Clinical features and survival of 338 multiple myeloma patients treated with hematopoietic stem cell transplantation or conventional chemotherapy.

Therapeutic approaches against multiple myeloma (MM) have largely changed during the past decade. Hematopoietic stem cell transplantation (HSCT) and licensing of immunomodulators and proteasome inhibitors have resulted in better response and increased overall survival rates compared to previous conventional therapies. To assess the impact that these new strategies have had on outcome of patients with symptomatic MM in Spain, we conducted an epidemiological retrospective analysis of 338 newly diagnosed patients with stage II-III MM who started first-line treatment over a 2-yr period (2003-2005) by collecting data from their medical records. Most patients had been diagnosed with secretory MM (94.4%), 41.7% stage II and 58.3% stage III. The presence of bone lesions (72.2%), as well as anemia (79.8%) and elevated beta2-microglobulin levels (62.3%), was a common finding; in contrast, hypercalcemia and elevated serum creatinine were less frequent (25% each). First-line treatment had consisted of either conventional chemotherapy (62%) or induction treatment plus autologous HSCT (38%), as per standard clinical practice. HSCT not only resulted in greater objective response rates (93% vs. 50%), but also contributed to a significant increase in 3-yr survival (85% vs. 49.7%; 95% CI, range 77-91 vs. 41-58; P < 0.001). Overall, 55% of patients presented treatment-related adverse events, mainly hematological. Toxicity rates were higher among patients treated with alkylating-based regimens and in those undergoing transplantation. In conclusion, data analysis shows an adequate balance between increased response rates and safety that supports the use of up-front high-dose HSCT therapy in younger patients. Most importantly, this study provides further confirmation that the introduction of HSCT has significantly prolonged survival of patients with MM.

Bendamustine, bortezomib and prednisone for the treatment of patients with newly diagnosed multiple myeloma: results of a prospective phase 2 Spanish/PETHEMA trial.

Bendamustine is a bifunctional alkylating agent with proven activity in myeloma. In this study 60 newly diagnosed myeloma patients were given bendamustine plus bortezomib and prednisone in a regimen consisting of one cycle of bortezomib twice weekly for 6 weeks (1.3 mg/m(2) on days 1, 4, 8, 11, 22, 25, 29, and 32), plus bendamustine (90 mg/m(2) on days 1 and 4) and prednisone. The following cycles included bortezomib once weekly. Patients who were transplant candidates proceeded to stem cell collection after four cycles and the transplant was performed after six cycles. Patients who were not candidates for transplantation received up to nine cycles. Forty-two patients were transplant candidates and after six cycles, 50% achieved at least a very good partial response, with 24% having complete responses; 35 proceeded to a transplant, and the complete response rate was 54%. Seventeen patients continued up to nine cycles, and 57% achieved at least a very good partial response, including 26% with complete responses. The 2-year progression-free survival and overall survival rates were 62% and 86%, respectively. The safety profile was manageable, but stem cell mobilization was compromised in 35% of patients. In summary, this combination is effective in untreated patients, with an acceptable toxicity profile, but given the introduction of second-generation novel agents and monoclonal antibodies, the combination will probably be better reserved for relapsing patients, in whom stem cell collection is not needed, while cost-effective combinations with non-cross-resistant drugs continue to represent a medical need. This trial was registered with ClinicalTrials.gov, number NCT01376401.

Influence of preinfarction angina on the release kinetics of endothelial progenitor cells and cytokines during the week after infarction.

BACKGROUND: Preinfarction angina, a possible form of ischaemic preconditioning, improves the prognosis in patients who experience a major ischaemic event; though the associated pathophysiology is not yet fully understood. The aim of this study was to determine the possible involvement of endothelial progenitor cells (EPC), the vascular endothelial growth factor (VEGF) and the hepatocyte growth factor (HGF) in the development of preinfarction angina. METHODS AND RESULTS: We studied 41 patients (60·5 ± 12 years; 34% women) and 14 healthy controls; 43·9% of the patients had preinfarction angina. No differences were found in the baseline characteristics of the two groups. Although the EPC, VEGF and HGF were raised as compared with the control group, no significant differences were found according to the presence or absence of preinfarction angina in the levels of EPC (baseline, P = 0·25; day 3, P = 0·11; day 7, P = 0·32), VEGF (baseline, P = 0·96; day 3, P = 0·06; day 7, P = 0·57) or HGF (baseline, P = 0·18; day 3, P = 1; day 7, P = 0·86). An association was seen in the patients who had preinfarction angina between the EPC levels at baseline and on days 3 and 7 and the HGF on admission with the time from the angina to the STEMI (ß = -0·070; ß = -0·066; ß = -0·081; ß = -80·16; P < 0·05), showing a reduction in the level of EPC cells for each hour passed since the event. CONCLUSIONS: No differences were found in the release kinetics of EPC, VEGF or HGF after a first infarction according to whether the patients had angina during the week before the infarction.

[Retrospective analysis of the efficacy and tolerability of anagrelide in patients with essential thrombocytemia: Spanish registry of essential thrombocytemia]. / Análisis retrospectivo de la eficacia y la tolerabilidad de anagrelida en pacientes con trombocitemia esencial: registro español de trombocitemia esencial.

BACKGROUND AND OBJECTIVE: A retrospective analysis of a registration database was used to assess the efficacy and tolerability of anagrelide for treating essential thrombocythemia (ET). The study was conducted by analysing information on response to treatment, time to response and tolerability. PATIENTS AND METHOD: A total of 411 patients with ET from 54 centres in Spain were included in a retrospective chart review. Patients who had started treatment with anagrelide as a first- or second-line therapy before December 31, 2004 were included. RESULTS: Of 411 patients, anagrelide was given as a first-line therapy in 110 patients, following hydroxyurea in 280 patients, and following other drugs in 21 patients. Overall response (OR) with anagrelide was 81.2% (77,0-84,9; p=0,05). Complete response (platelets <400x10(9)/L) was observed in 53.6% (48,6-58,5; p=0,05) and partial response (<600x10(9)/L) in 27.6% (23,4-32,2; p=0,05) of patients. There was no significant correlation of previous treatment with OR rate (p=0.103) despite a higher OR for previously untreated patients (86.4%) than for previously treated patients (79.3%). The most frequent treatment-related adverse reactions were headache (13.1%), palpitations (10.2%) and tachycardia (7.5%). CONCLUSIONS: The observed response rates and tolerability profile are similar to those reported previously. Anagrelide is well tolerated and effective in reducing platelets to target levels in patients with ET.

[Incidence and mortality of massive transfusion in a university hospital: study of the period 2001-2005]. / Incidencia y mortalidad de la transfusión masiva en un hospital universitario: estudio del período 2001-2005.

BACKGROUND AND OBJECTIVE: There are few epidemiological studies on massive transfusion (MT), although they may be important to evaluate possible strategies to reduce the number of transfused units, as well as transfusion side-effects. We, therefore, retrospectively assessed the incidence of MT at our institution (a 700-bed university hospital) during a 5-year period. PATIENTS AND METHOD: Local blood bank records were searched for MT episodes occurred from January 2001 to December 2005. MT was defined as the transfusion of 8 or more packed red cell (PRC) units within 24 h. Patient's clinical data were exclusively gathered from the blood requesting form. RESULTS: Overall, 304 episodes of MT were identified in 288 patients (one episode per week), who received 4,845 PCR units (3,515 units within the first 24 h), because of ruptured aortic aneurism (n = 62), poly-trauma (n = 57), upper digestive bleeding (n = 51), cardiac surgery (n = 41), elective surgery (n = 36), emergency surgery (n = 30), and oncology surgery (n = 27). Mortality rate was 48%, and multivariate analysis identified age (odds ratio [OR] =1.023; 95% confidence interval [CI]. 1.006-1.040) and number of PRC transfused within the first 24 h (OR = 1.094; 95% CI, 1.0032-1.160) as weak but significant independent predictors of mortality, whereas poly-trauma diagnosis was a protective factor (OR = 0.325; 95% CI, 0.112 - 0,940). CONCLUSIONS: Overall, the mortality rate among patients receiving MT was very high, and was influenced by the number of transfused units, patient's age, and admitting diagnose. As the majority of the MT episodes occurred within the surgical or polytrauma context, possible strategies to reduce the volume of MT are discussed.

[Coronary disease extension determines mobilization of endothelial progenitor cells and cytokines after a first myocardial infarction with ST elevation]. / La extensión de la enfermedad coronaria determina la movilización de las células progenitoras endoteliales y las citocinas tras un primer infarto de miocardio con elevación del ST.

INTRODUCTION AND OBJECTIVES: Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease. METHODS: We studied the release kinetics in 32 patients admitted for a first myocardial infarction with ST elevation, grouped according to whether they had single or multivessel disease, and 26 controls. RESULTS: The patients had a higher number of endothelial progenitor cells and angiogenic cytokines than the controls at all 3 measurements (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+, CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The levels of these cell subsets were all higher in the patients with single-vessel disease and at all 3 measurements. The vascular endothelial growth factor levels were raised during the first week and the hepatocyte growth factor showed an early peak on admission for infarction. No significant differences were seen in the cytokines according to coronary disease extension. CONCLUSIONS: Although the release kinetics of different subsets of endothelial progenitor cells in patients with a first acute myocardial infarction with ST elevation was similar in those with single vessel disease to those with multivessel disease, the number of circulating endothelial progenitor cells was greater in the patients with single vessel disease. The vascular endothelial growth factor levels were raised during the first postinfarction week and the hepatocyte growth factor were higher on admission.

Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient.

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results.

Length of sedimentation reaction in blood: a comparison of the test 1 ESR system with the ICSH reference method and the sedisystem 15.

The aim of this study was to compare the performance of the automatic TEST 1 ESR system, SIRE Analytical Systems (TEST 1), with that of the the Sedisystem 15, Becton Dickinson (SEDI), and the International Council for Standardization in Haematology reference method (Westergren) for measuring the length of sedimentation reaction in blood (LSRB). This reaction was measured in 418 paired blood samples drawn in K2-EDTA vacuum tubes and specific tubes from patients scheduled for routine LSRB measurement. The TEST 1 system uses micro-sedimentation and quantitative capillary photometry technology, whereas the SEDI uses a CCD camera. For Westergren, a 200 mm column with 3.0 mm internal diameter was used. Compared to Westergren, TEST 1 gives accurate values of LSRB in most of the samples (mean of differences: 0.99 +/- 10.4 mm; 95% CI, -0.807 to 2.78 mm; n =131). Similar results were obtained in the comparison with SEDI (mean of differences: -0.626 +/- 8 mm; 95% CI, -1.756 to 0.5 mm; n = 195). Compared to those of fresh blood samples, LSRB values were significantly lower in 24 h stored samples, either at 4 degrees C (21.5 +/- 2.3 vs. 19.4 +/- 2.2 mm; p (Spearman's coefficient of correlation): 0.981; n = 44) or at room temperature (19.1 +/- 2.5 vs. 16.2 +/- 2.1 mm; p: 0.903; n = 46). In conclusion, TEST 1 is a rapid, reliable system for automatic measurement of LSRB in standard K2-EDTA blood samples. It has a very low imprecision and maintains a good performance in 24 h stored samples. In addition, due to its operational characteristics (60 samples/20 min) it is a suitable tool for clinical laboratories with a high work load as well as for emergency laboratories.

Detection and removal of fat particles from postoperative salvaged blood in orthopedic surgery.

BACKGROUND: Although transfusion or return of salvaged shed blood has become popular in major orthopedic procedures, this blood-saving method is still controversial because shed blood may be contaminated with chemical and tissular debris, such as fat particles, which may increase the risk of fat embolism after bone surgery. STUDY DESIGN AND METHODS: In an effort to find an easy, reliable method for determination of both fat particle content and removal from shed blood, analyses of perioperative blood samples were performed with a cell counter (Technicon H3 [H3]) in orthopedic patients undergoing spinal fusion in which postoperative shed blood was collected and returned with a blood collection canister. A screen or surface filter was intercalated in the return line to eliminate microaggregates, fat particles, and/or WBCs. RESULTS: Fat particles in shed blood are clearly detected as a condensed, sigmoidal-shaped area at the right-hand side of the PMN zone in the channel in which the H3 measures particles according to their degree of lobularity. This signal can be reproduced by the addition of animal or vegetable fat to venous blood, but not by the addition of activated platelets or RBC membranes. Fat particles, together with WBCs and microaggregates, in shed blood were effectively removed by surface filters, whereas screen filters were not effective. CONCLUSION: The use of the TH3 seems to be an easy, reliable, and low-cost approach for monitoring fat particle content and removal from postoperative salvaged shed blood in orthopedic procedures.

Retinoblastoma: reporte de la consulta de oncología oftalmológica del Hospital Francisco Antonio Rísquez desde abril 1992 hasta septiembre 1995 / Retinoblastoma: repport of the ophthalmologic oncology consulation of the Hospital Francisco Antonio Rísquez since april 1992 until september 1995

Se revisaron las historias médicas de pacientes con diagnóstico de retinoblastoma evaluados en la consulta de Oncología Oftalmológica del Hospital F.A. Rísquez, desde abril de 1992 hasta septiembre de 1995. De un total de 63 casos registrados, 50 casos pertenecen al estudio prospectivo multidisciplinario E.C.R.O.M.U.S. actualmente en desarrollo. Observamos que 56 por ciento de los pacientes estadiados mediante la clasificación de Howarth modificada correspondieron al estadio II y 34 por ciento al estadio III. La mortalidad registrada hasta la fecha es de 14 casos