Systemic monoclonal antibody therapy for eliminating minimal residual leukemia in a rat bone marrow transplant model

In an animal bone marrow transplant (BMT) model that mimics the human clinical condition, we evaluated the effectiveness of monoclonal antibody (MoAb) therapy in eliminating minimal residual disease (MRD) in a leukemic host. Leukemic rats were prepared with marrow ablative but noncurative doses of busulfan (BU) and cyclophosphamide (CY). Two days after syngeneic BMT, rats were treated with MoAb. Although all control rats died of leukemia relapse, 58% of those treated with MoAb were cured without any demonstrable effect on the rate of peripheral blood leukocyte recovery. Furthermore, the level of complement, an important effector in suppressing leukemia proliferation in the normal rat, was not adversely affected by BU/CY, BMT and MoAb. Thus, we demonstrated in an animal model that MoAb therapy may be a useful, nontoxic adjunct to high-dose chemotherapy and BMT in eliminating MRD.     

P-glycoprotein expression in plasma-cell myeloma is associated with resistance to VAD

Tumor cell-associated expression of multidrug resistance (MDR) was quantitated in 22 patients with DNA-aneuploid myeloma using 2-parameter flow cytometry with monoclonal antibody (MoAb) C-219 for the detection of cytoplasmic p-170 and propidium iodide for nuclear DNA content. The proportion of cells expressing p-170 and the intensity of p-170-related fluorescence were determined for each patient. Among the 14 patients treated with vincristine-adriamycin-dexamethasone (VAD), the proportion of p-170-positive cells distinguished sensitive from resistant disease (P less than .01). Among a subgroup of seven patients with MDR analysis available prior to VAD therapy, two subsequent nonresponders had high proportions of C-219-reactive cells. The presence de novo of high proportions of p-170-expressing cells in another still untreated patient and in a further individual with resistance to dexamethasone and interferon (not associated with MDR) warrants systematic analysis of p-170 expression prior to therapy to determine its clinical implications for response to MDR-associated drugs as combined in the VAD regimen. Concurrent MDR expression by aneuploid tumor cells and cells in the diploid subcompartment may represent involvement of diploid cells in the myeloma disease process.     

Transverse Sinus Stenting for Pseudotumor Cerebri: A Cost Comparison with CSF Shunting

BACKGROUND AND PURPOSE:Transverse sinus venous stent placement has been shown to lower intracranial pressure in patients with venogenic pseudotumor cerebri and to reverse, or at least stabilize, its symptoms and signs. There have been no studies comparing the cost of venous stenting with the time-honored treatment for pseudotumor cerebri–CSF shunting. The purpose of this study was to compare the cost of trasverse sinus stenting versus CSF shunting for the treatment of pseudotumor cerebri.MATERIALS AND METHODS:This work was a retrospective cost analysis of individual resource use in 86 adults who were stented for pseudotumor cerebri during a 12-year period compared with resource use in 110 children who were shunted for hydrocephalus during a 3-year period.RESULTS:There was no significant difference between the cost of inserting an initial venous stent ($13,863 ± 4890) versus inserting an initial CSF shunt ($15,797 ± 5442) (P = .6337) or between inserting an additional venous stent ($9421 ± 69) versus revising a CSF shunt ($10,470 ± 1245) (P = .4996). There were far fewer additional venous stent insertions per patient than there were subsequent CSF shunt revisions; 87% of stents placed required just 1 stent procedure, whereas only 45% of shunts required 1 shunt procedure. The main cause of the cost difference was the need for repeated revisions of the shunts, especially when they became infected—24 instances of a total 143 shunt procedures (16.8%) at an average cost of $84,729, approximately 5 times the cost of an initial shunt insertion.CONCLUSIONS:Venous stenting costs significantly less per 100 procedures than does CSF shunting, due largely to the high cost of treating shunt infections and the need for repeated shunt revisions.

Transverse sinus venous stent placement is an effective treatment for pseudotumor cerebri (PTC)^1–3; however, its cost has not been assessed or compared with the cost of the traditional alternative—CSF shunting. The annual cost of treating PTC in the United States exceeds US $444 million, and the annual cost of all CSF shunts—not just for PTC—exceeds $1 billion.^4,5 We wanted to estimate the cost of transverse sinus venous stenting and compare it with the cost of CSF shunting. Because pediatric hydrocephalus typically requires CSF shunt insertion, this pediatric group was the most suitable one available for cost comparison. Since the advent of venous sinus stenting for PTC, no patient has undergone CSF shunting at our institution for PTC. We reviewed the cost per patient for stent-versus-shunt insertion and reviewed the cost in terms of failed procedures, infection, and the need for revision, representing the full cost of these procedures.