Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34(+) cells and a fixed CD3(+) dose
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C C Dvorak1, A L Gilman, B Horn
1Department of Pediatrics, Division of Allergy, Immunology, and Blood and Marrow Transplant, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA 94143-1278, USA. dvorakc@peds.ucsf.edu
Insights
This study shows that megadoses of CD34+ cells from haploidentical donors lead to successful engraftment and immune recovery in children undergoing stem cell transplantation. Outcomes were favorable for both nonmalignant and malignant conditions, with low rates of severe GVHD.
Area of Science:
- Hematology
- Immunology
- Pediatric Oncology
Background:
- Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for various pediatric hematological and malignant conditions.
- Haploidentical HSCT offers a viable alternative when matched donors are unavailable, but requires strategies to ensure engraftment and manage graft-versus-host disease (GVHD).
Purpose of the Study:
- To evaluate the efficacy and safety of CD34+ selected peripheral blood stem cells (PBSCs) from haploidentical donors in pediatric patients.
- To assess engraftment kinetics, hematoimmunological reconstitution, and GVHD incidence following this transplantation approach.
Main Methods:
- A prospective phase II clinical trial involving 21 pediatric patients with hematological malignancies or nonmalignant conditions.
- Conditioning regimen included total body irradiation (TBI), thiotepa, fludarabine, and Thymoglobulin.
- Patients received megadoses of CD34+ cells with a fixed dose of CD3+ cells from haploidentical related donors, utilizing the CliniMACs system for cell selection.
Main Results:
- Successful engraftment was observed in 90% of patients, with prompt recovery of neutrophils and platelets.
- The incidence of Grade II acute GVHD was 32%, with no cases of Grade III-IV acute GVHD. Chronic extensive GVHD occurred in 35% of patients.
- The estimated 2-year event-free survival (EFS) was 62%. Patients with nonmalignant diseases had a 100% 2-year EFS, while those with malignancies in remission had a 56% 2-year EFS.
Conclusions:
- Megadose CD34+ cell transplantation with a fixed CD3+ cell dose from haploidentical related donors is effective in pediatric patients.
- This strategy promotes good engraftment and hematoimmunological reconstitution with manageable GVHD.
- Favorable outcomes, particularly event-free survival, were achieved in pediatric patients with nonmalignant diseases and those with malignancies transplanted in remission.
Abstract:
We conducted a prospective phase II trial utilizing the CliniMACs system to perform CD34(+)-cell selection of PBSCs from haploidentical donors to evaluate engraftment and hematoimmunological reconstitution. In total, 21 children with hematological malignancies or nonmalignant conditions underwent conditioning with 1200 cGy TBI, thiotepa, fludarabine and Thymoglobulin. Patients received megadoses of CD34(+) cells (median: 22 × 10(6)/kg) with a fixed dose of 3 × 10(4)/kg CD3(+) cells/kg, and engraftment occurred in 90% with prompt recovery of neutrophils and platelets. Grade II acute GVHD (aGVHD) was seen in 32% (95% confidence interval (CI), 15-54%) of evaluable patients, there was no grade III-IV aGVHD, and chronic extensive GVHD was seen in 35% (95% CI, 17-59%) of patients. The estimated 2-year EFS was 62% (95% CI, 48-83%) with a median survivor follow-up of 49 months (range: 18-119 months). Patients with nonmalignant diseases had an estimated 2-year EFS of 100% (95% CI, 56-100%) and patients with malignancies in remission had an estimated 2-year EFS of 56% (95% CI, 22-89%). Megadose CD34(+) cells with a fixed CD3(+) cell dose from haploidentical related donors resulted in good outcomes for pediatric patients with nonmalignant diseases and those with malignant diseases transplanted in remission.
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