High dose chemoradiotherapy is traditionally used to ensure donor engraftment after unrelated and mismatched donor BMT. Conditioning usually includes TBI at doses> 1000cGy in fractionated schemas at low dose rates (7-10 cGy/min). TBI given in this fashion with additional immunosuppressive chemotherapy results in significant early and late treatment related morbidity and mortality. Single low dose TBI administered at a high dose rate produces durable engraftment with minimal toxicity in adults (Adkins, et al, Blood Supplement, 1999). This Phase II study was hence extended to include children undergoing matched or mismatched URD BMT. Between March 1998 and June 2000, 11 children, mean age 12 years (range 6-20), underwent URD BMT following conditioning with cyclophosphamide (60 mg/kg/day × 2)and single 550 cGy dose of TBI (at 30 cGy/min). GVHD prophylaxis included cyclosporine, methotrexate and corticosteroids. 5 patients had AML in CR2,4 had ALL in CR2, 1 had biphenotypic leukemia in CR1 and 1 had Burkitt's lymphoma in CR2. 6 recipients (54%) were HLA (A.B.DRB Didentical to donors, 5 (46%) were mismatched at 1 locus serologically or DRB1 mismatched. The mean dose of T replete marrow was 4.39 × 108 (range 0.3-7.5) TNC/kg and 4.97 x 106 (range 1.42-20.1) CD34+ cells/kg. All received the 3 target methotrexate doses on days 1, 3 and 6. 1 recipient (9%) who was mismatched with the donor had graft rejection. All other évaluable recipients had complete donor chimerism (99-100%), assessed by VNTR on day +30, +180 and +365. In 8 patients that engrafted, the ANC was >500/mm3 on day + 14(11-17) and platelets were >20,000/cu.mm3 on day +28 (17-47). Toxicity related to conditioning was minimal. 3 patients developed mild mucositis. Of note, 2 patients with Downs Syndrome developed no mucositis. Severe organ toxicity did not occur. Acme GVHD was absent in 5 (62%) and grade 2-4 in 3 (37%). Localized chronic GVHD developed in 2 (28%). 4 recipients died, 2 with early sepsis and 2 with GVHD after mismatched transplants. The mean follow up in 6 patients that have engrafted and survived is 449 (60-850) days, with only one relapse at 180 days. Conclusion: Low dose single exposure TBI (550 cGy) administered at a high dose rate results in early and durable engraftment in pediatrie recipients of URD BMTwith a low rate of graft failure, treatment related toxicity and GVHD.
|Issue number||11 PART II|
|State||Published - Dec 1 2000|