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Klin Padiatr 2014; 226(06/07): 351-356
DOI: 10.1055/s-0034-1390504
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Children with Relapsed or Refractory Nephroblastoma: Favorable Long-term Survival after High-dose Chemotherapy and Autologous Stem Cell Transplantation

Vorteilhaftes Langzeitüberleben von Kindern mit rezidivierten Nephroblastomen nach Hochdosis-Chemotherapie und autologem Stammzellrescue
T. Illhardt   *
1   Department of Pediatric Oncology, University Children’s Hospital, Tuebingen, Germany
,
M. Ebinger   *
2   Department of Pediatric Oncology, University of Saarland, Homburg, Germany
,
C. P. Schwarze
1   Department of Pediatric Oncology, University Children’s Hospital, Tuebingen, Germany
,
T. Feuchtinger
1   Department of Pediatric Oncology, University Children’s Hospital, Tuebingen, Germany
,
R. Furtwängler
2   Department of Pediatric Oncology, University of Saarland, Homburg, Germany
,
P. G. Schlegel
3   Departments of Pediatric Hematology and Oncology, and Stem Cell Transplantation Program, University Children’s Hospital, University of Wuerzburg, Wuerzburg, Germany
,
T. Klingebiel
4   Department of Pediatric Oncology, University Hospital Frankfurt, University of Frankfurt, Frankfurt, Germany
,
J. Greil
5   Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany
,
J. F. Beck
6   Department of Pediatric Hematology and Oncology, University Hospital Jena, Jena Germany
,
R. Handgretinger
1   Department of Pediatric Oncology, University Children’s Hospital, Tuebingen, Germany
,
P. Lang
1   Department of Pediatric Oncology, University Children’s Hospital, Tuebingen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
28 November 2014 (online)

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Abstract

Background: High-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) is a treatment option for pediatric patients with relapsed nephroblastoma. We present long term results of 9 patients treated between 1993 and 2013 at our center.

Procedure: Reinduction therapy was carried out according to GPOH and SIOP recommendations. The conditioning regimen consisted of carboplatin (1 200 mg/m²), etoposide (800 mg/m² or 40 mg/kg) and melphalan (180 mg/m²). Purging of the grafts with immunomagnetic CD34 positive selection was performed in 5 patients.

Results: 8 of 9 Patients (90%) are alive without evidence of disease after a median follow-up of 8.5 years. Leukocyte engraftment occurred after a median of 10 days (range 8–12). Median numbers of 667/µl CD3+, 329/µl CD4+, 369/µl CD8+T cells and 949/µl B cells were reached after 180 days. No negative impact of CD34 selection was observed. No transplantation-related death occurred. Acute toxicity comprised mucositis III°–IV° in all and veno-occlusive disease in one patient. Long term effects probably related to treatment occurred in 3/7 evaluable patients and comprised hearing impairment, reduced renal phosphate reabsorption, mild creatinine elevation and hypothyroidism (n=1, each).

Conclusion: Thus, in our experience HDC with ASCR is an effective treatment of recurrent or refractory nephroblastoma with acceptable side effects. However, a randomized trial proving its efficiency with a high level of evidence is needed.

Zusammenfassung

Hintergrund: Hochdosischemotherapie mit autologem Stammzellrescue ist eine Therapieoption für paediatrische Patienten mit rezidivierten Nephroblastomen. Wir präsentieren Langzeitergebnisse von 9 Patienten, die in den Jahren 1993–2013 in unserem Zentrum auf diese Weise therapiert wurden.

Methods: Reinduktionstherapie wurde nach Empfehlung der SIOPH-GPOH durchgeführt. Das Konditionierungsregime bestand aus Carboplatin (1 200 mg/m²), Etoposid (800 mg/m² oder 40 mg/kg) und Melphalan (180 mg/m²). Immunomagnetische CD-34 positive Selektion wurde bei 5 Patienten durchgeführt.

Results: 8 von 9 Patienten sind nach einem medianen Follow-Up von 8,5 Jahren ohne Nachweis der Erkrankung am Leben. Der Leukozyten-Take wurde im Median nach 10 Tagen erreicht (Range 8–12). Nach 180 Tagen wurden hinsichtlich der Immunrekonstitution im Median 667/µl CD3+Zellen, 329/µl CD4+ Zellen, 369/µl CD8+ Zellen und 949/µl B-Zellen erreicht. Es wurde kein negativer Einfluss auf die Immunrekonstitution durch CD34-Selektion beobachtet. Kein Patient starb an den Nebenwirkungen der Transplantation. Die akuten Nebenwirkungen beinhalten Mukositis °III–°IV bei allen Patienten und veno-occlussive disease (VOD) bei einem Patienten. Langzeitfolgen, die eventuell mit der Therapie in Zusammenhang stehen traten in 3/7 evaluierbaren Patienten auf und beinhalten Hörstörungen, leichte Kreatininerhöhung, Störung der Phosphatrückresorption und Hypothyreodismus (jeweils 1 ×).

Schlussfolgerung: Nach unserer Erfahrung ist Hochdosischemotherapie mit autologem Stammzellrescue eine effektive Therapieoption für rezidivierte und refraktäre Nephroblastome mit tolerablen Nebenwirkungen. Jedoch ist eine große randomisierte Studie notwendig um die Effizienz mit hoher Evidenz beweisen zu können.

Key words

nephrobastoma - stem-cell transplantation - high-dose chemotherapy - Wilm’s disease

Schlüsselwörter

Wilmstumor - Nephoblastom - autologes Stammzellrescue - Hochdosischemotherapie

* Toni Illhardt and Martin Ebinger contributed to this work equally and share first authorship.


 

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