Total Body Irradiation Among Recipients of Tcrαβ /CD19- Depleted Grafts in a Cohort of Children with Hematologic Malignances: Single Center Experience

Purpose: to analyze the radiation-induced organ-specific toxicity and survival outcomes in pediatric patients after hematopoietic stem cell transplantation (HSCT) with TCRαβ /CD19- depletion and myeloablative total body irradiation (TBI)-based conditioning regimen.

Methods and Materials: We analyzed retrospectively a cohort of 197 patients (pts) with different hematological malignances. ALL – 150 pts: 1^st CR – 40 pts; 2^nd CR – 77; advanced – 33 pts; AML – 24 pts: active disease – 20 pts, 1^st CR – 1 pt; 2^nd CR - 3 pts; others (JMML, NHL etc.) – 23 pts. All the patients received allo-HSCT with TCRαβ /CD19- Depletion at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between 07/2014 and 04/2020. TBI (1200 cGy given twice daily in 6 fractions or once daily given in 4 fractions) was used as a part of HSCT conditioning regimens. The TBI technique included the irradiation of whole body using IMRT (TomoTherapy Helical System and IMRT Vmat on Elekta Linac) with following organ sparing: lungs, kidneys, lenses. The lung dose was prescribed as V8<40% (i.e the volume of each lung receiving 8 Gy, not to exceed 40%). The mean kidney dose was prescribed at < 8Gy. Forty-four patients received additional simultaneous integrated boost (SIB) up to 15 Gy or consecutive boost up to 18 Gy to different sites (bone marrow, etc.). Age of patients was from 3 to 21 y.o. (median - 10 y.o.). 26 pts were treated under anesthesia. Haploidentical HSCT was performed in 172 pts, allo-HSCT from matched unrelated donor was performed in 14 pts, from matched related donor – in 12 pts.

We register acute toxicity (nausea/vomit/diarrhea, headache, veno-occlusive disease (VOD)) - during radiation therapy and 30 days after SCT, subacute toxicity - up to 100^th day after SCT and late toxicity – at least 100 days after SCT according RTOG scale.

Results:

Follow-up period was from 0,3 to 7,2 years (median follow up period – 2 years). OS for all the patients was 66,7%±3,8%; EFS was 63,0%±3,6%; the transplant-related mortality rate was 8,9±2,1%. OS in patients with acute leukemia was 69,9±4,2% in ALL-group and 44,8±11,0% in AML-group (p=0,015). Mean survival time for patients with ALL was 4,3 years. EFS for pts with ALL was 66,7±4,1%; TRM = 8,4±2,3%. EFS for pts with AML was 43,1±10,3%; TRM = 16,3±7,5%. TRM in patients with 1^st and 2^nd CR was 5,5%±2,9%. TBI-related toxicity not significantly contribute to TRM, as most cases were infection-related. Acute toxicity during radiation therapy was registered among 100% of pts, in 97% of pts acute toxicity didn’t exceed grade 1-2 according to RTOG scale. Among 3% of pts - grade 3 acute toxicity (nausea/vomiting/headache/diarrhea) was observed. We also registered VOD in 3 pts (all of them received SIB to bone marrow). Subacute toxicity was registered in 0.5% of patients (n=1) (interstitial pneumonia 3-4 stage according RTOG). Radiation-induced kidney toxicity was not registered.

Conclusion: The developed TBI method included in conditioning regimen before allogenic SCT with TCRαβ /CD19-depletion in pediatric pts has tolerable organ-specific toxicity and predictable results of survival outcomes.