کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5524417 1546242 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phase I Trial of Total Marrow and Lymphoid Irradiation Transplantation Conditioning in Patients with Relapsed/Refractory Acute Leukemia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Phase I Trial of Total Marrow and Lymphoid Irradiation Transplantation Conditioning in Patients with Relapsed/Refractory Acute Leukemia
چکیده انگلیسی


- The total marrow and lymphoid irradiation/cyclophosphamide/etoposide conditioning regimen is safe up to a dose of 2000 cGy
- Radiation to off-target critical organs is lower than typically delivered by total body irradiation
- The results showed an acceptable risk for graft-versus-host disease and were encouraging for disease control

Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue. We conducted a phase I trial in 51 patients (age range, 16 to 57 years) with relapsed/refractory acute leukemia undergoing HSCT (matched related, matched unrelated, or 1-allele mismatched unrelated) with active disease, combining escalating doses of TMLI (range, 1200 to 2000 cGy) with cyclophosphamide (CY) and etoposide (VP16). The maximum tolerated dose was declared at 2000 cGy, as TMLI simulation studies indicated that >2000 cGy might deliver doses toxic for normal organs at or exceeding those delivered by standard TBI. The post-transplantation nonrelapse mortality (NRM) rate was only 3.9% (95% confidence interval [CI], .7 to 12.0) at day +100 and 8.1% (95% CI, 2.5 to 18.0) at 1 year. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 43.1% (95% CI, 29.2 to 56.3) and for grade III and IV, it was 13.7% (95% CI, 6.9 to 27.3). The day +30 complete remission rate for all patients was 88% and was 100% for those treated at 2000 cGy. The overall 1-year survival was 55.5% (95% CI, 40.7 to 68.1). The TMLI/CY/VP16 conditioning regimen is well tolerated at TMLI doses up to 2000 cGy with a low 100-day and 1-year NRM rate and no increased risk of GVHD with higher doses of radiation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biology of Blood and Marrow Transplantation - Volume 23, Issue 4, April 2017, Pages 618-624
نویسندگان
, , , , , , , , , , , , , , , ,