Long‐term survival after autologous peripheral blood stem cell transplantation in two patients with malignant rhabdoid tumor of the kidney

A 5‐month‐old male with stage II malignant rhabdoid tumor of the kidney (MRTK) and a 24‐month‐old male with stage III MRTK were treated with surgical resection of tumors and chemotherapy of alternating ICE (ifosfamide, carboplatin, and etoposide) and VDC (vincristine, doxorubicin, and cyclophosphamide), followed by high‐dose chemotherapy using etoposide, carboplatin, and melphalan with autologous hematopoietic stem cell transplantation (SCT). Two patients have been alive without any evidence of disease for 30 and 37 months after diagnosis, respectively, and require no medication. Consolidation with SCT should be further studies for selected patients with high‐risk MRTK. Pediatr Blood Cancer 2009;52:888–890. © 2009 Wiley‐Liss, Inc.     

Multimodal treatment including tandem high‐dose chemotherapy and autologous stem cell transplantation in children with anaplastic ependymomas

In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto‐SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto‐SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto‐SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto‐SCT, and 13 subsequently underwent the second HDCT/auto‐SCT. One patient died from hepatic VOD during the second HDCT/auto‐SCT; other toxicities occurring during tandem HDCT/auto‐SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5‐year overall and event‐free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto‐SCT could be a feasible option for improving survival in children with anaplastic ependymomas.     

Treatment of unresectable malignant rhabdoid tumor of the orbit with tandem high-dose chemotherapy and gamma-knife radiosurgery

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that primarily occurs in very young children. We report here a patient with a primary MRT of the orbit who received tandem high-dose chemotherapy and gamma-knife radiosurgery. Although the tumor was not completely removed, and the initial chemotherapy failed, the patient achieved long-term survival after this modality of treatment. This approach may be one to be further considered in patients with MRT.     

High‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation for recurrent primary mediastinal malignant germ cell tumor: A case report

A 15‐yr‐old boy presented with an anterior mediastinal mass, multiple lung metastases and obstruction of the left brachiocephalic vein, the superior vena cava and the subclavian vein. Tumor biopsy by CT guidance confirmed a diagnosis of GCT. Five courses of BEP therapy were performed, and CT of the chest revealed reduction in the anterior mediastinal mass and disappearance of the multiple lung metastases. We performed the anterior mediastinal mass extraction followed by adjuvant chemotherapy consisting of ICE and TIP. However, the AFP levels became elevated soon after. Abnormal accumulation was observed in the right upper lung by DW‐MRI. After the operation, two courses of TI chemotherapy and two courses of HDCT followed by auto‐PBSCT were performed. He was complicated with auditory disorder and renal dysfunction. Although HDCT followed by auto‐PBSCT was effective for the relapsed primary mediastinal GCT, a treatment strategy avoiding late complications is warranted.     

Feasibility and effectiveness of treatment strategy of tandem high‐dose chemotherapy and autologous stem cell transplantation in combination with 131I‐MIBG therapy for high‐risk neuroblastoma

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using ¹³¹I‐MIBG for high‐risk neuroblastoma. Patients with high‐risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received ¹³¹I‐MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high‐risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with ¹³¹I‐MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of ¹³¹I‐MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5‐year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high‐risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with ¹³¹I‐MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment‐related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of ¹³¹I‐MIBG therapy. Tandem HDCT/ASCT combined with HD ¹³¹I‐MIBG therapy could be feasible for patients with high‐risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.     

High‐dose treatment for malignant rhabdoid tumor of the kidney: No evidence for improved survival—The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) experience

1 Background

Malignant rhabdoid tumor of the kidney (MRTK) is the most aggressive childhood renal tumor with overall survival (OS) rates ranging from 22% to 42%. Whether high‐dose chemotherapy with autologous stem‐cell transplantation (HDSCT) in an intensive first‐line treatment offers additional benefit is an ongoing discussion.

2 Methods

A retrospective analysis of all 58 patients with MRTK from Austria, Switzerland, and Germany treated in the framework of consecutive, prospective renal/rhabdoid tumor studies SIOP9/GPO, SIOP93‐01/GPOH (where SIOP is International Society of Pediatric Oncology and GPOH is German Society of Pediatric Oncology and Hematology), SIOP2001/GPOH, and European Rhabdoid Tumor Registry from 1991 to 2014.

3 Results

Median age at diagnosis was 11 months. Fifty percent of patients had metastases or multifocal disease at diagnosis (Stage IV). Local stage distribution was as follows: not done/I/II/III—1/6/11/40. Fifteen (26%) patients underwent upfront surgery. Thirty‐seven (64%) patients achieved a complete remission, 17 (29%) relapsed, 34 (59%) died of disease progression, and two (3%) died of treatment‐related complication. Mean time to the first event was 3.5 months. Two‐year EFS/OS (where EFS is event‐free survival) for the whole group was 37 ± 6%/38 ± 6%. Metastases/multifocal disease, younger age, and local stage III were associated with significantly inferior survival. Eleven (19%) patients underwent HDSCT (carboplatin + thiotepa, n = 6; carboplatin + etoposide + melphalan, n = 4; others, n = 1); 2‐year OS in this group was 60 ± 15% compared to 34 ± 8% in the non‐HDSCT group (P = 0.064). However, the time needed from radiologic to histologic diagnosis, stem‐cell harvest, and HDSCT must also be taken into account to avoid selection bias by excluding the highest risk group with early progression (<90 days). Thus, 2‐year EFS only for patients without progression until day 90 was 60 ± 16% consolidated by HDSCT compared to 62 ± 11% without (P = 0.8).

4 Conclusion

Our retrospective analysis suggests comparable outcomes for patients with and without HDSCT, if adjusted for early disease progression.     

Busulfan and melphalan as consolidation therapy with autologous peripheral blood stem cell transplantation following Children's Oncology Group (COG) induction platform for high‐risk neuroblastoma: Early results from a single institution

Bu‐Mel as preparative therapy prior to autologous stem cell rescue was recently shown to be superior to the conventional CEM regimen for HR NBL in Europe. There are no data available on the feasibility and toxicity of Bu‐Mel as consolidation therapy following the COG‐type induction regimens used in North America. We report early complications and outcomes of patients with HR NBL who received Bu‐Mel for consolidation following COG‐based induction. Retrospective analysis of all patients who had received Bu‐Mel as preparative regimen prior to stem cell rescue for HR NBL was carried out. Toxicity, outcomes, and any delays to receiving radiation or anti‐GD2 antibody therapy were analyzed. Six patients undergoing PBSCT had received Bu‐Mel. The treatment was well tolerated. Mucositis was the main toxicity; three patients had developed neutropenia fever and none developed pulmonary toxicity. One patient had developed moderate SOS that responded to conservative management. All patients were able to receive and tolerate post‐transplant local radiotherapy and ch.14.18 anti‐GD2 antibody therapy without any delays. All patients are alive with no disease recurrence. The Bu‐Mel regimen is well tolerated and is feasible post‐COG‐type induction platform.     

The challenges of high‐dose chemotherapy in CNS tumors

High‐dose, myeloablative chemotherapy with hematopoietic stem cell rescue is used in children and young adults with brain tumors for which conventional therapy is either excessively toxic (e.g., radiotherapy in infants) or ineffective. Thus, the aims of such strategies are to improve both quantity and quality of life. Whether high‐dose chemotherapy is less neurotoxic and more effective than other therapeutic approaches is still controversial. We will consider the difficulties in analyzing published data and the challenges of designing effective clinical trials that test high‐dose chemotherapy in patients with brain tumors. Pediatr Blood Cancer 2010;54:652–653. © 2010 Wiley‐Liss, Inc.     

Renal function after tandem high-dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor

Lee SH, Paik KH, Sung KW, Son MH, Yoo KH, Koo HH, Kim JY, Cho EJ. Renal function after tandem high‐dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor. Pediatr Transplantation 2011: 15: 855–860. © 2011 John Wiley & Sons A/S. Abstract: Despite increasing evidence that tandem HDCT and autoSCT might improve the survival of patients with high‐risk solid tumors, patients with Wilms tumor may be at high risk of acute and chronic renal impairment during and after tandem HDCT/autoSCT because they usually have a single kidney. We investigated the feasibility of tandem HDCT/autoSCT in patients with Wilms tumor, focusing on renal function. Six patients with relapsed/progressed Wilms tumor were assigned to undergo tandem HDCT/autoSCT. One patient developed transient ARF during the first HDCT/autoSCT. All other patients underwent the second HDCT/autoSCT as scheduled. Acute renal dysfunction during the second HDCT/autoSCT was transient and manageable. Indicators of glomerular function such as creatinine clearance, serum creatinine, and albumin excretion were in the normal range at three yr after tandem HDCT/autoSCT. Subclinical tubular dysfunctions, such as increased excretion of β‐N‐acetylglucosaminidase and β2‐microglobulin, were identified at one and three yr after tandem HDCT/autoSCT; however, no patient required treatment for these conditions. These results are helpful to consider tandem HDCT/autoSCT as a treatment option in patients with Wilms tumor. Longer duration of follow‐up and close monitoring of tubular function are required if tandem HDCT/autoSCT is indicated in patients with Wilms tumor.