Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data.

Plerixafor was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to enhance stem cell mobilization for autologous transplant in patients with lymphoma and multiple myeloma. In this study, we present the first European compassionate use experience in mobilization failures, patients who are hardest to remobilize but were not included in registration trials. A total of 56 consecutive patients from 15 centers in Spain and the United Kingdom were included: age 60 (33-69) years; 29 men (32 with myeloma and 24 with lymphoma); 2 lines of previous chemotherapy (1-10); 73 previously failed mobilization attempts with G-CSF (28), chemotherapy plus G-CSF (43) or G-CSF plus SCF(2). Overall, 71% of patients reached ≥ 10 CD34+ cells per µL with plerixafor on day 5 after a 7.6-fold expansion from day 4. A total of 42 patients (75%) collected ≥ 2 × 106, average 3.0 ± 1.7 (0.4-10.6) CD34+ cells per kg with plerixafor plus G-CSF. There were no severe drug-related adverse events. In all, 35 patients (63%) underwent transplant, receiving an average of 3.1±1.2 (1.9-7.7) × 106 CD34+ cells per kg. All patients engrafted neutrophils (day 12; 13.4 ± 0.8; 8-30) and platelets (day 15; 18.5 ± 2.4; 8-33). In our experience, plerixafor offers an effective alternative to collect sufficient CD34+ cells for autologous SCT from patients who fail conventional mobilization methods, with good tolerance and a high success rate.

Plerixafor (Mozobil) for stem cell mobilization in patients with multiple myeloma previously treated with lenalidomide.

Lenalidomide and other new agents have considerable activity in multiple myeloma (MM) and have changed the landscape of treatment. Data suggest that lenalidomide therapy before autologous hematopoietic stem cell transplantation has a detrimental effect on stem cell mobilization. This retrospective study examined the efficacy of plerixafor in combination with G-CSF among patients with MM previously treated with lenalidomide (median, 4 cycles; range, 1-20 cycles). Data were analyzed for 60 patients who received plerixafor plus G-CSF for frontline mobilization in a phase 3 clinical trial or an expanded access program (n=20) or for remobilization in a compassionate use program (n=40). The overall median number of CD34+ cells collected was 5.6 × 10(6) per kg (range, 0.45 × 10(6)-37.2 × 10(6)). The minimum number of CD34+ cells (2 × 10(6) per kg) was collected from 86.7% of patients in a median of 1 day. This minimum was collected from 100% of patients who underwent frontline mobilization and 80% of patients who underwent remobilization. These data suggest that CD34+ hematopoietic stem cells can be successfully and predictably collected with combination plerixafor plus G-CSF for primary or secondary mobilization in the majority of patients with MM who have been previously treated with lenalidomide.

Selection of glycoprotein IIb/IIIa inhibitors for upstream use in patients with diabetes experiencing unstable angina or non-ST segment elevation myocardial infarction. What have we learned in the last 10 years?

Coronary disease accounts for the majority of deaths among patients with diabetes and the thrombotic milieu accelerated by diabetes results in unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) or death. Upstream use of a glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor with percutaneous coronary intervention (PCI) as part of an early invasive approach is preferred. However substantial numbers of patients present to rural or non-teaching hospitals without immediate access to a catheterization laboratory. Enhanced GP IIb/IIIa receptor mobilization, TXA2 production and platelet activation together present an extensive thrombotic challenge that may not be overcome with current doses of GP IIb/IIIa inhibitors when used without PCI. Heterogeneity of platelet aggregometric analysis may have identified GP IIb/IIIa doses used in clinical trials that may not fully overcome the thrombotic challenge in patients with diabetes. GUSTO-IV ACS failed to demonstrate a difference in mortality when used without PCI. The PURSUIT trial provided evidence that eptifibatide decreases death or non-fatal myocardial infarction (MI) in the main group and in the diabetic subgroup. Reductions in this primary endpoint were driven by the reduction in non-fatal MI. The PRISM and PRISM-PLUS trials demonstrated a reduction in death, MI or refractory ischaemia at 48 h or 7 days in the main cohort but not specifically in patients with diabetes. Data supporting use of GP IIb/IIIa inhibitors are inconsistent, raising the question of whether these agents should be used at all without PCI. Variability in experimental methodology of platelet aggregometry and selection of anticoagulant used during dose finding studies may have generated doses that are insufficient to overcome the thrombotic burden. A new marker of active inflammation, sCD40L is found to be upregulated at subtherapeutic doses of GP IIb/IIIa inhibitors, suggesting that rebound inflammatory processes may partially account for absence of clear evidence of benefit with some GP IIb/IIIa inhibitors in patients with diabetes experiencing UA/NSTEMI.

A synopsis of the clinical uses of argatroban.

Argatroban, a direct thrombin inhibitor, has been used in Japan since the early 1980's and was recently approved for use in the United States for patients with heparin-induced thrombocytopenia. However, its use has been studied in other clinical settings including, myocardial infarction, percutaneous coronary intervention and cerebral thrombosis. The doses used in the different clinical situations vary, but argatroban offers the advantage of not requiring renal adjustment. Because of its small molecular weight, argatroban has the ability to inhibit both clot bound and soluble thrombin. This paper provides a comprehensive review of both indicated and off label uses of argatroban. Pharmacology, pharmacokinetics, adverse events and drug interactions with argatroban are also discussed.

Impact of a pharmacist on drug costs in a coronary care unit.

The impact of clinical pharmacy services on direct drug costs in a coronary care unit (CCU) was studied. An observational, nonrandomized study was conducted on all patients admitted to the CCU to evaluate the impact of clinical pharmacy services on direct drug costs. Clinical pharmacy services were introduced into the CCU in July 1998. Patient characteristics, mean drug costs per admission, mean drug category costs per admission, and total hospital costs per admission were determined for October 1997 to June 1998 (nonintervention period), July 1998 to March 1999 (intervention period 1), and April 1999 to December 1999 (intervention period 2). The Clini-Trend program was used to estimate the total reduction in drug costs associated with documented pharmacist interventions from January to December 1999. Mean patient age, sex, admitting diagnosis-related group, Medicare case-mix index, ventilator days, length of stay, and number of deaths did not differ significantly among the three study periods. Mean +/- S.D. drug costs per admission for the nonintervention period were $374.05 +/- $75.51. With the introduction of clinical pharmacy services, mean +/- S.D. drug costs per admission were $381.94 +/- $66.16 (p > 0.1 for intervention period 1 compared with the nonintervention period) and $233.74 +/- $84.16 (p = 0.002 for intervention period 2 compared with the nonintervention period). From January to December 1999, 4151 pharmacist interventions were documented. The estimated reduction in drug costs associated with the interventions totaled $372,384. A pharmacist's clinical services in the CCU allowed for significant estimated reductions in total drug costs.

Pharmacokinetics and pharmacodynamics of low-molecular-weight heparins and glycoprotein IIb/IIIa receptor antagonists in renal failure.

Data regarding the use of low-molecular-weight heparins (LMWHs) and glycoprotein (GP) IIb/IIIa receptor antagonists in patients with renal failure are limited. Renal failure has the potential to increase the risk of adverse drug events associated with LMWHs and GP IIb/IIIa receptor antagonists. This is due to changes in the pharmacokinetic and pharmacodynamic profiles of these agents in patients with renal failure. Until more data are available, clinicians should consider alternative therapies in this patient population.

Drug-induced thrombocytopenia in the coronary care unit.

Drug-induced thrombocytopenia is a phenomenon that causes significant morbidity and mortality among patients. Practitioners should be able to recognize the clinical manifestations of drug-induced thrombocytopenia, differentiate it from other causes, and manage it appropriately. Numerous case reports have documented drug-induced causes of thrombocytopenia. The following article focuses on the characteristics and management of drug-induced thrombocytopenia secondary to medications commonly encountered in the coronary care unit. Pharmacotherapeutic agents that are most commonly implicated in this setting include ticlopidine, unfractioned heparin, glycoprotein (GP)IIb/IIIa inhibitors, H(2)-receptor antagonists, quinidine and antibiotics. Case reports were obtained through a comprehensive search of the Medicine database and subsequently complemented by bibliographic reviews of the agents just specified. Reports that exhibited possible, probable, and definite associations with drug-induced thrombocytopenia are included in the article.