What is Wilms Tumor ?
Wilms tumor, the most common primary malignant renal tumor of childhood, is highly sensitive to chemotherapy and radiation, and current cure rates exceed 85%. Ten to 15% of patients with favorable histology and 50% of patients with anaplastic tumors experience tumor progression or relapse. Similar to newly diagnosed Wilms tumor, relapsed Wilms tumor is a heterogeneous disease, and current treatment strategies stratify intensity and scheduling of the treatment modalities based on prognostic features. For newly diagnosed disease, the most important prognostic features are stage and histology. Similar risk-adapted strategies are being attempted for the 15% of patients who experience relapse. Success rates after relapse range from 25%–45%. For patients with adverse prognostic factors (histologically anaplastic tumors, relapse less than 6–12 months after nephrectomy, second or subsequent relapse, relapse within the radiation field, bone or brain metastases) event-free survival is less than 15%. However, recent trials with HDC and autologous HSCT have reported 3- or 4-year OS rates from 60%–73%.
Hematopoietic Stem-Cell Transplantation (HSCT) in Wilms Tumor.
Most studies of autologous HSCT for high-risk Wilms tumor have been very small series or case reports.[11,13,41] A systematic review and meta-analysis have also been published and comprise the focus of this review.
• The AHRQ review discussed above also addressed HSCT in pediatric patients with Wilms tumor, concluding: Low-strength evidence on overall survival suggests no benefit with single HSCT compared to conventional therapy for the treatment of high-risk relapsed Wilms tumor. 13 –
• A meta-analysis reported on the efficacy of autologous HSCT in recurrent Wilms’ tumor for articles published between 1984 and 2008 that reported survival data. Six studies were included for a total of 100 patients, and patient characteristics and treatment methods were similar across studies, although there was variation in the preparative regimens used.[11,13,41,43-45] Patients were between the ages of 11 months and 16 years, and had similar primary tumor stage, relapse location and time to relapse across studies. The 4-year OS among the 100 patients was 54.1% (42.8-64.1%) and 4-year EFS based on 79 patients was 50.0% (37.9-60.9%). A multivariate analysis found that site of relapse and histology were important predictors for survival, in that patients who did not have a lung-only relapse had more than 3 times the risk of death or recurrence than patients who relapsed in the lungs only, and the patients with unfavorable histology had more than twice the risk of death compared to those with favorable histology (hazard ratios 3.5 and 2.4, respectively). The authors compared the survival rates from these 6 studies in which the patients were treated with autologous HSCT to patients treated with conventional chemotherapy between 1995 and 2002. The authors found that, in general, the chemotherapy treated patients had comparable or improved 4-year survival compared to the HSCT group, however, there was a suggestion that patients with lung-only stage 3 and 4 relapse may benefit from autologous HSCT with a 21.7% survival advantage over the chemotherapy patients (however the ranges were very wide): 4-year OS for the stage 3 and 4 patients with lung only relapse treated with HSCT versus chemotherapy was 74.5% (51.7-87.7%) and 52.8% (29.7-71.5%), respectively.
Evidence on the use of HSCT in treatment of Wilm’s tumor has not firmly established the safety or effectiveness of transplant over standard care. Additional comparative clinical trials are needed to isolate the treatment effect of HSCT, and to establish the patient populations most likely to experience treatment benefit.
Clinical Practice Guidelines
No evidence-based clinical practice guidelines were identified on the use of autologous or allogeneic HSCT in the treatment of Wilms’ tumor.