Sk Kumar

..The trial was registered at www.clinicaltrials.gov (NCT00564889)...

..No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442)...

..Based on the current findings, we conclude that the presence of trisomies in patients with t(4;14), t(14;16), t(14;20), or p53 deletion abnormalities in MM ameliorates the usual adverse impact associated with these prognostic markers...

..However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification...

..It is not clear whether this paradigm holds true in the context of new therapies, such as immunomodulatory drugs (IMiDs)...

..This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs...

..We recommend collection of PBSC within 6 months of initiation of therapy with lenalidomide containing regimens to minimize the risk of mobilization failures...

..To examine whether the outcome of patients with primary systemic amyloidosis (AL) has improved over time and to identify predictors of early mortality in patients with AL...

..The toxicity of transplant as well as the outcome appears comparable to younger patients. Patients with MM should not be excluded from HDT solely on the basis of their chronological age...

..In addition, the newer drugs are being explored as maintenance therapy following SCT. This review summarizes the current approach to the treatment of newly diagnosed myeloma in transplant-eligible patients...

..CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy...

..9 vs 37.1 months; P < .001. In multivariate analysis, dFLC was independent of other prognostic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL...

..A system including both these risk factors allows better prediction of outcome...

..VDCR is well tolerated and highly active in this population. No MTD was reached; the recommended phase 2 cyclophosphamide dose in VDCR is 500 mg/m(2), which was the highest dose tested...

..This review focuses on recent findings in the context of previous studies demonstrating a benefit for SCT compared with conventional therapies...

..Patients who relapse within 12 months of an auto-SCT have a poor outcome and should be offered trials evaluating novel treatment approaches...

....

..This article summarizes the recent advances in the treatment of newly diagnosed myeloma and suggests a treatment algorithm for approaching newly diagnosed myeloma...

..The role of ASCT will clearly be redefined in the coming years with improvements in other therapies...

..6 months for Dex and were not reached for Thal-Dex and Len-Dex groups, P=0.2. For patients undergoing early ASCT for myeloma, the nature of initial treatment utilized has no long-term impact on the outcome of ASCT...

..Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma...

..To determine the prognostic value of serum uric acid (UA) in patients with primary systemic (light chain) amyloidosis (AL)...

..8 vs 29.9 months; P < .001). In this study, we demonstrate improved outcome of patients with myeloma in recent years, both in the relapsed setting as well as at diagnosis...

..While we still lack definitive data answering some of these questions, we have attempted to interpret the current state of knowledge, and provide a perspective on the current issues and controversies in this disease...

....

..Thalidomide analogs with a better safety profile are currently undergoing evaluation in the clinic...

..This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence...

..It also highlights the importance of achieving at least a 90% reduction in the FLC-diff to improve the outcome of patients with light-chain AL...

..Patients with high-risk genetic and biochemical features do poorly with conventional therapies, and allogeneic transplantation offers the potential for long-term disease control...

..This book chapter addresses the approaches taken to evaluate monoclonal plasma cell disorders, and the different markers and techniques that are important for the study of these diseases...

..74, 0.7, and 0.7, respectively. Here we demonstrate the prognostic value for GEP risk stratification in a group of patients primarily treated with novel agents. This trial was registered at www.clinicaltrials.gov as #NCT00098475...

..65). The lack of response to initial induction therapy does not appear to preclude a good response to SCT. We recommend that patients with primary refractory MM be offered early SCT...

..Transplantation should be offered to selected patients over age 65 years or selected patients with creatinine elevation...

..Here we describe a patient who developed pneumomediastinum, pneumopericardium, subcutaneous emphysema and pneumothorax secondary to severe bronchiolitis obliterans complicating the post bone marrow transplantation course...

..We found that the relationship between renal recovery and free light chain reduction was present only in patients with biopsy proven cast nephropathy showing the importance of extracorporeal light chain removal in this disease...

..This report describes a patient with agnogenic myeloid metaplasia and Klinefelter syndrome, an association not previously reported...

..Conversely, the 75% of patients remaining have more favorable outcomes using existing - albeit non-curative - therapeutic options...

..Thalidomide has significant activity in early-stage myeloma and has the potential to delay progression to symptomatic disease. This approach must be further tested in randomized trials...

..The combination of pomalidomide and dexamethasone (Pom/dex) is highly active and well tolerated in patients with lenalidomide-refractory myeloma...

..In this review, we will examine treatment for chronic ITP in adults in the pre-splenectomy, splenectomy, and post-splenectomy settings...

..002). We conclude that a slow lymphocyte recovery after allogeneic BMT for AML is strongly predictive of subsequent relapse and that the type of GVHD prophylaxis should be considered when analyzing lymphocyte recovery...

..Although not conclusive, this result lends further support to the hypothesis that angiogenesis is a relevant therapeutic target in myeloma...

..03). Relapse-free survival was similar for the two groups. We conclude that omitting day +11 MTX appears to increase the risk of severe acute GVHD...

..07). The expression of CD138, CD56 and CD54 were higher among the CD45- PCs. This study demonstrates important biological correlates of CD45 expression on myeloma cells...

..007. BM MVD at the time of initial diagnosis is an important prognostic factor for OS and PFS in patients undergoing autologous transplantation as frontline therapy for myeloma...

..18. No significant differences were observed in the progression-free and overall survival at 1 year post transplant. Single agent dexamethasone appears to be an effective alternative to VAD for induction therapy prior to HDT in myeloma...

..The rapid response to corticosteroid treatment and the fact that such therapy was delayed until after intubation in all the mechanically ventilated cases point to a therapeutic benefit...

..We conclude that GVHD prophylaxis with CYA-PRED is associated with a higher overall rate of cGVHD compared to CYA-MTX. The type of GVHD prophylaxis should be considered when comparing the incidence of cGVHD reported in different studies...

..We have concisely reviewed the current knowledge regarding mechanisms of its anti-neoplastic activity and the results of various clinical trials in oncology...

..0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC > or =500 cells/microl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies...

..Such patients could be considered for interventions aimed at prevention of relapse, including rapid withdrawal of immunosuppressive medication or donor lymphocyte infusion...

..001). These findings suggest that the serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma, and can be incorporated into the ISS for improved risk stratification...

..Sorafenib, through multiple mechanisms exerts potent anti-myeloma activity and these results favor further clinical evaluation and development of novel sorafenib combinations...

..The mean post-transplant hospital stay for those with GI tract bleeding was 37 days compared with 14.5 days for those who did not have GI tract bleeding (P = 0.0047)...

..The primary outcome assessed whether this combination would increase the rate of development of new active lesions on cranial MRI scans vs GA alone...

..Demonstration of the presence of VEGFR2 in our study provides a potential biological explanation for the preclinical activity observed with VEGFR2 inhibitors...

..However, there was no significant change in MVD following transplant (P=0.8, paired t-test). Abnormal bone marrow angiogenesis appears to persist in the bone marrow following ASCT for CML, at least in the short term...

..Expression of extracellular matrix (ECM), including collagens and proteoglycans, is increased following atherosclerosis and restenosis...

..These studies demonstrate the potential utility of sc rAAV serotype 6-based vectors in transduction of DC for genetic vaccination approaches...

..These data indicate that therapies targeting apoptotic pathways may be effective in MM treatment and warrant clinical evaluation of ABT-737 and similar drugs alone or in combination with other agents in the setting of MM...

..Additional studies are warranted to confirm this preliminary observation and investigate the mechanism of action...

..The current study provides additional data on both the long-term outcome of splenectomy in adults with ITP and the management of postsplenectomy relapse...

..This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents...

..TTP after tandem transplants (with its higher associated mortality) cannot be superior to TTP achieved with optimally timed serial transplants. Individualized HDT-ASCT for patients with MM is possible and may optimize results...

..This study showed that, in newly diagnosed MM, ALC is an independent prognostic factor for OS, suggesting a significant role of host immune status in the survival of MM...

..Unraveling the mechanisms of the syndrome both in the context of ASCT and in general are challenges for the future...

..Achievement of FLC response was a better predictor of survival than achievement of complete hematologic response or normalization of the FLC ratio. FLC measurements both before and after PBSCT are important predictors of patient outcome...

..Also of importance are prognosis, features that predict outcome, the suitability of transplant candidates, and post-transplantation maintenance therapy...

..In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation...

..We hypothesized that patients with CR before HDT-ASCT (BCR) will have their disease burden reduced further and experience a longer TTP and perhaps OS...

..The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM...

..Achievement of renal response was associated with improved survival. These results suggest that early intervention with aggressive therapy is not only justified but recommended to achieve optimal response...

..001), even after eliminating bias from early death. The degree of response was affected by the intensity of chemotherapy conditioning, septal thickness, and cardiac biomarkers. Hematologic response translates to longer survival...

..The significant expansion of myeloma cells after HDT-ASCT is clearly evident. Clinical trials must be designed that take into account these kinetic aspects of the disease...

..Collectively, these observations not only suggest a model in which Mcl-1 confers TRAIL resistance by serving as a buffer for Bak, Bim, and Puma, but also identify sorafenib as a potential modulator of TRAIL sensitivity...

..5 years. This must be remembered when making treatment decisions for these patients and must be factored in when assessing the efficacy of new therapies...

..Primary cardiac sarcomas are uncommon. The authors undertook to review the Mayo Clinic's experience with primary cardiac sarcomas consisting of 34 patients seen over a 32-year period...