Intravenous cyclophosphamide-resistant systemic lupus erythematosus in Arizona

Abstract

Systemic lupus erythematosus (SLE) tends to be severe and to have a variable response in childhood. We undertook this retrospective study to assess response rates and outcome in 14 children with SLE. Mean age at onset was 12.8+/-3.1 years. Ten patients were female and 4 were male, and 12 patients (86%) were Hispanic. Creatinine clearance prior to therapy was 104+/-36 ml/min. All had hematuria and proteinuria with a protein/creatinine ratio of 3.9+/-4.8. WHO classification of renal biopsies revealed class IV in 64%, class III in 21%, and class V in 14%. Patients were treated with 6-monthly pulses of intravenous cyclophosphamide (IVCY) followed by longer-duration pulses. The mean duration of follow-up was 3.7+/-3.3 years. Of the 14 patients, 3 (21%) achieved systemic remission but all relapsed subsequently; 7 of 14 achieved renal remission, although 6 relapsed. Six (42%) had adverse outcomes, defined by death, dialysis, or need for bone marrow transplant. All 6 had failed 6 months of IVCY, suggesting that patients who demonstrate resistance to initial IVCY therapy have an unfavorable outcome and a high likelihood of complications. In summary, we report a poor response to standard therapeutic protocols with higher relapse rates, as well as significant adverse outcomes.

Clinicopathology of childhood‐onset renal systemic lupus erythematosus

“…Conversely, our CRR rate was more than three times higher than that found among African-American children ( Table 6) by Lau et al 5 But why our CRR rate compares favourably with Chinese children 37 and better than African Americans 5 who share similar racial origin with our patients is unclear. Compared with other studies (21-41%), 8,36,37 our relapse rate (14.3%) was much lower. Our disease activity (28.6%) is similar to that in Egyptian (22.2%), 8 but higher than in Serbian children (7.5%).…”

Long-Term Efficacy and Safety of Quadruple Therapy in Childhood Diffuse Proliferative Lupus Nephritis

“…[2,3,11] Diffuse proliferative lupus glomerulonephritis is the most common and the most severe histologic type of lupus nephritis, occurring in 40-75% of children with SLE. [11][12][13][14][15] In our study, DPLN was also found to occur in 56.5% of all patients, being the most common type of lupus nephritis.…”

“…[15,17] The most widely used intravenous cyclophosphamide regimen consists of monthly infusions with 500-1,000 mg/m 2 doses for six months, followed by 2-4 monthly infusions for 18-24 months. [13,[17][18][19][20][21] Compared with daily oral cyclophosphamide (1-3 mg/kg/day), the intravenous route has been accepted to have the advantage of less severe side effects, like cystitis and bladder cancer, as the cumulative doses are smaller. [17] However, not all investigators encounter such difficulties if the daily oral dose of cyclophosphamide does not exceed 1.5 mg/kg/day and daily treatment does not exceed 4-6 months.…”

“…[3][4][5] In the literature, the studies on the prognosis of childhood SLE are limited, and they mostly include all types of SLE nephritis. [11,13,21,30,34,35] Barbano et al [21] reported the outcome of 33 patients with childhood-onset SLE and compared the effects of treatment of monthly intravenous cyclophosphamide with corticosteroids alone or combined with azathioprine. They found that survival was better and protection of renal function lasted longer in the former group without evident short-or long-term side effects.…”

The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis

“…However, the high prevalence of serious adverse effects has been of concern, particularly in children and adolescents [4,13,[23][24][25][26][27][28][29]. The toxic effects of IV CYC often depend on the Fig.…”