Patient-reported late effects of single fraction total body irradiation for non-malignant haematological disease transplant conditioning

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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