Details

Autor(en) / Beteiligte

• Pichler, Herbert
• Sedlacek, Petr
• Meisel, Roland
• Beier, Rita
• Faraci, Maura
• Kalwak, Krzysztof
• Ifversen, Marianne
• Müller, Ingo
• Stein, Jerry
• Vettenranta, Kim
• Kropshofer, Gabriele
• Kolenova, Alexandra
• Karlhuber, Susanne
• Glogova, Evgenia
• Poetschger, Ulrike
• Peters, Christina
• Suttorp, Meinolf
• Matthes‐Leodolter, Susanne
• Balduzzi, Adriana

Titel

Haematopoietic stem cell transplantation after reduced intensity conditioning in children and adolescents with chronic myeloid leukaemia: A prospective multicentre trial of the I‐BFM Study Group

Ist Teil von

• British journal of haematology, 2024-07, Vol.205 (1), p.268-279

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary This prospective multicentre trial evaluated the safety and the efficacy of a thiotepa/melphalan‐based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) in children and adolescents with chronic myeloid leukaemia (CML) in chronic phase (CP). Thirty‐two patients were transplanted from matched siblings or matched unrelated donors. In 22 patients, HSCT was performed due to insufficient molecular response or loss of response to first‐ or second‐generation tyrosine kinase inhibitor (TKI), with pretransplant BCR::ABL1 transcripts ranging between 0.001% and 33%. The protocol included a BCR::ABL1‐guided intervention with TKI retreatment in the first year and donor lymphocyte infusions (DLI) in the second‐year post‐transplant. All patients engrafted. The 1‐year transplant‐related mortality was 3% (confidence interval [CI]: 0%–6%). After a median follow‐up of 6.3 years, 5‐year overall survival and event‐free survival are 97% (CI: 93%–100%) and 91% (CI: 79%–100%) respectively. The current 5‐year leukaemia‐free survival with BCR::ABL1 <0.01% is 97% (CI: 88%–100%) and the current TKI‐ and DLI‐free survival is 95% (CI: 85%–100%). The incidence of chronic graft‐versus‐host disease (GvHD) was 32%, being severe in four patients (13%). At last follow‐up, 31 patients are GvHD‐free and have stopped immunosuppression. RIC HSCT following pretreatment with TKI is feasible and effective in children and adolescents with CP‐CML with an excellent disease‐free and TKI‐free survival. The thiotepa/melphalan‐based RIC HSCT with MSD or MUD allografts tested in 32 children and adolescents with CML‐CP after TKI pre‐treatment was associated with an excellent 5‐year OS and 5‐year EFS of 97% and 91% respectively. The 1‐year TRM was low at 3%. Disease control was robust, with a current 5‐year LFS (BCR::ABL1 <0.01%) of 97% under stringent post‐transplant transcript monitoring and a well‐defined strategy for post‐transplant interventions. Major limitations of this trial are low patient numbers and considerable rates of GvHD.