performed either on the anterior superior iliac spine (ASIS) or the posterior superior iliac spine (PSIS), the choice between these two sites depending largely upon practice at individual centres. No previous study has attempted to ascertain which of these two sites is preferable for needle BMB. We studied 72 biopsies, of which 36 were of the PSIS and 36 of the ASIS, measuring the length of the cylinder and the area of the histologic section. We asked those patients who had undergone BMB at both sites which had been the less painful. The cylinders obtained from the PSIS were found to have a significantly greater length and area than those obtained from the ASIS (P < 0.00001). Of the 13 patients who underwent BMB at both sites, 11 reported the PSIS biopsy to have been distinctly less painful (P = 0.012). We conclude that needle BMB of the PSIS provides samples of greater length and area, and is less painful, than that of the ASIS.

One randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS in patients failing to achieve CR or near-CR with a single transplant. However, other studies failed to show benefit from a second transplant. The aim of our study was to investigate the efficacy in terms of response improvement and survival from a second transplant intensification in patients with chemosensitive disease who failed to achieve CR or near-CR with a first high-dose procedure. Patients diagnosed with MM from Oct 1999 to Dec 2004 younger than 70 years received 6 courses of VBMCP/VBAD and responding patients were intensified with busulphan/melphalan or MEL-200 followed by stem cell support. Patients not achieving CR or near-CR were planned to undergo a second transplant (second auto with CVB - cyclophosphamide, etoposide and BCNU - or MEL-200 intensification or an allo-RIC with Fludarabine/MEL-140 conditioning, if sibling donor available). Eighty-eight patients received a second autologous transplant while 26 underwent an allo-RIC. Thirty-seven percent of the patients given a second autologous transplant improved their response status (CR 11%, near-CR: 6%, PR: 9% and MR 11%) while 63% showed “no change”, progressive disease or early death. A response was observed in 45% of patients undergoing the allo-RIC (CR: 33%, PR: 4%, MR: 8%). The CR rate was significantly higher with allo-RIC (33% vs. 11%, p= 0.02). There was a trend towards a higher TRM with the allo-RIC (5% vs. 16%, p=0.09). Although the median EFS (26 vs 19 m) and OS (57 m vs not reached in allo-RIC) from the second high-dose procedure were not significantly different, there is a plateau in the “allo-RIC” group beyond 3 years of the second procedure not observed in the autologous arm. Conclusions: an allo-RIC transplant after an autologous procedure results in a significantly higher CR rate than a second autologous transplant, and despite the lack of significant differences in survival between the two transplant modalities, there is a plateau in the allogeneic group not observed in the autologous arm.

It has been shown in non-randomized studies that tandem transplant results in an increased CR rate. A randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS in patients failing to achieve CR or near-CR with a single transplant. However, other studies failed to show a survival benefit from a second transplant. The aim of our study was to investigate the feasibility and efficacy in terms of response up-grading and survival from a second transplant intensification in patients with chemosensitive disease who failed to achieve CR or near-CR with a first transplant. Patients diagnosed with MM from Oct 1999 to Dec 2003 younger than 70 years received 6 courses of VBMCP/VBAD chemotherapy and responding patients were intensified with busulphan/melphalan or MEL-200 followed by stem cell support. Patients not achieving CR or near-CR were planned to undergo a second transplant (either a second auto with CVB - cyclophosphamide, etoposide and BCNU - intensification or a dose-reduced intensity “allo” with Fludarabine/MEL-140 conditioning, depending on sibling donor availability). It is of note that 99 (55%) did not receive the second HDT procedure because patient refusal -28 pts-, lack of CD34–17 pts-, progressive disease - 16 pts-, poor PS -15 pts-, physician decision -14 pts-, others -8 pts-. Patients who did not proceed with the second transplant were significantly older (58 vs. 55 yrs, p= 0.001) and had higher serum beta2-microglobulin levels (4.7 vs. 3.5, p=0.02). Fifty nine patients received a second autologous transplant while 23 underwent a “mini-allo”. Twenty-eight percent of the patients given a second autologous transplant achieved an up-graded response (CR or near-CR: 7%, PR: 10% and MR 12%) while 61% showed “no change”, progressive disease or early death. A response up-grade was observed in 43% of patients undergoing a “mini-allo” procedure (CR: 26%, PR: 4%, MR: 3%). The CR rate was significantly higher with the allogeneic procedure (26 vs. 5%, p=0.01). However, there was a trend towards a higher TRM with the “miniallo” procedure (5% vs. 17% (p=0.09). The survival from the second high-dose procedure was not significantly different between the two transplant modalities (2nd auto vs “mini-allo”). Conclusions. in about one-half of the patients in whom a tandem transplant is planned the second high-dose procedure is not performed, a dose-reduced intensity allogeneic transplant after an autologous procedure results in a significantly higher CR rate than a tandem autologous transplant, with the current follow-up we found no significant differences in survival between the two transplant modalities.

It is assumed that patients with primary refractory myeloma are the most likely to benefit from early HDT. In four series the CR rate was between 8 and 40% and the overall survival ranged from 4 to 6 years. However‚ the number of patients with progressive disease vs those with “stable disease” was not given in published series. The aim of our study was to investigate the efficacy in terms of response up-grading and survival of early HDT in patients with primary refractory myeloma. From October 1999 to December 2003 patients with MM younger than 70 years were given 6 courses of VBMCP/VBAD chemotherapy. Patients with refractory disease were scheduled to receive a tandem transplant‚ the first procedure intensified with busulphan-12 mg/kg-/melphalan-140 or melphalan-200 and the second with the CVB -cyclophosphamide‚ etoposide and BCNU- or with a dose-reduced intensity “allo” conditioned with fludarabine/melphalan-140‚ depending on sibling donor availability. Response and progression were defined according to the EBMT criteria. Forty-nine patients with primary refractory disease were identified. Twenty patients showed progression after their initial chemotherapy while 29 patients had “non-responding‚ non-progressive disease”. Eighty percent of the patients achieved some degree of response after the first autologous transplant (CR or near-CR: 8%‚ PR: 56%‚ MR: 16%) while 10% did not respond and 10% died from the procedure. Twenty-four patients were given a second transplant (autologous: 17‚ allogeneic: 7). Forty-six percent of the 17 patients who received a second autologous transplant upgraded their response (CR: 6%‚ PR: 17%‚ MR: 23%) while 41% had progressive disease or “no-change” and 13% died from the procedure. Three of the seven patients who underwent a dose-reduced intensity “allo” responded (2 CR‚ 1 PR) while two had progressive disease and two died from transplant-related complications. The median survival of the whole series of 49 patients was 32 months. Patients who had progressive disease after the initial chemotherapy had a significantly shorter survival than those who showed “non-responsive‚ non-progressive disease” (median 21 months vs. not reached‚ p=0.003). Finally‚ patients with “non-responding‚ non-progressive disease” had similar survival than those with chemosensitive disease intensified with HDT in the GEM trial. Conclusions. A high-dose therapy approach in patients with primary refractory myeloma results in a high overall response‚ but the CR rate is low‚ patients with progressive disease to the initial chemotherapy have short survival despite intensive therapy‚ and patients with “non-responding‚ non-progressive disease” have similar survival than chemosensitive patients. Whether the good outcome of the latter patients is mainly due the effect of HDT or to the natural history of a more indolent disease remains to be determined.