Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases

Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211–labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation

“…The safety and efficacy of radioimmunotherapy for conditioning in HCT have previously been explored in several clinical studies, where ␤-emitter based RIT successfully has been used to augment conditioning regimens. [1][2][3][4] Less explored are the ␣-emitters, which could be more suitable for conditioning in HCT as their short path length and high linear energy transfer enable delivery of highly localized cytotoxic radiation with minimal nonspecific irradiation of surrounding tissue. 5,8,34,35 In relation to HCT, ␣-emitter-labeled mAbs alone as conditioning have only been investigated by our group.…”

“…Thyroid-stimulating hormone (TSH) and free T 4 were analyzed in a total of 5 dogs at end of study (H271, H388, H379, H251, and H267). TSH, free T 4 , and thyroid histopathology were normal in 3 dogs, whereas evidence of subclinical hypothyroidism was observed in H267 (TSH: at 0.67 ng/mL; free T 4 : 3 ng/mL) and H388 (TSH: at 0.54 ng/mL; free T 4 : 2.1 ng/mL), which showed evidence of subclinical hypothyroidism (TSH, upper normal limit 0.5 ng/mL; free T 4 , normal range 0.7-3.1 ng/mL).…”

“…The efficacy and safety of this approach have been demonstrated in several clinical trials where antibody-coupled ␤-emitters, such as yttrium-90 ( 90 Y), rhenium-188 ( 188 Re), and iodine-131 ( 131 I), have been used to augment a variety of high-dose and reduced-intensity conditioning regimens. [1][2][3][4] The long path length of ␤-emitters, which makes them ideal in the setting of poorly perfused or bulky tumors, also makes them less optimal in situations with small volume tumors, minimal residual disease, or as part of an HCT conditioning regimen. 5 It has been estimated that only 1.5% and 17% of the energy from 90 Y-and 131 I-labeled mAbs, respectively, is deposited in tumors that are 200 m in diameter, whereas the rest is deposited in surrounding tissue resulting in nonspecific toxicity.…”

Future of Allogeneic Hematopoietic Stem Cell Transplantation for Chemotherapy-Resistant Pediatric Acute Leukemia: Potential Advances

“…in some children with refractory leukemia [12]. Alternative approaches to enhance the potency of conditioning include inclusion of potent chemotherapeutic agents, such as clofarabine, or dose escalation of total body irradiation.…”

Stem Cell Transplantation for Primary Immunodeficiency

“…A highly favorable ratio of marrow dose to other organ dose was demonstrated, and stable engraftment was achieved with complete donor chimerism in 13 out of 16 (81%) patients. One patient with Griscelli syndrome and who had secondary graft failure after the first HLA haploidentical transplantation achieved stable complete donor chimerism with radioimmunotherapy alone [45].…”