A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation.

Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m(2) intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25-2·4 months). The progression-free and overall survivals were 8 months and 46·5 months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).

B-lymphoblastic leukemia/lymphoma associated with t(8;13)(p11;q12)/ ZMYM2 (ZNF198)-FGFR1 : rare case and review of the literature.

Myeloid and lymphoid neoplasms with fibroblastic growth factor receptor-1 (FGFR1) abnormalities originate from mutated pluripotent stem cells and have a heterogeneous clinical presentation. There are 12 identified partner genes commonly involved in FGFR1 translocation at an 8p11 breakpoint. In FGFR1-related neoplasms, T-lymphoblastic lymphoma with eosinophilia is the most common clinical scenario, whereas acute B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare. To date, only 7 cases of B-ALL/LBL with FGFR1 abnormalities have been reported. Here, we report an additional case of a 64-year-old gentleman with leukocytosis, eosinophilia and diffuse mediastinal and general lymphadenopathy. Bone marrow examination showed patchy infiltrates of immature precursors/blasts, along with myeloid/eosinophilic hyperplasia. Immunophenotyping confirmed increased B lymphoblasts (30-40%). Karyotyping revealed cytogenetic abnormalities, including t(8;13)(p11;q12)/ZMYM2 (ZNF198)-FGFR1 and trisomy 21. The patient did not respond to hyper-CVAD chemotherapy and within 4 months developed acute myelomonocytic leukemia and expired 11 months after the initial diagnosis. Similar cases from the literature are reviewed.

Subcutaneous alemtuzumab for Sézary Syndrome in the very elderly.

Sézary Syndrome (SS) is an aggressive T-cell malignancy often presenting in advanced age and associated with poor prognosis. There is no standard therapy and because of co-morbidities, elderly patients are particularly challenging to treat. Alemtuzumab is an anti-CD52 monoclonal antibody that has activity in SS but is profoundly immunosuppressive, leading to great hesitation about its use in older patients. We treated five octogenarian patients with SS with subcutaneous (SQ) alemtuzumab, at relapse or as initial therapy, for 5-9 weeks. With the exception of transient grade 1-2 hematological toxicity and asymptomatic cytomegalovirus (CMV) (two patients) and Epstein-Barr virus (EBV) (one patient) reactivation, no other toxicities were observed. The clinical and hematological complete response (CR) rate was 100%. Three patients achieved durable responses (8+ to 17+ months). Alemtuzumab was safely administered and showed significant activity in very elderly SS patients.

Septicemic plague in a community hospital in California.

Diagnosis of a case of septicemic plague acquired in rural California was delayed because of a series of confounding events, resulting in concern about reliance on community hospitals as sentinels for detecting potential bioterrorism-related events. An epizootic study confirmed the peridomestic source of Yersinia pestis infection.

The antimicrobial peptide LL-37 is expressed by keratinocytes in condyloma acuminatum and verruca vulgaris.

BACKGROUND: LL-37 is a peptide belonging to the cathelicidin family of antimicrobial peptides. Recent investigations have suggested that the expression of antimicrobial peptides is an important mechanism for resistance to microbial infection. OBJECTIVE: The aim of this study was to determine whether LL-37 is expressed in papillomavirus-infected epidermis from patients with condyloma acuminatum or verruca vulgaris. METHODS: Biopsy specimens from 3 patients with condyloma and 2 patients with verruca vulgaris and 6 normal skin samples were studied by immunostaining with an antibody specific to LL-37 and control rabbit serum. Western blots were performed on skin extracts from normal skin and verrucae. RESULTS: A large increase in the expression of LL-37 was seen within keratinocytes of all involved samples and in the extracts of verrucae analyzed by Western blot. CONCLUSION: This study shows the antimicrobial peptide LL-37 is induced within the epidermis during the development of verruca vulgaris. This expression represents a previously unknown immunologic response to papillomavirus infection and may represent an important step in the pathogenesis of this disorder.