Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission. Role of intensification therapy in outcome

Abstract

Summary:The use of peripheral blood stem cells (PBSC) in autolog- In order to determine if peripheral blood stem cells ous transplantation (PBSCT) has demonstrated advantages (PBSC) collected after priming with G-CSF in AML inover the use of marrow (ABMT) in several hematological first complete remission (CR) can be used for autologmalignancies and solid tumors. 1,2 In fact, a faster hematopoous transplantation and to evaluate the efficacy of early ietic reconstitution in PBSCT, resulting in lower infectious intensification therapy as in vivo purging, we studied 35 and haemorrhagic morbidity-mortality than in ABMT, has consecutive patients with AML in first CR. After stanbeen widely observed. 3,4 These advantages are particularly dard induction and consolidation chemotherapy, 24 of evident in patients autografted for acute myelogenous leuthem were treated with one (10 patients) or two (14 kemia (AML), in whom engraftment is slower than in acute patients) cycles of high-dose cytarabine plus etoposide lymphocytic leukemia, and further delays occur as a conseprior to PBSC collection. G-CSF was used as the primquence of purging or heavy chemotherapy administered ing agent. Of the 35 patients scheduled for peripheral before marrow cell harvest. 5,6 In addition, a lower freblood stem cell transplantation (PBSCT), three relapsed quency of neoplastic cells in peripheral blood has been before transplantation, and the 32 remaining underwent reported in this entity. 7,8 PBSCT. High-dose therapy consisted of either totalIn recent years, different methods of mobilization to body irradiation plus cyclophosphamide or busulphan obtain peripheral blood progenitors have been developed. plus cyclophosphamide. The median number of CD34 + High-dose cyclophosphamide or polychemotherapy alone cells infused was 3.24 × 10 6 /kg (range 0.15-14). The or associated with growth factors (mainly GM-CSF or Gmedian times to reach a PMN count of 0.5 × 10 9 /l and CSF) have generally yielded a good number of blood prea platelet count of 50 × 10 9 /l were 12 (8-28) and 30 (11-cursors, enough to assure an early engraftment. 9-12 How-345) days, respectively. There was no transplant-related ever, its use has been considerably reduced because of the mortality. Twelve patients relapsed between 2 and 21 dependence on 'timing' and the additional hematological months post-PBSCT. With a median follow-up of 28 and nonhematological toxicities. Lately, the capacity of a months, actuarial disease-free survival (DFS) is single growth factor to induce mobilization to peripheral 52.41 ؎ 9% in the intent-to-treat group and blood of hematopoietic precursors which are capable of 57.4 ؎ 9.8% in patients who underwent PBSCT. The restoring a complete and sustained hematopoiesis has freprobability of DFS is significantly higher for patients quently been reported. 13,14 Nevertheless, the presence of who receive early intensification therapy prior to both GM or G-CSF receptors in leukemic blast cells, the PBSC collection and PBSCT as compared with patients reported capa...

Analysis of feasibility of myeloablative therapy and autologous peripheral stem cell (PBSC) transplantation in the elderly: an interim report

“…26 The therapy of acute leukemias using myeloablative therapy followed by PBSC autotransplant has been recently introduced and studies are ongoing. 5,27 We treated two patients with leukemia and our experience confirms feasibility and the lack of procedure-related problems.…”

“…[1][2][3][4][5][6][7] Nevertheless most reports focus on patients younger than 60 years due to higher procedurerelated risk in older patients. [6][7][8] Few reports concerning the use of high-dose therapy and autologous bone marrow 6,8 or peripheral stem cell transplantation 9,10 in the elderly are available, although growing interest in treating older patients has been shown.…”

Factors influencing hematopoietic recovery after autologous blood stem cell transplantation in patients with acute myeloblastic leukemia and with non-myeloid malignancies

“…As regards CFU-GM, threshold values have ranged between Ͼ5-10 ϫ 10 4 /kg 25 and Ͼ50 CFU-GM ϫ 10 4 /kg 23 whereas other authors have failed to find an influence of this variable on the rate of engraftment. 27 In respect to the CD34 + cell dose, Demirer et al 24 and Martin et al 26 reported that patients transplanted with Ͼ2.5 ϫ CD34 + 10 6 /kg had a faster recovery of platelet counts, and in a co-operative study, patients transplanted with Ͼ12 ϫ 10 6 /kg CD34 + cells had a more rapid neutrophil and platelet recovery as compared with those receiving Ͻ3 ϫ 10 6 /kg. 27 Lastly, in a recently published report by the Bordeaux group, the number of CD34 + cells, but not the number of CFU-GM infused, showed a significant influence on the speed of engraftment.…”

“…1 In studies of patients with AML, very few reports have evaluated the influence of the infused progenitor cell dose on engraftment, and those published included only a low number of patients. 5,[23][24][25][26][27] Thus, the minimum or optimal dose to be infused in this disease has not yet been defined. As regards CFU-GM, threshold values have ranged between Ͼ5-10 ϫ 10 4 /kg 25 and Ͼ50 CFU-GM ϫ 10 4 /kg 23 whereas other authors have failed to find an influence of this variable on the rate of engraftment.…”

Double reinforcement with fludarabine/high-dose cytarabine enhances the impact of autologous stem cell transplantation in acute myeloid leukemia patients

“…7,8 Thus, intensification of induction/ consolidation chemotherapy, mainly based on high-dose cytarabine, has been suggested to improve in vivo purging prior to auto-SCT. [9][10][11] Combination chemotherapy regimens based on fludarabine and high-dose cytarabine, such as FLAG or FLAN, are known to be effective in myeloproliferative disorders. [12][13][14] Reinforced chemotherapy mainly based on a double high-dose consolidation regimen is a new way to enhance in vivo purging prior to auto-SCT and has not been previously reported.…”