Bortezomib-induced motor neuropathy: A case report.

INTRODUCTION: Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma, Waldenström's macroglobulinemia, mantle cell lymphoma. The most reported adverse effects include fatigue, thrombocytopenia, gastrointestinal symptoms, and peripheral neuropathy, which mostly manifests as sensory neuropathic symptoms. We present a case of a patient who experienced motor neuropathy after initiating treatment with bortezomib. CASE REPORT: An 87-year-old male was diagnosed with multiple myeloma and started on treatment with bortezomib, dexamethasone, and lenalidomide (VRd). After five cycles of therapy, he developed lower extremity weakness, which was severely debilitating, affecting his ability to walk, and this prompted his visit to the emergency department. MANAGEMENT AND OUTCOME: The patient was admitted for further workup and underwent electromyography, which was consistent with demyelinating polyneuropathy with active denervation. His symptoms were attributed to bortezomib, and his VRd regimen was held. His symptoms failed to improve despite discontinuation of bortezomib. He then received steroids and intravenous immunoglobulin (IViG) with a gradual resolution of his symptoms. He was thereafter restarted on only lenalidomide and dexamethasone with no recurrence of his neuropathy. DISCUSSION: Clinicians need to be aware of the likely risk for motor neuropathy associated with bortezomib. Risk factors like older age and pre-existing neuropathy can predispose patients to this adverse effect, and clinicians should monitor for this toxicity and facilitate dose reduction or discontinuation of therapy if warranted. Sometimes, patients may also need further treatment with steroids or IVIG.

Reversing the effects of antiplatelet agents in the setting of intracranial hemorrhage: a look at the literature.

Patients are increasingly being prescribed antiplatelet agents (APAs) for a growing number of medical and surgical conditions. These agents are associated with an increased risk of hemorrhage, including intracranial hemorrhage (ICH). In the setting of warfarin use and ICH, strategies to reverse the drug effects have improved outcomes. No such strategy exists for APAs, and these patients continue to have poor posthemorrhage outcomes. One strategy is the use of platelet transfusions to provide functional, circulating platelets. Studies have shown mixed results regarding the benefit of this practice. Other strategies include the use of desmopressin and recombinant factor VIIa. More studies are necessary to delineate the effectiveness of the various strategies.

Outcomes of plasma exchange in patients with transplant-associated thrombotic microangiopathy based on time of presentation since transplant.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA-TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA-TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA-TMA since transplant. Thirty-three patients diagnosed with TA-TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All-cause day-30 and day-100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P-value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30-day and 100-day all-cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P-value = 0.25 and 0.08, for 30- and 100-day all-cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA-TMA. The overall efficacy of PE is poor; however, patients who present with TA-TMA ≥100 days after transplant may have better outcome and lower mortality.

Infusion technique of hematopoietic progenitor cells and related adverse events (CME).

BACKGROUND: The use of hematopoietic progenitor cell (HPC) transplant has risen over the past two decades. A variety of adverse events (AEs) of varying severity have been noted during HPC infusions. These AEs have been associated with several factors such as the amount of dimethyl sulfoxide and white blood cells in the HPC product. We performed a single-institution retrospective analysis to determine the effect of two different HPC infusion techniques, manual push with syringes versus infusion from bags with the aid of gravity, on the occurrence of infusion-related AEs. STUDY DESIGN AND METHODS: Infusions between December 2008 and November 2010 involving peripheral blood HPCs were reviewed. Pertinent clinical and HPC product-related information was recorded. Data were analyzed to determine the incidence of infusion-related AEs and its association with patient and product-related variables. RESULTS: We found 461 AEs in 645 patients during the study period. A total of 325 (50%) experienced at least one AE. Flushing was the most common type of AE followed by nausea and hypertension. The use of syringe infusion was more commonly associated with AEs (odds ratio, 1.82 [95% confidence interval, 1.32-2.50]; p=0.002). Other independent risk factors were cryopreserved products and the amount of polymorphonuclear leukocytes in the product. CONCLUSION: To our knowledge, this is the first study examining the effect of two different infusion techniques on infusion-related AEs. Our findings suggest that the use of bags for infusion protected the patients from AEs.

Risks and adverse outcomes associated with emergency-release red blood cell transfusion.

BACKGROUND: Group O red blood cell (RBC) units are used for emergency transfusions and are often uncrossmatched when transfused. We sought to determine the risk of alloimmunization and identify acute adverse outcomes of this practice. STUDY DESIGN AND METHODS: The transfusion medicine database was searched for emergency-release transfusion (ERT) episodes from January 2006 through December 2010. The data collected included age and sex of the recipient, blood bank history, survival after the ERT episode, antibody screen results, antibody identifications, and compatibility of released units. RESULTS: A total of 1444 ERT episodes took place involving 1407 patients. A total of 4144 RBC units were released. Of the 129 positive antibody screens, 34 had no antibody on further work-up, 14 had autoantibodies, 48 had a single antibody specificity, and 25 had multiple antibody specificities. Seven patients developed an antibody that could be attributed to the ERT episode, and 15 patients developed an antibody after ERT and additional RBC transfusions. There were 32 reported suspected transfusion reactions. No acute hemolytic transfusion reactions were reported. Seven patients were given a total of 10 incompatible RBC units. Of these patients, one developed a delayed serologic transfusion reaction. The rate of alloimmunization attributable to ERT was 3%. Overall, the rate of incompatible transfusion was less than 0.3% and the rate of a delayed hemolytic transfusion reaction was approximately 0.02%. CONCLUSION: There is minimal risk associated with the release of emergency uncrossmatched blood in the setting of an acutely bleeding patient. [Correction statement added after online publication 15-Oct-2012: the number of patients with autoantibodies, single antibody specificity and multiple antibody specificity has been update.].

Primary Bone Lymphoma: A Case Series and Review of Literature.

Primary bone lymphoma (PBL) is a subtype of lymphoma that exclusively affects skeletal tissue. Despite the relatively common involvement of skeletal structures as a manifestation of non-Hodgkin's lymphoma (NHL), primary and exclusive involvement of the skeletal system is rare. The prevalence of PBL is estimated to be 3-7% amongst primary bone tumors and less than 2% amongst all lymphomas in adults. However, the definition of primary bone lymphoma has been inconsistent over time. Within our institution, we identified four cases of primary bone lymphoma based on diagnostic criteria formed from the general consensus of multiple organizations, including the World Health Organization (WHO) and International Extranodal Lymphoma Study Group (IELSG). Here, we discuss the distinct characteristics amongst these cases in addition to performing a systematic review of current literature regarding this lymphoproliferative entity.

A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes.

PURPOSE: The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease. EXPERIMENTAL DESIGN: To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth. RESULTS: Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone. CONCLUSION: These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease.