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The objectives of this study were to review epidemiological, clinical and biological aspects associated with the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in multiple myeloma (MM) patients, with special emphasis on the genetic aspects. A detailed review of previously described risk factors as well as recent genetic findings mostly comprises this work. The most recent meeting abstracts and relevant articles published in journals covered by the Science Citation Index and Medline are also examined. The review pays special attention to the genetic component of BRONJ. A total of 15 series and 14 guidelines or revisions were selected to fit the aims of the review. Gene variability was reviewed in depth to give a clinical illustration on the genetic aspects of BRONJ. Crude prevalence and 5-year cumulative incidence were considered as the most important end points for predictive purposes. Several acquired factors were recognized as predictors for BRONJ in MM, especially intravenous bisphosphonates, dental trauma and advanced age. Among genetic factors, polymorphisms on CYP2C8 gene arise as a promising risk factor. Bisphosphonate-related osteonecrosis of the jaw can be predicted with a conjunction of genetic and environmental risk factors. [ABSTRACT FROM AUTHOR]

Melphalan & Prednisone (MP) is considered as the standard therapy for Multiple Myeloma (MM) patients not eligible for high-dose therapy. Here, we report the results of a phase I-II study to evaluate the feasibility and efficacy of the association of PLD to the conventional MP regimen during the first six cycles of the front-line therapy for untreated MM patients older than 70. Thirty patients were included in the study with a median age of 77 years (71-84) and a M/F ratio of 17/13. The phase I of the study demonstrated that the maximum tolerable dose of PLD in this setting was 30 mg/m2, so it was the final dose evaluated in the study. Twenty-nine patients were valuable for response, which was: complete in 4 (14%) partial in 15 (52%) minor/no changes in 7 (24%) and progressive in 3 (10%). The median progression free survival (PFS) was 24 months. The median overall survival (OS) has not been reached yet, with a 3-year probability for OS and PFS of 52 and 37%, respectively. Haematological toxicity was frequent but usually weak/moderate (grades 1 & 2 of the WHO scale) and it was resolved only with dose delays. Infection was a relatively frequent event (30% of patients), but only in 4 cases it was of grade 3. No cases of palmar-plantar erythrodysesthesia were observed. In conclusion, pegylated liposomal doxorubicin can be safely added to the other chemotherapeutic drugs in the treatment of elderly MM patients, which can be very useful for patients in whom novel agents are not tolerated or inefficient. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Almost all automated hematology cell analyzers use methods based on either the impedance (PLTi) or the optical (PLTo) properties of the cells for performing platelet counts. To improve the accuracy of platelet counts in peripheral blood (PB), the use of CD61 (GPIIIa) MoAbs (ImmunoPLT method) has recently been introduced in an automated hematology blood-analyzer system (Cell-Dyn 4000, Abbott Diagnostics).Study Design and Methods: A comparative evaluation was made of the accuracy and precision of the three methods currently available in the Cell-Dyn 4000 automated hematology cell analyzer for counting the number of platelets per microliter of PB in a total of 47 patients with chemotherapy-induced thrombocytopenia. A flow cytometric PB platelet count was also performed in parallel and used as an external reference.Results: PB platelet counts showed a good correlation among the PLTo, CD61-ImmunoPLT, and flow cytometric methods. In contrast, the PLTi procedure usually provided an overestimation of the number of platelets per microliter. Although a good correlation was observed between the flow cytometric reference method and both the ImmunoPLT and PLTo methods, the highest degree of agreement was found for the ImmunoPLT techniques (94% vs. 67%). A comparative analysis of the PLTo and CD61-ImmunoPLT methods with regard to their value for predicting platelet transfusion needs on the basis of specific flow cytometric platelet count thresholds showed a good correlation when the cutoff level of 10,000 platelets per microL was used. In contrast, at the threshold of 20,000 platelets per microL, slight differences were observed between the PLTo and CD61-ImmunoPLT procedures for predicting transfusion needs.Conclusion: Such results indicate that, if the CD61-ImmunoPLT method is used in the platelet transfusion decision-making process, unnecessary platelet transfusions could be avoided in up to 17.5 percent of persons with a PLTo count of <20,000 platelets per microL. [ABSTRACT FROM AUTHOR]

The number of CD34+ cells has been described as the best parameter for predicting the quality of engraftment in peripheral blood progenitor cell (PBPC) transplantation in the early post-transplant period. In this study we have determined the optimal number of CD34+cells in order to maintain engraftment in the long term in a series of 100 patients receiving autologous PBPC transplantation. Based on our previous experience on the speed of early hematopoietic recovery, four subgroups of patients were established: patients infused less than 0.75 × 106/kg CD34+ (n = 9), 0.75 to 1.25 (n = 24), 1.25 to 2.0 (n = 37) and more than 2.0 (n = 30). These groups were designated as low, intermediate-low, intermediate-high and high CD34 groups, respectively. Transitory loss of neutrophil engraftment was observed in 67%, 30%, 16% and 6% of patients in the four mentioned CD34 groups respectively, with statistically significant differences between the different groups. Significant differences were also observed between the low CD34 group and the rest of the groups as regards platelet and red blood cell transfusion requirements, fever episodes, days of hospitalization and antibiotic requirements throughout the first year. Our results show that the dose of CD34+ cells influences engraftment also in the late post-transplant period, and correlates with transfusion and antibiotic requirements, fever episodes and days of hospitalization during the first year post-transplant. [ABSTRACT FROM AUTHOR]

The outcome of multiple myeloma has substantially improved over the past decade, mainly due to recently approved drugs, such as thalidomide, lenalidomide, and bortezomib. Nevertheless, most patients still relapse and, therefore, drugs with new mechanisms of action are urgently needed to overcome this resistance. In this Review, we discuss some of the new targeted therapeutic strategies under assessment in preclinical and clinical studies in multiple myeloma. Unfortunately, the single-agent clinical activity of most of these new drugs has been limited; nevertheless, their effectiveness might be enhanced by their rational combination with each other or with conventional agents. [ABSTRACT FROM AUTHOR]