Treatment of high-risk relapsed Wilms tumor with dose-intensive chemotherapy, marrow-ablative chemotherapy, and autologous hematopoietic stem cell support: experience by the Italian Association of Pediatric Hematology and Oncology.
BACKGROUND
We evaluated an intensified chemotherapy strategy in children with Wilms tumor who relapsed with high-risk features.


METHODS
From January 2001 to June 2006, we treated 20 consecutive children with reinduction chemotherapy (using ifosfamide/carboplatin/etoposide in 15/20 cases), with (n = 15) or without (n = 5) subsequent high-dose chemotherapy and hematopoietic stem cell support, surgery where feasible, and radiation therapy. The median time to relapse was 10 months after nephrectomy. All but two children initially received doxorubicin as first-line therapy.


RESULTS
All patients were assessed for outcome: 13 are currently alive, 12 of them in remission a median 25 months since their relapse, one with progressing tumor. The treatment was unsuccessful in eight children: the disease progressed during reinduction in three, and relapsed in five. There was one toxic death. All transplanted patients engrafted to a neutrophil count >0.5 x 10(3)/microl after a median 11 days, and to an unsustained platelet count >25,000/microl after a median of 13 days. Three-year disease-free and overall survival rates were 56 +/- 12% and 55 +/- 13%, respectively. Neither recurrence within 12 months of nephrectomy nor extra-lung recurrence negatively affected outcome. A survival advantage was demonstrated in patients without disease evidence prior to transplant.


CONCLUSIONS
A disease-free survival rate nearing 50% is a realistic target in children with high-risk recurrent Wilms tumor. The benefit of autologous hematopoietic stem cell transplantation for consolidation deserves to be investigated in a randomized, controlled study.
Spreafico
Filippo
F
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. filippo.spreafico@istitutotumori.mi.it
Bisogno
Gianni
G
Collini
Paola
P
Jenkner
Alessandro
A
Gandola
Lorenza
L
D'Angelo
Paolo
P
Casazza
Gabriella
G
Piva
Luigi
L
Luksch
Roberto
R
Perotti
Daniela
D
Pession
Andrea
A
Fagioli
Franca
F
Dallorso
Sandro
S
D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D009392:Nephrectomy; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000401:mortality / Q000628:therapy*
D000970:Antineoplastic Agents