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Date of Award

Spring 2021

Degree Name

Master of Medical Science (Physician Assistant)

Department

Physician Assistant; College of Health Sciences

First Advisor

Shannon Diallo

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is a disease that primarily effects children and is the most common malignancy in pediatric patients. The prognosis for standard risk patients is a 90% survival rate, but for high risk patients the prognosis is not as promising. High-risk patients are often given a hematopoietic stem cell transplant (HSCT) following complete remission status, patients are prepared for the HSCT with a combination of chemotherapy and total body irradiation (TBI). TBI is associated with negative long-term sequelae and even secondary cancers. This review analyzes the use of high dose chemotherapy in place of TBI for HSCT conditioning regimens in high risk pediatric ALL patients.

Methods: A literature search was conducted through Google Scholar, PubMed, and Arcadia University’s Landman Library online resources in October 2019. A total of seven articles were chosen using exclusion criteria including publication date, participant age range, and participant ALL classification as high risk. The study design, results and validity of each of these articles was analyzed and compared.

Results: The literature review revealed that while chemotherapy only based regimens may be comparable to TBI based regimens in myeloablative preparation for HSCT, further research needs to be done to directly compare the specific regimens in a larger sample size. Only three of the seven articles had reliable validity. The most notable of the conclusions from the reliable articles was that overall survival (OS) and 7 year event free survival (EFS) were comparable between a group that received TBI with chemotherapy prior to their HSCT and a group that received only chemotherapy prior to their HSCT. Another article found that EFS was increased when patients were transplanted during complete remission 1 (CR1) versus later stages of remission (CR2+), this is likely due to increased exposure to toxic agents and radiation after multiple treatment efforts in patients who have relapsed.

Discussion: Most of the studies provided data on differing variables and were retrospective cohort studies, making it challenging to directly compare the conclusions of each study. Significant conclusions about TBI versus chemotherapy alone were made by one reliable study. Some studies had limitations, such as inadequate statistical power due to a low number of participants.

Conclusion: Overall, inadequate statistical power and a lack of certainty in the benefits of chemotherapy over TBI in terms of long-term sequelae as well as efficacy prevent these findings from being clinically significant. More research needs to be conducted on high risk patients with ALL directly comparing TBI in conjunction with chemotherapy to chemotherapy alone for HSCT. Future studies should consider larger participant numbers, conducting randomized control trials rather than retrospective cohort or single arm studies, and evaluating patient quality of life when receiving certain regimens.

Comments

References

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Do pediatric patients classified as high-risk following relapse of acute lymphocytic leukemia, have an increased rate of 3-year event-free survival if treated with chemotherapy and radiation before receiving an allogenic HSCT, as compared to patients treated with chemotherapy alone before an allogenic HSCT?

Introduction: Acute lymphoblastic leukemia (ALL) is a disease that primarily effects children and is the most common malignancy in pediatric patients. The prognosis for standard risk patients is a 90% survival rate, but for high risk patients the prognosis is not as promising. High-risk patients are often given a hematopoietic stem cell transplant (HSCT) following complete remission status, patients are prepared for the HSCT with a combination of chemotherapy and total body irradiation (TBI). TBI is associated with negative long-term sequelae and even secondary cancers. This review analyzes the use of high dose chemotherapy in place of TBI for HSCT conditioning regimens in high risk pediatric ALL patients.

Methods: A literature search was conducted through Google Scholar, PubMed, and Arcadia University’s Landman Library online resources in October 2019. A total of seven articles were chosen using exclusion criteria including publication date, participant age range, and participant ALL classification as high risk. The study design, results and validity of each of these articles was analyzed and compared.

Results: The literature review revealed that while chemotherapy only based regimens may be comparable to TBI based regimens in myeloablative preparation for HSCT, further research needs to be done to directly compare the specific regimens in a larger sample size. Only three of the seven articles had reliable validity. The most notable of the conclusions from the reliable articles was that overall survival (OS) and 7 year event free survival (EFS) were comparable between a group that received TBI with chemotherapy prior to their HSCT and a group that received only chemotherapy prior to their HSCT. Another article found that EFS was increased when patients were transplanted during complete remission 1 (CR1) versus later stages of remission (CR2+), this is likely due to increased exposure to toxic agents and radiation after multiple treatment efforts in patients who have relapsed.

Discussion: Most of the studies provided data on differing variables and were retrospective cohort studies, making it challenging to directly compare the conclusions of each study. Significant conclusions about TBI versus chemotherapy alone were made by one reliable study. Some studies had limitations, such as inadequate statistical power due to a low number of participants.

Conclusion: Overall, inadequate statistical power and a lack of certainty in the benefits of chemotherapy over TBI in terms of long-term sequelae as well as efficacy prevent these findings from being clinically significant. More research needs to be conducted on high risk patients with ALL directly comparing TBI in conjunction with chemotherapy to chemotherapy alone for HSCT. Future studies should consider larger participant numbers, conducting randomized control trials rather than retrospective cohort or single arm studies, and evaluating patient quality of life when receiving certain regimens.