Pediatric Autologous Hematopoietic Stem Cell Transplantation: Safety, Efficacy, and Patient Outcomes. Literature Review

Abstract

Autologous stem cell transplantation (auto-HSCT) is a part of the therapeutic strategy for various oncohematological diseases. The auto-HSCT procedure enables hematological recovery after high-dose chemotherapy, otherwise not tolerable, by the infusion of autologous hematopoietic stem cells. Unlike allogeneic transplant (allo-HSCT), auto-HSCT has the advantage of lacking acute-graft-versus-host disease (GVHD) and prolonged immunosuppression, however, these advantages are counterbalanced by the absence of graft-versus-leukemia. Moreover, in hematological malignancies, the autologous hematopoietic stem cell source may be contaminated by neoplastic cells, leading to disease reappearance. In recent years, allogeneic transplant-related mortality (TRM) has progressively decreased, almost approaching auto-TRM, and many alternative donor sources are available for the majority of patients eligible for transplant procedures. In adults, the role of auto-HSCT compared to conventional chemotherapy (CT) in hematological malignancies has been well defined in many extended randomized trials; however, such trials are lacking in pediatric cohorts. Therefore, the role of auto-HSCT in pediatric oncohematology is limited, in both first- and second-line therapies and still remains to be defined. Nowadays, the accurate stratification in risk groups, according to the biological characteristics of the tumors and therapy response, and the introduction of new biological therapies, have to be taken into account in order to assign auto-HSCT a precise role in the therapeutic strategies, also considering that in the developmental age, auto-HSCT has a clear advantage over allo-HSCT, in terms of late sequelae, such as organ damage and second neoplasms. The purpose of this review is to report the results obtained with auto-HSCT in the different pediatric oncohematological diseases, focusing on the most significant literature data in the context of the various diseases and discussing this data in the light of the current therapeutic landscape.

Keywords:

• autologous stem cell transplant
• pediatric age
• acute leukemia
• chronic myeloid leukemia
• Hodgkin lymphoma
• non-Hodgkin lymphoma

Abbreviations

4-HC, 4-hydroperoxycyclophosphamide; αIFN, alpha interferon; AIEOP, associazione italiana Ematologia Oncologia Pediatrica; ALCL, Anaplastic large cell lymphoma; ALL, acute lymphoblastic leukemia; Allo-HSCT, allogeneic hematopoietic stem cell transplant; ALWP, Acute Leukemia Working Party; AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; ATO, arsenic trioxide; ATRA, all-trans retinoic acid; Auto-HSCT, autologous hematopoietic stem cell transplant; BAL, B-cell acute leukemia; BCR-ABL1, breakpoint cluster region-Abelson 1; BL, Burkitt Lymphoma; BM, bone marrow; BU, Busulfan; CA, cytarabine; CCyR, cytogenetic complete remission; CI, Cumulative Incidence; CIBMTR, Center for International Blood and Marrow Transplant Research; CML, Chronic myeloid leukemia; CNS, central nervous system; COG, Childrens’ Oncology Group; CR, complete remission; CR2, second-complete remission; CsA, cyclosporine A; CT, Chemotherapy; CT scan, computed tomography; CY, Cyclophosphamide; DFS, disease-free survival; DLBCL, diffuse large B-cell NHL; DP, disease progression; EBMT, European Blood Bone Marrow Transplantation; EBMTR, European Bone Marrow Transplantation Registry; EFS, event-free survival; ETP, Etoposide; G-CSF, granulocyte-colony stimulating factor; GHSG, German Hodgkin’s Lymphoma Study Group; GO, gemtuzumab ozogamicin; GVL, graft-versus-leukemia; HD, high dose; HL, Hodgkin Lymphoma; I-BFM-SG, International Berlin-Frankfurt-Munster Study Group; JSHCT, Japan Society for Hematopoietic Cell Transplantation; LBL, Lymphoblastic lymphoma; MAC, myeloablative conditioning; MEL, Melphalan; MFC, multiparametric flow cytometry; MoAbs, monoclonal antibodies; MRD, minimal residual disease; MSKCC, Memorial Sloan Kettering Cancer Center; NHL, non-Hodgkin lymphoma; NRM, Non-relapse Mortality; OS, overall survival; PBSC, peripheral blood stem cells; PFS, progression-free survival; PMBCL, primary mediastinal large B-cell NHL; PML-RARA, Promyelocytic Leukemia-Retinoic acid receptor; PR, partial remissione; PRC, polymerase-chain reaction; PTCL, Nonanaplastic peripheral T-cell lymphomas; RIC, reduced intensity conditioning; SD, stable disease; SD-CT, standard-dose chemotherapy; TBI, total body irradiation; TKIs, tyrosine kinase inhibitors; T-LBL, T-lymphoblastic lymphoma; TRM, transplant-related mortality; VCR, Vincristine; VHR, very-high risk.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation; took part in drafting and in critically reviewing the article. All authors gave final approval of the version to be published. The authors have agreed on the journal to which the article has been submitted and agree to be accountable for all aspects of the work. Our main text and Tables have been edited and revised by a native English teacher.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

No financial support was received for this study.