We report on the use of leuprolide to prevent heavy menstrual bleeding that often occurs before platelet engraftment in premenopausal women undergoing bone marrow transplantation (BMT). Leuprolide, a synthetic analog of gonadotropin-releasing hormone (Gn-RH-a), was given to 34 patients by intravenous bolus injection, 1 mg daily, until platelet recovery. The median duration of therapy was 50 days (range 16-170). When necessary, patients self-administered the drug after discharge from the hospital. No adverse effects could be related directly to the use of leuprolide. Leuprolide effectively prevented menstruation in 25 patients (73%), failed in seven (21%), and two patients were not evaluable. The success of leuprolide therapy was related to the time of onset of treatment, as anticipated from the gradual effect of Gn-RH-a on the menstrual cycle. The failure rate was only 6% (one of 16 patients) when leuprolide was started at least 2 weeks prior to the development of thrombocytopenia, compared to a failure rate of 33% (six of 18 patients) when leuprolide was started at a later time. We conclude that leuprolide as a single agent is a safe and effective method to prevent menstrual bleeding during BMT. Additional studies are needed to determine the best timing for the onset of therapy and the relative benefit of leuprolide compared to other prophylactic approaches in patients with lengthy thrombocytopenia.

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e20596 Background: Myeloid growth factors are used to treat and prevent chemotherapy-induced neutropenia (CIN). Filgrastim and its long-acting version pegfilgrastim are granulocyte colony-stimulating factors (G-CSF), whereas sargramostim is a dual granulocyte- macrophage colony-stimulating factor (GM-CSF). This study analyzed the budget impact of substituting GM-CSF for G-CSF in the management of CIN from the perspective of a US health plan. Methods: A spreadsheet model was developed to compute annual and per-member-per-month (PMPM) costs associated with CSFs. Inputs included cancer prevalence, the proportion of patients receiving chemotherapy and G/GM-CSFs, incidence and cost of relevant adverse events (e.g., bone pain), and G/GM-CSF drug acquisition and administration costs. Incidence and cost of infection- and febrile neutropenia-related hospitalizations, based on recent analysis of medical insurance claims data, were also used. Cost savings (2006 USD) were assessed for utilization share switches from G-CSF to GM-CSF. Results: For a health plan with 1 million members, an estimated 976 patients received G/GM-CSF annually. Increasing baseline utilization shares for pegfilgrastim, filgrastim, and sargramostim of 70/30/0%, respectively, to alternative shares of 50/25/25% yielded substantial cost savings (see Table ), primarily related to G/GM-CSF acquisition and administration costs. Savings for patients switching from pegfilgrastim were greater than for patients switching from filgrastim. Results were sensitive to assumptions for drug cost and frequency of administration, but cost savings were observed for most scenarios. Conclusions: This study suggests that health plans can realize substantial cost savings by substituting sargramostim for filgrastim and pegfilgrastim in CIN patients. With 25% of sargramostim substitution, the cost saving could reach ≈$2 million for a health plan with 1 million members, or a saving of 16 cents per member per month. [Table: see text] [Table: see text]

Background: Immune ablation with autologous stem cell transplant has been studied in small phase I/II trials with modest success. However, the administration of granulocyte colony-stimulating factor (G-CSF) has led to disease flare in a number of patients. Immunoablative dosing of cyclophosphamide (CTX) without stem cell rescue has been beneficial in a variety of autoimmune disorders, including CIDP, lupus, and myasthenia gravis, as well as inducing durable complete responses in patients with severe aplastic anemia. Therefore, we attempted this method in patients with intractable MS. Methods: Patients were hospitalized; treatment was initiated with CTX at 50 mg/kg/day for four consecutive days. Patients were supported with adequate hydration and forced diuresis to prevent hemorrhagic cystitis. G-CSF was started 6 days after the completion of chemotherapy at 5 mcg/kg/day until the absolute neutrophil count (ANC) >1000 per UL for 2 consecutive days. Patients received supportive transfusions to maintain a hemoglobin of >8gm/dL and platelet count of >10 thousand/UL. Antibiotic therapy was administered per institutional guidelines for febrile neutropenia. Results: Four of planned 10 patients with definite MS, median age 26 (range 23–37), have been treated since February, 2005. All had progressive neurologic decline refractory to standard therapy and also to moderate-dose intermittent pulse IV CTX (1 gm/m2 total dose per cycle) with concurrent IV glucocorticoids. They had received a median of 6.5 (range 3–8) prior cycles, to a total median dose 15,600 (range 10,000–20,000) mg of CTX. The median duration of hospitalization was 19.5 (range 16–21) days. Hematologic toxicity was of short duration, and all patients became neutropenic on day 9. Median duration of neutropenia was 11 (range 7–15) days, with grade IV neutropenia lasting a median of 10.5 (range 6–12) days. Two of 4 patients developed grade III anemia requiring packed red blood cell transfusions; no patient developed grade IV anemia. All patients required supportive transfusions with platelets for grade IV thrombocytopenia, lasting a median of 4.5 (range 2–8) days. Treatment was well tolerated, without serious non-hematologic adverse events. The most common side effect was nausea, mild in 2 patients and moderate in 1 patient. 2 patients experienced diarrhea. 1 patient developed hematuria requiring cystoscopy and bladder irrigation. Three of 4 patients received IV antibiotics for neutropenic fevers; no sources of infection were identified. One patient developed reactivation of oral herpetic lesions despite prophylactic acyclovir. One patient had self-limited mild stomatitis. All patients experienced improvement of neurologic functions, two were clinically dramatic; 3 patients also had dramatic improvement of MRI findings. Conclusion: This is the first report of immune ablation in recalcitrant MS using high dose cyclophosphamide without stem cell rescue. Despite multiple previous CTX doses, all 4 patients responded clinically to high dose therapy, and treatment was remarkably well tolerated with short duration of hematologic toxicity. No disease relapses occurred during chemotherapy or administration of G-CSF. Further follow-up and additional patients are required to evaluate long-term efficacy and late toxicities.