A novel intensive induction therapy for high‐risk neuroblastoma utilizing sequential peripheral blood stem cell collection and infusion as hematopoietic support

Pradhan, Kamnesh R.; Johnson, Cynthia S.; Vik, Terry A.; Sender, Leonard S.; Kreissman, Susan G.

doi:10.1002/pbc.20594

Cited by 12 publications

(15 citation statements)

References 50 publications

(58 reference statements)

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“…Bacteremia in 26% of the cycles is comparable to rates with similarly myelosuppressive regimens. 36,37 In patients who, when treated with HD-ICE, had poor hematologic reserve (evidenced by thrombocytopenia) because of extensive prior treatment, including stem cell transplantation after myeloablative chemotherapy or recent 131 I-MIBG therapy, PBSC rescue was received in the outpatient clinic. Engraftment was uncomplicated, and full hematologic recovery enabled patients to meet eligibility criteria for formal clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…This point is evident in our current and prior reports on salvage chemotherapy for NB [8][9][10][11] as well as in experience with 131 I-MIBG therapy. 39 PBSC support also has allowed the investigation of novel submyeloablative induction chemotherapy regimens against NB 37,40 and other solid tumors in children. 36,41 We conclude that, in patients with high-risk NB, turning to HD-ICE for salvage or consolidative therapy is an attractive option because of noncross-resistance with widely used retrieval regimens.…”

Section: Discussionmentioning

confidence: 99%

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Ifosfamide, carboplatin, and etoposide for neuroblastoma

Kushner

Modak

Krämer

et al. 2012

Cancer

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BACKGROUND:The authors report a retrospective analysis of high-dose ifosfamide, carboplatin, and etoposide (HD-ICE) for patients with refractory or relapsed neuroblastoma (NB). A major reason for using this regimen was the long time since patients received previous treatment with a platinum compound. The authors also summarized the published experience on ICE in patients with NB. METHODS: Treatment comprised ifosfamide (2000 mg/m 2 daily for 5 days), carboplatin (500 mg/m 2 daily for 2 days), and etoposide (100 mg/m 2 daily for 5 days). Patients who had poor hematologic reserve (platelet count <100,000/lL) from previous therapy received peripheral blood stem cells (PBSCs) after HD-ICE. Disease status before and after HD-ICE was defined according to International Neuroblastoma Response Criteria (expanded to include 123 I-metaiodobenzylguanidine findings). Publications that were informative about ICE for NB were reviewed. RESULTS: Seventy-four patients received 92 cycles of ICE, including 37 patients who received PBSC rescue. Grade 3 toxicities were rare: 1-3 patients had encephalopathy, mucositis, or gastroenteritis. Bacteremia was documented in 24 of 92 cycles (26%). The absolute neutrophil count reached 500/lL on day 17-30 (median, day 22) in patients who had satisfactory hematologic reserve. Disease regressions (major and minor responses) were achieved by 14 of 17 patients (82%) with a new relapse, 13 of 26 patients (50%) with refractory NB, and 12 of 34 patients (35%) who were treated for progressive disease during chemotherapy (P ¼ .005). In the literature, patients received ICE at lower dosages and achieved major response rates >36% in phase 1 and 2 studies (in which less comprehensive staging evaluations were used) that involved resistant NB and >70% in induction for newly diagnosed NB. CONCLUSIONS: HD-ICE is appealing as salvage treatment or consolidative therapy because of its anti-NB activity and the low risk of major nonhematologic toxicity. PBSC support is unnecessary for patients who had intact hematologic reserve.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ifosfamide, carboplatin, and etoposide for neuroblastoma

Kushner

Modak

Krämer

et al. 2012

Cancer

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“…This point is evident in our present and previous reports on salvage chemotherapy for NB [9][10][11] and in experience with 131 I-MIBG therapy. 17 PBSC support has also allowed investigation of novel sub-myeloablative induction chemotherapy regimens against NB 15,18,19 and other solid tumors in children. 14,20 In our series, PBSC infusions were performed in the outpatient clinic and engraftment was uncomplicated.…”

Section: Discussionmentioning

confidence: 99%

“…The 10% incidence of bacteremia with 5D/5D was comparable to, or lower than, rates with similarly myelosuppressive regimens. 14,15 Patients with relapsed NB often have poor hematological reserve due to previous STC after myeloablative chemotherapy or recent 131 I-MIBG therapy; thrombocytopenia can limit treatment options and leave patients ineligible for clinical trials. This obstacle to further cytotoxic or investigative therapy can be overcome via the infusion of PBSCs.…”

Section: Discussionmentioning

confidence: 99%

5-day/5-drug myeloablative outpatient regimen for resistant neuroblastoma

Kushner

Modak

Krämer

et al. 2012

Bone Marrow Transplant

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5-day/5-drug (5D/5D) is a novel high-dose regimen administered with autologous hematopoietic SCT (HSCT). It was designed to maximize cytoreduction via high dosing of synergistically interacting agents, while minimizing morbidity in patients with resistant neuroblastoma (NB) and ineligible for clinical trials due to myelosuppression from previous therapy. 5D/5D comprises carboplatin 500 mg/m 2 /day on days 1-2, irinotecan 50 mg/m 2 /day on days 1-3, temozolomide 250 mg/m 2 /day on days 1-3, etoposide 200 mg/m 2 /day on days 3-5 and cyclophosphamide 70 mg/kg/day on days 4-5. HSCT is on day 8. Sixteen patients received 21 courses. Treatment was in the outpatient clinic. Responses were noted against progressive disease (PD) that had developed while patients were off, or receiving only low-dose, chemotherapy but not against PD that emerged despite high-dose chemotherapy. Responses were also seen in patients with PD or stable disease after 131 I-metaiodobenzylguanidine therapy. Grade 3 toxicities were limited to transient elevations in liver enzymes (three courses) and hyponatremia (one course). Bacteremia occurred in 2/21 (10%) courses. Hematological recovery allowed patients to be enrolled on clinical trials. In conclusion, 5D/5D (including HSCT) spares vital organs, entails modest morbidity, shows activity against resistant NB and helps patients meet eligibility requirements for formal clinical trials. Keywords: novel therapeutics; neuroblastoma; salvage therapy INTRODUCTION Standard chemotherapy for high-risk neuroblastoma (NB) includes dose-dense or dose-intensive and myeloablative regimens using alkylating agents, platinum compounds, topoisomerase-II inhibitors, and, most recently, the topoisomerase-I inhibitor topotecan. 1 Common salvage chemotherapy regimens for resistant NB combine topoisomerase-I inhibitors (topotecan, irinotecan) with alkylators (cyclophosphamide, temozolomide), 2-4 topoisomerase-II inhibitors (doxorubicin, etoposide) 5,6 or both classes of drugs. 7 For patients with NB resistant to a wide range of agents, and ineligible for clinical trials, we have used a 5-day/5-drug (5D/5D) regimen consisting of carboplatin-irinotecan-temozolomideetoposide-cyclophosphamide, followed by autologous hematopoietic SCT (HSCT). The development of 5D/5D was based on previous Memorial Sloan-Kettering Cancer Center (MSKCC) studies that used its five components. [8][9][10] These agents have broad anti-NB activity, display synergistic antineoplastic effects, penetrate into the central nervous system and lack overlapping extramedullary toxicities. The 5D/5D regimen's manageable and tolerable acute toxicity allows outpatient administration, an important consideration given the issue of quality of life for heavily previous-treated patients.HSCT is also performed in the outpatient setting. HSCT is necessary because high dosing makes this regimen strongly myelosuppressive, possibly even myeloablative, especially in patients with pre-existing poor hematological reserve due to previous therapy. HSCT results in normal bloo...

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“…[1][2][3] Although a concern for PBSC collection and reinfusion in these patients is the potential risk of reinfusion of neuroblastoma tumor cells that may contribute to relapse, 5,6 Kreissman et al 7 reported that centralized immunomagnetic purging of PBSCs did not impact the effect-free and overall survival rates at 2 years. The risk of contamination may be lower if CB is the source of HSCs.…”

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confidence: 99%