Background: Pediatric patients with chronic myeloid leukemia (CML) who present in blast phase (de novo BP) make up about 7-10% of cases and have a poor prognosis. There is no standard treatment for these pediatric cases, but early hematopoietic stem cell transplantation (HSCT) is advised based on adult data. More pediatric-specific treatment information is needed to guide clinical practice.

Methods: A retrospective analysis was performed on pediatric patients diagnosed with de novo CML-BP, according to the World Health Organization 2022 criteria, who received HSCT during May 2023 to March 2025 at the Division of Pediatric Blood Diseases Center, Blood Diseases Hospital, Chinese Academy of Medical Sciences.

Results: Seven patients, aged 10.1 to 15.9 years, were enrolled: five with lymphoid de novo BP (LBP) and two with myeloid de novo BP (MBP), including four females and three males. All patients exhibited elevated leukocytes ranging from 21 to 490 x 10^9/L. The BCR::ABL1 fusion transcripts comprised one p190 isoform and six p210 isoforms, with no mutations detected. Among the five LBP patients, three presented with typical acute lymphoblastic leukemia (ALL) characteristics, exhibiting 71.2% to 96% lymphoblasts in the bone marrow without granulocytosis (Pts 1, 3, and 4). Differential diagnosis was established using fluorescence in situ hybridization during induction treatment, as BCR::ABL1 was detected not only in lymphoblasts but also in mature granulocytes or nucleated red blood cells. Following diagnosis, patients received either ALL or AML based regimens, combined with tyrosine kinase inhibitor (TKI). Specifically, dasatinib was administered to four patients, while olverembatinib for three patients. The median time from diagnosis to HSCT was 3.7 months, with a range of 2.5 to 7.9 months. All patients exhibited negative minimal residual disease by flow cytometry before HSCT, indicating the clearance of blasts. However, complete cytogenetic response (CCyR) was achieved in only four patients, and major molecular response (MMR) was observed in just one patient. The median BCR::ABL1 level was 0.2825%, ranging from 0.0000% to 37.7799%. Two patients with LBP underwent haploidentical donor transplants, whereas three patients with LBP and two patients with MBP received unrelated cord blood transplants with an HLA compatibility of 8-9 out of 10. All patients attained complete donor chimerism within 20 days. Granulocyte reached engraftment at a median period of 18 days (range: 14-28 days), while platelet at a median period of 29 days (range: 14-90 days). Prophylaxis for graft-versus-host disease (GVHD) routinely included cyclosporine A and mycophenolate mofetil, with or without methotrexate. Only two patients developed grade 1-2 GVHD, which was effectively managed, and no serious infections occurred. Patients were monitored for a median period of 12 months (range: 5-20 months). Bone marrow assessments were conducted at 1, 3, 6, 9, and 12 months during the first year following HSCT, and at six-month intervals throughout the second year. All patients achieved MMR 1 month following transplantation, with four patients attaining BCR::ABL1 negativity. TKIs were administered between 2 and 4 months post-HSCT. Two patients selected dasatinib, while five opted for olverembatinib. Among the three patients who remained BCR::ABL1 positive, olverembatinib was administered between 2 and 2.5 months, resulting in BCR::ABL1 negativity for two patients and a two-fold reduction for one patient by the third month. Of the four patients who tested negative at 1 month, one reverted to positive at 3 months; however, with the addition of olverembatinib, this patient regained negativity by 6 months.

Conclusion: Prompt HSCT for de novo CML-BP, combined with early TKI maintenance post-transplantation, appears to contribute to effective disease management. Additionally, unrelated cord blood donors seem to provide a viable source for transplantation. Furthermore, olverembatinib has demonstrated favorable safety and efficacy profiles both pre- and post-transplantation. However, extended follow-up and larger participant cohorts are necessary to substantiate these findings.

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2025
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