Brian H Kushner

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (154)1337.82 Total impact

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    ABSTRACT: Relapse of high-risk neuroblastoma (HR-NB) is deemed invariably fatal. Yet increasing numbers of HR-NB patients achieve 2nd complete/very good partial remission (CR/VGPR) - hence, the urgency of finding successful consolidative therapy. Identifying efficacy in patients without assessable disease, however, is problematic. We now report the first study to provide outcome data for this poor-prognosis group of patients. To prevent another relapse, HR-NB patients in >2nd CR/VGPR received anti-GD2 murine antibody 3F8+granulocyte-macrophage colony-stimulating factor+isotretinoin. Upon meeting the phase II trial's target aim for progression-free survival (PFS) in the initial cohort of 33 patients, the trial was amended to allow patients who developed human anti-mouse antibody (HAMA) to receive rituximab to ablate HAMA + low-dose maintenance chemotherapy until immunotherapy could resume. For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33%+5% and 48%+5%, respectively. Among the 33 long-term progression-free survivors, 19 had MYCN amplification, 19 had previously received anti-GD2 immunotherapy+isotretinoin (as first-line therapy), and 15 never received maintenance chemotherapy. In a multivariate analysis of prognostic factors, only absence of minimal residual disease in bone marrow after two cycles of immunotherapy, before initiation of isotretinoin or anti-HAMA therapy, was significantly favorable for both PFS and OS. Long-term PFS is possible for HR-NB patients who achieve >2nd CR/VGPR and receive consolidation that includes anti-GD2 immunotherapy+isotretinoin, even if patients received those biological treatments before relapse. Results from this prospective study will aid in the development of future phase II studies in this growing ultra-high-risk patient population.
    OncoImmunology 05/2015; 4(7):00-00. DOI:10.1080/2162402X.2015.1016704 · 6.27 Impact Factor
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    ABSTRACT: Desmoplastic small round cell tumor (DSRCT), a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400-700 mg/m2/day for 3 days) + thiotepa (300 mg/m2/day for 3 days) ± topotecan (2 mg/m2/day for 5 days). All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant). 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm.
    Sarcoma 05/2015; 2015:1-9. DOI:10.1155/2015/269197
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    ABSTRACT: ABSTRACT Desmoplastic small round cell tumor (DSRCT) was proposed as a distinct disease entity by William L Gerald and Juan Rosai in 1991. Over 850 patients have been reported in the medical literature. A specific translocation, t(11;22)(p13;q12), is seen in almost all cases, juxtaposing the EWS gene to the WT1 tumor suppressor gene. DSRCT is composed of nests of small round cells with polyphenotypic differentiation, typically a mixture of epithelial, mesenchymal and neural features, surrounded by a prominent desmoplastic stroma. DSRCT has a predilection for adolescent and young adult males, and primarily involves the abdominal cavity and pelvis. Survival is low despite their initial response to multimodal treatment. Most patients relapse with disseminated disease that is unresponsive to further therapy.
    Future Oncology 04/2015; 11(7):1071-81. DOI:10.2217/fon.15.32 · 2.48 Impact Factor
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    ABSTRACT: BACKGROUND Osteochondromas are benign bony protrusions that can be spontaneous or associated with radiotherapy (RT). Current treatment of high-risk neuroblastoma includes dose-intensive chemotherapy, local RT, an anti-GD2 monoclonal antibody (MoAb), and isotretinoin. Late effects are emerging.METHODS The authors examined osteochondromas in 362 patients who were aged <10 years when diagnosed with neuroblastoma, had received a MoAb plus isotretinoin since 2000, and had survived >24 months from the time of the first dose of the MoAb. The incidence rate of osteochondroma was determined using the competing risks approach, in which the primary event was osteochondroma calculated from the date of neuroblastoma diagnosis and the competing event was death without osteochondroma.RESULTSA total of 21 osteochondroma cases were found among 14 patients who were aged 5.7 to 15.3 years (median, 10.4 years) and 3.1 to 11.2 years (median, 8.2 years) from the time of neuroblastoma diagnosis. The cumulative incidence rate was 0.6% at 5 years and 4.9% at 10 years from the neuroblastoma diagnosis. Nine osteochondromas were revealed incidentally during assessments of neuroblastoma disease status or bone age. Thirteen osteochondromas were detected outside RT portals and had characteristics of spontaneous forms. Complications were limited to pain necessitating surgical resection in 3 patients, but follow-up was short at 0.3 to 7.7 years (median, 3.5 years).CONCLUSIONS Osteochondromas in long-term survivors of neuroblastoma should be expected because these benign growths can be related to RT and these patients undergo radiologic studies over years, are monitored for late toxicities through and beyond adolescence, and receive special attention (because of concerns about disease recurrence) if they develop a bony protuberance. A pathogenic role for chemotherapy, anti-GD2 MoAbs, or isotretinoin remains speculative. Cancer 2015. © 2015 American Cancer Society.
    Cancer 02/2015; 121(12). DOI:10.1002/cncr.29316 · 4.89 Impact Factor
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    Journal of Clinical Oncology 11/2014; 32(36). DOI:10.1200/JCO.2014.58.1678 · 18.43 Impact Factor
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    ABSTRACT: Anti-GD2 murine antibody 3F8 plus subcutaneously-administered (sc) granulocyte-macrophage colony-stimulating factor (GM-CSF) was used against primary refractory neuroblastoma in metastatic osteomedullary sites. Large study size and long follow-up allowed assessment of prognostic factors in a multivariate analysis not reported with other anti-GD2 antibodies. In a phase II trial, 79 patients without prior progressive disease were treated for persistent osteomedullary neuroblastoma documented by histology and/or metaiodobenzyl-guanidine (MIBG) scan. In the absence of human anti-mouse antibody, 3F8+scGM-CSF cycles were repeated up to 24 months. Minimal residual disease (MRD) in bone marrow was measured by quantitative reverse transcription-polymerase chain reaction pre-enrollment and post-cycle #2, before initiation of 13-cis-retinoic acid. Study endpoints were: 1) progression-free survival (PFS) compared with the predecessor trial of 3F8 plus intravenously-administered (iv) GM-CSF (26 patients), and 2) impact of MRD on PFS. Using all 105 patients from the two consecutive 3F8+GM-CSF trials, prognostic factors were analyzed by multivariate Cox regression model. Complete response rates to 3F8+scGM-CSF were 87% by histology and 38% by MIBG. Five-year PFS was 24%±6% which was significantly superior to 11%±7% with 3F8+ivGM-CSF (p=0.002). In the multivariate analysis, significantly better PFS was associated with R/R or H/R FCGR2A polymorphism, sc route of GM-CSF, and early MRD response. MYCN amplification was not prognostic. Complement consumption was similar with either route of GM-CSF. Toxicities were manageable, allowing outpatient treatment. 3F8+scGM-CSF is highly active against chemoresistant osteomedullary neuroblastoma. MRD response may be an indicator of tumor sensitivity to anti-GD2 immunotherapy. Correlative studies highlight the anti-neoplastic potency of myeloid effectors. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 11/2014; 135(9). DOI:10.1002/ijc.28851 · 5.09 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S730. DOI:10.1016/j.ijrobp.2014.05.2127 · 4.26 Impact Factor
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    ABSTRACT: The authors exploited a large database to investigate the outcomes of patients with high-risk neuroblastoma in the contemporary era. All patients with high-risk neuroblastoma aged <12 years who were treated during induction at the authors' institution from 2000 through 2011 were studied, including 118 patients with MYCN-amplified [MYCN(+)] disease and 127 patients aged >18 months with MYCN-nonamplified [MYCN(-)] stage 4 disease. A complete response/very good partial response (CR/VGPR) to induction was correlated with significantly superior event-free survival (EFS) (P < .001) and overall survival (OS) (P < .001) compared with a partial response or less. Patients with MYCN(+) and MYCN(-) disease had similar rates of CR/VGPR to induction (P = .366), and those with MYCN(+) and MYCN(-) disease who attained a CR/VGPR had similar EFS (P = .346) and OS (P = .542). In contrast, only MYCN(+) patients had progressive disease as a response to induction (P < .001), and early death from progressive disease (<366 days after diagnosis) was significantly more common (P < .001) among those with MYCN(+) disease. Overall, among patients who had a partial response or less, MYCN(+) patients had significantly inferior EFS (P < .001) and OS (P < .001) compared with MYCN(-) patients, which accounted for the significantly worse EFS (P = .008) and OS (P = .002) for the entire MYCN(+) cohort versus the MYCN(-) cohort. Patients with MYCN(-), high-risk neuroblastoma display a broad, continuous spectrum with regard to response and outcome, whereas MYCN(+) patients either have an excellent response to induction associated with good long-term outcome or develop early progressive disease with a poor outcome. This extreme dichotomy in the clinical course of MYCN(+) patients points to underlying biologic differences with MYCN(+) neuroblastoma, the elucidation of which may have far-reaching implications, including improved risk classification at diagnosis and the identification of targets for treatment. Cancer 2014. © 2014 American Cancer Society.
    Cancer 07/2014; 120(13). DOI:10.1002/cncr.28687 · 4.89 Impact Factor
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    ABSTRACT: Purpose: To report on a phase I trial designed to find the maximally tolerated dose in children of the immunologic adjuvant OPT-821 in a vaccine containing neuroblastoma-associated antigens (GD2 and GD3; NCT00911560). Secondary objectives were to obtain preliminary data on immune response and activity against minimal residual disease (MRD). Treatment also included the immunostimulant β-glucan. Experimental design: Patients with neuroblastoma in ≥2nd complete/very good partial remission received vaccine subcutaneously (weeks 1-2-3-8-20-32-52). Vaccine contained 30 μg each of GD2 and GD3 stabilized as lactones and conjugated to the immunologic carrier protein keyhole limpet hemocyanin; and OPT-821, which was dose escalated as 50, 75, 100, and 150 μg/m(2) per injection. Oral β-glucan (40 mg/kg/day, 14 days on/14 days off) started week 6. Results: The study was completed with 15 patients because there was no dose-limiting toxicity at 150 μg/m(2) of OPT-821 (the dosing used in adults). Thirteen of fifteen patients received the entire protocol treatment, including 12 who remain relapse-free at 24+ to 39+ (median 32+) months and 1 who relapsed (single node) at 21 months. Relapse-free survival was 80% ± 10% at 24 months. Vaccine and β-glucan were well tolerated. Twelve of fifteen patients had antibody responses against GD2 and/or GD3. Disappearance of MRD was documented in 6 of 10 patients assessable for response. Conclusions: This immunotherapy program lacks major toxicity and is transportable to any outpatient clinic. Patient outcome is encouraging but the efficacy is uncertain because of the complexity and heterogeneity of prior therapies. A larger phase II trial is underway.
    Clinical Cancer Research 02/2014; 20(5). DOI:10.1158/1078-0432.CCR-13-1012 · 8.72 Impact Factor
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    ABSTRACT: Background: Posterior reversible encephalopathy syndrome (PRES) comprises clinical and radiologic findings with rapid onset and potentially dire consequences. Patients experience hypertension, seizures, headache, visual disturbance, and/or altered mentation. Magnetic resonance imaging reveals edematous changes in the brain (especially in the parietal and occipital lobes). In this report, the authors describe PRES associated with antidisialoganglioside (anti-GD2 ) monoclonal antibody (MoAb) immunotherapy, which is now standard for high-risk neuroblastoma but has not previously been implicated in PRES. Methods: Successive clinical trials using the anti-GD2 MoAb 3F8 (a murine immunoglobulin 3 MoAb specific for GD2) for patients with neuroblastoma involved multiple cycles of standard-dose 3F8 (SD-3F8) (20 mg/m2 daily for 5 days per cycle) or 2 cycles of high-dose 3F8 (HD-3F8) (80 mg/m2 daily for 5 days per cycle) followed by cycles of SD-3F8. Results: PRES was diagnosed in 5 of 215 patients (2.3%), including 3 of 160 (1.9%) who received SD-3F8 and 2 of 55 (3.6%) who received HD-3F8 (P = .6). All 5 patients had a rapid return to clinical-radiologic baseline. PRES occurred in 3 of 26 patients (11.5%) whose prior treatment included external-beam radiotherapy to the brain (2 of 6 patients status-post total body irradiation and 1 of 20 patients status-post craniospinal irradiation) compared with 2 of 189 patients (1.1%) who had not received prior brain irradiation (P = .01). Hypertension, which is strongly linked to PRES, reached grade 3 toxicity in 12 of 215 patients (5.6%), including the 5 patients with PRES and 7 patients without PRES. Conclusions: Patients who receive anti-GD2 MoAb immunotherapy should be closely monitored for, and undergo urgent treatment or evaluation of, symptoms that may herald PRES (eg, hypertension or headaches). Prior brain irradiation may be a predisposing factor for PRES with this immunotherapy.
    Cancer 08/2013; 119(15). DOI:10.1002/cncr.28137 · 4.89 Impact Factor
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    ABSTRACT: β-glucans are complex, naturally-occurring polysaccharides that prime leukocyte dectin and complement receptor 3. Based on our preclinical findings, indicating that oral barley-derived (1 → 3),(1 → 4)-β-D-glucan (BG) synergizes with the murine anti-GD2 antibody 3F8 against neuroblastoma, we conducted a Phase I clinical study to evaluate the safety of this combinatorial regimen in patients affected by chemoresistant neuroblastoma. In this setting, four cohorts of six heavily pre-treated patients bearing recurrent or refractory advanced-stage neuroblastoma were treated with 3F8 plus BG. Each cycle consisted of intravenous 3F8 at a fixed dose of 10 mg/m(2)/day plus concurrent oral BG, dose-escalated from 10 to 80 mg/Kg/day, for 10 d. Patients who did not develop human anti-mouse antibodies could be treated for up to 4 cycles. Twenty-four patients completed 50 cycles of therapy. All patients completed at least one cycle and were evaluable for the assessment of toxicity and responses. The maximum tolerated dose of BG was not reached, but two patients developed dose-limiting toxicities. These individuals developed grade 4 thrombocytopenia after one cycle of BG at doses of 20 mg/Kg/day and 40 mg/Kg/day, respectively. Platelet counts recovered following the administration of idiopathic thrombocytopenic purpura therapy. There were no other toxicities of grade > 2. Eleven and 13 patients manifested stable and progressive disease, respectively. Thirteen out of 22 patients with pre-treatment positive (123)I-MIBG scans demonstrated clinical improvement on semiquantitative scoring. Responses did not correlate with BG dose or with in vitro cytotoxicity. In summary, 3F8 plus BG is well tolerated and shows antineoplastic activity in recurrent or refractory advanced-stage neuroblastoma patients. Further clinical investigation of this novel combinatorial immunotherapeutic regimen is warranted.
    OncoImmunology 03/2013; 2(3):e23402. DOI:10.4161/onci.23402 · 6.27 Impact Factor
  • Journal of Clinical Oncology 02/2013; 31(5):650-1. DOI:10.1200/JCO.2012.47.4593 · 18.43 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 11/2012; 84(3):S169. DOI:10.1016/j.ijrobp.2012.07.438 · 4.26 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 11/2012; 84(3):S640-S641. DOI:10.1016/j.ijrobp.2012.07.1710 · 4.26 Impact Factor
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    B H Kushner · S Modak · K Kramer · E M Basu · S S Roberts · N-Kv Cheung
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    ABSTRACT: 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.Bone Marrow Transplantation advance online publication, 22 October 2012; doi:10.1038/bmt.2012.202.
    Bone marrow transplantation 10/2012; 48(5). DOI:10.1038/bmt.2012.202 · 3.57 Impact Factor
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    ABSTRACT: Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare malignancy typically involving the peritoneum in young men. Whole abdominopelvic radiation therapy (WAP-RT) using conventional 2-dimensional (2D) radiation therapy (RT) is used to address local recurrence but has been limited by toxicity. Our objectives were to assess the benefit of intensity modulated radiation therapy (IMRT) on toxicity and to update the largest series on radiation for DSRCT. Methods and materials: The records of 31 patients with DSRCT treated with WAP-RT (22 with 2D-RT and 9 with IMRT) between 1992 and 2011 were retrospectively reviewed. All received multi-agent chemotherapy and maximal surgical debulking followed by 30 Gy of WAP-RT. A further focal boost of 12 to 24 Gy was used in 12 cases. Boost RT and autologous stem cell transplantation were nearly exclusive to patients treated with 2D-RT. Toxicities were assessed with the Common Terminology Criteria for Adverse Events. Dosimetric analysis compared IMRT and simulated 2D-RT dose distributions. Results: Of 31 patients, 30 completed WAP-RT, with a median follow-up after RT of 19 months. Acute toxicity was reduced with IMRT versus 2D-RT: P=.04 for gastrointestinal toxicity of grade 2 or higher (33% vs 77%); P=.02 for grade 4 hematologic toxicity (33% vs 86%); P=.01 for rates of granulocyte colony-stimulating factor; and P=.04 for rates of platelet transfusion. Post treatment red blood cell and platelet transfusion rates were also reduced (P=.01). IMRT improved target homogeneity ([D05-D95]/D05 of 21% vs 46%) and resulted in a 21% mean bone dose reduction. Small bowel obstruction was the most common late toxicity (23% overall). Updated 3-year overall survival and progression-free survival rates were 50% and 24%, respectively. Overall survival was associated with distant metastasis at diagnosis on multivariate analysis. Most failures remained intraperitoneal (88%). Conclusions: IMRT for consolidative WAP-RT in DSRCT improves hematologic toxicity in particular. Although the long-term efficacy of current treatment options remains disappointing, the improved therapeutic index of IMRT may aid in generalizing its use and allowing the addition of novel approaches such as intraperitoneal immunotherapy.
    International journal of radiation oncology, biology, physics 10/2012; 85(1). DOI:10.1016/j.ijrobp.2012.09.005 · 4.26 Impact Factor
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    ABSTRACT: 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/μL) 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/μL 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 = .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.
    Cancer 09/2012; 119(3). DOI:10.1002/cncr.27783 · 4.89 Impact Factor
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    ABSTRACT: Purpose: Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. Patients and methods: One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. Results: At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). Conclusion: Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.
    Journal of Clinical Oncology 08/2012; 30(26):3264-70. DOI:10.1200/JCO.2011.41.3807 · 18.43 Impact Factor
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    ABSTRACT: Current therapies for high-risk neuroblastoma (NB) necessitate the availability of several aliquots of autologous peripheral blood stem cells to reverse-associated myelosuppression. Priming with the CXCR4 inhibitor plerixafor plus G-CSF was associated with successful stem cell harvest in 5/7 heavily prior-treated patients with stage 4 NB who had previously failed G-CSF priming. Minimal residual disease was not detected in harvested cells from any patient despite the presence of disease in bone/bone marrow in 6/7. Hematopoietic reconstitution was achieved in all three patients receiving plerixafor-primed stem cells after myeloablative therapy. Plerixafor is an effective and safe agent for stem cell collection in patients with NB.
    Pediatric Blood & Cancer 03/2012; 58(3):469-71. DOI:10.1002/pbc.23132 · 2.39 Impact Factor
  • Brian H Kushner · Kim Kramer · Shakeel Modak · Nai-Kong V Cheung
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    ABSTRACT: We report a retrospective study of a novel regimen for neuroblastoma (NB) resistant to standard induction or salvage chemotherapy which now routinely includes topotecan. Forty-five patients received carboplatin (500 mg/m(2)/day, 2×)-irinotecan (50 mg/m(2)/day, 5×)-temozolomide (250 mg/m(2)/day, 5×) (HD-CIT). Only one course was planned. Patients with thrombocytopenia indicative of poor bone marrow (BM) reserve resulting from extensive prior therapy received peripheral blood stem cells (PBSCs) post-HD-CIT. Modest acute toxicity allowed outpatient treatment. Low-grade diarrhea was common; there was no mucositis, nephrotoxicity, or cardiotoxicity. Myelosuppression was prolonged but uncomplicated. The absolute neutrophil count reached 500/µl on days 20-30 (median, 25) in 25 patients with satisfactory BM reserve, and on days 9-14 (median, 11) post-PBSC infusion. Anti-NB activity was common against refractory (non-progressing) disease or new relapse occurring off therapy (68% objective response rate), but not against disease progressing on therapy. Seven of 26 patients treated for refractory NB are progression-free and in complete remission following subsequent therapy, including anti-G(D2) immunotherapy, at ≥ 29+ months post-HD-CIT. HD-CIT is appealing as salvage or consolidative therapy because of anti-NB activity and modest non-hematologic toxicity. PBSC support is unnecessary when BM reserve is intact. The wide antineoplastic activity of its three components and their potential for activity against disease in the central nervous system support applicability to other cancers.
    Pediatric Blood & Cancer 03/2011; 56(3):403-8. DOI:10.1002/pbc.22855 · 2.39 Impact Factor

Publication Stats

4k Citations
1,337.82 Total Impact Points


  • 1985–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Pediatrics
      • • Department of Surgery
      • • Department of Pathology
      New York, New York, United States