New frontiers in pediatric Allo-SCT

Abstract

The inaugural meeting of 'New Frontiers in Pediatric Allogeneic Stem Cell Transplantation' organized by the Pediatric Blood and Transplant Consortium (PBMTC) was held at the American Society of Pediatric Hematology and Oncology Annual Meeting. This meeting provided an international platform for physicians and investigators active in the research and utilization of pediatric Allo-SCT in children and adolescents with malignant and non-malignant disease (NMD), to share information and develop future collaborative strategies. The primary objectives of the conference included: (1) to present advances in Allo-SCT in pediatric ALL and novel pre and post-transplant immunotherapy; (2) to highlight new strategies in alternative allogeneic stem cell donor sources for children and adolescents with non-malignant hematological disorders; (3) to discuss timing of immune reconstitution after Allo-SCT and methods of facilitating more rapid recovery of immunity; (4) to identify strategies of utilizing Allo-SCT in pediatric myeloproliferative disorders; (5) to develop diagnostic and therapeutic approaches to hematological complications post pediatric Allo-SCT; (6) to enhance the understanding of new novel cellular therapeutic approaches to pediatric malignant and non-malignant hematological disorders; and (7) to discuss optimizing drug therapy in pediatric recipients of Allo-SCT. This paper will provide a brief overview of the conference.

Figure 1. 1a. Event-free survival probability (pEFS) and 1b. cumulative incidence of subsequent relapse (CIR) in patients with first (n = 77) or second (n = 14) relapse of acute lymphoblastic leukemia by minimal residual disease (MRD) status before allogeneic stem-cell transplantation (SCT)

MRD > 10⁻³ leukemic cells: n = 33; censored, n = 11; deaths, n = 5; relapses, n = 17;1a. pEFS (4 years) = 0.31 ± 0.09; 1b. CIR (4 years) = 0.54 ± 0.09. MRD < 10⁻³ and ≥ 10⁻⁴ leukemic cells: n = 12; censored, n = 3; deaths, n = 2; relapses, n = 7; 1a. pEFS (3.5 years) = 0.19 ± 0.12; 1b. CIR (3.5 years) = 0.64 ± 0.16. MRD < 10⁻⁴ leukemic cells: n = 10; censored, n = 5; deaths, n = 3; relapses, n = 2; 1a. pEFS (3.5 years) = 0.48 ± 0.16; 1b. CIR (3.5 years) = 0.20 ± 0.14. MRD not detectable: n = 36; censored, n = 24; deaths, n = 9; relapses, n = 3; 1a. pEFS (4 years) = 0.64 ± 0.09; 1b. CIR (4 years) = 0.11 ± 0.06. 1a. EFS, log-rank, P = .036. 1b. CIR, Gray, P < .001. From Bader P, Kreyenberg H, Henze GH, Eckert C, Reising M, Willasch A et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. J Clin Oncol 2009; 27(3): 377-84.

Figure 2. Probability of leukemia-free survival

A indicates chemotherapy recipients after an early first relapse; B, transplant recipients with TBI regimens after an early first relapse; C, transplant recipients with non-TBI regimens after an early first relapse; D, chemotherapy recipients after late first relapse; E, transplant recipients with TBI regimens after late first relapse; and F, transplant recipients with non-TBI regimens after late first relapse. From Eapen M, Raetz E, Zhang MJ, Muehlenbein C, Devidas M, Abshire T et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood 2006; 107(12): 4961-7.

Figure 3. OS in 268 patients with nonmalignant disorders in UCBT according to cell dose infused (×10⁷/kg) and HLA differences

From Cairo MS, Rocha V, Gluckman E, Hale G, Wagner J. Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors. Biol Blood Marrow Transplant 2008; 14(1 Suppl 1): 44-53.

Figure 4. Clinical outcomes

Neutophil engraftment after double UCB, MRD, MUD and MMUD transplantation. From Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116(22): 4693-9.