The Use of Purged and Non-Purged Transplantation for Peripheral Blood Stem Cell in Treatment of High Risk Neuroblastoma

By: Michael Lam, MD, MPH


A picture of cancer cells that may be targeted by various neuroblastoma treatment regimensYoung adults and children under the age of 30 who had high risk neuroblastoma were randomly assigned to receive both treatment and use of a regimen of the condition commonly known as non-purged or the other method known as immunomagnetically purged peripheral blood stem cells. There are treatments known as myeloblative chemo radiotherapy and immunomagnetically purged autologous bone marrow transplant that has demonstrated results that show improvements in outcomes for patients who have the condition of high risk neuroblastoma.

High risk neuroblastoma recurs at a rate this is high and it this is usually found in the bone marrow and bone. The children?s cancer group conducted research that showed promise with better improved outcomes for myeloblative chemotherapy combined with immunomagnetic bead purged autologous bone marrow compared to a more conventional dose of chemotherapy. It can be stated that immunocytology can be effective in determining if there is tumor growth of neuroblastomaor cells in the marrow of the bone.

As of the current date of this publication, there have been few studies or randomised control trials conducted for selective purged peripheral blood stem cells in any form of cancer. Non-purged and purged groups share similar outcomes that establish support for myeloablative therapy of high risk neuroblastoma when established by non-purged peripheral blood stem cells. It has been found that only 1% of peripheral blood stem cell samples had a detectable tumour by way of immunocytology and that is why peripheral blood stem cell testing has been eliminated from the studies of the children?s oncology group.

A woman undergoing neuroblastoma treatmentAbout 51% of patients who participated in the study received or aachieved a positive complete or very good partial result from the use of the treatment of induction chemotherapy, which can be compared to 87.5% previously reported with a smaller study. The trial demonstrated escalated levels of carboplatin, melphalan and etoposide and the omission of total body radiation. This was also whilst maintaining a period of 5 years of event free survival that was found to be akin to result reported in the myeloblative chemotherapy with addition isotretinoin segment. Total body radiation, was replaced with irradiation directed at the primary site of the tumour. Characteristics associated with total body radiation include; cataracts, abnormalities with dental structure and function, radiation pneumonitis, short stature and dysfunction of the thyroid. The escalated chemotherapy treatment exposed patients to toxic effects, demonstrated grade 3 or higher sinusoidal obstructive syndrome, which led to 3% of patients passing away. Results were obtained from a study of high dose tandem chemotherapy that demonstrated similarities.

However, immunomagnetic purging of peripheral blood stem cells may have not always shown improvements in outcomes. This may have been due to tumours residual in nature or the use of incomplete purging in the regimen. Preclinical modelling presents with immunomagnetic purging being successful in removing 3-4 logs of cancerous or tumour cells residing with the bone marrow when initiating with 10-20% tumour cell count. All five of the studied peripheral blood stem cell products that had tumours detectable by immunocytology led to the tumours being undetectable after the purging effect.

The study conducted included an amount of patients to achieve a complete response, but the numbers of patients were insufficient to resolve the complication of whether or not residual tumours were residing in patients was due to a failure of purging to improve patient outcomes. The patients in the study all took isotretinoin and patients in both groups of the research study, received a post consolidation of antibody plus cytokines. This post consolidation therapy would have shown elimination of tumours that were cell infused as a by-product which could have obscured results shown from the effects of purging.

Neuroblastoma Treatment Conclusion

Picture of samples that may be used to determine if a particular neuroblastoma treatment is effectiveThe study was conducted and designed with the goal of assessing the effects of purging with patients who have high risk neuroblastoma. The study had no intention as to the assessment of the outcomes in patients who suffer from stage 4 diseases whom are aged 18 months or older. Due to insufficient evidence, differences in outcomes in the treatment groups were present, but due to this limitation it became a non-issue. To be mentioned also is the limitation from the lack of information regarding TLDA analyses throughout purging before and after. The study however, measured a subset of patients with the methodology of urging which may have brought about interference in the interpretation of TLDA assay. To conclude, results demonstrate support for effectiveness and use of non-purged peripheral blood stem cell medications that is followed by myeloblative therapy of high risk neuroblastoma.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23890779

 
? Copyright 2016 Michael Lam, M.D. All Rights Reserved.

A picture of cancer cells that may be targeted by various neuroblastoma treatment regimens