Recurrent Mixed Cryoglobulinemia (MCS): A Case Report and Literature Review.

We report a case of recurrent mixed type II cryoglobulinemia with difficult diagnosis and treatment dilemma and uncertain prognosis in view of limited studies. A 60-year-old male with history of essential mixed cryoglobulinemia 12 years ago treated successfully with six months of cyclophosphamide and prednisone presented with bilateral lower extremity pupuric rash and swelling. He was found to have proteinuria, hematuria, RBC casts, low serum complement levels, and acute kidney injury (AKI). Initial therapy with methylprednisone and oral cyclophosphamide was ineffective (patient developed respiratory failure due to alveolar hemorrhage). Additional labs revealed positive type II cryoglobulins, high free Kappa/Lambda, UPEP with minimal urine protein, SPEP with marked hypogammaglobulinemia, and negative tests for HIV, HCV, ANA, and ANCA. More aggressive therapy with daily plasmapheresis and rituximab was instituted with very good clinical response. He achieved clinical remission but developed another flare 8 months later. Kidney biopsy showed membranoproliferatve glomerulonephritis with cryoglobulin deposits. Flow cytometry and biopsy of bone marrow was consistent with lymphoplasmacytic lymphoma. His diagnosis was eventually confirmed and responded clinically to another course of rituximab and plasmapheresis, but prognosis is yet to be seen.

Chronic myelogenous leukemia in eastern Pennsylvania: an assessment of registry reporting.

BACKGROUND: Chronic myelogenous leukemia (CML) has been reportable to the Pennsylvania Cancer Registry (PCR) since the 1980s, but the completeness of reporting is unknown. This study assessed CML reporting in eastern Pennsylvania where a cluster of another myeloproliferative neoplasm was previously identified. METHODS: Cases were identified from 2 sources: 1) PCR case reports for residents of Carbon, Luzerne, or Schuylkill County with International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes 9875 (CML, BCR-ABL+), 9863 (CML, NOS), and 9860 (myeloid leukemia) and date of diagnosis 2001-2009, and 2) review of billing records at hematology practices. Participants were interviewed and their medical records were reviewed by board-certified hematologists. RESULTS: PCR reports included 99 cases coded 9875 or 9863 and 9 cases coded 9860; 2 additional cases were identified by review of billing records. Of the 110 identified cases, 93 were mailed consent forms, 23 consented, and 12 medical records were reviewed. Hematologists confirmed 11 of 12 reviewed cases as CML cases; all 11 confirmed cases were BCR/ABL positive, but only 1 was coded as positive (code 9875). CONCLUSIONS: Very few unreported CML cases were identified, suggesting relatively complete reporting to the PCR. Cases reviewed were accurately diagnosed, but ICD-0-3 coding often did not reflect BCR-ABL-positive tests. Cancer registry abstracters should look for these test results and code accordingly.

Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099.

PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin (TC) as first-line treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS This multicenter, open-label, phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB (pleural effusion) or IV NSCLC, without restrictions by histology or epidermal growth factor receptor expression. Patients were randomly assigned to cetuximab/TC or TC. TC consisted of paclitaxel (225 mg/m(2)) or docetaxel (75 mg/m(2)), at the investigator's discretion, and carboplatin (area under the curve = 6) on day 1 every 3 weeks for < or = six cycles; cetuximab (400 mg/m(2) on day 1, 250 mg/m(2) weekly) was administered until progression or unacceptable toxicity. The primary end point was progression-free survival assessed by independent radiologic review committee (PFS-IRRC); overall response rate (ORR), overall survival (OS), quality of life (QoL), and safety were key secondary end points. PFS and ORR assessed by investigators were also evaluated. Results Median PFS-IRRC was 4.40 months with cetuximab/TC versus 4.24 months with TC (hazard ratio [HR] = 0.902; 95% CI, 0.761 to 1.069; P = .236). Median OS was 9.69 months with cetuximab/TC versus 8.38 months with TC (HR = 0.890; 95% CI, 0.754 to 1.051; P = .169). ORR-IRRC was 25.7% with cetuximab/TC versus 17.2% with TC (P = .007). The safety profile of this combination was manageable and consistent with its individual components. CONCLUSION The addition of cetuximab to TC did not significantly improve the primary end point, PFS-IRRC. There was significant improvement in ORR by IRRC. The difference in OS favored cetuximab but did not reach statistical significance.

Bortezomib, ascorbic acid and melphalan (BAM) therapy for patients with newly diagnosed multiple myeloma: an effective and well-tolerated frontline regimen.

BACKGROUND: We conducted a single-arm, multicentre phase 2 study to evaluate bortezomib, ascorbic acid and melphalan (BAM) for patients with newly diagnosed multiple myeloma (MM). METHODS: Induction consisted of up to eight 28-d cycles of bortezomib 1.0 mg/m(2) on days 1, 4, 8 and 11, plus oral ascorbic acid 1 g and oral melphalan 0.1 mg/kg on days 1-4, followed by maintenance bortezomib 1.3 mg/m(2) every 2 wk until progression. RESULTS: Among 35 patients enrolled (median age 70 yr), responses occurred in 23/31 evaluable patients (74%) including five (16%) complete, three (10%) very good partial, six (19%) partial and nine (29%) minimal responses. Six patients (19%) had stable disease. Thus, disease control was achieved in 29 (94%) patients. Median times to first and best responses were 2 and 3 months (ranges 1-5 and 1-7), respectively. Median time to progression was 19 months and median overall survival has not been reached (range 2-23+ months). Grade 3 and 4 adverse events occurred in 17 and 5 patients, respectively; the most common were neutropenia, neuropathy and thrombocytopenia. CONCLUSIONS: BAM is an efficacious, well-tolerated and steroid- and immunomodulatory drug (IMiD)-free frontline treatment regimen for MM patients.

Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss.

PURPOSE: Patients with monoclonal gammopathy of undetermined significance (MGUS) have increased rates of bone resorption, osteopenia, osteoporosis, and risk of fractures. This study was undertaken to determine the efficacy and safety of zoledronic acid for patients with MGUS and enhanced bone loss. EXPERIMENTAL DESIGN: In this phase II open-label study, 54 patients with MGUS and osteopenia or osteoporosis were administered zoledronic acid 4 mg i.v. at 0, 6, and 12 months. The primary efficacy end point was bone mineral density, assessed using a dual-energy X-ray absorptiometry scan in the lumbar (L)-spine done at screening and at 13 months (1 month after the final zoledronic acid infusion). RESULTS: At study end for all patients (N = 54), L-spine T-scores improved by a median of +0.27 (range, -0.38 to +3.91), corresponding to a median increase in bone mineral density of +15.0% (range, -18.0% to +1,140.0%; P < 0.0001). Hip T-scores improved by a median of +0.10 (range, -2.40 to +2.03), corresponding to a median increase of +6.0% (range, -350.0% to +165.0%). During the study, no new fractures, osteonecrosis of the jaw, or significant renal adverse events were reported. CONCLUSIONS: Zoledronic acid administered i.v. at a dosage of 4 mg every 6 months for three doses total was well-tolerated and substantially improved bone mineral density for patients with MGUS and bone loss. Zoledronic acid may be effective for the prevention of new fractures in this high-risk population.

Randomized phase II trial of a toll-like receptor 9 agonist oligodeoxynucleotide, PF-3512676, in combination with first-line taxane plus platinum chemotherapy for advanced-stage non-small-cell lung cancer.

PURPOSE: This study assessed the efficacy of the combination of standard taxane plus platinum chemotherapy with the synthetic Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB to IV NSCLC were randomly assigned (one to two ratio) to receive four to six cycles of taxane/platinum chemotherapy alone or with 0.2 mg/kg of subcutaneous PF-3512676 on days 8 and 15 of each 3-week cycle. The primary end point was objective response rate (ORR). RESULTS: Baseline demographics were similar between treatment arms, although significantly more patients in the PF-3512676 arm had stage IV disease (85% compared with 62% in the chemotherapy-alone arm). The modified intent-to-treat analysis (n = 111) demonstrated a 38% ORR (confirmed and unconfirmed) in the PF-3512676 arm (n = 74) and 19% in the chemotherapy-alone arm (n = 37) by investigator evaluation. Blinded, independent radiologic review for 90 patients showed a similar trend in confirmed response rate (19% and 11%, respectively). Median survival was 12.3 months in the PF-3512676 arm and 6.8 months in the chemotherapy-alone arm, and 1-year survival was 50% and 33%, respectively. Mild to moderate local injection site reactions and flu-like symptoms were the most common PF-3512676-related adverse events, but grade 3/4 neutropenia, thrombocytopenia, and anemia were all reported more commonly for patients in the PF-3512676 arm. CONCLUSION: The addition of PF-3512676 to taxane plus platinum chemotherapy for first-line treatment of NSCLC improves objective response and may improve survival. Confirmatory phase III trials are ongoing.