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

• DOI: 10.1111/bjh.19535
• Publication Date: 2024-05-28T04:33:51Z
• Authors: Herbert Pichler; Petr Sedlacek; Roland Meisel; Rita Beier; Maura Faraci; Krzysztof Kalwak; Marianne Ifversen; Ingo Müller; Jerry Stein; Kim Vettenranta; Gabriele Kropshofer; Alexandra Kolenova; Susanne Karlhuber; Evgenia Glogova; Ulrike Poetschger; Christina Peters; Meinolf Suttorp; Susanne Matthes‐L...; Adriana Balduzzi
• Keywords: Male; Transplantation Conditioning; Adolescent; chronic myeloid leukaemia; allogeneic stem cell transplantation; children and adolescents; chronic myeloid leukaemia; reduced intensity conditioning;; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; General medicine, internal medicine and other clinical medicine; reduced intensity conditioning; Treatment Outcome; children and adolescents; allogeneic stem cell transplantation; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Child, Preschool; Humans; Female; Prospective Studies; Child; Protein Kinase Inhibitors

SummaryThis 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.