Optimizing care for high-risk neuroblastoma patients treated with dinutuximab: Challenges for the multidisciplinary team

Current treatment protocols for high-risk neuroblastoma include high-dose chemotherapy, surgery, stem cell transplantation and radiation. Recently, dinutuximab, a chimeric monoclonal antibody, specifically targeting the disialoganglioside highly expressed on neuroblastoma cells, has been licensed. Its incorporation in maintenance therapy represents a promising treatment approach. The introduction of its use was a challenge for the entire multidisciplinary team in our pediatric hematology and oncology ward just as for the pharmacy team. An overview of the key points that were observed is presented.

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Treatment Intensification of Traditional BFM Therapy with 3 Chemotherapy Blocks and Double Delayed Intensification (Protocol II) Improves Outcome in Infants with High Risk (HR) Acute Lymphoblastic Leukemia (ALL): Results of Two Consecutive AIEOP Studies.

Blood ◽

10.1182/blood.v106.11.871.871 ◽

2005 ◽

Vol 106 (11) ◽

pp. 871-871 ◽

Cited By ~ 1

Author(s):

Carmelo Rizzari ◽

Maria Grazia Valsecchi ◽

Paola De Lorenzo ◽

Maurizio Aricò ◽

Giuseppe Basso ◽

...

Keyword(s):

High Risk ◽

Lymphoblastic Leukemia ◽

Treatment Strategies ◽

High Dose Chemotherapy ◽

P Value ◽

High Dose ◽

Treatment Intensification ◽

Treatment Protocols ◽

Hematopoietic Stem ◽

The Impact

Abstract Introduction: Cure rates of ALL in children aged less than one year (i.e. infants) at diagnosis are in the range of 35–40%. Encouraging results have been recently reported in infants by using intensified treatment, including high dose chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Aim: To evaluate the impact of the two treatment strategies adopted in the AIEOP ALL 91 and 95 studies on the outcome of ALL in infants. Patients and Methods: Fifty-two infants with ALL were enrolled between 1991 and 1999 in two consecutive studies, named AIEOP ALL 91 and ALL 95. Infants with an identified t(4;11) translocation had to be included in the high risk (HR) groups whilst those without this genetic abnormality could be treated in the intermediate (IR) or HR groups according to presenting features and treatment response. Patients belonging to the IR groups received a traditional BFM back-bone based treatment (protocols I, M and II), while those classified in the HR groups underwent an tensified treatment including induction (BFM protocol IA only, in study AIEOP ALL 91, and IA+IB in study ALL 95), consolidation with either 9 blocks of non-cross-resistant drugs (ALL 91) or 3 blocks followed by the 8-drug reinduction regimen - BFM protocol II - repeated twice (ALL 95). All patients were given a continuation phase (reinforced in HR patients of study ALL 95 by vincristine/prednisone pulses). Overall treatment duration was 2 years in both studies. Results: Infants in studies ALL 91 (n=21) and ALL 95 (n=31) had similar biological and clinical characteristics. The overall event-free survival (EFS) at 5 years was 45.0% (SE 7.0%). The EFS, after censoring for HSCT in 1st CR, was 38.1% (SE 11.4%) in ALL 91 and 51.6% (SE 9.9%) in ALL 95 (p-value=0.29). Patients treated in the IR arm of the two studies had a similar outcome. Better results were obtained in patients treated in the HR arm of ALL 95 study, where 9/17 chemotherapy-only patients and 3/4 HSCT patients are alive in CCR as compared to 1/7 and 0/2, respectively, in patients treated in the ALL 91 study. Discussion: These data show that full traditional BFM therapy intensified by 3 post-induction chemotherapy blocks and double protocol II (adopted in study ALL 95), is associated with a better outcome in infants with HR ALL.

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Acute and late toxicity following adjuvant high-dose chemotherapy for high-risk primary operable breast cancer

European Journal of Cancer ◽

10.1016/s0959-8049(02)80298-2 ◽

2002 ◽

Vol 38 (11) ◽

pp. S95

Author(s):

I Svane

Keyword(s):

Breast Cancer ◽

High Risk ◽

Late Toxicity ◽

High Dose Chemotherapy ◽

Operable Breast Cancer ◽

High Dose ◽

Primary Operable Breast Cancer

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Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma

Cancers ◽

10.3390/cancers13092096 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2096

Author(s):

Celina L. Szanto ◽

Annelisa M. Cornel ◽

Sara M. Tamminga ◽

Eveline M. Delemarre ◽

Coco C. H. de Koning ◽

...

Keyword(s):

T Cells ◽

High Risk ◽

Nk Cells ◽

Immune Cell ◽

High Dose Chemotherapy ◽

Immune Monitoring ◽

High Dose ◽

Effector Cells ◽

Gm Csf ◽

Immune Cell Subsets

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.

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Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Cancers ◽

10.3390/cancers13143479 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3479

Author(s):

Andrea Morales-Martinez ◽

Fernando Lozano-Sanchez ◽

Alberto Duran-Peña ◽

Khe Hoang-Xuan ◽

Caroline Houillier

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Elderly Patients ◽

Treatment Strategies ◽

Central Nervous System Lymphoma ◽

High Dose Chemotherapy ◽

Current Treatment ◽

Cns Lymphoma ◽

High Dose ◽

Consolidation Phase

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

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