Long Term Effects of TBI Based Versus Non-TBI Based Myeloablative Conditioning in AYA AML Patients, a Systematic Review

Allogenic hemopoietic stem cell transplant (allo-HCT) continues to be an important aspect in the treatment paradigm for AML, including for adolescent young adult (AYA) AML patients. The conditioning regimen AYA AML allo-HCT patients receive not only affects their disease outcomes but their long-term outcomes as well. They may have to deal with lifelong consequences, despite being in remission, from their conditioning regimen. Thus, it is important to clarify the role total body irradiation (TBI) based myeloablative conditioning (MAC) has on long term outcomes in this patient population, in comparison to non-TBI based MAC. By comparing these MAC regimens, we can further improve the long-term outcomes of this patient population. Evaluate long term outcomes of AYA AML allo-HCT patients who received TBI versus non-TBI MAC. PRISMA guidelines were used; eligibility criteria included reports comparing TBI and non-TBI MAC in AYA AML allo-HCT patients. AYA patients are defined as 15-39 years old. A systematic search of reports was conducted using search terms AML, AYA, TBI, non-TBI, allo-HCT, and long-term outcomes or related synonyms with the following: Google scholar, WOS, Embase, PMC, Medline, Cochrane, and Pubmed. Of 345 articles generated, two met eligibility criteria; an article by Lee et al and an article by Mizuno et al. Both are retrospective and used registry data- CIBMTR, and TRUMP of JHST with JDCHCT respectively. Mizuno et al had 2350 patients with median age at transplant 31 years old and 47% received TBI MAC. Lee et al had 826 patients with a median age of 29 years old and 76% received TBI MAC. Both studies showed no difference in OS between the two groups, at 10 and 3 years respectively. In patients transplanted while in CR, TBI MAC was associated with lower relapse rates compared to non-TBI group (Mizuno 19.8% vs 24.1%, P = 0.047; Lee et al 13% vs 19%, P= 0.01). This was not observed in non-CR patients for Mizuno et al. There was no difference of NRM in Lee et al or Mizuno et al non-CR patients. Mizuno et al CR patients had increased NRM and aGVHD in the TBI versus non-TBI group (NRM: 14.7% vs 11.1%; P = .021, aGVHD (35.5% vs 29.2%; P = .038). Similar aGVHD and cGVHD rates were seen in both groups in Lee et al, and in non-CR patients in Mizuno et al. Mizuno et al CR patients had similar cGHVD rates. Lee et al found that TBI MAC had higher risk of developing cataracts (HR 4.98; 95% CI, 2.42% to 10.24%; P=.001). TBI MAC did not correlate with other late effects such as AVN, DM, or gonadal dysfunction, or secondary neoplasms. Mizuno et al did not investigate these effects. This review highlights the need for further investigation of AYA patients in transplant. With the help of registry data there can be strides in improvement. AYA AML patients who received TBI based MAC may have a higher risk of cataracts and not of other late effects; however, this needs further exploration.