Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma.

Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10-6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade ≥3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade ≥2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01916252 and EudraCT as #2012-005683-10.

Rapid Aneurysmal Sac Expansion Following Endovascular Repair of a Dissecting Thoracoabdominal Aneurysm.

Endovascular repair of dissecting thoracoabdominal aneurysms (TAAA) is challenging and often requires multiple procedures. A 61-year-old man with a dissecting type-II TAAA treated first by placement of a thoracic endograft, and subsequently implantation of a fenestrated endograft. Six months postoperatively, a 10-mm increase of the aorta was observed. A reentry tear in left external iliac artery (EIA) was perfusing the false lumen in a retrograde fashion connecting with the endoleak caused by the inferior mesenteric artery and lumbar arteries. False lumen embolization of the left EIA and outflow vessels was performed. Thrombosis and rapid decrease of false lumen diameter was then observed. This case illustrates the complexity of endovascular management of extensive chronic aortic dissections.

Applicability of Zenith p-branch Standard Fenestrated Endograft in Our Series.

BACKGROUND: In the endovascular treatment of abdominal aortic aneurysm (AAA) with short or absent infrarenal neck, the delay in the availability of fenestrated device and its high cost, have led to the manufacture of standardized models. Another option is the endografts with stents in parallel; however, regulated criteria for their use and long-term studies are lacking. The aim of this study was to assessed whether the AAA treated with fenestrated device or stents in parallel in our department, complied with the characteristics for the placement of the new endograft p-branch(®). Furthermore, the differences between the p-branch and the implanted prosthesis were analyzed. METHODS: Single-center and descriptive study of 41 aneurysms treated consecutively from 2008 to 2015. The anatomic characteristics analyzed were: relative distances between the visceral arteries, time position, diameter in the sealing area and number of fenestrations, and its compatibility with the p-branch. RESULTS: The anatomic compatibility rate with the p-branch options was 73.2% (30 cases). Of the 11 incompatible cases, 6 were due to misalignment of the visceral branches, 2 due to the aortic neck diameter being greater, another because the femoral access was inappropriate, and 2 more due to the fenestration configuration. Of the 30 cases in which compatibility existed, in 12 (40%) the configuration used coincided with the p-branch. In 13 cases, the number of fenestrations was higher than those actually used, with 23 fenestrations carried out and 39 hypothetical fenestrations with the new endograft. In the 5 remaining cases, a fenestration for the celiac trunk was necessary to achieve an adequate seal. CONCLUSIONS: The p-branch could meet the needs of three-quarters of the aortic anatomies of our series, with favorable expectations on cost and waiting time. However, in most cases either a higher number of fenestrations are needed for visceral arteries or the proximal seal was shorter than would be ideal.

Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma.

INTRODUCTION: Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). MATERIALS AND METHODS: We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a "resistance" parameter that reflects the stagnation in the response after an initial descent. RESULTS: Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P = .02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P = .02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. CONCLUSION: This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.

Subclavian-axillary arterial thrombosis and distal embolisation after traumatic anterior glenohumeral dislocation. / Trombosis arterial subclavioaxilar y embolización distal tras luxación glenohumeral anterior traumática.

Arterial vascular injury associated with anterior dislocation of the shoulder is a rare but potentially devastating complication, often seen in the context of high-energy trauma or penetrating injury. It is a medical emergency that can compromise both the viability and functionality of the limb, as well as the patient's life if it is not identified early and treated properly. However, its diagnosis can be difficult, since it requires a high index of suspicion. The presence of an axillary artery thrombosis after shoulder dislocation resulting from low-energy trauma is extremely rare, even more so with subacute clinical presentation associated with embolism to the radial artery.

Acquired hemophilia A: three different presentations of the same disease.

Acquired hemophilia A is a rare disorder characterized by the presence of an autoantibody (mainly immunoglobulin G) to the clotting factor VIII with a clinical resemblance to hemophilia A. This autoantibody may arise because of dysregulation of the immune system. It is associated with various autoimmune or dermatologic diseases, pregnancy, or drug ingestion, but in almost 50% patients, the cause is unknown. In the present study, we have reported three different clinical presentations of acquired hemophilia. In two cases, the underlying disorder was the probable respiratory chronic disease (asthma), and in the other, it was idiopathic. We reviewed the response to a given treatment. The severity of the clinical presentation was different in all the cases, and was taken into account when we decided on the best course of treatment. The present report presents two patients successfully treated with a tapering course of steroids, and one with the anti-CD20 monoclonal antibody not given as first line treatment.

Tandem transplants with different high-dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Osea phase II trial.

Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200-ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV-ASCT2). All patients were in response after MEL200-ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200-ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV-ASCT2. The final CR rate was 48%. The 5-year survival (OS) was 55%[95% confidence interval (CI) 43-67%] while the event-free survival (EFS) was 28% (95% CI 15-39%). CR status after CBV-ASCT2 was the most important prognostic factor for OS and EFS (P = 0.00001), although no differences in outcomes were detected when the patients in CR after MEL200-ASCT1 were compared with those who obtained CR after CBV-ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200-ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high-dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.