Hyperfractionated total body irradiation for bone marrow transplantation. results in seventy leukemia patients with allogeneic transplants

TBI has been used widely in the setting of BMT over the past 3 decades. Early research demonstrated feasibility and efficacy in the myeloablative setting, in preparation first for allogenic BMT and later for autologous stem cell rescue. As experience with TBI increased, its dual roles of myeloablation and immunosuppression came to be recognized. Toxicity associated with myeloablative TBI remains significant, and this treatment is generally reserved for younger patients with excellent performance status. Reduced intensity conditioning regimens may be useful to provide immunosuppression for patients who are not candidates for myeloablative treatment. Efforts to reduce toxicity through protection of normal tissue using methods of normal tissue blocking and use of TLI, rather than TBI, continue. In the future, modalities such as helical tomotherapy, proton radiotherapy and radioimmunotherapy, may have roles in delivery of radiation to the BM and lymphoid structures with reduced normal tissue toxicity. With further investigation, these efforts may expand the therapeutic ratio associated with TBI, allowing safer delivery to a broader range of patients.

Section: Goals Of Tbimentioning

confidence: 98%

Section: Protection Of Normal Tissue During Tbimentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

Hill‐Kayser

Plastaras

Tochner

et al. 2010

“…[15][16][17][18][19][20][21][22] Studies have shown that the severity depends on both dose rate and total dose administered. [22][23][24][25][26] Several strategies have emerged to address this complication, including increasing the fractionation schedule to decrease the radiation dose administered at any one time [26][27][28][29][30][31][32][33][34] and reducing the lung dose directly by utilizing lung shielding. 17,28 Several studies have described an association between lung dose reduction and pulmonary-related mortality and overall survival.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary function following total body irradiation (with or without lung shielding) and allogeneic peripheral blood stem cell transplant

Soule

Simone

Savani

et al. 2007

Our purpose was to determine if total body irradiation (TBI) with lung dose reduction protects against subsequent radiation-induced deterioration in pulmonary function. Between July 1997 and August 2004, 181 consecutive patients with hematologic malignancies received fractionated TBI before allogeneic peripheral blood stem cell transplant. The first 89 patients were treated to a total dose of 13.6 Gy. Thereafter, total body dose was decreased to 12 Gy with lung dose reduction to 9 or 6 Gy. All patients underwent pulmonary function test evaluation before treatment, 90 days post-treatment, then annually. Median follow-up was 24.0 months. Eighty-nine patients were treated with lung shielding, and 92 without. At 1-year post transplant, there was a small but significant difference in lung volume measurements between patients with lung shielding and those without. This was not observed at the 2-year time point. When stratified by good (4100% predicted) or poor (p100% predicted) baseline lung function, patients with poor function demonstrated protection at 1 year with lung shielding, while those with good initial lung function did not. TBI with or without lung dose reduction has a small but statistically significant effect on pulmonary function measured at 1 year but not 2 years post irradiation.

“…50 To overcome these side effects, a fractionated TBI dose with higher biologically effective leukaemic cell kill may give superior suppression of malignant disease while limiting adverse effects on other tissues. 46,51,52 Data supplied by the acute leukaemia working party (ALWP) of the EBMT confirm the superiority of fractionated TBI for children with ALL in CR2 (n ¼ 525, median dose: 12 Gy, divided into two or more fractions, DFS: 5672%) vs single fraction TBI (n ¼ 245, median dose: 10 Gy, DFS 4473%; P ¼ 0.0008). In the same database, this was not observed for children with AML in CR1.…”

Section: Discussionmentioning

confidence: 88%

HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI

Willemze

Geskus

Noordijk

et al. 2007

To examine relapse, survival and transplant-related complications in relationship to disease-and pre-treatment-related characteristics, we evaluated 132 children, who consecutively received an allogeneic HLA-identical SCT for acute leukaemia in our centre: ALL in first remission (n ¼ 24), ALL in second remission (n ¼ 53) and AML in first remission (n ¼ 55). The source of the stem cells was bone marrow in all but three cases. Most patients (89%) were pre-treated with cyclophosphamide and an age-related dose of TBI. Initially, GVHD prophylaxis consisted of long-course MTX only (n ¼ 24), later shortcourse MTX and CsA (n ¼ 102) was given. All patients were nursed in strictly protective isolation and received total gut decontamination to suppress their potentially pathogenic enteric microflora. The 5-year probability of overall survival was 63, 53 and 74% for ALL1, ALL2 and AML1, respectively (median follow-up: 10.6 years). The overall transplant-related mortality was 6%. The incidence of acute GVHD was 17%; 6% was grades II-IV. A higher total biologically effective TBI dose (BED) resulted in a decreased relapse frequency (P ¼ 0.034) and increased overall survival. AML patients with acute GVHD got no relapse (P ¼ 0.02); this was not the case in ALL patients. Fractionated TBI regimens with higher BED should be evaluated in prospective studies.