Treatment with bortezomib‐based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib‐based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL‐pPCL and 17 with secondary PCL‐sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR‐group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow‐up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow‐up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity. Am. J. Hematol. 89:145–150, 2014. © 2013 Wiley Periodicals, Inc.     

The effect of SLActive surface in guided bone formation in osteoporotic-like conditions

Objectives: The aim of the study was to evaluate new bone formation under etched titanium (SLA) and modified‐etched hydrophilic titanium (modSLA) domes placed on the calvarium of healthy, osteoporotic and osteoporotic treated with bisphosphonates rabbits. Methods: Experimental osteoporosis was induced by ovariectomy (OV) and calcium‐deficient diet in 24 New Zealand female rabbits. Twelve OV rabbits were treated with weekly dozes of alendronate (Fosamax^®) (B) while 12 OV rabbits received no treatment (O). Another 12 rabbits were sham operated and used as healthy controls (C). At 6 weeks following OV, one modSLA and one SLA titanium dome were placed in the parietal bones of each rabbit. The animals were sacrificed at 30 and 120 days following the dome placement. Various histomorphometric measurements were performed in the most central of the undecalcified sections produced. Results: After 30 days of healing, in the C group, the total bone (TB) area was 37.6% and 37.0% under the modSLA and SLA domes, respectively. In the O group, the TB was 35.7% and 24.8%. In the B group, TB was 37.0% and 32.1%, respectively. After 120 days of healing, in the C group TB was 40.1% and 36.4%, respectively. In the O group, TB was 29.6% and 27.9%, respectively. In the B group, TB was 49.7% and 42.5%, respectively. Hierarchical analysis of variance showed that the type of titanium dome significantly influenced new bone and the amount of new bone being in contact with inner surface of the dome (BIC) independently of the observation period and group (P<0.05). The administration of bisphosphonates influenced the BIC (P<0.05). Conclusion: The use of modSLA surface may promote bone healing and osseointegration in osteoporotic rabbits, whereas administration of bisphosphonates may compromise the osseointegration of the newly formed bone at the early healing period. To cite this article:
Mardas N, Schwarz F, Petrie A, Hakimi A‐R, Donos N. The effect of SLActive surface in guided bone formation in osteoporotic‐like conditions.
Clin. Oral Impl. Res. 22 , 2011; 406–415.
doi: 10.1111/j.1600‐0501.2010.02094.x     

Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.