Methods |
Randomised controlled trial with two arms: BMT compared with PBSCT in haematological malignancies
Participating centre(s): 1 Institute of Cancer Research, Sutton, Surrey, United Kingdom
Recruitment period: June 1995 to August 1997
41 participants randomised, 39 participants evaluated (2 participants excluded: 1 participants due to fulminant relapse, 1 donor withdrew after enrolment but before donating)
Intervention arm: 19 participants evaluated
Control arm: 20 participants evaluated
Median follow‐up time: 33 months
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Participants |
Inclusion criteria: between 18 and 55 years old, malignant haematological disease (primary refractory disease) requiring allogeneic hematopoietic stem‐cell transplantation, HLA‐identical sibling donor
Exclusion criteria: not reported
Median age: Intervention: 37 years, control: 34 years
Recipient/donor sex (male/female): not reported
Underlying disease: malignant haematological disease (primary refractory disease) requiring allogeneic haematopoietic stem cell transplantation
Stage of Disease: Intervention arm: low risk N = 12, high risk N = 7, acute myeloid leukaemia in first (N = 3) remission, acute lymphoid leukaemia in first (N = 2) and 2nd (N = 1) remission and first relapse (N = 1), chronic myeloid leukaemia in chronic (N = 6) phase, chronic lymphoid leukaemia (N = 1), non‐Hodgkin lymphoma (N = 1), myelodysplastic syndrome (N = 1), multiple myeloma (N = 1), acute biphenotypic leukaemia in primary refractory (N = 1) and first remission (N = 1); control arm: low risk N = 9, high risk N = 11, acute myeloid leukaemia in first (N = 4) and 2nd (N = 1) remission, acute lymphoid leukaemia in first (N = 1) and first relapse (N = 2), chronic myeloid leukaemia in chronic (N = 4) and accelerated phase (N = 2), chronic lymphoid leukaemia (N = 1), myelodysplastic syndrome (N = 1), multiple myeloma (N = 1), acute biphenotypic leukaemia primary refractory (N = 1) in first relapse (N = 2)
HLA matching: all participants have HLA‐identical sibling donors
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Interventions |
Conditioning regimen: Intervention arm: 6 patients received busulphan and cyclophosphamide, 12 patients received melphalan and total body irradiation, 1 received etoposide and total body irradiation; control arm: 7 patients received busulphan and cyclophosphamide, 12 patients received melphalan and total body irradiation, 1 patient received etoposide and total body irradiation
GvHD prophylaxis: all participants received cyclosporine started intravenously at 3 mg/kg daily and was switched to oral (12.5 mg/kg daily) just before discharge from hospital until day +180 without acute GvHD and methotrexate (15 mg/m² on day +1 and 10 mg/m² on days +3, +6, +11)
Intervention arm: received bone marrow stem cells
Control arm: received peripheral blood stem cells
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Outcomes |
Reported outcomes: time to neutrophil and platelet engraftment, incidence of acute GvHD grades II to IV, incidence of chronic GvHD, relapse, overall survival
Non‐reported outcomes: incidence of extensive chronic GvHD, non‐relapse mortality, disease‐free survival, transplant‐related mortality
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Notes |
Source of funding: "The study was supported by Chugai Pharmaceuticals (Japan), Bud Flanagan Leukaemia Fund, and UK National Health Service"
Conflict of interest: not reported
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Risk of bias |
Bias |
Authors' judgement |
Support for judgement |
Random sequence generation (selection bias) |
Low risk |
Method of randomisation not mentioned, but we assume that central randomisation and allocation was performed using a computer random number generator |
Allocation concealment (selection bias) |
Unclear risk |
Insufficient information to permit judgement |
Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
"The study was double‐blinded to eliminate the subjective aspects to assessment and care that could potentially affect the outcome of such a comparison." "Masking depended on the harvested stem cells being frozen in bags that made the source indistinguishable when frozen, thawed, and re‐infused" |
Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
"The study was double‐blinded to eliminate the subjective aspects to assessment and care that could potentially affect the outcome of such a comparison." "Masking depended on the harvested stem cells being frozen in bags that made the source indistinguishable when frozen, thawed, and re‐infused" |
Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Two participants excluded: one due to fulminant relapse, one donor withdrew after enrolment but before donating |
Selective reporting (reporting bias) |
Low risk |
"The study protocol was approved by the institutional review board (scientific and ethics committees) of the Royal Marsden Hospital, and all patients and donors provided informed consent" |
Other bias |
Low risk |
The study appears to be free of other sources of bias |