High-dose cyclophosphamide for severe systemic lupus erythematosus

Abstract

Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.

High-Dose Chemotherapy without Stem Cell Transplantation for Refractory Childhood Systemic Lupus Erythematosus

“…The average duration of neutropenia is shorter by 4 days compared with that after single high-dose Cy 200 mg/kg reported by Petri et al [11] and Gladstone et al [12] , and thus, the early treatment-related risk consequently decreases. Our patients have shorter neutropenic duration, because the dose of Cy we delivered at 1.2 g/m 2 daily for 4 days (which is also a megadose) is lower than that of 50 mg/kg daily for 4 days (totally 200 mg/kg).…”

“…Therefore, intensive chemotherapy with high-dose Cy, at a dose of up to 200 mg/kg, can lead to profound immunosuppression or immunoablation without myeloablation, and ASCT following highdose Cy is unnecessary. Recently, there were some reports on successful use of high-dose Cy without ASCT for adult patients with refractory autoimmune diseases including acute aplastic anemia [15] , autoimmune neurologic diseases [16] , myasthenia gravis [17] and SLE [11,12] . In this trial, we show that childhood patients with SLE, who did not respond to conventional therapy, responded well to intensive chemotherapy.…”

“…Moreover, transplant-related mortality in the range between 2 and 17% is one of the major limitations of ASCT [7][8]10] . Recently, 2 reports showed the efficacy of intensive chemotherapy with high-dose Cy (200 mg/ kg) without stem cell support in adult refractory SLE [11,12] . High-dose Cy has induced long-term remission in adult patients.…”

Therapieoptionen bei karzinomerkrankten Frauen mit Kinderwunsch

“…B. M. Behcet, glomeruläre Nephritiden, Pemphigus vulgaris oder Lupus erythematodes), bei denen zytotoxische Therapien mit alkylierenden Agenzien appliziert werden, stellen ebenfalls eine Indikation für fertilitätserhaltende Maßnahmen dar [25]. Patientinnen mit diesen Erkrankungen könnten in Zukunft auch einer ovariellen Biopsie, Kryokonservierung und späteren Autotransplantation zugeführt werden.…”

High-dose intravenous cyclophosphamide therapy in severe SLE

“…In this issue of Lupus, Gladstone et al, describe four patients undergoing high dose intravenous cyclophosphamide therapy which resulted in signi cant improvement in a potentially life-threatening disease that had previously failed to respond to conventional therapy. 7 This type of therapy is not without risk and Gladstone et al's patients suffered adverse events including neutropenic fever, veno-occlusive liver disease and sepsis. However, one patient did have a successful twin pregnancy (albeit complicated by active lupus during gestation), suggesting that ovarian failure is not always a complication of such high dose cyclophosphamide therapy.…”