Tandem High-Dose Therapy in Rapid Sequence for Children With High-Risk Neuroblastoma

Grupp, Stephan A.; Stern, Julie W.; Bunin, Nancy; Nancarrow, Cheryl Medeiros; Ross, Alan O.; Mogul, Mark; Adams, Roberta H.; Grier, Holcombe E.; Gorlin, Jed B.; Shamberger, Robert C.; Marcus, Karen J.; Neuberg, Donna; Weinstein, Howard J.; Diller, Lisa

doi:10.1200/jco.2000.18.13.2567

Cited by 113 publications

(94 citation statements)

References 29 publications

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“…In fact, all six of our patients with CNS relapse were treated post-SCT with one or both of these biological therapies; four also took oral etoposide, which is used for CNS malignancies. The inclusion of total body irradiation in myeloablative therapies may reduce the risk of NB relapse in the CNS, 36,37 but that modality has been largely replaced by high-dose chemotherapy strategies. 38,39 Of note, a recent report described CNS relapses in four of 15 patients treated with the widely used myeloablative regimen of carboplatin-etoposide-melphalan.…”

Section: Discussionmentioning

confidence: 99%

“…35 As our experience attests, increasing numbers of children with high-risk NB are becoming long-term event-free survivors, with 3-year EFS rates (from diagnosis) in pilot studies as high as 50-60%. [36][37][38] Sophisticated use of conventional and myeloablative chemotherapy has improved remission rates and eradication of occult residual NB can be achieved with biological therapies such as 13-cisretinoic acid and monoclonal antibodies. Evidence of efficacy against CNS disease, however, is lacking for 13-cis-retinoic acid and monoclonal antibodies do not reach the CNS.…”

Section: Discussionmentioning

confidence: 99%

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Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Kushner

Krämer

Modak

et al. 2006

Bone Marrow Transplant

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We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m 2 / day, Â 4 days; thiotepa 300 mg/m 2 /day, Â 3 days; and carboplatin B500 mg/m 2 /day, Â 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cisretinoic acid, 7oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.78%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day þ 9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Kushner

Krämer

Modak

et al. 2006

Bone Marrow Transplant

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“…Patients who underwent an autologous HSCT received a variety of conditioning regimens including BEAM for Hodgkin's disease, 14 CD10/CD9-depleted autologous transplants for acute lymphoblastic leukemia, 15 and tandem HSCT for patients with high-risk neuroblastoma and other solid tumors. 16 Patients who had positive HSV titers received acyclovir (100 mg/m 2 from day À5 until day þ 24 or discharge) and those who had positive CMV titers or patients undergoing allogeneic HSCT whose donor had positive CMV titers received acyclovir (dose from day À2 until day þ 30 or discharge). A subset of patients (transplanted between January 1995 and December 1998) who were either CMV titer positive or patients undergoing allogeneic HSCT whose donor had positive CMV titers received gancyclovir (6 mg/kg, three times/week until day þ 120) in addition to acyclovir prophylaxis.…”

Section: Patients and Hsct Regimensmentioning

confidence: 99%

Herpes zoster infection in the post-hematopoietic stem cell transplant pediatric population may be preceded by transaminitis: an institutional experience

Berman

Berry

et al. 2005

Bone Marrow Transplant

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Herpes zoster (HZ), a varicella-zoster virus reactivation, frequently complicates hematopoietic stem cell transplantation (HSCT). Its incidence, complications, and associated risk factors in 310 children undergoing HSCT were reviewed. In all, 61 of 201(32%) patients who had undergone allogeneic and 10 of 109 (9%) patients who had undergone autologous HSCT developed HZ. Of 90 VZV seropositive allogeneic patients, 50 (53%) developed HZ. Seven (17%) of 41 VZV seropositive autologous patients developed HZ. Although a substantial number of patients develop HZ in the early post-HSCT period, risk for HZ persists and HZ can occur up to 5 years post-HSCT. Risk factors for HZ included age 410 years (Po0.0001), allogeneic HSCT (Po0.001), and total body irradiation (TBI) (Po0.059) in allogeneic recipients. Of 37, 22 (59%) patients experienced an elevated alanine aminotransferase (ALT), unassociated with GVHD, in the month preceding HZ. Of the 48/64 patients (75%) hospitalized for treatment (median stay, 6 days; range, 2-39), length of stay was unaffected by donor type but increased by cutaneous dissemination and visceral involvement (P ¼ 0.023 and 0.034, respectively) in allogeneic patients. Consideration of HZ infection particularly in patients 410 years of age with elevated ALT after TBIconditioned allogeneic HSCT may permit earlier diagnosis and therapeutic intervention.

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“…The dilemma is thus whether TBI induced sequelae sufficiently severe to justify a clear decrease in survival or can TBI be replaced by something else? The answer may be with busulfan containing regimens (Hartmann et al, 1999) or from tandem therapies as used in some LMCE3 patients (Philip et al, 1993;Grupp et al, 2000). However, high dose busulfan is responsible for acute visceral toxicities, and for delayed endocrinological toxicities (Hartmann et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis

et al. 2002

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The Lyon-Marseille-Curie-Est (LMCE) of France cooperative group has previously reported successive series of unselected stage four children older than 1 year at diagnosis with metastatic neuroblastoma (LMCE 1 and 3). The goal of LMCE 5 study was to increase progression free survival rate as compared to LMCE 1 and 3. Based on improvements reported with post induction chemotherapy, the LMCE 5 used post induction for all children, but omitted total body irradiation and immunomagnetic purging in megatherapy regimen for all children. Twenty-five sequentially diagnosed children received an induction regimen which compared with previous induction included an increased dose of etoposide and cyclophosphamide, delivered similar dose of cisplatinum, and deleted doxorubicin and vincristin. After surgery treatment was stratified based on response and eligible children received etoposide carboplatin (LMCE 5A : n=10)+doxorubicin (LMCE 5B -C n=13) followed by megatherapy (melphalan without total body irradiation and unpurged peripheral blood stem cell rescue). The increase in drug doses during induction did not improve remission rate. The progression free survival at 6 years is 8%. It is significantly worse than LMCE 3, and equivalent to LMCE 1 study though toxic death rate has decreased with increasing experience. Failure to improve the response rate during induction and reducing the megatherapy regimen may be the main factors in this disappointing result. Modified strategies for induction, non toxic alternative to total body irradiation, and post megatherapy regimen should be developed.

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Tandem High-Dose Therapy in Rapid Sequence for Children With High-Risk Neuroblastoma

Abstract: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.

Cited by 113 publications

References 29 publications

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system

Herpes zoster infection in the post-hematopoietic stem cell transplant pediatric population may be preceded by transaminitis: an institutional experience

The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis

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