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Autologous Grafting in Childhood ALL and Long-term Results

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

Leukemia volume 15, pages 50–56 (2001)Cite this article

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) × 106 CD34+ cells/kg were collected from each patient and a median of 7.5 (range, 4.1–12.6) × 106 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+ cells; the second step, performed after incubation with anti-CD19 MoAbs, allowed the depletion of 99% (range, 93–100) of the CD19+ cells, kept within the magnetic field of the immunodepletion column, with a median recovery of 73% (range, 55–87) of the collected CD34+ cells. Molecular analysis assessed the in vitro eradication of detectable leukemic cells. A median reinfusion of 5.2 (range, 3.2–9.1) × 106 CD34+ cells/kg for each patient (median viability, 90%), after conditioning with the ‘TBI-VP16-CY’ regimen, allowed prompt engraftment and immunological reconstitution; no patients experienced severe transplant-related toxicity or major infections. One patient relapsed 7 months after transplantation, while 10 patients are alive in clinical and molecular remission, at a median follow-up of 29 months (range, 15–40) (2-year EFS, 89%, s.e. 9). In conclusion, the procedure proved to be reproducible for pediatric purified autografting, highly efficient concerning stem cell recovery and depletion of leukemia-lineage specific cells, and promising in terms of final outcome.

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Acknowledgements

The authors wish to thank the ‘Comitato Maria Letizia Verga per lo studio e la cura della leucemia del bambino’ and the ‘Fondazione Tettamanti’ for their continuous support, Miss Sara Vaghi for secretarial assistance and Miss Joanna Upton for linguistic consultancy. This work was partially supported by grants from the Associazione Italiana Ricerca sul Cancro (AIRC) and Ministero Università Ricerca Scientifica e Tecnologica (MURST) (to AB).

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Authors and Affiliations

  1. Clinica Pediatrica Università di Milano-Bicocca, Ospedale San Gerardo, Monza, Italy

    A Balduzzi, G Gaipa, S Bonanomi, E D'Aniello, R Schirò, D Longoni, C Uderzo & A Biondi

  2. Centro Trasfusionale, Ospedale San Gerardo, Monza, Italy

    M Dassi, P Perseghin & F Buscemi

  3. Ematologia, Ospedali Riuniti, Bergamo, Italy

    A Rambaldi

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Balduzzi, A., Gaipa, G., Bonanomi, S. et al. Purified autologous grafting in childhood acute lymphoblastic leukemia in second remission: evidence for long-term clinical and molecular remissions. Leukemia 15, 50–56 (2001). https://doi.org/10.1038/sj.leu.2402004

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