CNS prophylaxis in acute lymphoblastic leukemia (ALL) includes systemic and intrathecal chemotherapy. Radiotherapy is rarely indicated, individually in high-risk patients. In patients with initial leukemic CNS infiltration or relapse of ALL in the CNS, radiotherapy should be considered if systemic or intrathecal therapy fails. Radiotherapy should also be considered in patients with ALL or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) with a history of pre-transplant CNS involvement. According to the current guidelines of the International Lymphoma Radiation Oncology Group (ILROG), a radiation dose of 18-24 Gy is recommended, optimally 2 weeks at the end of systemic treatment, but no less than 48-72 hours. You can find the full ILROG recommendations here: https://www.ilrog.org/main-st
Specifics of Leukemia Relapse in the CNS
Because this is a prognostic situation, for selected high-risk patients (with pre-transplant history of CNS infiltration at baseline or in relapse undergoing allo-SCT for ALL or AML) it is recommended to consider craniospinal radiotherapy: AML with the addition of RT shows an improvement of 5 years RFS at 32% (comparable to patients without a history of CNS leukemic infiltration) vs. 6% of patients with intrathecal therapies only.
Recommended Volume of Radiation in Case of Leukemia Relapse in the CNS
Retrospective data show the importance of larger RT fields in this situation – craniospinal irradiation (CSI) instead of whole brain radiotherapy (WBRT). ILROG recommends undergoing CNS radiotherapy before hematopoietic cell transplantation (HCT) in patients with leukemia with a history of CNS involvement (baseline or relapse), regardless of CNS infiltration response to systemic and intrathecal treatment. There is some evidence that the patient may benefit more from CSI before allo-SCT. The preferred procedure in this case is CSI over WBRT. These procedures are taken from pediatric protocols.
Arguments Supporting Proton Radiotherapy
In this case, proton radiotherapy has major advantages over other forms of radiotherapy. These advantages include zero radiation exposure to organs in front of vertebral bodies and minimal systemic toxicity (reduction of nausea, vomiting, diarrhea). Additionally, proton radiotherapy is suitable for highly pretreated patients with the necessary dose reduction to the lungs, intestinal loops, heart and other organs.
References and professional literature on the issue of radiotherapy in hematooncological diseases:
Dabaja BS(1), Hoppe BS(2), Plastaras JP(3). PROTON THERAPY FOR ADULTS WITH MEDIASTINAL LYMPHOMAS: THE INTERNATIONAL LYMPHOMA RADIATION ONCOLOGY GROUP (ILROG) GUIDELINES. Blood. 2018 Aug 14. pii: blood-2018-03-837633 http://www.bloodjournal.org/content/132/16/1635?sso-checked=true
Rates of Toxicity and Outcomes After Mediastinal Proton Therapy For Relapsed/Refractory Lymphoma Tseng, Y.D. et al. International Journal of Radiation Oncology • Biology • Physics , Volume 99, Issue 2 , S62 – S63. https://www.redjournal.org/article/S0360-3016(17)31205-1/fulltext
Pinnix CH. C., Yahalom J., Specht L., Dabaja B.S: Radiation in Central Nervous System Leukemia: Guidelines From the International Lymphoma Radiation Oncology Group https://www.ncbi.nlm.nih.gov/pubmed/?term=30102203
Mayadev JS, et al. Impact of cranial irradiation added to intrathecal conditioning in hematopoietic cell transplantation in adult acute myeloid leukemia with central nervous system involvement. Int J Radiat Oncol Biol Phys. 2011;80(1):193–198. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3297488/
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