Facet joint components may be at risk for injury due to facet joint compression during rear-impact accelerations of 3.5 g and above. Capsular ligaments are at risk for injury at higher accelerations.

Purpose Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. Patients and Methods Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible. Patients received oral lenalidomide 25 mg/d continuously until disease progression or unacceptable toxicity. The primary end point was overall response rate; secondary end points included safety, tumor control rate (stable disease or better), time to response, duration of response, time to progression, progression-free survival, and overall survival. Results Objective responses were noted in 11 of 26 patients (overall response rate, 42%; 95% CI, 23% to 63%), including four complete responses and one unconfirmed complete response. The tumor control rate was 73%. The median time to response and duration of response were 1.9 months and not estimable, respectively, and the median time to progression was 3.8 months. The median progression-free survival and overall survival were 3.8 and 20.3 months, respectively. The most frequent grade ≥ 3 adverse events were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%), which were all manageable and reversible. Conclusion Lenalidomide demonstrated clinically meaningful antitumor activity and an acceptable toxicity profile in patients with relapsed or recurrent aggressive ATL, hinting at its potential to become a treatment option. Further investigations of lenalidomide in ATL and other mature T-cell neoplasms are warranted.

Use of proteasome inhibitors (PIs) has been the therapeutic backbone of myeloma treatment over the past decade. Many PIs are being developed and evaluated in the preclinical and clinical setting. The first-in-class PI, bortezomib, was approved by the US food and drug administration in 2003. Carfilzomib is a next-generation PI, which selectively and irreversibly inhibits proteasome enzymatic activities in a dose-dependent manner. Ixazomib was the first oral PI to be developed and has a robust efficacy and favorable safety profile in patients with multiple myeloma. These PIs, together with other agents, including alkylators, immunomodulatory drugs, and monoclonal antibodies, have been incorporated into several regimens. This review summarizes the biological effects and the results of clinical trials investigating PI-based combination regimens and novel investigational inhibitors and discusses the future perspective in the treatment of multiple myeloma.

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The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, are involved in a number of facets of the regulation of hematopoiesis at the level of hematopoietic stem (HSCs) and progenitor (HPCs) cells. Modulation of this ligand-receptor interaction may be of clinical utility. We now report that: (1) the CC chemokine, macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3) synergizes with AMD3100 (an antagonist of the binding of SDF-1/CXCL12 to CXCR4) to rapidly mobilize HPCs to the blood of mice; moreover, the combination of granulocyte colony-stimulating factor (G-CSF) with AMD3100 and MIP-1alpha/CCL3, given in a specific sequence, mobilizes the greatest number of HPCs compared to any combination of two of these mobilizing agents; (2) pretreatment of recipient mice with Diprotin A, an inhibitor of CD26/Dipeptidylpeptidase IV (DPPIV), enhances the competitive HSCs repopulating capacity of untreated donor cells; (3) the survival-enhancing effects of SDF-1/CXCL12 on HPCs subjected in vitro to delayed addition of growth factors (GFs) are mediated in part through the cell cycle-related proteins p21(cip1/waf1) (as assessed using p21(cip1/waf1) -/- and +/+ mice) and Mad2 (using Mad2 +/- and +/+ mice); and (4) deletion of CD26/DPPIV on mouse bone marrow cells increases the survival-enhancing effects of SDF-1/CXCL12 on HPCs. These results demonstrate the means to increase the mobilization of HPCs, the engrafting capability of HSCs, and responsiveness of HPCs to the survival-enhancing activity of SDF-1/CXCL12, effects that may be of practical value.

BACKGROUND When skeletal metastasis is the presenting problem and the primary site is occult, there is a need to identify the primary site as soon as possible. However, the search for the primary tumor is often time‐consuming and difficult. The purpose of this study was to analyze the efficacy of particular diagnostic approaches and to devise an efficient and optimal diagnostic strategy. METHODS Among 213 patients with skeletal metastasis treated between 1990 and 1996 were 64 in whom skeletal lesions were the first manifestation of malignancy. The authors retrospectively analyzed both the final diagnosis and the process by which it was made in these 64 cases. RESULTS The primary cancer was identified antemortem in 56 (88%) of the 64 patients by examination and in 3 patients at autopsy. Lung carcinoma, the most frequently observed primary lesion, was identified in 23 patients. Other primary lesions were prostate carcinoma in 11 patients, breast carcinoma in 5, and hepatocellular carcinoma in 5. The primary malignancy was not determined in 5 patients. Thoracic and abdominal computed tomography (CT) scans were useful, especially in the diagnosis of patients with lung, hepatocellular, renal cell, and pancreatic carcinomas. Tumor markers were abnormally elevated in 73% of patients with carcinomas. CONCLUSIONS Although thoracic and abdominal CT scans were useful, examination of the gastrointestinal tract and pelvic CT scan seldom revealed the primary lesion and therefore should not be performed as an initial routine study in the absence of abdominal symptoms. Tumor markers are useful in differentiating carcinoma from hematologic malignancy and primary bone tumor. Cancer 1999;86:533–7. © 1999 American Cancer Society.

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A rear-end collision is most likely to injure the lower cervical spine by intervertebral hyperextension at a peak T1 horizontal acceleration of 5 g and above. These results may aid in the design of injury prevention systems and more precise diagnoses of whiplash injuries.