To assess complete remission before subjecting nongermline metastatic
retinoblastoma patients to an autologous peripheral stem cell transplant, we tested for patient-specific
retinoblastoma tumor suppressor gene (RB1) mutant alleles in cerebrospinal fluid (CSF) and bone marrow. In 1 child with CSF and 1 with bone marrow
metastases, allele-specific polymerase chain reaction (AS-PCR) detected the biallelic RB1 mutations specific to their
tumors. The
tumor of Child A was homozygous for R251X, and in Child B, it was homozygous for R358X. In Child A, the R251X mutation was detected in mutant controls diluted to 1:12,800 but not in CSF samples, corroborating clinical remission after
chemotherapy. In Child B's bone marrow, AS-PCR for R358X was strongly positive at the detection of relapse, and subsequent bone marrow samples corroborated clinical remission after
chemotherapy. No mutant
tumor RB1 alleles were detected in their harvested peripheral blood stem cells. Both children were deemed suitable candidates for supralethal-dosage
consolidation chemotherapy followed by autologous peripheral stem cell rescue of the bone marrow aimed at curing their metastatic
retinoblastoma. When Child A recurred, the mutant
tumor RB1 allele was detected 3.5 months before conventional pathology detected
retinoblastoma tumor cells in the CSF. Assaying
tumor-specific RB1 mutations complements cytological and immunohistochemical assessment of
retinoblastoma involvement of CSF and bone marrow.
Tumor cells can be detected in numbers lower than possible by conventional methods. An early diagnosis of relapse may allow an early institution of new
therapy. A prospective international multicenter trial of the rare patients with metastatic
retinoblastoma would assess the role of molecular monitoring in surveillance for
minimal residual disease and recurrence.