A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children

Pediatr Nephrol. 2001 Mar;16(3):271-82. doi: 10.1007/s004670000523.


For over 30 years cyclophosphamide (CYC) and chlorambucil (CHL) have been used to treat children with relapsing steroid-sensitive nephrotic syndrome (SSNS). A meta-analysis on treatment protocols, efficacy, and side effects of CYC and CHL was performed from the literature. Thirty-eight studies comprising 1,504 children and 1,573 courses of cytotoxic drug therapy were systematically evaluated. Relapse-free survival rates increased with the cumulative dosage of CHL and CYC and were higher in children with frequently relapsing than steroid-dependent NS. The fatality rate of the treatment was approximately 1%. Leukopenia occurred in one-third of patients treated with either drug. Severe bacterial infections developed in 1.5% of the patients under CYC and in 6.8% under CHL. Seizures were observed in 3.6% of children treated with CHL. Malignancies were observed in 14 children after high doses of either drug. Females rarely developed permanent gonadal damage. However, no safe threshold for a cumulative amount of CYC was found in males, but there was a marked increase in the risk of oligo- or azoospermia with higher cumulative doses. From this meta-analysis we recommend CYC 2-3 mg/kg body weight for 8-12 weeks as the standard scheme. CHL has higher rates of severe side effects and should be considered a second-line drug.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Child
  • Chlorambucil / administration & dosage
  • Chlorambucil / adverse effects
  • Chlorambucil / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Humans
  • Nephrotic Syndrome / complications
  • Nephrotic Syndrome / drug therapy*
  • Recurrence


  • Antineoplastic Agents, Alkylating
  • Chlorambucil
  • Cyclophosphamide