Purified autologous grafting in childhood acute lymphoblastic leukemia in second remission: evidence for long-term clinical and molecular remissions

Abstract

Autologous transplantation is a treatment option for relapsed childhood acute lymphoblastic leukemia (ALL) in second complete remission (CR2) when a suitable donor is not available. In an attempt to prevent relapses originating from graft leukemic contamination, the experimental protocol of in vitro purification of leukapheretic products with monoclonal antibodies (MoAbs), previously reported for adults, was adopted in 11 of 12 consecutive patients (median age, 9 years) with B cell precursor ALL in CR2 after late relapse (median, 37; range, 31-51 months after the onset) enrolled between July 1997 and July 1999 at a single pediatric center. At a median of 12 days after the mobilizing chemotherapy followed by G-CSF, a median of 13.9 (range, 5.9-18.7) × 10 6 CD34 + cells/kg were collected from each patient and a median of 7.5 (range, 4.1-12.6) × 10 6 CD34 + cells/kg underwent the purification procedure. The first step of immunorosetting allowed a one-log reduction of the total cell count, by eliminating more than 90% of the CD11b

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

“…Informed consent was obtained from the parents or guardians for all patients. 26 All consecutive low-risk relapse patients are reported.…”

“…26 Briefly, the first step of immunorosetting aimed to reduce the total cell count, by eliminating CD11b þ cells. The second step, using a column inserted in a SuperMACS (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany) magnetic cell separator device, was performed after incubation with anti-CD19 MoAbs conjugated with paramagnetic microbeads (Miltenyi Biotec) to deplete virtually all CD19 þ cells and recover most CD34 þ cells.…”

“…[15][16][17][18][19][20][21][22][23][24][25] In 2001, we reported a study that showed the feasibility and efficacy of an innovative protocol for autologous transplantation of purified peripheral hematopoietic stem cells in 12 pediatric patients with pediatric B-cell-precursor ALL after isolated extramedullary and/or late relapse. 26 This strategy aimed to ensure the best available treatment for low-risk relapsed ALL children and to avoid the toxicity of allogeneic transplantation. In an attempt to prevent further relapse, a combined approach of immunological purification and myeloablative TBI was adopted.…”

Peripheral blood stem cell collection in children with acute leukemia: effectiveness of the ‘DIAVE’ mobilizing regimen

“…6,7 The collection of large doses of HSC allows purification procedures, aiming at achieving complete removal of possibly contaminating leukemic cells. 8,9 Even though autologous transplantation is widely used in adults, limited experiences of PB mobilization have been reported so far in children, other than in solid tumors. 10,11 In this study we report on the effectiveness of the new regimen 'DIAVE' in children with AL in terms of the high proportion of patients 'mobilizing' and high level of 'mobilized stem cells'.…”

Strategies of the donor search for children with second CR ALL lacking a matched sibling donor

“…15,16 Indications for auto-HSCT are limited to a small subset of children with either late marrow relapse or extramedullary recurrence. 17,18 A recent survey by the European Bone Marrow Transplant group showed that prior to May 1996, the majority of allografts (70%) were performed from HLA MSDs. During the last 10 years, the number of alternative HSCTs, including UDs, partially matched family donor and UCB HSCTs, has increased significantly (P ¼ o0.0001) and reached 61% of the allografts carried out between 1999 and 2002 ( Figure 1).…”