Expanded Donor Stem Cells for Poor Graft Function After Stem Cell Transplantation in Children

Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT) and may cause persistent low blood cell counts despite donor-cell engraftment. This single-center, open-label, Phase I pilot study will enroll three children aged 6-18 years with PGF after allogeneic HSCT who have not responded adequately to conventional hematopoietic supportive treatments. CD34-positive hematopoietic stem cells will be collected from each participant's original related transplant donor and expanded outside the body for \~10 days using the small-molecule compound HEB-001 together with the cytokines stem cell factor, thrombopoietin, and FLT3 ligand. The expanded cells will then be administered as a single intravenous infusion. The main objectives are to assess acute infusion-related adverse events during the first 30 days and to examine genetic stability through 1 year. Preliminary hematopoietic recovery will be assessed using neutrophil and platelet recovery and donor chimerism. All participants will receive the investigational cell infusion; there is no comparator group.

Inclusion Criteria: * Age 6-18 years, regardless of sex. * Availability of a related stem cell donor who was also the donor for the participant's original HSCT. * Poor graft function following allogeneic HSCT, defined as ANC \28 days with reduced bone marrow cellularity, after exclusion of acute GVHD, recurrence of the underlying disease, drug toxicity, and severe infection. * Insufficient autologous hematopoietic stem cell reserve and failure of conventional hematopoietic supportive treatment according to the protocol, including persistent neutropenia despite appropriate G-CSF; persistent severe thrombocytopenia or transfusion dependence despite thrombopoietin-receptor agonist treatment where indicated; unsuitability for or refusal of donor lymphocyte infusion, or an unfavorable benefit-risk assessment; and an investigator assessment that other supportive approaches do not provide sustained hematopoietic recovery. * No active infection, including normal body temperature for at least 72 hours and no evidence of infection on relevant cultures or imaging assessments. * No acute or chronic GVHD, or GVHD no greater than Grade 1, as specified in the protocol (see harmonisation note). * Written informed consent provided by the participant and/or legal guardian in accordance with applicable requirements. Exclusion Criteria: * Inherited bone marrow failure syndrome (e.g., Fanconi anemia) or hematologic malignancy. * History of non-hematologic malignancy. * Severe cardiac, hepatic, or renal dysfunction, including LVEF \2 × the upper limit of normal. * Central nervous system involvement, including CNS infection or CNS involvement by malignancy. * History of hypersensitivity to culture components, including HEB-001 or the cytokines used for ex vivo expansion.