Network Meta-analysis of 5-HT3 Receptor Antagonists for Prevention of Acute Nausea and Vomiting Caused by High-dose Chemotherapy / 中国药学杂志

OBJECTIVE: To evaluate the efficacy of 5-HT3 antagonists in the prevention of acute nausea and vomiting caused by high-dose chemotherapy using the network Meta-analysis system. METHODS: Developing retrieval strategies, system retrieves electronic databases such as Pubmed, EMbase, Cochrane Library, VIP, Wanfang and CNKI (as of October 2018), to find a randomized controlled trial (RCT) that uses 5-HT3 receptor antagonist alone to prevent nausea and vomiting caused by high-dose chemotherapy in adults. Quality assessment and data extraction were performed on eligible RCTs, with outcomes including acute nausea and vomiting. The RESULTS of the included RCT studies were combined using traditional STA analysis and network Meta-analysis using STATA13.0 software and WINBUG software.The RESULTS of the included RCT studies were combined using traditional Meta-analysis and network Meta-analysis. RESULTS: A total of 20 studies were included, involving a total of 4 042 patients with high-dose emetogenic chemotherapy.Seven interventions were included (granstron, ondansetron, ramosetron, tropisetron, dolasetron, azasetron, and palonosetron) with a total arm count of 41.The traditional Meta RESULTS showed that palonosetron was more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy than ondansetron, and the difference was statistically significant (P0.05). Ondansetron may be inferior to granisetron (OR=1.238), but the difference is not statistically significant (P>0.05).For acute nausea caused by high-dose chemotherapy, ondansetron may be inferior to granisetron (OR=1.232), but the difference was not statistically significant (P>0.05).Ramosetron may be better than granisetron (OR=0.632), but the difference was not statistically significant (P>0.05).Network Meta-analysis found that ondansetron was inferior to palonosetron in the treatment of acute vomiting due to high-dose chemotherapy (OR=0.60, 95%CI:0.39-0.88). Palonosetron was superior to ramosetron (OR=2.54, 95% CI:1.16-5.80). SCURA RESULTS showed that the best treatment for acute nausea caused by high-dose chemotherapy was palonosetron, followed by ramosetron, dolasetron, ondansetron, granisetron and tropisetron. The best treatment for acute vomiting caused by high-dose chemotherapy is palonosetron, followed by ramosetron, azasetron, dolasetron, tropisetron, granisetron and ondansetron. The RESULTS of the network Meta-analysis are basically consistent with those obtained by traditional Meta-analysis. CONCLUSION: Compared with the first-generation 5-HT3 receptor antagonist, palonosetron is more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy, ramosetron is more effective than other first-generation 5-HT3 receptor antagonists. Whether the RESULTS of this study will guide the clinical practice still requires a large-scale prospective study designed specifically to verify.

Rehabilitation in a Patient with POEMS Syndrome Following High-dose Chemotherapy with Autologous Peripheral Blood Stem Cell Transplantation / The Japanese Journal of Rehabilitation Medicine

POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome is an extremely rare neurological disease exhibiting various symptoms. Few reports have investigated rehabilitation in this disease. The present study reported the details of rehabilitation in a 40-year-old man with POEMS syndrome. Abnormal sensation was initially observed in the distal legs, followed by deterioration of muscle strength. He was admitted to our hospital 2 months after onset and received high-dose chemotherapy with autologous peripheral blood stem cell transplantation for acute exacerbation of polyneuropathy. Electrophysiological examination revealed axonal neuropathy. Gradual improvement in muscle strength was observed after high-dose chemotherapy with autologous peripheral blood stem cell transplantation. He was able to walk with a knee-ankle-foot orthosis and crutches at the time of discharge, but he used a wheelchair for routine activities. He could ascend and descend stairs in his house with bottom shuffling. As it is difficult to predict the extent of ultimate improvement and timing of remission in this disease, it is important to devise a rehabilitation program from a long-term perspective and to aim at recovery of independence for daily living activities and social reintegration using supportive devices and compensatory methods.

Rehabilitation in a Patient with POEMS Syndrome Following High-dose Chemotherapy with Autologous Peripheral Blood Stem Cell Transplantation / The Japanese Journal of Rehabilitation Medicine

POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome is an extremely rare neurological disease exhibiting various symptoms. Few reports have investigated rehabilitation in this disease. The present study reported the details of rehabilitation in a 40-year-old man with POEMS syndrome. Abnormal sensation was initially observed in the distal legs, followed by deterioration of muscle strength. He was admitted to our hospital 2 months after onset and received high-dose chemotherapy with autologous peripheral blood stem cell transplantation for acute exacerbation of polyneuropathy. Electrophysiological examination revealed axonal neuropathy. Gradual improvement in muscle strength was observed after high-dose chemotherapy with autologous peripheral blood stem cell transplantation. He was able to walk with a knee-ankle-foot orthosis and crutches at the time of discharge, but he used a wheelchair for routine activities. He could ascend and descend stairs in his house with bottom shuffling. As it is difficult to predict the extent of ultimate improvement and timing of remission in this disease, it is important to devise a rehabilitation program from a long-term perspective and to aim at recovery of independence for daily living activities and social reintegration using supportive devices and compensatory methods.

Tandem High-dose Chemotherapy and Autologous Stem Cell Transplantation in Children with Brain Tumors : Review of Single Center Experience

The prognosis of brain tumors in children has improved for last a few decades. However, the prognosis remains dismal in patients with recurrent brain tumors. The outcome for infants and young children in whom the use of radiotherapy (RT) is very limited because of unacceptable long-term adverse effect of RT remains poor. The prognosis is also not satisfactory when a large residual tumor remains after surgery or when leptomeningeal seeding is present at diagnosis. In this context, a strategy using high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) has been explored to improve the prognosis of recurrent or high-risk brain tumors. This strategy is based on the hypothesis that chemotherapy dose escalation might result in improvement in survival rates. Recently, the efficacy of tandem HDCT/auto-SCT has been evaluated in further improving the outcome. This strategy is based on the hypothesis that further dose escalation might result in further improvement in survival rates. At present, the number of studies employing tandem HDCT/auto-SCT for brain tumors is limited. However, results of these pilot studies suggest that tandem HDCT/auto-SCT may further improve the outcome. In this review, we will summarize our single center experience with tandem HDCT/auto-SCT for recurrent or high-risk brain tumors.

Tandem High-dose Chemotherapy and Autologous Stem Cell Transplantation in Children with Brain Tumors : Review of Single Center Experience

The prognosis of brain tumors in children has improved for last a few decades. However, the prognosis remains dismal in patients with recurrent brain tumors. The outcome for infants and young children in whom the use of radiotherapy (RT) is very limited because of unacceptable long-term adverse effect of RT remains poor. The prognosis is also not satisfactory when a large residual tumor remains after surgery or when leptomeningeal seeding is present at diagnosis. In this context, a strategy using high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) has been explored to improve the prognosis of recurrent or high-risk brain tumors. This strategy is based on the hypothesis that chemotherapy dose escalation might result in improvement in survival rates. Recently, the efficacy of tandem HDCT/auto-SCT has been evaluated in further improving the outcome. This strategy is based on the hypothesis that further dose escalation might result in further improvement in survival rates. At present, the number of studies employing tandem HDCT/auto-SCT for brain tumors is limited. However, results of these pilot studies suggest that tandem HDCT/auto-SCT may further improve the outcome. In this review, we will summarize our single center experience with tandem HDCT/auto-SCT for recurrent or high-risk brain tumors.

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas

Despite increasing evidence that high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) might improve the survival of patients with high-risk or recurrent solid tumors, therapy effectiveness for bone and soft tissue sarcoma treatment remains unclear. This study retrospectively investigated the feasibility and effectiveness of HDCT/auto-SCT for high-risk or recurrent bone and soft tissue sarcoma. A total of 28 patients (18 high-risk and 10 recurrent) underwent single or tandem HDCT/auto-SCT between October 2004 and September 2014. During follow-up of a median 15.3 months, 18 patients exhibited disease progression and 2 died of treatment-related toxicities (1 veno-occlusive disease and 1 sepsis). Overall, 8 patients remained alive and progression-free. The 3-year overall survival (OS) and event-free survival (EFS) rates for all 28 patients were 28.7% and 26.3%, respectively. In the subgroup analysis, OS and EFS rates were higher in patients with complete or partial remission prior to HDCT/auto-SCT than in those with worse responses (OS, 39.1% vs. 0.0%, P = 0.002; EFS, 36.8% vs. 0.0%, P < 0.001). Therefore, careful selection of patients who can benefit from HDCT/auto-SCT and maximal effort to reduce tumor burden prior to treatment will be important to achieve favorable outcomes in patients with high-risk or recurrent bone and soft tissue sarcomas.

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Evaluation of Cardiac Function in Children with Solid Tumors, who Underwent Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation / 임상소아혈액종양

BACKGROUND: Even though the five year survival rate and prognosis of childhood solid tumors have been improved through the introduction of dose-escalation using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), changes in cardiac function have not yet been studied. We therefore evaluated cardiac function after tandem HDCT/auto-SCT.METHODS: This study retrospectively analyzed 56 pediatric patients who were diagnosed with solid tumors and who underwent tandem HDCT/auto-SCT at Samsung Medical Center. We investigated the cardiac function of these patients using echocardiography to evaluate the parameters of the left ventricular ejection fraction, e/e', and left ventricular Tei index.RESULTS: The mean left ventricular ejection fraction, e/e', and left ventricular Tei index at one year after the second HDCT/auto-SCT were 65.7%, 0.32, and 8.6, respectively. When compared those with before the first tandem HDCT/auto-SCT, there were no significant negative changes. We evaluated the changes in cardiac function in different subgroups, based on doxorubicin, radiotherapy involving heart, and the age of the patient at diagnosis. There were no significant changes of cardiac function after the treatment in any of the subgroups. Clinical heart failure did not develop in any of the patients.CONCLUSION: This study showed no significant negative changes in cardiac function at one year after tandem HDCT/auto-SCT. However, long-term follow-up studies of cardiac function in survivors and further studies of cardiac function are needed.

Optimal Time to Start Peripheral Blood Stem Cell Collection in Children with High-Risk Solid Tumors

In order to clarify the optimal timing for peripheral blood stem cell (PBSC) collection, PBSC collection records of 323 children who were scheduled to undergo autologous stem cell transplantation from two study periods differing in the timing of PBSC collection were analyzed. In the early study period (March 1998 to August 2007, n=198), PBSC collection was initiated when the peripheral WBC count exceeded 1,000/microL during recovery from chemotherapy. Findings in this study period indicated that initiation of PBSC collection at a higher WBC count might result in a greater CD34+ cell yield. Therefore, during the late study period (September 2007 to December 2012, n=125), PBSC collection was initiated when the WBC count exceeded 4,000/microL. Results in the late study period validated our conclusion from the early study period. Collection of a higher number of CD34+ cells was associated with a faster hematologic recovery after transplant in the late study period. Initiation of PBSC collection at WBC count > 4,000/microL was an independent factor for a greater CD34+ cell yield. In conclusion, PBSC collection at a higher WBC count is associated with a greater CD34+ cell yield, and consequently a faster hematologic recovery after transplant.

High-dose therapy combined with autologous peripheral blood stem cell transplantation in patients with peripheral T-cell lymphoma: A retrospective study / 肿瘤

Objective: To explore the value of high-dose therapy/autologous hematopoietic stem cell transplantation (HDT/AHSCT) in the treatment of patients with peripheral T-cell lymphoma (PTCL). Methods: The medical records of 50 patients with PTCL who received HDT/AHSCT were retrospectively analyzed. The followed-up was performed. Results: No HDT/AHSCT-related death occurred. The median follow-up time was 13 months (range: 1-136). The 2-year progression-free survival (PFS) and 2-year overall survival (OS) were 59.0% and 65.0%, respectively. Univariate analysis showed that the patients achieving complete remission (CR) before HDT/AHSCT had superior 2-year PFS and 2-year OS as compared with those of the patients not achieving CR (2-year PFS: 72.8% vs 41.9%, P = 0.003; 2-year OS: 88.2% vs 41.9%, P = 0.002). The 2-year PFS was 76.8% for the patients who were sensitive to the firstline treatment (CR1/PR1) as compared with 30.8% for the patients who were sensitive to the secondline treatment (CR2/PR2) (P = 0.001). The 2-year OS for patients achieving CR1/PR1was also much better than that for patients achieving CR2/PR2 (81.1% vs 46.2%, P = 0.015). Furthermore, Erythrocyte sedimentation rate (ESR) before transplantation was an important factor for 2-year PFS and 2-year OS (P = 0.004, P = 0.018). Serum lactate dehydrogenase (LDH) level before transplantation was another important factor for 2-year PFS (P = 0.044). Multivariate analysis showed that the therapeutic response (achieving CR) before transplantation was an independent factor for 2-year OS [risk ratio: 4.879 (95% confidence interval: 1.583-15.034), P = 0.006]. No independent factors for 2-year PFS were observed. Subgroup analysis revealed that the patients with angioimmunoblastic T-cell lymphoma and advanced natural killer (NK)/T-cell lymphoma who received HDT/AHSCT during first CR may have benefit in survival from HDT/AHSCT. Conclusion: HDT/AHSCT can be used as safe and effective first-line consolidation therapy or salvage therapy in patints with PTCL and partially improve the prognosis. Prospective randomized controlled trials are necessary to confirm the suitable pathologic subtype and the best pretransplantation status for HDT/AHSCT.

Evaluation of Cardiac Function in Children with Solid Tumors, who Underwent Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation / 임상소아혈액종양

BACKGROUND: Even though the five year survival rate and prognosis of childhood solid tumors have been improved through the introduction of dose-escalation using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), changes in cardiac function have not yet been studied. We therefore evaluated cardiac function after tandem HDCT/auto-SCT. METHODS: This study retrospectively analyzed 56 pediatric patients who were diagnosed with solid tumors and who underwent tandem HDCT/auto-SCT at Samsung Medical Center. We investigated the cardiac function of these patients using echocardiography to evaluate the parameters of the left ventricular ejection fraction, e/e', and left ventricular Tei index. RESULTS: The mean left ventricular ejection fraction, e/e', and left ventricular Tei index at one year after the second HDCT/auto-SCT were 65.7%, 0.32, and 8.6, respectively. When compared those with before the first tandem HDCT/auto-SCT, there were no significant negative changes. We evaluated the changes in cardiac function in different subgroups, based on doxorubicin, radiotherapy involving heart, and the age of the patient at diagnosis. There were no significant changes of cardiac function after the treatment in any of the subgroups. Clinical heart failure did not develop in any of the patients. CONCLUSION: This study showed no significant negative changes in cardiac function at one year after tandem HDCT/auto-SCT. However, long-term follow-up studies of cardiac function in survivors and further studies of cardiac function are needed.

The efficacy and safety of high-dose adjuvant chemotherapy with paclitaxel and thiotepa in postoperative breast cancer patients with high risk of recurrence / 肿瘤

Objective: Patients with high-risk breast cancer has a high recurrence rate. The clinical value of high-dose adjuvant chemotherapy supported by autologous HSCT (hematopoietic stem cell transplantation) for postoperative breast cancer patients with high risk of recurrence remains controversial. This study was to explore the efficacy and safety of high-dose adjuvant chemotherapy with paxlitaxel and thiotepa supported by autologous HSCT for postoperative breast cancer patients with high risk of recurrence. Methods: Twenty-four postoperative breast cancer patients (stages II-III) with high risk of recurrence were enrolled in this study. The patients received paclitaxel 175 mg/m2 and G-CSF (granulocyte colony-stimulating factor) 5 μg/kg for mobilization and collection of peripheral blood CD34+ stem cells. Then two cycles of high-dose adjuvant chemotherapy were given subsequently [11 patients: paclitaxel 175 mg/m2 + thiotepa 150 mg/m2 + carboplatin (area under curve = 6; 300 mg/m2 divided in two days); 13 patients: paclitaxel 175 mg/m2 + thiotepa 150 mg/m2) every 28 d]. The CD34+ stem cells were infused for an autologous HSCT on day 2 after chemotherapy, and the G-CSF was started on day 3 after chemotherapy and discontinued until the peripheral WBC (white blood cell) count reached over 10.0×109/L continuously for three days. The adverse effects of high-dose adjuvant chemotherapy were observed. The median DFS (disease-free survival) and the three-year DFS rate were calculated. Results: The median follow-up was 32 months (3-62 months). The median DFS was 32 months. The three-year DFS rate was 56.3%. High-dose chemotherapy had a good safety profile and no treatment-related death. Conclusion: High-dose chemotherapy with paclitaxel and thiotepa supported by autologous HSCT in postoperative breast cancer patients with high risk of recurrence has a good safety profile and can obtain a better benefit of DFS as compared with standard-dose chemotherapy. These results suggest that this treatment strategy deserves further exploration. Copyright © 2013 by TUMOR.

High-dose chemotherapy and autologous peripheral blood stem cell transplantation in the treatment of children and adolescents with Ewing sarcoma family of tumors / 소아과

PURPOSE: We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. METHODS: We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. RESULTS: A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was 44.4%+/-16.6% and disease status at the time of HDCT/autoPBSCT tended to influence survival (57.1%+/-18.7% of cases with CR vs. 0% of cases with non-CR, P=0.07). CONCLUSION: Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment.

Hematologic Recovery after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk Solid Tumors

Although the number of studies using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) for the treatment of high-risk pediatric solid tumors has been increasing, documentation of hematologic recovery after tandem HDCT/autoSCT is very limited. For this reason, we retrospectively analyzed the hematologic recovery of 236 children with high-risk solid tumors who underwent tandem HDCT/autoSCT. The median numbers of CD34+ cells transplanted during the first and second HDCT/autoSCT were 4.3 x 10(6)/kg (range 0.6-220.2) and 4.1 x 10(6)/kg (range 0.9-157.6), respectively (P = 0.664). While there was no difference in neutrophil recovery between the first and second HDCT/autoSCT, platelet and RBC recoveries were significantly delayed in the second HDCT/autoSCT (P < 0.001 and P < 0.001, respectively). Delayed recovery in the second HDCT/autoSCT was more prominent when the number of transplanted CD34+ cells was lower, especially if it was < 2 x 10(6)/kg. A lower CD34+ cell count was also associated with increased RBC transfusion requirements and a higher serum ferritin level after tandem HDCT/autoSCT. More CD34+ cells need to be transplanted during the second HDCT/autoSCT in order to achieve the same hematologic recovery as the first HDCT/autoSCT.

Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.

Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.

Treatment of high-risk neuroblastoma / 소아과

Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose 131I-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB.

High-dose chemotherapy and autologous stem cell transplantation for pediatric brain tumors

The prognosis of brain tumors in children has improved for the last 2-3 decades. However, the prognosis remains dismal in patients with relapsed tumors. The outcome for infants and young children is also poor. For younger children, the ability to use of radiotherapy (RT) is very limited because of the unacceptable long-term adverse effects of RT. The prognosis is also not satisfactory when a large residual tumor remains after surgery or when leptomeningeal seeding is present at diagnosis. In this context, a strategy using high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) has been explored to improve the prognosis of recurrent or high-risk brain tumors. It was found that at least some patients with relapsed tumors can be salvaged with HDCT/autoSCT. For infants and young children, it was possible to avoid or defer RT until 3 years of age while maintaining or improving survival rates. Investigators also have explored the efficacy of HDCT/autoSCT in patients with newly diagnosed embryonal tumors to further improve the survival rate or to reduce the craniospinal RT dose without jeopardizing the survival rate. Preliminary results were encouraging although the numbers of patients was small. Recently, a few investigators have evaluated the efficacy of sequential HDCT/autoSCT to further improve the outcome. This strategy is based on the hypothesis that further dose escalation might result in further improvement in survival rates. At present, the number of studies employing a sequential HDCT/autoSCT strategy is limited. However, preliminary results of these studies suggest that sequential HDCT/autoSCT may further improve outcomes.

Reduced-dose craniospinal radiotherapy followed by high-dose chemotherapy and autologous stem cell rescue for children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuroectodermal tumor

BACKGROUND: In this study, we investigated the effects of reduced-dose craniospinal radiotherapy (CSRT) followed by tandem high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in children with a newly diagnosed high-risk medulloblastoma (MB) or supratentorial primitive neuroectodermal tumor (sPNET). METHODS: Between March 2005 and April 2007, patients older than 3 years with a newly diagnosed high-risk MB or sPNET were enrolled. The patients received two cycles of pre-RT chemotherapy consisting of cisplatin, etoposide, vincristine, and cyclophosphamide (cycle A), and carboplatin, etoposide, vincristine, and ifosphamide (cycle B), followed by CSRT with 23.4 Gy and local RT with 30.6 Gy. After four cycles of post-RT chemotherapy (cycles A, B, A, and B), tandem double HDCT with ASCR was performed. RESULTS: A total of 13 patients (MB=11, sPNET=2) were enrolled. Of these, one patient progressed, one patient died of septic shock after the second cycle of B, and one patient relapsed after the third cycle of B. The 3-year event-free survival (EFS) rate of the patients intended for HDCT was 76.9%, whereas the 3-year EFS rate of the patients who received HDCT was 100%. No treatment-related mortality occurred during HDCT. CONCLUSION: Although the follow-up period was short and the patient cohort was small in size, the results of this study are encouraging. The limited toxicity and favorable EFS rate observed in children treated with reduced-dose CSRT followed by HDCT and ASCR warrant further exploration in a larger study population.