Dosimetry of single fraction high dose total body irradiation as measured by thermoluminescent dosimeters

Introduction: Patients with severe complications of non-malignant haematological disease are considered as candidates for curative treatment with an allogenic bone marrow transplant (ABMT). A non-myeloablative conditioning regimen is used; consisting of an alkylating agent and single fraction total body irradiation (SFTBI) at a dose of 2-4.5 Gy (dose rate 150mu/min). This is distinct from high dose fractionated total body irradiation (TBI) used in a myeloablative conditioning regimen; for which the late effects are well documented. There is however no dedicated study on the late effects associated with low dose SFTBI. Methods: We undertook a single institution study focusing on patient reported outcomes after SFTBI (January 2003 – January 2019) delivered more than 1-year previously, prior to an AMBT in patients aged under 16-years for non-malignant haematological conditions. A 19-point questionnaire was conducted with study subjects over the phone. The primary outcome was late effects as reported by patients. Secondary outcomes were patient demographics. Results: Fifty patients were screened, 31 were invited to take part and 24 consented to participate. Pulmonary toxicity was the most common visceral effect reported (5 patients), followed by kidney (3) and cardiac (2). No patients reported cataracts, diabetes or secondary malignancy. Two patients were on sex hormone replacement although no evidence of female menstrual delay was demonstrated. The majority (21) were enrolled in mainstream schools. Conclusion: Late effects do occur after SFTBI, but are mild and occur less frequently compared to high dose TBI. The consent process with children/parents prior to SFTBI should reflect this.

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Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol

BMJ Open ◽

10.1136/bmjopen-2020-040467 ◽

2020 ◽

Vol 10 (12) ◽

pp. e040467

Author(s):

Seitaro Terakura ◽

Takaaki Konuma ◽

Masatsugu Tanaka ◽

Yukiyasu Ozawa ◽

Makoto Onizuka ◽

...

Keyword(s):

Cord Blood ◽

Study Protocol ◽

Total Body Irradiation ◽

Graft Failure ◽

Cord Blood Transplantation ◽

Conditioning Regimen ◽

High Dose ◽

Blood Transplantation ◽

Total Body ◽

Randomised Controlled

IntroductionA better long-term quality of life after umbilical cord blood transplantation (CBT) is observed compared with transplants from other alternative donors, whereas graft failure and relapses after CBT are still major issues. To minimise graft failure and relapse after CBT, intensification of conditioning by the addition of high-dose cytosine arabinoside (CA) and concomitant continuous use of granulocyte-colony stimulating factor (G-CSF) are reported to convey a significantly better survival after CBT in some retrospective studies. To confirm the effect of G-CSF plus CA combination, in addition to the standard conditioning regimen, cyclophosphamide (CY)/total body irradiation (TBI), we design a randomised controlled study comparing CA/CY/TBI with versus without G-CSF priming (G-CSF combined conditioned cord blood transplantation [G-CONCORD] study).Methods and analysisThis is a multicentre, open-label, randomised phase III study that aimed to compare G-CSF+CA/CY/TBI as a conditioning regimen for CBT with CA/CY/TBI. Patients with acute myeloid leukaemia or myelodysplastic syndrome, aged 16–55 years, are eligible. The target sample size is 160 and the registration period is 4 years. The primary endpoint is the 2-year disease-free survival rate after CBT. The secondary endpoints are overall survival, relapse, non-relapse mortality, acute and chronic graft-versus-host disease, engraftment rate, time to neutrophil recovery, short-term adverse events, incidence of infections and causes of death.This study employs a single one-to-one web-based randomisation between the with-G-CSF versus without-G-CSF groups after patient registration. Combination of high-dose CA and CY/TBI in both groups is used for conditioning.Ethics and disseminationThe study protocol was approved by the central review board, Nagoya University Certified Review Board, after the enforcement of the Clinical Trials Act in Japan. The manuscripts presenting data from this study will be submitted for publication in quality peer-reviewed medical journals. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journals.Trial registration numbersUMIN000029947 and jRCTs041180059.

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Allogeneic hematopoietic cell transplantation for patients with high-risk acute lymphoblastic leukemia in first or second complete remission using fractionated total-body irradiation and high-dose etoposide: A 15-year experience

Experimental Hematology ◽

10.1016/s0301-472x(03)00231-5 ◽

2003 ◽

Vol 31 (10) ◽

pp. 981-986 ◽

Cited By ~ 39

Author(s):

Catriona H.M Jamieson ◽

Michael D Amylon ◽

Ruby M Wong ◽

Karl G Blume

Keyword(s):

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Complete Remission ◽

Cell Transplantation ◽

Total Body Irradiation ◽

Hematopoietic Cell Transplantation ◽

Lymphoblastic Leukemia ◽

Hematopoietic Cell ◽

High Dose ◽

Total Body

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Histologic changes in dental morphology induced by high dose chemotherapy and total body irradiation

Oral Surgery Oral Medicine Oral Pathology ◽

10.1016/s0030-4220(06)80107-6 ◽

1994 ◽

Vol 77 (1) ◽

pp. 56-60 ◽

Cited By ~ 38

Author(s):

Göran Dahllöf ◽

Björn Rozell ◽

Carl-Magnus Forsberg ◽

Birgit Borgström

Keyword(s):

Total Body Irradiation ◽

High Dose Chemotherapy ◽

High Dose ◽

Dental Morphology ◽

Total Body ◽

Histologic Changes

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Fractionated versus single-dose total body irradiation at low and high dose rates to condition canine littermates for DLA-identical marrow grafts

Blood ◽

10.1182/blood.v83.11.3384.3384 ◽

1994 ◽

Vol 83 (11) ◽

pp. 3384-3389 ◽

Cited By ~ 30

Author(s):

R Storb ◽

RF Raff ◽

FR Appelbaum ◽

HJ Deeg ◽

TC Graham ◽

...

Keyword(s):

Dna Repair ◽

Single Dose ◽

Dose Rate ◽

Total Body Irradiation ◽

High Dose Rate ◽

Lymphoid Cells ◽

High Dose ◽

Dose Rates ◽

Total Body ◽

Allogeneic Marrow

Abstract We explored in dogs the immunosuppressive properties of 450 cGy total body irradiation (TBI) delivered from two opposing 60Co sources, as assessed by the criterion of successful engraftment of allogeneic genotypically DLA-identical littermate marrow. Two questions were asked in this study. Firstly, does dose rate affect the immunosuppressive effect of TBI when administered in a single dose? Secondly, does fractionation alter the immunosuppression of TBI when delivered at a very fast dose rate? Dose rates studied included 7 and 70 cGy/min, and fractionation involved four fractions of 112.5 cGy each, with 6-hour minimum interfraction intervals. Six of 7 dogs receiving 450 cGy single- dose TBI at 70 cGy/min showed sustained engraftment of the allogeneic marrow, compared with 1 of 7 dogs receiving single-dose TBI at 7 cGy/min (P = .01). Fractionated TBI at 70 cGy/min resulted in sustained allogeneic engraftment in 3 of 10 dogs, a result that was statistically significantly worse than that with single-dose TBI at 70 cGy/min (P = .03) and not statistically different (P = .24) from that with fractionated TBI delivered at 7 cGy/min (0 of 5 dogs engrafted). A single dose of 450 cGy of TBI delivered at a rate of 70 cGy/min is significantly more immunosuppressive than the same total dose delivered at 7 cGy/min. Fractionated TBI at 70 cGy/min is significantly less immunosuppressive than single-dose TBI at 70 cGy/min and not significantly different from fractionated TBI administered at 7 cGy/min. Results are consistent with the notion that significant DNA repair in lymphoid cells is possible during interfraction intervals at the relatively high dose rate of 70 cGy/min.

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High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.12.2559 ◽

1994 ◽

Vol 12 (12) ◽

pp. 2559-2566 ◽

Cited By ~ 51

Author(s):

C H Weaver ◽

F B Petersen ◽

F R Appelbaum ◽

W I Bensinger ◽

O Press ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Malignant Lymphoma ◽

Total Body Irradiation ◽

Advanced Disease ◽

High Dose ◽

Hematopoietic Stem ◽

Total Body ◽

M Estimates

PURPOSE To evaluate a high-dose treatment regimen of fractionated total-body irradiation (TBI), etoposide, and cyclophosphamide (Cy) followed by autologous stem-cell transplantation (ASCT) in patients with malignant lymphoma. PATIENTS AND METHODS Fifty-three patients with non-Hodgkin's lymphoma (NHL; n = 43) or Hodgkin's disease (HD; n = 10) received 12.0 Gy of fractionated TBI, etoposide 60 mg/kg, and Cy 100 mg/kg followed by infusion of autologous hematopoietic stem cells. RESULTS Thirty-one of 53 patients are alive a median of 643 (range, 177 to 1,144) days after transplant. The 2 year Kaplan-Meier (K-M) estimates of survival, event-free survival (EFS), and relapse for all 53 patients were 54%, 45%, and 43%, respectively. Sixteen of 24 patients with less advanced disease and 10 of 29 patients with more advanced disease survive free of disease for K-M estimates of EFS of 61% and 31%, respectively (P = .006). The K-M estimates of relapse were 34% for patients with less advanced disease and 53% (P = .05) for patients with more advanced disease. The K-M estimates of dying from causes other than relapse were 8% in patients with less versus 25% in patients with more advanced disease (P = .09). CONCLUSION These data indicate that approximately 60% of patients transplanted early after failure of initial therapy for malignant lymphoma are projected to be disease-free more than 2 years after treatment with fractionated TBI, etoposide, and Cy and infusion of autologous hematopoietic stem cells. The transplant-related mortality rate is low and relapse is the main cause of treatment failure in patients with less advanced disease. For patients with more advanced disease, the K-M estimates of both transplant-related deaths (25%) and relapse (53%) remain major problems.

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High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.4.576 ◽

1988 ◽

Vol 6 (4) ◽

pp. 576-582 ◽

Cited By ~ 37

Author(s):

S Riddell ◽

F R Appelbaum ◽

C D Buckner ◽

P Stewart ◽

R Clift ◽

...

Keyword(s):

Acute Leukemia ◽

Total Body Irradiation ◽

Disease Free Survival ◽

Lymphocytic Leukemia ◽

Myelogenous Leukemia ◽

Phase Iii ◽

High Dose ◽

Severe Toxicity ◽

Total Body ◽

Disease Free

Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.

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