Treatment of Pediatric Hodgkin Lymphoma

Olson, Michael R.; Donaldson, Sarah S.

doi:10.1007/s11864-008-0058-0

Cited by 23 publications

(14 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several investigators have reported the efficacy of auBMT for most patients with rrHL [6,[10][11][12]22]. Although direct clinical trial comparison data are lacking, the collective experience is that outcomes for patients with rrHL are best if these patients undergo auBMT as opposed to non-auBMT regimens [6][7][8]10]. For example, in 1 study of adult patients that directly compared salvage chemotherapy to high-dose chemotherapy with auBMT, those who received auBMT had an EFS almost twice as high as those that did not receive auBMT (53% compared with 27%) and also had increased OS (54% compared with 47%) [5].…”

Section: Discussionmentioning

confidence: 99%

“…Attempts to cure children with incompletely responsive or rapidly relapsed disease (recurrence 12 months from end of therapy) with salvage chemotherapy strategies that do not include auBMT have been less successful, with reported overall survival (OS) as low as 47% and event-free survival (EFS) as low as 27% [5]. High-dose chemotherapy followed by auBMT is effective therapy for patients with relapsed or refractory HL (rrHL) and has become a standard approach for such patients, with OS ranging from 43% to 95% [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Improved Outcomes after Autologous Bone Marrow Transplantation for Children with Relapsed or Refractory Hodgkin Lymphoma: Twenty Years Experience at a Single Institution

Garfin

Link

Donaldson

et al. 2015

Biology of Blood and Marrow Transplantation

Self Cite

View full text Add to dashboard Cite

The purpose of this study is to evaluate the survival of pediatric patients undergoing autologous bone marrow transplantation (auBMT) for relapsed or refractory Hodgkin lymphoma (rrHL) and to identify factors that might contribute to their outcome. We reviewed the records and clinical course of 89 consecutive rrHL patients ≤ 21 years old who underwent auBMT at Stanford Hospitals and Clinics and the Lucile Packard Children's Hospital, Stanford between 1989 and 2012. We investigated, by multiple analyses, patient, disease, and treatment characteristics associated with outcome. Endpoints were 5-year overall and event-free survival. Our findings include that cyclophosphamide, carmustine, and etoposide (CBV) as a conditioning regimen for auBMT is effective for most patients ≤ 21 years old with rrHL (5-year overall survival, 71%). Transplantation after the year 2001 was associated with significantly improved overall survival compared with our earlier experience (80% compared with 65%). Patients with multiply relapsed disease or with disease not responsive to initial therapy fared less well compared with those with response to initial therapy or after first relapse. Administration of post-auBMT consolidative radiotherapy (cRT) also appears to contribute to improved survival. We are able to conclude that high-dose chemotherapy with CBV followed by auBMT is effective for the treatment of rrHL in children and adolescents. Survival for patients who undergo auBMT for rrHL has improved significantly. This improvement may be because of patient selection and improvements in utilization of radiotherapy rather than improvements in chemotherapy. Further investigation is needed to describe the role of auBMT across the entire spectrum of patients with rrHL and to identify the most appropriate preparative regimen with or without cRT therapy in the treatment of rrHL in young patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improved Outcomes after Autologous Bone Marrow Transplantation for Children with Relapsed or Refractory Hodgkin Lymphoma: Twenty Years Experience at a Single Institution

Garfin

Link

Donaldson

et al. 2015

Biology of Blood and Marrow Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…2 However, long term effects of therapy have prompted several groups to attempt reduction of therapy, particularly in children with low risk HL. These attempts have varied in their approach, including elimination of radiation therapy 16 , the use of non-alkylator chemotherapy, 4, 5 or response based reduction of chemotherapy and/or radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

“…1 The therapy for lower risk patients, Ann Arbor Stages I, IIA and IIIA 1 is very effective with event free survivals and overall survivals greater than 90% 2, 3 . Although intensive combined modality chemotherapy and radiation therapy regimens have achieved excellent results, concern over short and long-term side-effects are substantial and many groups are currently evaluating reduced forms of therapy 4–8 .…”

Section: Introductionmentioning

confidence: 99%

Response‐dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: A report from the Children's Oncology Group

Tebbi

Mendenhall

London

et al. 2012

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Background Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes. Methods Protocol P9426, a response-dependent and reduced treatment for low risk Hodgkin lymphoma (stages I, IIA, and IIIA1) was designed in 1994 based on a previous pilot project. Patients were enrolled from 10/15/1996 to 09/19/2000. Patients were randomized to receive or not receive Dexrazoxane and received 2 cycles of chemotherapy consisting of Doxorubicin, Bleomycin, Vincristine, and Etoposide. After 2 cycles, patients were evaluated for response. Those in complete response (CR) received 2550 cGy of involved field radiation therapy (IFRT). Patient with partial response or stable disease, received 2 more cycles of chemotherapy and IFRT at 2550 cGy. Results There were 294 patients enrolled, with 255 eligible for analysis. The 8 year event free survival (EFS) between the Dexrazoxane randomized groups did not differ (EFS 86.8 + 3.1% with DRZ, and 85.7 + 3.3% without DRZ (p=0.70). Forty five percent of patients demonstrated CR after two cycles of chemotherapy. There was no difference in EFS by histology, rapidity of response, or number of cycles of chemotherapy. Six of the eight secondary malignancies in this study have been previously reported. Conclusions Despite reduced therapy and exclusion of most patients with Lymphocyte Predominant histology, EFS and overall survival are similar to other reported studies. The protocol documents that it is safe and effective to reduce therapy in low risk Hodgkin lymphoma based on early response to chemotherapy with rapid responding patients having the same outcome as slower-responding patients when given 50% of the chemotherapy.

show abstract

“…Recurring somatic mutations in these genes are not known to occur in the pediatric solid tumor or ALL setting. Among the lymphomas known to show NF-κB activation in the adult setting, Hodgkin lymphoma and primary mediastinal B-cell lymphoma occur in the pediatric age range [31,32]. Further preclinical evaluations of MLN4924 will depend upon emerging data from adult preclinical and clinical testing and on future advances in the understanding of the molecular basis of pediatric cancers.…”

Section: Discussionmentioning

confidence: 99%

Initial testing of the investigational NEDD8‐activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program

Smith

Maris

Görlick

et al. 2011

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Background MLN4924 is an investigational first-in-class small molecule inhibitor of NEDD8-activating enzyme (NAE). NAE is an essential component of the NEDD8 conjugation pathway, controlling the activity of a subset of ubiquitin-proteasome system (UPS) E3 ligases, multiprotein complexes that transfer ubiquitin molecules to substrate proteins. Procedures MLN4924 was tested against the PPTP in vitro panel using 96 hour exposure time at concentrations ranging from 1.0 nM to 10 μM. It was tested in vivo at a dose of 100 mg/kg [66 mg/kg for the acute lymphoblastic leukemia (ALL) xenografts] administered orally twice daily × 5 days. Treatment duration was 3 weeks. Results The median relative IC50 for MLN4924 against the PPTP cell lines was 143 nM, (range 15 nM to 678 nM) with that for the Ewing panel being significantly lower (31 nM). MLN4924 induced significant differences in EFS distribution compared to control in 20 of 34 (59%) evaluable solid tumor xenografts. MLN4924 induced intermediate activity (EFS T/C values > 2) in 9 of the 33 evaluable xenografts (27%), including 4 of 4 glioblastoma xenografts, 2 of 3 Wilms tumor xenografts, 2 of 5 rhabdomyosarcoma xenografts, and 1 of 4 neuroblastoma xenografts. For the ALL panel, 5 of 8 evaluable xenografts showed intermediate activity for the EFS T/C measure. MLN4924 did not induce objective responses in the PPTP solid tumor or ALL panels. Conclusions MLN4924 showed potent activity in vitro and in vivo showed tumor growth inhibitory activity against a subset of the PPTP solid tumor and ALL xenografts.

show abstract

Treatment of Pediatric Hodgkin Lymphoma

Cited by 23 publications

References 41 publications

Improved Outcomes after Autologous Bone Marrow Transplantation for Children with Relapsed or Refractory Hodgkin Lymphoma: Twenty Years Experience at a Single Institution

Improved Outcomes after Autologous Bone Marrow Transplantation for Children with Relapsed or Refractory Hodgkin Lymphoma: Twenty Years Experience at a Single Institution

Response‐dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: A report from the Children's Oncology Group

Initial testing of the investigational NEDD8‐activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program

Contact Info

Product

Resources

About