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46 88;1089-97. 25. To LB, Haylock DN, Simmons PJ, Juttner CA. The biology and clinical use of blood stem cells. Blood 1997; 89:2233-58. 26. Roberts MM, To LB, Gillis D, et al. Immune reconstitution following peripheral blood stem cells transplantation, autologous bone marrow transplantation and allogenic bone marrow transplantation. Bone Marrow Transplantat 1993; 12:469-76. 27. Link H, Arseniev L, Bahre O, et al. Combined transplantation of allogenic bone marrow and CD34+ blood cells. Blood 1995; 86:2500-5. 28. Tabilio A, Aversa F, Regazzi T, et al. Hematopoietic and stromal reconstitution after haploidentical allogenic bone marrow transplantation. Blood 1996; 88 (Suppl 1):263a. 29. Friedrich W., Muller S., Schreiner T., Wiesneth M. (1996) Purified CD34+ blood stem cells from HLAhaploidentical parental donors for transplantation in SCID. The 6th Biennal Sandoz-Keystone Symposium on BMT "Blood cells and Bone Marrow Transplantation" Keystone, Colorado,USA Abs205. 30. To LB, Haylock DN, Dowse T, et al. A comparative study of the phenotype and proliferative capacities of peripheral blood (PB) CD34+ cells mobilized by four different protocols and those of steady-phase PB and marrow CD34+ cells. Blood 1994; 84:2930-9. 31. Yan XQ, Hartley C, McElroy P, Chang A, McCrea C, McNiece J. Peripheral blood progenitor cells mobilized by recombinant human granulocyte colony-stimulating factor plus recombinant rat stem cell factor contain long term engrafting cells capable of cellular proliferation for more than two years as shown by serial transplantation in mice. Blood 1995; 85:2303-7. 32. Drize N, Chertkov J, Sadovnikova E, Tiessen S, Zander A. Long-term maintenance of hematopoiesis by irradiated mice by retrovirally transduced peripheral blood stem cells. Blood 1997; 89:1811-7. 33. Dunbar CE, Cottler-Fox M, O'Shaughnessy JA, et al. Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long term engraftment after autologous transplantation. Blood 1997; 85:3048-52. 34. Kessinger A. Autologous transplantation with peripheral blood stem cells: a review of clinical results. J Clin Apheresis 1990; 5:97-9. 35. Kessinger A, Smith DM, Strandjord SE, et al. Allogenic transplantation of blood-derived, T cell-depleted hemopoietic stem cells after myeloablative treatment in a patient with acute lymphoblastic leukemia. Bone Marrow Transplant 1989; 4:643-7. 36. Brito-Babapulle F, Bowcock SJ, Marcus RE, et al. Autografting for patients with chronic myeloid leukemia in chronic phase: peripheral blood stem cells may have a finite capacity for mantaining hematopoiesis. Br J Haematol 1989; 73:76-80. haematologica vol. 85(supplement to n. 11):November 2000
haematologica 2000; 85(supplement to n. 11):47-53 original paper Treatment of childhood acute lymphoblastic leukemia after the first relapse: curative strategies CORNELIO UDERZO,* GIORGIO DINI,° FRANCO LOCATELLI, # ROBERTO MINIERO, @ PAOLO TAMARO^ *Clinica Pediatrica, Centro TMO, Ospedale S. Gerardo di Monza, Università di Milano; ° Istituto G. Gaslini, Centro TMO, Genova; # Clinica Pediatrica, Centro TMO, Policlinico S. Matteo, Università di Pavia ; @ Clinica Pediatrica, Ospedale S. Luigi, Orbassano (Torino); ^Clinica Pediatrica, Ospedale Burlo Garofolo, Università di Trieste, Italy ABSTRACT Background and Objectives. Treatment of recurrent childhood acute lymphoblastic leukemia (ALL) has been controversial in the last decade. Conventional intensive chemotherapy (CHEMO) can cure up to 30% of children who have relapsed after ALL: similar results have been obtained with autologous bone marrow transplantation (ABMT), but allogeneic bone marrow transplantation (AlloBMT) seems to be the best therapeutic option. In this review the authors point out the contribution of current strategy in the setting of children with ALL who experience a first relapse and should be offered optimal treatment in order to obtain the best disease-free survival (DFS). The principal objective of this issue is to reach a possible consensus on the more controversial points regarding factors considered strong predictors of the outcome of the relapsed patients, second-line chemotherapy, optimal timing and type of transplantation. Evidence and Information Source. Data published in the literature over the last decade concerning early and late relapse in childhood ALL suggest that improvements in cure rates may be achieved by intensification of the relapse treatment both with chemotherapy and with different types of transplantation. An accurate search for Medline data has been performed in order to understand the risk-benefit ratio of aggressive therapy adopted in this setting. State of Art. Modern first-line treatment protocols for childhood ALL have contributed to curing an ever larger number of patients but this strategy could be responsible for creating a more resistant leukemic clone at the time of systemic or extramedullary relapse. This hypothesis emerges from a number of single or multicenter experiences; thus clinical and biological features in relapsed patients are being studied crefully in order to understand which riskdirected second-line therapy should be best adopted. The BFM group classified ALL relapses as “very early”, “early”, or “late” according to the time from diagnosis to first relapse (i.e. 18 and
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