Autologous hematopoietic stem cell transplantation for children and young adults

Autologous hematopoietic stem cell transplant (auto HSCT) uses patient-derived stem cells to facilitate recovery from myeloablative high-dose chemotherapy for cancer. The concept is that higher doses of certain agents, particularly alkylators, will be 3 to 15 times more potent than conventional doses and will be useful as consolidation therapy after initial cytoreduction, provided nonhematologic toxicity remains acceptable. Use of intensive chemotherapy may also permit deferral or avoidance of radiotherapy in young children.

1 What are hematopoietic stem cells?

Stem cells are self-renewing blood cell progenitors present in the bone marrow that also circulate at low levels in the peripheral blood. Egress of stem cells from marrow to peripheral blood can be enhanced by administration of hematopoietic growth factors (“mobilization”) to facilitate collection (“harvesting”) for infusion after myeloablative chemotherapy.

2 What pediatric cancers are treated by auto HSCT?

Current pediatric indications for auto HSCT are newly diagnosed high-risk neuroblastoma and infant medulloblastoma, recurrent germ cell tumors, and recurrent lymphoma (Hodgkin lymphoma and non-Hodgkin lymphoma). Neuroblastoma is most frequent, accounting for 43% of the 3076 pediatric autotransplants reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 2008 and 2014 (Khandelwal, 2017). Other pediatric applications of auto HSCT have included relapsed Ewing sarcoma (ES), retinoblastoma, and brain tumors other than medulloblastoma.

3 What are some newer applications of auto HSCT?

Auto HSCT has been used to support recovery from myeloablative or lymphoablative chemotherapy in refractory autoimmune disorders such as juvenile idiopathic arthritis and in pediatric multiple sclerosis after failure of standard therapy.

Another type of auto HSCT involves the genetic modification of patient stem cells for correction or amelioration of certain inherited disorders, referred to as “ex vivo gene therapy.” Examples include adenosine deaminase deficiency, X-linked cerebral adrenoleukodystrophy, metachromatic leukodystrophy, and hemoglobinopathies (thalassemia and sickle cell anemia). A growing number of pediatric diseases can be successfully cured by hematopoietic stem cell-based gene therapy (Staal, 2019).

A related procedure is a collection of autologous mononuclear cells by leukapheresis for production of chimeric antigen receptor (CAR) T-cells, modified to express a transgene encoding a tumor-specific CAR, then infusing the manufactured CAR T-cells to treat the cancer. CAR T-cell therapy is approved for relapsed or refractory childhood acute lymphocytic leukemia and may be used as definitive therapy or as a bridge to allogeneic HSCT. Investigational applications of CAR T-cell therapy in pediatrics include lymphoma, acute myeloid leukemia (AML), solid tumors, and central nervous system (CNS) tumors.

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