A randomised study comparing the antiplatelet and antinflammatory effect of clopidogrel 150 mg/day versus 75 mg/day in patients with ST-segment elevation acute myocardial infarction and poor responsiveness to clopidogrel: Results from the DOUBLE study

Introduction

The antiplatelet effect of standard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infarction (STEMI) has never been studied. In this study we compared the antiplatelet effect of a 75 mg daily maintenance dose of clopidogrel with 150 mg in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

Materials and methods

Fifty-four patients with STEMI undergoing PCI were randomly allocated to receive either 75 mg/day clopidogrel (group 1) or 150 mg/day (group 2) for 1 month. Platelet function, measured by 5 different assays, was determined at 3 time points: 38 ± 8 hours after the procedure, 1 week and 1 month after randomization.

Results

In group 1, mean ± SD platelet reactivity index (PRI) measured with the VASP assay was 57.7 ± 15.7% and 46.9 ± 15.7% at 1 week and 1 month, respectively, compared to 38.8 ± 15.7% and 34.9 ± 12.6% in group 2 (p = 0.0001). Same results were observed for light transmittance aggregometry, whole blood aggregometry and VerifyNow, but not for thromboelastometry. In contrast to what may be expected, the 75 mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect. Furthermore, patients in group 2 had a nearly 50% reduction in C-reactive protein levels both at 1 week and 1 month.

Conclusion

In patients with STEMI and poor responsiveness to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation.     

Oxaliplatin‐based chemotherapy (dexamethasone,high‐dose cytarabine,and oxaliplatin) ± rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma

BACKGROUND:

Patients affected by relapsed or primary refractory lymphomas currently have a poor prognosis and no standard salvage treatment options. This study was carried out to assess the efficacy and safety of a dexamethasone, high‐dose cytarabine, and oxaliplatin as salvage therapy in those patients, replacing cisplatin with oxaliplatin in the standard dexamethasone, cytarabine, and cisplatin scheme.

METHODS:

Seventy patients with relapsed or refractory aggressive non‐Hodgkin or Hodgkin lymphoma were treated from September 2001 to September 2007. The median age of patients was 51 years (range, 19‐75 years). Histological subtypes were: diffuse large B‐cell lymphoma (n = 47) and Hodgkin lymphoma (n = 23). The overall response rate was 73% (51 of 70), with 30 (43%) complete remissions and 21 (30%) partial remissions. Fifty‐two patients were treated with dexamethasone, high‐dose cytarabine, and oxaliplatin as second‐line chemotherapy. Forty‐eight patients were enrolled in an autologous stem cell transplantation program; forty (83%) finally proceeded to high‐dose consolidation and autografting.

RESULTS:

No grade 3 or 4 nonhematological toxicity was demonstrated; in particular, no renal or neurotoxicity was reported. After a median follow‐up period of 21 months (range, 2‐87 months), 22 (31%) patients had died. Probabilities of 2‐year progression‐free survival (PFS) and overall survival (OS) were 44% and 71%, respectively. In the chemosensitive patients, the PFS and OS were 52% and 83%, respectively. The only factor that significantly correlated with better OS was the response to therapy.

CONCLUSIONS:

This study confirms that dexamethasone, high‐dose cytarabine, and oxaliplatin ± rituximab is an effective and feasible outpatient regimen for salvage therapy in patients affected by relapsed or refractory lymphoma. Moreover, the feasibility and efficacy of this scheme as an in vivo chemosensitive test in patients in autotransplantation programs was confirmed. Cancer 2010. © 2010 American Cancer Society.     

Periodontal changes in patients undergoing radiotherapy

BACKGROUND: The purpose of this study was to evaluate changes in the periodontium in patients who received head and neck radiation therapy. METHODS: Periodontal clinical parameters (probing depth, clinical attachment level, gingival recession, plaque index, and bleeding on probing) were assessed on 27 patients before and 6 to 8 months following radiation therapy in the head and neck area. RESULTS: The greatest changes occurred in clinical attachment level: overall, 70.3% of the patients showed a loss, with 92% evincing loss in the mandible. Attachment loss was directly related to the field of radiation and was greater when the jaws were actually included in the irradiated area. CONCLUSION: Periodontal status should be evaluated prior to and following radiation therapy in the oral-maxillary-facial region to help ensure that periodontal health is maintained in oncology patients.     

Fludarabine, Arabinosyl Cytosine and Idarubicin (FLAI) for Remission Induction in Poor-Risk Acute Myeloid Leukemia

Progress in treatment of acute myeloid leukemia (AML) is slow and treatment intensification alone has limited effects, particularly in poor-risk cases. Poor-risk cases, that are identified mainly by prior history, leukemic cell mass and cytogenetic abnormalities, share multiple mechanisms of drug resistance that are responsible for treatment failure. Since Pgp-mediated resistance to anthracycline can be reduced with Idarubicin (IDA) and resistance to arabinosyl cytosine (AC) can be reduced with Fludarabine (FLUDA), we tested a combination of high dose AC (2000mg/sqm, 5 doses), FLUDA (30 mg/sqm, 5 doses) and IDA (12mg/sqm, 3 doses) for remission induction and consolidation in 45 consecutive cases of poor-risk AML. The complete remission (CR) rate was 71 % after the first course and 82% overall, with a projected 2-year survival and relapse-free survival of 44% and 50% respectively. Non-hematologic toxicity was very mild, that is very important in elderly patients, but hemopoietic toxicity was substantial, with a time to hematologic recovery of 3 to 4 weeks and two cases of death in CR. Peripheral blood stem cells (PBSC) could be mobilized and collected successfully only in 11 cases. This three-drug combination is effective and has a limited non-hematologic toxicity, but FLUDA may increase the difficulty of obtaining PBSC early after remission induction.     

Visceral larva migrans in French adults: a new disease syndrome?

Visceral larva migrans is apparently an endemic disease among adults in southwest France. Thirty-seven adults living in the Midi-Pyrenees region of France were confirmed as having visceral larva migrans based on an increased specific antibody titer to Toxocara canis as detected by enzyme-linked immunosorbent assay (ELISA) and by the Western blot method. The disease was characterized clinically by weakness, pruritis, rash, difficulty breathing, abdominal pain, and pathologically by allergic manifestations including eosinophilia and increased serum immunoglobulin (Ig) E levels. Conditional logistic regression analysis using a control group of 37 hospital patients with other conditions who were individually matched to patients with visceral larva migrans by age and sex revealed an increased risk for visceral larva migrans associated with hunting or living in a household with a hunter (odds ratio (OR) = 9.0, p = 0.02) and with living in a village of less than 500 persons (OR = 5.7, p = 0.04). Owning two or more dogs compared with owning one or no dogs increased the risk of visceral larva migrans for hunting or living in a household with a hunter (OR = 9.6 vs. OR = 4.5) and for persons living in nonhunting households (OR = 2.1 vs. OR = 1.0). These findings, however, could not be duplicated when 60 age- and sex-matched neighbors were used as a second control group.     

Hairy cell leukemia. A therapeutical update

This is a review of current treatment for hairy cell leukemia (HCL). Data for this analysis were obtained from the Italian HCL Registry, as well as from other published series. We have given space to the impact of interferon and pentostatin on the management of this disease. Other issues are also discussed, such as the relevance of achieving a complete remission with respect to overall and relapse-free survival. We include a final section on recommendations which may prove useful in designing an appropriate therapeutic strategy.     

Human lymphoblastoid interferon for hairy cell leukemia: results from the Italian Cooperative Group

Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.     

Maintenance therapy with recombinant interferon alpha-2B (alpha IFN) in prognostically unfavourable aggressive non-Hodgkin's lymphomas (NHL)

Fifteen patients from a series of 37 consecutive patients with aggressive NHL who achieved a complete remission (CR) with first line chemotherapy were defined at high or high-intermediate risk of relapse according to International Prognostic Risk Index and were treated with alpha IFN as maintenance therapy for two years. After a median follow-up of 62 months only 3/15 patients (20%) relapsed and 2/15 (13.3%) died in the alpha IFN treated group, favourably comparing with the expected relapse and death rate in that setting; on the other hand 40.9% of 'low risk' patients from the same series, who did not receive alpha IFN, had relapsed. alpha IFN maintenance therapy appears to result in prolonged response duration and survival in patients with aggressive and prognostically unfavourable NHL.