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Ex Vivo Expansion of Hematopoietic Stem Cells from Human Umbilical Cord Blood-derived CD34+ Cells Using Valproic Acid
Published on: April 11, 2019
Collection and use of peripheral blood stem cells in young children with refractory solid tumors
1Division of Pediatric Hematology/Oncology, Children's Hospital of Orange County, Orange, CA 92668, USA.
Insights
Peripheral blood stem cell (PBSC) collections are safe and effective for children undergoing chemotherapy. PBSC support can improve blood count recovery in young patients receiving intensive treatments.
Area of Science:
- Pediatric Hematology/Oncology
- Stem Cell Transplantation
- Cellular Therapy
Background:
- Pediatric patients undergoing intensive chemotherapy often require hematopoietic stem cell support.
- Peripheral blood stem cells (PBSCs) are an alternative to bone marrow for transplantation.
- Mobilization strategies using G-CSF/GM-CSF alone or with chemotherapy are used for PBSC collection.
Purpose of the Study:
- To evaluate the safety and efficacy of peripheral blood stem cell (PBSC) collections in children aged 4 years or younger.
- To assess the impact of PBSC support on hematological recovery following myeloablative and submyeloablative chemotherapy regimens.
- To analyze PBSC collection yields and patient outcomes.
Main Methods:
- Retrospective analysis of 44 PBSC collections from 15 children (8-46 months) with PNET/medulloblastoma, neuroblastoma, or other diagnoses.
- PBSC mobilization using G-CSF/GM-CSF or chemotherapy plus G-CSF/GM-CSF.
- Evaluation of hematological recovery (ANC and platelet counts) after myeloablative and submyeloablative chemotherapy with PBSC support.
Main Results:
- PBSC collections were well tolerated in all pediatric patients.
- Average yields were 6.80 x 10^8 mononuclear cells/kg and 57.60 x 10^6 CD34+ cells/kg.
- Patients receiving PBSC support after myeloablative chemotherapy showed median ANC recovery by day 10 and platelet recovery by day 15.
- Children receiving ICE chemotherapy plus PBSCs demonstrated faster ANC and platelet recovery compared to historical controls receiving ICE plus G-CSF.
Conclusions:
- Peripheral blood stem cell collection and transplantation are safe and well-tolerated in young children and infants.
- PBSC support can enhance hematological recovery following both myeloablative and multi-cycle submyeloablative chemotherapy.
- This approach offers a viable strategy for supporting pediatric patients undergoing intensive cancer therapy.
Abstract:
Fifteen children 4 years of age or under (8-46 months), weight 7.8 to 17 kg, underwent 44 peripheral blood stem cell (PBSC) collections. Diagnoses included PNET/medulloblastoma (five), neuroblastoma (five), and others (five). PBSCs were collected following G-CSF/GM-CSF or chemotherapy plus G-CSF/GM-CSF mobilization. All PBSC collections were well tolerated. The average yield per collection was 6.80 x 10(8) mononuclear cells/kg (1.1-30 x 10(8)/kg) or 57.60 x 10(6) CD34+/kg (1.37 to 480 x 10(6)/kg). Eight patients underwent stem cell transplantation following myeloablative chemotherapy. Six of the eight children who received PBSC following myeloablative therapy also received autologous bone marrow (0.7 to 3.6 x 10(8) MNC/kg). One heavily pretreated patient experienced delayed hematologic reconstitution, while the remaining seven patients had a median ANC recovery to > 0.5 x 10(3)/microliter by day +10 (9-11 days) and platelets > 50 x 10(3)/microliter by day +15 (12-17 days). Seven patients received PBSCs following repetitive submyeloablative chemotherapy (ICE: ifosfamide 1.8 g/m2/day, etoposide 100 mg/m2/day x 5, carboplatin 400 mg/m2/day x 2) or other similar combination chemotherapy. Median days to recover ANC > or = 1 x 10(3)/microliter and platelets > or = 100 x 10(3)/microliter in children receiving ICE + PBSCs were 10 and 14 days, respectively, compared with 16 and 22 days in children receiving ICE + G-CSF in historical controls. In conclusion, collection and use of PBSCs to support either myeloablative chemotherapy or multicycle submyeloablative chemotherapy is well tolerated and may enhance hematological recovery in young children and infants.
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