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Successful double autografts for patients with relapsed clear cell sarcoma of the kidney

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K Yumura-Yagi
K Yumura-Yagi
K Yumura-Yagi
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M Inoue
M Inoue
M Inoue
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R Wakabayashi
R Wakabayashi
R Wakabayashi
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S Mabuchi
S Mabuchi
S Mabuchi
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Abstract and Figures

Although the prognosis of clear cell sarcoma of the kidney (CCSK) has improved, when metastases occur the probability of cure is very low. We have treated two pediatric patients with relapsed CCSK, one with multiple bone metastases and another with brain metastases. After one or two courses of re-induction chemotherapy and radiation therapy to the sites of metastasis, they received double high-dose chemotherapy with autologous bone marrow rescue. Conditioning regimens were ifosphamide plus melphalan for the first autograft and busulfan plus thiotepa for the second. Hematological recovery was prompt, and no severe complications were observed. They are doing well without evidence of recurrence at 19 and 49 months after the second autograft, respectively.
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Bone Marrow Transplantation, (1998) 22, 381–383
1998 Stockton Press All rights reserved 0268–3369/98 $12.00
http://www.stockton-press.co.uk/bmt
Case report
Successful double autografts for patients with relapsed clear cell
sarcoma of the kidney
K Yumura-Yagi
1
, M Inoue
1
, R Wakabayashi
2
, S Mabuchi
2
, M Nakayama
3
, A Yoneda
4
, K Imura
4
and K Kawa-Ha
1
1
Department of Pediatrics,
3
Department of Pathology,
4
Department of Pediatric Surgery, Osaka Medical Center and Research
Institute for Maternal and Child Health, Osaka; and
2
Division of Hematology/Oncology, Hyogo Children’s Hospital, Hyogo, Japan
Summary:
Although the prognosis of clear cell sarcoma of the kid-
ney (CCSK) has improved, when metastases occur the
probability of cure is very low. We have treated two
pediatric patients with relapsed CCSK, one with mul-
tiple bone metastases and another with brain metast-
ases. After one or two courses of re-induction chemo-
therapy and radiation therapy to the sites of metastasis,
they received double high-dose chemotherapy with
autologous bone marrow rescue. Conditioning regimens
were ifosphamide plus melphalan for the first autograft
and busulfan plus thiotepa for the second. Hematolog-
ical recovery was prompt, and no severe complications
were observed. They are doing well without evidence of
recurrence at 19 and 49 months after the second auto-
graft, respectively.
Keywords: clear cell sarcoma of the kidney (CCSK);
bone marrow transplantation; childhood
Clear cell sarcoma of the kidney (CCSK) was first
described by Kidds
1
in 1970, and its histologic character-
istics were defined thereafter.
2,3
It was also called bone-
metastasizing renal tumor of childhood by Marsden et al
2
due to its unusual pattern of spread.
Investigation of the efficacy of therapies for CCSK in the
National Wilms’ Tumor Study (NWTS)-1, NWTS-2 and
NWTS-3 revealed that addition of doxorubicin to the com-
bination of vincristine plus dactinomycin improved the 6-
year relapse-free survival rate of this tumor.
3
However,
about one-third of children with CCSK died due to treat-
ment failure. The prognosis for relapsed cases is very poor
and no convincing treatment strategy has been thus far
established.
4
We present two patients with CCSK relapsing
during the treatment of NWTS-3 who received intensive
treatments including double autografts. They have
remained in second remission longer than first remission.
Correspondence: K Yumura-Yagi, Department of Pediatrics, Osaka Medi-
cal Center and Research Institute for Maternal and Child Health, 840
Murodo-cho, Izumi, Osaka, 594–1101, Japan
Received 24 November 1997; accepted 30 March 1998
Case reports
Case 1
A 22-month-old boy presented in April 1992 with a history
of vomiting and abdominal distention. A CT scan showed
a large mass in the left renal fossa. Bone marrow aspiration,
CT scan of the lung and brain, and bone scintigrams
showed no metastases. A left radical nephrectomy was car-
ried out and the resected kidney contained a large tumor
which weighed 710 g and measured 11.2 ×11 ×8.9 cm.
Microscopic examination showed nests or cords of cells
separated by a network of small capillaries. The nuclei of
the tumor cells were finely granular, imparting an ‘empty’
appearance compatible with CCSK.
Chemotherapy consisting of 10 doses of vincristine
(VCR) weekly, 5 days of dactinomicin (AMD) in the first
week and 3 days of doxorubicin (DOX) in the sixth week,
and two alternating sequences: AMD on days 1–5 com-
bined with VCR on days 1 and 5, and DOX on days 1–3
repeated every 6 weeks for 65 weeks was started on 19
May 1992 after 10.5 Gy of radiation to the left abdomen.
In February 1993, tumors of the skull were detected, and
bone scintigrams revealed multiple high-uptake regions,
three in the skull (frontal and left parietal bones) and one
in the distal end of the left femur. X-ray of the left femur
showed a large defect of the bone with a fracture at the
distal end. A CT scan of the lung, ultrasound examination
of the abdomen and bone marrow aspiration revealed no
other sites of metastasis. Chemotherapy consisting of
100 mg/m
2
of etoposide (VP-16), 10 mg/m
2
of 4′-O-tetra-
hydropyranyladriamycin (THP) and 20 mg/m
2
of cisplatin
(CDDP) on days 1–5 was started, and the size of the tumors
in the skull reduced promptly. After one course of chemo-
therapy, his unpurged marrow was collected and stored.
Twenty-five Gy of radiation were given to the regions of
the skull and femur after two courses of chemotherapy. He
underwent double high-dose chemotherapy with autologous
bone marrow rescue in June and September of 1993. Con-
ditioning regimens were ifosphamide (IFO) plus melphalan
(L-PAM) for the first autograft, and busulfan (BU) plus
thiotepa (TT) for the second one, as shown in Table 1.
Biopsy of the frontal bone was carried out in July 1993,
but no viable tumor cells were detected. Hematological
Double autografts for CCSK
K Yumura-Yagi
et al
382
Table 1 Summary of double grafts in two cases
Case 1 Case 2
1st graft 2nd graft 1st graft 2nd graft
Conditioning regimen ifosfamide +melphalan
a
busulfan +thiotepa
b
ifosfamide +melphalan
a
busulfan +thiotepa
b
Date of graft 7/6/1993 8/9/1993 7/11/1995 1/3/1996
Infused MNC dose 1.9 ×10
8
/kg 1.9 ×10
8
/kg 6 ×10
7
/kg 5.8 ×10
7
/kg
Hematological recovery
Neutrophil ⬎500/
␮
l day 11 day 12 day 17 day 17
Reticulocyte ⬎1% day 14 day 6 day 41 day 31
Platelet ⬎50 000/
␮
l day 18 day 37 day 41 day 46
Complications
Febrile duration 3 days 5 days 0 0
Liver dysfunction no no no no
Renal dysfunction no no no no
a
Ifosfamide 2.5 g/m
2
on day −7 to day −3, melphalan 140 mg/m
2
on day −3 and 70 mg/m
2
on day −2.
b
Busulfan 1.25 mg/kg 4 times a day on day −8 to day −5, thiotepa 200 mg/m
2
twice a day on days −4 and −3.
MNC =mononuclear cell.
recovery was prompt and no severe complications were
observed (Table 1). The patient is in complete remission
more than 49 months after the second megatherapy.
Case 2
A 9-month-old boy presented in May 1993 with abdominal
distention. A CT scan revealed a large left renal tumor,
and nephrectomy was carried out on 3 June 1993. Ascites
containing tumor cells were present, and separation of the
tumor from the descending colon was difficult. Microscopic
examination yielded the same findings as case 1, and a
diagnosis of stage III CCSK was made. After 24 Gy of
radiation therapy to the left abdomen, chemotherapy
according to course DD of NWTS-3 was started. In May
1994 his bone marrow was collected and stored, and
chemotherapy was continued until August 1994. The
patient became drowsy with vomiting in April 1995 and a
CT scan showed a large tumor in the left side of the brain.
A CT scan of the lung and abdomen, bone scintigrams and
bone marrow aspiration revealed no other sites of metasta-
sis. After administering 60 Gy of radiation therapy, the
brain tumor was completely resected. One course of chemo-
therapy consisting of VP-16 100 mg/m
2
on days 1–5, IFO
1 g/m
2
on days 1–4 and carboplatin (CBDCA) 600 mg/m
2
on day 5 was administered. In August 1995 the patient
bumped his head, resulting in a subdural hematoma. This
was removed, with no evidence of tumor cells. He received
double autografts with the same conditioning regimens as
for case 1, in November 1995 and February 1996, respect-
ively. He has been in complete remission for 19 months
since the second autograft.
Discussion
CCSK is recognized as a neoplasm distinct from Wilms’
tumor because of its histological characteristics and its
unique pattern of spread. Many investigators have noted
its poor prognosis. The clinical characteristics and natural
history of CCSK are as follows. Young children under 3
years old are affected, and metastases are rarely present at
onset. However, many patients develop metastases,
especially of the bone and brain, within several years.
The NWTS-III study demonstrated that chemotherapy
consisting of AMD, VCR and DOX, with addition of radi-
ation therapy to the tumor bed, improved the 6-year sur-
vival rate up to 71.9%.
3
However, cure of relapsed cases
is very difficult, and 3-year survival after relapse in Wilms’
tumors with unfavorable histology is only 7–15%.
4
We
treated two relapsed cases with intensive treatments includ-
ing double autografts. High-dose chemotherapy with auto-
logous bone marrow transplantation (ABMT) has been per-
formed for advanced or relapsed malignant solid tumors in
children. However, the efficacy of high-dose chemotherapy
for Wilms’ tumors with unfavorable histology remains
unclear. The European Bone Marrow Transplantation Solid
Tumor Registry presented 25 cases with a relapsed Wilms’
tumor who received high-dose therapy followed by
ABMT.
5
The report included six cases with an unfavorable
histology, but their precise histologic types were not shown.
Only one case with an unfavorable histology is alive with-
out recurrence at 36 months after ABMT. More recently,
a Swedish group reported four cases of relapsed Wilms’
tumor including one case of CCSK treated by ABMT, and
the case of CCSK sustained a further relapse.
6
Which agents other than dactinomycin, VCR and DOX
are effective for CCSK? A phase II trial of IFO and VP-
16 in relapsed cases suggested its efficacy.
7
In the present
cases, chemotherapy consisting of THP, VP-16 and CDDP
reduced the size of tumors in the skull of case 1. Although
the effects of CBDCA and CDDP on CCSK are obscure,
our findings suggest that combination with THP, VP-16 and
CDDP may be effective for CCSK. We have used L-PAM,
IFO, TT and BU in double grafts for high-risk neuroblas-
toma without severe complications, and obtained good
results.
8
The efficacy of these agents, other than IFO, for
CCSK is unknown. However, L-PAM has been widely used
for pediatric malignancies, and looks promising. High-dose
TT has also recently been used for both adult and pediatric
malignancies, such as melanoma, lymphoma, breast cancer,
neuroblastoma and leukemia. Saarinen et al
9
reported that
Double autografts for CCSK
K Yumura-Yagi
et al
383
one relapsed case of Wilms’ tumor with unfavorable his-
tology achieved complete remission after high-dose TT
with ABMT. High-dose therapy with BU combined with
cyclophosphamide is usually used for hematological malig-
nancies. The results of a phase II study of this therapy for
pediatric solid tumors showed efficacy in neuroblastoma,
non-Hodgkin’s lymphoma and rhabdomyosarcoma.
10
Although Wilms’ tumors were not included in the report,
BU is suggested to be a useful agent for pediatric malignant
solid tumors.
Based on these findings and our experience, we perfor-
med double grafts in the present cases. Since late relapse
in cases with CCSK have been reported, longer follow-up
is required to prove cure. However, complete remission has
continued for more than 4 years in one of the present cases
and the remission duration of the other case exceeds his
first remission period. We suggest that this strategy is a
good one for CCSK.
References
1 Kidds JM. Exclusion of certain renal neoplasms from the cate-
gory of Wilms tumor. Am J Pathol 1970; 59: 16a (Abstr.).
2 Marsden HB, Lennox EL, Lawler W et al. Bone-metastasizing
renal tumor of childhood. Br J Cancer 1978; 38: 437–441.
3 Green DM, Breslow NE, Beckwith JB et al. Treatment of chil-
dren with clear-cell sarcoma of the kidney: a report from the
National Wilms’ Tumor Study Group. J Clin Oncol 1994; 12:
2132–2137.
4 Grundy P, Breslow N, Green DM et al. Prognostic factors for
children with recurrent Wilms’ tumor: results from the second
and third National Wilms’ Tumor Study. J Clin Oncol 1989;
7: 638–649.
5 Garaventa A, Hartmann O, Bernard J-L et al. Autologous bone
marrow transplantation for pediatric Wilms’ tumor: the experi-
ence of European Bone Marrow Transplantation Solid Tumor
Registry. Med Pediat Oncol 1994; 22: 11–14.
6 Kullendorff CM, Bekassy AN. Salvage treatment of relapsing
Wilms’ tumour by autologous bone marrow transplantation.
Eur J Pediatr Surg 1997; 7: 177–179.
7 White L, McCowage G, Kannourakis G et al. Dose-intensive
cyclophosphamide with etoposide and vincristine for pediatric
solid tumors: a phase I/II pilot study by the Australia and New
Zealand Childhood Cancer Study Group. J Clin Oncol 1994;
12: 522–531.
8 Kawa-Ha K, Yumura-Yagi K, Inoue M et al. Results of single
and double autografts for high-risk neuroblastoma patients.
Bone Marrow Transplant 1996; 17: 957–962.
9 Saarinen US, Hovi L, Makiperna A et al. High-dose thiotepa
with autologous bone marrow rescue in pediatric solid tumors.
Bone Marrow Transplant 1991; 8: 369–376.
10 Hartmann O, Benhamou E, Beaujean F et al. High-dose busul-
fan and cyclophosphamide with autologous bone marrow
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a phase II study. J Clin Oncol 1986; 4: 1804–1410.
... Up until now, only three descriptive reports on clinical characteristics, treatment and outcome of relapsed CCSK have been published, including 11 patients in total (Table 1) (Kusumakumary et al, 1997;Yumura-Yagi et al, 1998;Radulescu et al, 2008). Therefore, data on clinical features of these patients are scarce and the contribution of chemotherapy, surgery, radiotherapy and highdose chemotherapy followed by ABMT to optimal treatment of relapsed CCSK has not been established as yet. ...
... Intensive treatment, including chemotherapy as well as achieving local control by complete surgery (where possible) and/or radiotherapy, seems to enhance consolidation of second CR. Summarising our study and previous reports, in total 24 relapsed CCSK patients received high-dose chemotherapy followed by ABMT, of which 12 patients (50%) were alive without disease after a median follow-up of 52 months (range, 9-103 months) (Kullendorff and Bekassy, 1997;Pein et al, 1998;Yumura-Yagi et al, 1998;Radulescu et al, 2008;Furtwängler et al, 2013). This seems to be promising, although it should be emphasised that this high-dose chemotherapy is mostly applied in a selected group of patients who already achieved a second CR. ...
Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: A combined SIOP and AIEOP study
Article
Full-text available
  • Jun 2014
Background: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. Patients and methods: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. Results: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%–32%), and 5-year overall survival (OS) was 26% (95% CI: 10%–42%). Conclusions: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.
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... There are only few therapy recommendations available, and an optimal treatment strategy has not yet been determined. 1 15 Overall, only half of the survivors were treated with high-dose chemotherapy. One of our patients received intrathecal mafosphamide, its benefit remains unclear, but it might be discussed in multilocular cerebral metastasis. ...
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Introduction Clear cell sarcoma of the kidney (CCSK) is a rare malignant childhood renal tumour. Recently, the central nervous system (CNS) was found to be the most frequent site of relapse associated with a poor outcome. Optimal treatment strategies are scarce. Patients and Methods Retrospective data analysis of all Austrian children with CCSK. They were enrolled in the Austrian‐Hungarian Wilms Tumour Study (AHWTS) 1989, the SIOP93‐01 or the SIOP2001 study between 1990 and 2019. Demographic, diagnostic, treatment‐related variables and survival data were analysed. Results We identified 12 children with CCSK (M = 7, F = 5; median age 1.6 years). All had localised disease (stage I: 2; stage II: 2; stage III: 8) at diagnosis, and a first complete remission (CR1) was achieved in 12/12. Six patients are in an ongoing CR1 (median follow‐up 10 years). Six other patients had a relapse (local 1; brain 5) a median time of 2.4 years from diagnosis. Two patients died of the disease 4 months and 2.8 years after first relapse. Four of five patients with CNS relapse are in CR2 with a median follow‐up time of 9.3 years after relapse diagnosis. Relapse treatment included a combination of chemotherapy, radiation and surgery. Two children received high‐dose chemotherapy followed by autologous stem cell rescue, and one child received intrathecal mafosphamide. Long‐term side effects after treatment were impaired tubular renal function (n = 4), cardiomyopathy (n = 1) and growth disorders (n = 1). Conclusions In this series, the brain was the most common site of relapse. Long‐term survival after recurrence was achievable with intensive multimodal therapy.
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... One case has fever and increased micturition also noted. Other symptoms that have been described are hematuria, vomiting, decreased oral intake, constipation and hypertension [21][22][23][24][25] in other studies which were absent in my study series. Some study suggested a predilection for involvement of the right kidney, in my study case 2 out 3 showed right predilection. ...
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Overall survival nomogram and relapse-related factors of clear cell sarcoma of the kidney: A study based on published patients
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Background Rarity limits the breadth of study on clear cell sarcoma of the kidney (CCSK). There is currently no predictive model that quantifies the overall survival (OS) of CCSK and a few large sample-based analysis of relapse-related factors. Methods Patients were collected both from the Surveillance, Epidemiology, and End Results (SEER) database and case report articles extracted from the global online document database to form 2 groups. The first was the OS group, which was used to build and verify the nomogram for predicting the OS of CCSK. Independent predictors of OS were screened by Cox regression analysis to develop the nomogram. Nomogram accuracy was assessed by C-index, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) curves. In addition, the difference in OS between receiving radiotherapy or not in stage I patients was analyzed by the Chi-square test. The second was the relapse group, which was used to analyze the relapse-related factors by Cox regression analysis and the Kaplan–Meier method with the log-rank test. Result 256 patients were included in the OS group. The stage, chemotherapy, and radiotherapy were independent OS-related factors of CCSK, and the nomogram for predicting the OS of CCSK was established based on them. The results of the C-index, ROC, calibration, and DCA curves showed that the nomogram has good discrimination, accuracy, and clinical profitability. The Chi-squared test showed no significant difference in OS with receiving radiotherapy or not in stage I patients. The relapse group included 153 patients, of which 60 relapsed. The univariate Cox regression analysis showed no correlation between radiotherapy and relapse. The multivariate Cox regression analysis showed that stage and surgery/chemotherapy sequence were the independent factors for relapse. The log-rank test of seven chemotherapeutic drugs showed that etoposide (E), cyclophosphamide (C), vincristine (V), and doxorubicin (D) (all P < 0.05) had significant differences in preventing relapse, and then drew the relapse-free survival curves of these four drugs. Conclusion Our nomogram accurately quantified the OS of CCSK. There was no significant difference in OS between receiving radiotherapy or not in stage I patients. Stage, surgery/chemotherapy sequence, and the use of ECVD were relapse-related factors. Radiotherapy had no significant contribution to preventing relapse.
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Position paper: Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol
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The International Society of Paediatric Oncology–Renal Tumour Study Group (SIOP–RTSG) has developed a new protocol for the diagnosis, treatment, and follow-up monitoring of childhood renal tumours — the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). This protocol has been designed to continue international collaboration in the treatment of childhood renal tumours and will be implemented in over 50 different countries. Clear cell sarcoma of the kidney, which is a rare paediatric renal tumour that most commonly occurs in children between 2 and 4 years of age, is specifically addressed in the UMBRELLA protocol.
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  • Aug 2013
  • COCHRANE DB SYST REV
BACKGROUND: Soft tissue sarcomas (STS) are a highly heterogeneous group of rare malignant solid tumors. Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) comprise all STS except rhabdomyosarcoma. In patients with advanced local or metastatic disease, autologous hematopoietic stem cell transplantation (HSCT) applied after high-dose chemotherapy (HDCT) is a planned rescue therapy for HDCT-related severe hematologic toxicity. The rationale for this update is to determine whether any randomized controlled trials (RCTs) have been conducted and to clarify whether HDCT followed by autologous HSCT has a survival advantage. OBJECTIVES: To assess the effectiveness and safety of HDCT followed by autologous HSCT for all stages of non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) in children and adults. SEARCH METHODS: For this update we modified the search strategy to improve the precision and reduce the number of irrelevant hits. All studies included in the original review were considered for re-evaluation in the update. We searched the electronic databases CENTRAL (2012, Issue 11) in The Cochrane Library , MEDLINE and EMBASE (05 December 2012) from their inception using the newly developed search strategy. Online trials registers and reference lists of systematic reviews were searched. SELECTION CRITERIA: Terms representing STS and autologous HSCT were required in the title or abstract. In studies with aggregated data, participants with NRSTS and autologous HSCT had to constitute at least 80% of the data. Single-arm studies were included in addition to studies with a control arm because the number of comparative studies was expected to be very low. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted study data. Some studies identified in the original review were re-examined and found not to meet the inclusion criteria and were excluded in this update. For studies with no comparator group, we synthesized the results for studies reporting aggregate data and conducted a pooled analysis of individual participant data using the Kaplan-Meyer method. The primary outcomes were overall survival (OS) and treatment-related mortality (TRM). MAIN RESULTS: The selection process was carried out from the start of the search dates for the update. We included 57 studies, from 260 full text articles screened, reporting on 275 participants that were allocated to HDCT followed by autologous HSCT. All studies were not comparable due to various subtypes. We identified a single comparative study, an RCT comparing HDCT followed by autologous HSCT versus standard chemotherapy (SDCT). The overall survival (OS) at three years was 32.7% versus 49.4% with a hazard ratio (HR) of 1.26 (95% confidence interval (CI) 0.70 to 2.29, P value 0.44) and thus not significantly different between the treatment groups. In a subgroup of patients that had a complete response before treatment, OS was higher in both treatment groups and OS at three years was 42.8% versus 83.9% with a HR of 2.92 (95% CI 1.1 to 7.6, P value 0.028) and thus was statistically significantly better in the SDCT group. We did not identify any other comparative studies. We included six single-arm studies reporting aggregate data of cases; three reported the OS at two years as 20%, 48%, and 51.4%. One other study reported the OS at three years as 40% and one further study reported a median OS of 13 months (range 3 to 19 months). In two of the single-arm studies with aggregate data, subgroup analysis showed a better OS in patients with versus without a complete response before treatment. In a survival analysis of pooled individual data of 80 participants, OS at two years was estimated as 50.6% (95% CI 38.7 to 62.5) and at three years as 36.7% (95% CI 24.4 to 49.0). Data on TRM, secondary neoplasia and severe toxicity grade 3 to 4 after transplantation were sparse. The one included RCT had a low risk of bias and the remaining 56 studies had a high risk of bias. AUTHORS' CONCLUSIONS: A single RCT with a low risk of bias shows that OS after HDCT followed by autologous HSCT is not statistically significantly different from standard-dose chemotherapy. Therefore, HDCT followed by autologous HSCT for patients with NRSTS may not improve the survival of patients and should only be used within controlled trials if ever considered.
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Bone-Metastasizing renal tumor of childhood
Article
Full-text available
  • Oct 1978
A primary renal tumour of childhood with histological appearances different from the nephroblastoma is described. This neoplasm, predominantly seen in boys, has a tendency to metastasize to bone. Such metastases are considered to be rare in nephroblastoma and this aspect in studies of Wilms' tumour series is thought to be due, for the most part, to the inclusion of a particular bone-metastasizing tumour in the material. Images Fig. 1 Fig. 2
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Treatment of children with clear-cell sarcoma of the kidney: a report from the National Wilms' Tumor Study Group
Article
  • Oct 1994
Purpose: To evaluate the effect of the sequential addition of doxorubicin (DOX) and cyclophosphamide (CTX) to the combination of vincristine (VCR) and dactinomycin (AMD) on the relapse-free survival of children with clear-cell sarcoma of the kidney (CCSK). Patients and methods: We determined the 6-year relapse-free survival rate for patients with CCSK treated on National Wilms' Tumor Study (NWTS)-1, NWTS-2, or NWTS-3 with the combination of VCR and AMD, with or without DOX, and for patients treated on NWTS-3 with the combination of VCR, AMD, and DOX with (regimen J) or without (regimen DD-RT) CTX. Results: The 6-year relapse-free survival rate for the eight children with CCSK treated with VCR, AMD, and radiation therapy was 25.0%, compared with 63.5% for the 58 children treated with VCR, AMD, DOX, and radiation therapy (P = .09). The 6-year relapse-free survival rate for children with CCSK treated on regimen DD-RT was 64.6%, compared with 58.2% for those treated on regimen J (P = .79). Conclusion: We conclude that the addition of DOX to the combination of VCR plus AMD appeared to improve the 6-year relapse-free survival rate of children with CCSK. The addition of CTX in the dose and schedule used in NWTS-3 did not improve the 6-year relapse-free survival rate of children with CCSK. Because 30% of relapses occurred more than 2 years after diagnosis, prolonged follow-up evaluation of patients with CCSK is necessary.
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Autologous bone marrow transplantation for pediatric Wilms' tumor: The experience of the European bone marrow transplantation solid tumor registry
Article
  • Jan 1994
  • Med Pediatr Oncol
This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary. © 1994 Wiley-Liss, Inc.
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High-dose thiotepa with autologous bone marrow rescue in pediatric solid tumors (Abstr)
Article
  • Dec 1991
  • BONE MARROW TRANSPL
High-dose thiotepa was given as a single agent at a total dose of 1125 mg/m2 with autologous bone marrow rescue to nine patients with recurrent/refractory/poor risk pediatric malignancies (primitive neuroepithelial tumor (PNET), two; neuroblastoma, one; Wilms' tumor, one; osteosarcoma, one; Ewing's sarcoma one, Hodgkin's disease one, high-grade glioma, two). The response rate in these heavily pretreated patients was 71% (five out of seven evaluable patients) including two complete responses (Wilms', glioma), three partial responses (osteosarcoma, Ewing's sarcoma, Hodgkin's disease), and two with stable disease (PNET, glioma). The median duration of response was 2.5 months. The extramedullary toxicity was acceptable with symptoms mainly of skin and gastrointestinal tract. The data indicate that high-dose thiotepa is effective in several types of recurrent pediatric solid tumors, and merits further evaluation in combination regimens.
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Prognostic factors for children with recurrent Wilms' tumor: Results from the Second and Third National Wilms' Tumor Study
Article
  • Jun 1989
The characteristics of 367 stage I-IV National Wilms' Tumor Study (NWTS) children who relapsed after initial treatment for unilateral disease in the second and third NWTS trials (NWTS-2 and -3) were analyzed to identify features predictive of survival. Although modifications in initial therapy resulted in a lower rate of first relapse in these two studies compared with NWTS-1, all previously identified prognostic factors after relapse remained statistically significant predictors of survival. Tumor histology, length of initial remission, initial therapy with two v three drugs, and site of relapse each were independently predictive of postrelapse survival. The 3-year postrelapse survival for all 367 patients was 30% +/- 3%; however, subgroups classified by these prognostic factors were identified that had 3-year postrelapse survival rates of greater than 40%. These subgroups included patients who had tumors of favorable histology (FH) that recurred (1) only in the lungs, (2) in the abdomen when radiotherapy (RT) was not initially given, or (3) that were originally stage I, (4) that were originally treated with only two drugs, or (5) that recurred 12 months or more after diagnosis. These results were achieved with the use of standard treatments, ie, surgery, RT, and chemotherapy using dactinomycin (AMD), vincristine (VCR), and Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH). It is suggested that patients in these groups might be managed with aggressive use of conventional therapies until newer chemotherapeutic agents and drug combinations are shown to be more effective. Patients with adverse prognostic features at relapse have a poor survival expectancy with standard measures. Salvage attempts for these patients are better based on experimental approaches.
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High-dose busulfan and cyclophosphamide with autologous bone marrow transplantation support in advanced malignancies in children: A phase II study
Article
  • Jan 1987
Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.
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Green DM, Breslow NE, Beckwith JB, Moksness J, Finklestein JZ, D’Angio GJTreatment of children with clear-cell sarcoma of the kidney: a report from the National Wilms’ Tumor Study Group. J Clin Oncol 12: 2132-2137
Article
  • Nov 1994
To evaluate the effect of the sequential addition of doxorubicin (DOX) and cyclophosphamide (CTX) to the combination of vincristine (VCR) and dactinomycin (AMD) on the relapse-free survival of children with clear-cell sarcoma of the kidney (CCSK). We determined the 6-year relapse-free survival rate for patients with CCSK treated on National Wilms' Tumor Study (NWTS)-1, NWTS-2, or NWTS-3 with the combination of VCR and AMD, with or without DOX, and for patients treated on NWTS-3 with the combination of VCR, AMD, and DOX with (regimen J) or without (regimen DD-RT) CTX. The 6-year relapse-free survival rate for the eight children with CCSK treated with VCR, AMD, and radiation therapy was 25.0%, compared with 63.5% for the 58 children treated with VCR, AMD, DOX, and radiation therapy (P = .09). The 6-year relapse-free survival rate for children with CCSK treated on regimen DD-RT was 64.6%, compared with 58.2% for those treated on regimen J (P = .79). We conclude that the addition of DOX to the combination of VCR plus AMD appeared to improve the 6-year relapse-free survival rate of children with CCSK. The addition of CTX in the dose and schedule used in NWTS-3 did not improve the 6-year relapse-free survival rate of children with CCSK. Because 30% of relapses occurred more than 2 years after diagnosis, prolonged follow-up evaluation of patients with CCSK is necessary.
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Dose-intensive cyclophosphamide with etoposide and vincristine for pediatric solid tumors: A phase I/II pilot study by the Australia and New Zealand Childhood Cancer Study Group
Article
  • Apr 1994
This pilot study of the Australia and New Zealand Childhood Cancer Study Group investigated the effectiveness and toxicity of a regimen incorporating vincristine (VCR), etoposide, and divided-dose, escalating cyclophosphamide (CPA) (VETOPEC) in 23 patients aged 1 to 20 years with solid tumors. Seventeen patients (group A) had recurrent or refractory tumors after prior multiagent therapy, and six patients (group B) with adverse prognostic indicators were treated at initial presentation. Treatment cycles were 21 to 28 days and consisted of vincristine (0.05 mg/kg) on days 1 and 14, with etoposide (2.5 mg/kg/d) plus escalating CPA on days 1, 2, and 3. The CPA dosage was escalated from 30 mg/kg/d in cycle no. 1 by 5 mg/kg/d in each cycle to a maximum of 55 mg/kg/d in cycle no. 6. Of 20 patients assessable for tumor response, 19 (95%) responded after two to six cycles of VETOPEC: seven complete responses (CRs); eight very good partial responses (VGPRs); and four partial responses (PRs). In group A, 13 of 14 (93%) assessable patients responded (five CRs, four VGPRs, four PRs), and in group B, five stage IV and one stage III patient achieved two CRs and four VGPRs. The principal toxicity was myelosuppression. Grade IV neutropenia occurred after 98% of cycles, and the incidence of grade IV thrombocytopenia increased from 37% after cycle no. 1 to 91% after cycle no. 6 (P = .002). A total of 115 cycles delivered were followed by 62 febrile admissions (54%), and showed a significant rise with increasing cycles (P = .001). One patient died of septicemia. This combination and scheduling produced a high response rate in patients with recurrent, refractory, or advanced solid tumors of childhood. Further studies of this regimen and of strategies to reduce hematologic toxicity are warranted.
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Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry
Article
  • Feb 1994
This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary.
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Results of single and double autografts for high-risk neuroblastoma patients
Article
  • Jul 1996
  • BONE MARROW TRANSPL
Although intensive therapy with autologous bone marrow transplantation (ABMT) has improved the outcome of advanced neuroblastoma, nearly half the patients with this disease still relapse after a single ABMT. In our previous study, 10 of 22 patients relapsed within 16 months post-transplantation. Predictive risk-factors for relapse were the presence of bone lesions at diagnosis, and a minor response or progressive disease at transplantation. In order to improve the outcome of these high-risk patients, we tested the feasibility of double autografts. To date, eight patients have been treated, and no treatment-related deaths were observed. Six remain in CR or with stable disease for 6 to 29 months. Although more cases and longer observation are needed to draw conclusions, these results are encouraging.
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