The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

BACKGROUND. Bortezomib is active in heavily pretreated multiple myeloma patients; the dose‐limiting toxicity is peripheral neuropathy (PN). METHODS. The authors retrospectively reviewed the incidence, severity, and risk factors for PN in 78 patients who received bortezomib. The median age was 57 years (range, 33–80 years), 62% of patients were men, and 37% of patients were African Americans. Seventeen patients (22%) had diabetes mellitus (DM), and 66 patients (85%) had received thalidomide. Before bortezomib treatment, 37% of the patients reported subjective, grade 1 or 2 PN. Patients received bortezomib alone (n = 10 patients) plus dexamethasone (n = 36 patients) and thalidomide (n = 20 patients) or chemotherapy (n = 12 patients). PN affected 52% of patients, including grade 3 and 4 PN in 15% and 7%, respectively. RESULTS. Twelve patients stopped bortezomib because of side effects that included PN (n = 9 patients), diarrhea (n = 2 patients) and cytomegalovirus pneumonia (n = 1 patient); 11 patients had dose reductions because of PN. Grade 4 PN affected 6 patients (sensory, n = 4 patients; motor/sensory, n = 2 patients). The onset of grade 4 PN was sudden rather than cumulative. Factors that were predictive of PN grade were baseline PN (P = .002), prior thalidomide use (P = .03), and the presence of DM (P = .03). Multiple myeloma responses included complete, near complete, and partial responses in 5% of patients, 10% of patients, and 27% of patients, respectively. Responses were independent of PN and of whether bortezomib was combined with chemotherapy or thalidomide. Patients remained on therapy longer for a median of 5 cycles (range, 2–36 cycles) when they received bortezomib plus thalidomide versus 3 cycles (range, 1–19 cycles) for the other combinations. PN therapy was mostly supportive. It was noteworthy that 6 of 9 patients with PN who received lenalidomide as salvage therapy after bortezomib had significant improvement in their symptoms. CONCLUSIONS. The risk of bortezomib‐related PN was greater in patients who had PN and DM at baseline. The authors concluded that an unexpected, symptomatic improvement of PN on lenalidomide is worth further investigation. Cancer 2007. © 2007 American Cancer Society.

Background: Livedoid vasculopathy (LV) is an occlusive thrombotic disease that affects primarily the small blood vessels of the lower extremities and often is associated with recurrent painful ulcerations. The pathogenesis of LV is unclear, but the disease is largely attributed to a hypercoagulable state. Factor V Leiden mutation, heterozygous protein C deficiency, homozygous hyperhomocysteinemia, and other inherited thrombophilias have been associated with LV. Plasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of the fibrinolytic system. Elevated levels of PAI-1 are found in some patients with thrombotic diseases. Some of these patients are homozygous for an allele of PAI-1 containing a stretch of 4 guanines at base −675 in the promoter region. This variant is associated with elevated PAI-1 protein levels, impaired fibrinolysis, and increased risk of thrombosis.Observations: A 33-year-old white woman had a 3-month history of painful enlarging ulcers on both ankles. Various therapies, including administration of oral antibiotic agents and prednisone up to 100 mg/d, to treat presumed vasculitis, were unsuccessful. Skin biopsy specimens revealed numerous thick-walled small blood ves-

ObjectiveThe authors review their initial experience with laparoscopic splenectomy in patients with hematologic diseases. Efficacy, morbidity, and mortality of the technique are presented, and other patient recovery parameters are discussed. Summary Background DataLaparoscopic splenectomy is performed infrequently and data regarding its safety and efficacy are scarce. Factors such as a high level of technical difficulty, the potential for sudden, severe hemorrhage, and slow accrual of operative experience due to a relatively limited number of procedures are-responsible. The potential patient benefits from the development of a minimally invasive form of splenectomy are significant. MethodsClinical follow-up, a prospective longitudinal database, and review of medical records were analyzed for all patients referred for elective splenectomy for hematologic disease from March 1992 to March 1995. ResultsLaparoscopic splenectomy was attempted in 43 patients and successfully completed in 35 (81%). Therapeutic platelet response to splenectomy occurred in 82% of patients with immune thrombocytopenic purpura and hematocrit level increased in 60% of patients with autoimmune hemolytic anemia undergoing successful laparoscopic splenectomy. The morbidity rate was 11.6% (5 of 43 patients), and the mortality rate was 4.7% (2 of 43 patients). Return

G3139, dexamethasone, and thalidomide are well tolerated and result in encouraging clinical responses in relapsed multiple myeloma patients.

Purpose: Inosine monophosphate dehydrogenase (IMPDH) inhibitors have been used to induce leukemia blast cell differentiation but have not been tested in multiple myeloma for activity. Currently, available IMPDH inhibitor, mycophenolate mofetil (MMF), which is known as an immunosuppressant, was shown to induce apoptosis in myeloma cell lines. On the basis of our preclinical studies, we designed a clinical study to test our hypothesis that MMF has antimyeloma activity.Experimental Design: A Phase I MMF dose escalation study was conducted in relapsed and refractory myeloma patients who had documented disease progression by myeloma markers or bone marrow plasmacytosis to determine the maximum tolerated dose, toxicities, and efficacy of the drug. To assess the activity of IMPDH inhibition in the myeloma cells of patients, we measured intracellular nucleotide triphosphate levels by high-performance liquid chromatography-based analysis and examined the correlation with clinical response.Results: Among the 11 study patients, MMF was generally well tolerated and was administered up to a maximum dose of 5g/day. The most common toxicity was grade 1 fatigue (n ‫؍‬ 4, 36%). One patient had a partial response (3g/day), four patients had stable disease, and six patients had progression of disease. There was a statistically significant difference in the intracellular dGTP level changes between the stable disease/partial response group versus progression of disease.Conclusions: MMF at 1 to 5 g/day daily dose is well tolerated by patients with relapsed and refractory multiple myeloma patients. Positive correlation between clinical response and depletion of intracellular dGTP level was shown. Future drug development to target this enzyme maybe useful in treating myelomas.

Post-transplant lymphoproliferative disorders (PTLD) complicate up to 10% of solid organ transplants. This retrospective study was conducted to review the PTLD experience among 2,300 recipients of solid organ or allogeneic bone marrow transplants from a single institution. Twenty-seven cases of PTLD were identified, leading to an overall incidence of 1.2%. Polymorphic B cell hyperplasia/lymphoma was the most common type. The median time to development of PTLD was 8.4 months. Ten patients had localized (stage I or II) disease, and 12 patients presented with B symptoms. Nine patients each were treated with systemic chemotherapy or surgical resection as part of the initial therapy. After a median follow-up duration of 2.6 years, the median survival has not been reached. There were no late relapses of PTLD, and 17 patients remain alive. Age, sex, organ source, LDH, stage, presence of extranodal disease, or presentation with B symptoms did not influence overall survival when examined by Cox proportional hazard model. Thirteen patients retained their graft function throughout PTLD treatment. This study confirms the ability to treat a significant proportion of PTLD patients with chemotherapy or surgical resection (depending on presentation), without sacrificing graft function in those receiving chemotherapy. Am. J. Hematol. 82:208-214, 2007. V V C 2006 Wiley-Liss, Inc.

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