Autologous Bone Marrow Transplantation in CML

Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-α


In chronic myelogenous leukemia (CML), autologous stem cell transplantation could be a promising new approach for patients with no cytogenetic response after interferon α (IFN-α) therapy. We report data on 28 CML patients autotransplanted in chronic phase with peripheral blood progenitor cells mobilized with G-CSF (5 μg/kg/day x 5 days) given subcutaneously while continuing IFN-α therapy. At mobilization, 23 patients (82%) were in complete hematological remission (CHR), 16 (57%) achieved a minor cytogenetic response (mcr). We obtained, after stimulation, a median of 37.4 × 109/l (6.9–108) white blood cells, 7.2 × 108/kg (2.2–16.6) mononuclear cells, 39 × 104/kg (4.8–403.5) CFU-GM and 4.2 × 106/kg (0–58.6) CD34+ cells. Six patients received GM-CSF after transplantation. All patients engrafted, with no significant influence stemming from the Sokal index score and pretransplantation IFN-α therapy duration. The first cytogenetic evaluation after transplantation showed 11 (39%) major cytogenetic response (Mcr), and nine (32%) mcr with no significant correlation between these responses, the Sokal index score, and pretransplantation IFN-α therapy duration, although there was a significant impact from GM-CSF administration (P = 0.01). After transplantation, 26 patients received IFN-α alone or associated with hydroxyurea. The median follow-up was 12 months after transplantation and 57 months after diagnosis. At the time of follow-up, nine patients were in CHR, six remained stable in chronic phase, three presented an mcr and one remained in Mcr. At the last follow-up, 22 patients were alive. We conclude that the results of this strategy are encouraging in poor IFN-α responders but that other prospective studies that try to maintain the cytogenetic responses obtained immediately after transplantation are needed.


Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor remains the only curative treatment for patients with chronic myelogenous leukemia (CML).1 Unfortunately, only 15% of all newly diagnosed CML patients are considered young enough for allogeneic BMT and have a suitable sibling donor.2 The remaining patients under the age of 50 years can undergo allogeneic marrow transplantation from phenotypically matched unrelated donors. The success of these transplantations requires totally identical class I and II HLA alleles between the recipient and the donor.34 Alpha interferon (IFN-α) therapy is associated with prolonged survival in chronic myelogenous leukemia following cytogenetic response.56 Recently, it has been demonstrated that the association of IFN-α and cytosine arabinoside improves cytogenetic response and survival.7 However, in patients who either cannot benefit from an allogeneic transplantation or do not respond to IFN-α, autologous stem cell transplantation must be considered.891011 Two main objectives are required when considering autotransplantation: an increase in the cytogenetic response and an improvement of overall survival.10 However, the potential contamination by leukemic progenitor cells that could induce relapse after transplantation1213 and the persistence of residual Ph-negative stem cells in long-term CML marrow cultures14 have prompted the search for methods of purging autologous stem cells. Different in vitro purging techniques have been experimented,151617181920 providing efficient suppression of leukemic cell growth in vitro. However, in vivo results do not differ from data obtained with a standard graft.21 Since 1978, different methods of in vivo purging have been evaluated, showing that it is possible to collect Ph-negative cells early in the course of hematopoietic recovery after intensive chemotherapy,22 with or without G-CSF.23 Reiffers et al24 reported that Ph-negative stem cells were mobilized with G-CSF in patients with CML in complete cytogenetic response or in major cytogenetic response (Mcr) after IFN-α therapy. More recently, Archimbaud et al25 have demonstrated that peripheral blood progenitor cell (PBPC) mobilization using G-CSF associated with IFN-α in CML patients in hematological remission, whatever the cytogenetic response, was feasible and allowed autografting.

This paper reports data on 28 CML patients who were autotransplanted long after diagnosis with PBPC collected by G-CSF associated with IFN-α. We analyzed the possible impact of different pre- and post-transplantation factors on PBPC mobilization and on the post-transplantation outcome.

Patients and methods

Patient characteristics

This study included 28 patients with CML Ph-positive in the first chronic phase. There were 21 males and seven females with a median age of 45 years (range 27–63 years). At diagnosis, 21 patients were evaluated for prognosis using the Sokal index: 12 patients (57%) had a low index score (<0.8), four (19%) an intermediate score, and five (24%) a high index score (>1.2). All patients received IFN-α for a median of 27 months (range 14–127) before apheresis and for a median of 29 months (range 16–128 months) before autotransplantation. The response to IFN-α therapy was analyzed according to MD Anderson criteria.26 After IFN-α therapy, all patients achieved complete hematological remission (CHR) and the best cytogenetic response observed in 25 evaluable patients was an Mcr for nine patients (36%) and a minor cytogenetic response (mcr) for 11 patients (44%). Five patients (20%) had no cytogenetic response during the progression of disease. Before mobilization, 23 patients (82%) remained in CHR. Cytogenetic responses observed at that time were: one Mcr (4%) with 20% Ph-positive cells, 16 mcr (57%) with a median of 74% Ph-positive cells (range 36–94%), and 11 with no cytogenetic response (39%).

Mobilization, harvest and cryopreservation of PBPCs

Patients were treated with G-CSF (filgrastim) at 5 μg/kg/day given subcutaneously until the last apheresis, while continuing IFN-α therapy at the same dosage given during the pretransplantation period. Harvest of PBPCs was performed daily, from day 5 of G-CSF therapy, with standard 2–3 blood volume aphereses using a Cobe Spectra (Cobe, Rungis, France) or a Fenwal CS-3000 (Baxter, Maurepas, France) blood separator. The target cell yield was greater than or equal to 6 × 108/kg mononucleated cells (MNC), containing more than 4 × 106/kg CD34+ cells and/or more than 10 × 104/kg CFU-GM. The PBSCs were then cryopreserved in 10% DMSO and 4% serum albumin using a controlled-rate freezer and stored in liquid nitrogen. In case of failure, IFN-α was stopped and patient PBPCs were harvested again after G-CSF administration alone at a dose of 10 μg/kg/day for 5 days.

Transplantation procedure

The pretransplantation conditioning regimen associated busulfan at 4 mg/kg/day given orally from day 6 to day 13 and melphalan 140 mg/m2 given intravenously on day 2. All patients during the autotransplantation period were placed in laminar air flow rooms. In an attempt to improve the percentage of Ph-negative cells obtained after transplantation,27 six patients received GM-CSF given on day 1 after transplantation at a dose of 5 μg/kg/day until granulocytes were greater than 0.5 × 109/l. The IFN-α therapy was resumed at reduced dosages upon normalization of blood counts after transplantation.

Mobilization evaluation and post-transplantation outcome

Harvested cells were estimated on numbers of MNC × 108/kg, CD34+ cells × 106/kg and CFU-GM × 104/kg. Similarly, each apheresis product was submitted to a conventional cytogenetic analysis on 50 metaphases after a 48-h culture with no stimulation. Engraftment and post-transplantation outcome were analyzed, and a longitudinal cytogenetic study during the post-transplant period was performed. The impact of the Sokal index score, IFN-α therapy duration, and addition of GM-CSF on engraftment and on cytogenetic response after transplantation were also studied.

Statistical analysis

The relationship between the characteristics was studied using nonparametric statistics based on the Spearman rank correlation test and on the Mann–Whitney (or Wilcoxon) rank sum test. All P values reported are two-tailed and reported as statistically significant if <0.05. Computations were performed using the BMDP PC-90 statistical program (BMDP Statistical Software, Los Angeles, CA, USA).


Efficacy and safety of PBPC mobilization and harvest

Seventy-four aphereses were performed with a median of three procedures (range 1–6) per patient (Table 1). Four patients failed to mobilize with IFN-α and G-CSF. In case of mobilization failure, IFN-α was stopped. All four patients mobilized successfully with G-CSF alone given at a dose of 10 μg/kg/day for 5 days. The association of G-CSF and IFN-α was well tolerated. Only some patients developed moderate bone pain. The median white blood cell count was 37.4 × 109/l (range 6.9–108) after stimulation. A median of 7.13 × 108 MNC/kg (range 2.2–14.3), 4.4 × 106/kg CD34+ cells (range 0–58.6), and 34 × 104/kg CFU-GM (range 2.6–403.5) was harvested. Fifty-eight apheresis products were evaluable for cytogenetic study. There was no significant variation between the percentage of Ph-positive cells in the successive aphereses and the percentage observed before mobilization. The median percentage of Ph-positive cells before mobilization was 93% (range 20–100), while it was 94% (range 36–100) in the first apheresis (n = 23), 90% (range 29–100) in the second apheresis (n = 17), and 77% (range 13–100) in the third apheresis (n = 12) (Table 2).

Table 1  Efficacy of PBPC mobilization: white blood cell counts, mononucleated cells (MNC), CFU-GM and CD34+ cell contents
Table 2  Cytogenetic analysis of bone marrow and apheresis products

Engraftment and post-transplantation outcome

All patients engrafted. The neutrophils reached a number greater than 0.5 × 109/l at a median of 17 days (range 12–57) and the platelets surpassed 50 × 109/l at a median of 20 days (range 10–149). The hematopoietic reconstitution was not influenced by the Sokal index score, nor by IFN-α therapy duration. The granulocyte recovery was faster for patients who received GM-CSF (P = 0.02). The first post-transplantation cytogenetic evaluation, performed 1 month after transplantation, is given in Table 3. All patients were evaluated immediately after transplantation for cytogenetic response. Eleven patients (39%) achieved an Mcr (vs one Mcr, nine mcr and one absence of cr before transplantation), nine patients (32%) achieved an mcr (vs five mcr and four absence of cr before transplantation) and eight patients had no cytogenetic response (vs two mcr and six absence of cr before transplantation). These cytogenetic responses corresponded to a median of 79% Ph-positive cells (range 0–100) for the entire population (n = 28), a median of 96% Ph-positive cells (range 30–100) for patients with no cytogenetic response before transplantation (n = 11) and a median of 32% (range 0–100) for pretransplantation cytogenetic responders (one Mcr and 16 mcr). No significant correlation was observed between cytogenetic response after transplantation and the Sokal score, nor between cytogenetic response and the duration of IFN-α therapy before transplantation (Table 4). The administration of GM-CSF had a significant effect on post-transplantation cytogenetic response (P = 0.01): in patients treated with GM-CSF, the median percentage of Ph-positive cells after transplantation was 66% (range 24–91) vs 93% before transplantation (range 56–100) while in patients without GM-CSF, the median percentage was 81% (range 0–100) vs 90% before transplantation (range 20–100%). Twenty-six patients received IFN-α after transplantation with a median interval of 120 days after transplantation (range 20–602). The IFN-α treatment was given at a median maximum dose of 29 millions of international units (MIU) (range 6–63 MIU) per week. In 16 patients, hydroxyurea was added to IFN-α. The median follow-up was 12 months (range 1–51) after transplantion and 57 months (range 27–142 months) after diagnosis. Fifteen patients had at least 12 months of follow-up after transplantation. At that time of follow-up, nine patients were in CHR and six patients remained stable in chronic phase, three patients presented an mcr (absence of cr immediately after transplantation), one patient remained in Mcr (Mcr immediately after transplantation) and 11 patients had no cr (four with no cr, three mcr, and four Mcr) immediately after transplantation. Six patients died after transplantation. Causes of death were severe infections (two cases: 9 months after transplantation/52 months after diagnosis; 10 months after transplantation/36 months after diagnosis), a neurologic problem (one case: 28 months after transplantation/55 months after diagnosis), pulmonary embolism (one case: 5 months after transplantation/36 months after diagnosis), osteosarcoma (one case: 16 months after transplantation/126 months after diagnosis), and blast crisis (one case: 11 months after transplantation/40 months after diagnosis).

Table 3  Immediate post-transplantation cytogenetic response
Table 4  Marrow cytogenetics before and after transplantation (median % and range of Ph+ cells) according to the Sokal index, IFN-α therapy duration, and post-transplantation GM-CSF addition


Without an allogeneic transplant donor, patients who did not obtain a complete or major cytogenetic response after IFN-α therapy presented a severe prognosis. High-dose therapy followed by autologous stem-cell transplantation could be a promising new approach.891011 Pretransplantation preparative regimen favors regrowth of normal stem cells, by modifying the myeloid microenvironment, even when patients are infused with 100% Ph-positive stem cells harvested at diagnosis.9

Alpha-interferon has been shown to have an inhibitory effect on hematopoiesis in vitro and in vivo.28 Previous studies have shown that G-CSF can mobilize stem cells either in healthy volunteer donors29 or in patients with hematological malignancies or solid tumors.30 Reiffers et al24 have demonstrated the feasibility of PBPC mobilization by IFN-α associated with G-CSF in CML patients who have a good response to IFN-α. Concomitantly, Archimbaud et al25 showed the feasibility of PBPC mobilization by IFN-α and G-CSF in CML patients whatever the duration of previous IFN-α therapy and the cytogenetic response. Results of mobilization (7.2 × 108/kg MNC, 4.6 × 106/kg CD34+ cells, 39 × 104/kg CFU-GM) observed in these series are comparable to those obtained by Reiffers et al24 (7.4 × 108/kg MNC, 2.7 × 106/kg CD34+ cells, 10.2 × 104/kg CFU-GM). Both of these studies and the present results demonstrate that G-CSF is capable of reversing the hematological toxicity of long-term treatment with IFN-α and thus is a very safe hematopoietic stem-cell mobilization technique which could be performed at any time during CML progression.

One study had shown a differential effect of growth factors on normal vs CML progenitors.31 At relapse after an allogeneic transplantation, G-CSF reinduced complete remission, probably by preferential stimulation of Ph-negative cells.32 Results reported by Reiffers et al24 and by Carreras et al33 suggested that G-CSF preferentially mobilized Ph-negative cells in patients having responded to IFN-α. Moreover, it has been demonstrated that in CML patients either at diagnosis or not responding to IFN-α, it was possible to collect Ph-negative progenitor cells early in the course of hematopoietic recovery after intensive chemotherapy with or without G-CSF.2223 Carella et al23 have indeed shown that anthracycline-containing regimens plus G-CSF, used in patients cytogenetically refractory to IFN-α, were able to mobilize completely/partially Ph-negative PBPCs in 35% of the initial population. This percentage seemed inferior to that obtained when this type of mobilizing therapy was performed soon after diagnosis34 and particularly when patients had not received IFN-α previously.35 However, these mobilizing regimens seemed to give a lower proportion of Ph-negative aphereses after mobilization by G-CSF than that observed by Reiffers et al.24 In our series, all patients except one were poor cytogenetic responders to IFN-α. We demonstrated the feasibility of PBPC mobilization by G-CSF combined with IFN-α, whatever the IFN-α therapy duration and the cytogenetic response before mobilization. We observed no severe complication during mobilization but we observed no preferential Ph-negative-cell mobilization.

At this step, an important point remaining to be investigated is the usefulness of these mobilized PBPCs for reconstituting long-term (Ph-negative) hemopoiesis after transplantation. After initial studies of autotransplantations in CML,891011 related to the evidence that many CML patients harbor Ph-negative cells, recent trends in CML autografting concern in vitro and in vivo attempts to separate Ph-positive from Ph-negative cells.141736373839 There was no difference regarding the time to hematopoietic recovery after autotransplantation between our series and the study carried out by Carella et al.34 Interesting results have been observed in terms of cytogenetic response after transplantation using partially or completely Ph-negative progenitors mobilized after intensive chemotherapy plus G-CSF with three Ccr, two Mcr, and four mcr among 15 evaluated patients.22 However, Carella et al34 reported no data on long-term Ph-negative hemopoiesis after transplantation. In our series, we noted a very interesting cytogenetic conversion immediately after transplantation, particularly in patients with minor cytogenetic response before transplantation. Unfortunately, this good immediate cytogenetic response after transplantation was not maintained during the long-term progression of CML after transplantation in spite of IFN-α therapy at times combined with hydroxyurea. The small number of patients and the absence of a control arm should not invalidate the post-transplantation cytogenetic response observed with the addition of GM-CSF. Cortes et al27 showed an increase of cytogenetic response when GM-CSF was associated with IFN-α. Three hypotheses were proposed to explain the favorable effect of the combination of GM-CSF and IFN-α. One of these hypotheses postulates that the normal stem cells might be suppressed to a point were they are unable to proliferate once the growth advantage of leukemic cells is controlled by IFN-α. It could be speculated that GM-CSF would then stimulate the normal residual stem cells to proliferate and constitute a larger proportion of hematopoietic cells. This hypothesis could be retained to explain the difference of Ph-negative hematopoietic cell reconstitution after transplantation between patients receiving GM-CSF and those not receiving it. Another hypothesis is that myeloid growth factors have a potent antileukemic effect against CML progenitors by inducing their terminal differentiation. Based on this, Gladstone et al40 have autografted high-risk CML patients using enriched normal progenitor autografts obtained by elutriation and GM-CSF incubation. Out of 10 patients, nine engrafted with 100% Ph-negative cells but relapsed cytogenetically, as we observed, at a median of 6 months. In our study, GM-CSF was stopped when a complete granulocytic recovery was obtained. The withdrawal could explain the lack of long-term maintenance of cytogenetic response observed after transplantation. Indeed, some authors have demonstrated that long term treatment combining GM-CSF and cytoreductive therapy was effective in prolonging a transient Ph-negative hematopoiesis after transplantation.41 Future goals could be holding the cytogenetic response obtained immediately after transplantation by maintenance therapy combining continuous IFN-α with discontinuous low doses of GM-CSF.

In conclusion, this study demonstrates that noninvasive hematopoietic stem-cell mobilization using the association of IFN-α and G-CSF is feasible at any time during CML progression, whatever the previous IFN-α therapy duration and the cytogenetic response premobilization. After reinfusion of these collected cells, we observed no engraftment trouble. However, the improved cytogenetic response obtained immediately after transplantation was not maintained in spite of post-transplantation IFN-α therapy requiring other prospective strategies.


  1. 1

    Thomas ED, Clift RA, Fefer A, Appelbaum FR, Beatty P, Bensinger WI, Buckner CD, Cheever MA, Deeg HJ, Doney K, Flournoy N, Greenberg P, Hansen JA, Martin P, McGuffin R, Ramberg R, Sanders JE, Singer J, Stevart P, Storb R, Sullivan K, Weiden PL, Witherspoon R . Marrow transplantation for the treatment of chronic myelogenous leukemia Ann Intern Med 1986 104: 155–162

  2. 2

    Goldman JM . Management of chronic myeloid leukemia Blood 1994 8: 21–29

  3. 3

    Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H, Yoshida T, Kimura A, Akaza T, Kamikawaji N, Kodera Y, Takaku F . Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program New Engl J Med 1998 339: 1177–1185

  4. 4

    Drobyski WR, Pelz C, Kabler-Babbitt C, Hessner M, Baxter-Lowe LA, Keever-Taylor CA . Successful unrelated marrow transplantation for patients over the age of 40 with chronic myelogenous leukemia Biol Blood Marrow Transplant 1998 4: 3–12

  5. 5

    Talpaz M . Prolonged survival in chronic myelogenous leukaemia following cytogenetic response to alpha interferon therapy Ann Intern Med 1995 122: 254–261

  6. 6

    Italian Cooperative Study Group on Chronic Myeloid Leukemia . Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia New Engl J Med 1994 330: 820–825

  7. 7

    Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F, Bouabdallah R, Guyotat D, Cheron N, Nicolini F, Abgrall JF, Tanzer J . Interferon alfa-2b combined with cytarabine vs interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group New Engl J Med 1997 337: 223–229

  8. 8

    Goldman JM . Options for the management of chronic myeloid leukemia Leuk Lymphoma 1990 3: 159–163

  9. 9

    Reiffers J, Goldman JM, Meloni G, Cahn JY, Gratwohl A on behalf of the Chronic Leukemia Working Party of the EBMT . Autologous stem cell transplantation in chronic myelogenous leukemia: a retrospective analysis of the European Group for Bone Marrow Transplantation Bone Marrow Transplant 1994 14: 407–410

  10. 10

    McGlave PB, De Fabritiis P, Deisseroth A . Autologous transplant therapy for chronic myelogenous leukemia prolongs survival: results from eight transplant groups Lancet 1994 343: 1486–1491

  11. 11

    Reiffers J, Mahon FX, Boiron JM, Fabères C, Cony-Makhoul P, Broustet A . Autografting in chronic myeloid leukemia: an overview Leukemia 1996 10: 385–388

  12. 12

    Brenner MK, Rill DR, Moen RC, Krance RA, Mirro J Jr, Anderson WF, Ihle JN . Gene-marking to trace origin of relapse after autologous bone marrow transplantation Lancet 1993 341: 85–86

  13. 13

    Deisseroth AB, Zu Z, Claxton D, Hananian EG, Fu S, Ellerson D, Goldberg L, Thomas M, Janicek K, Anderson WF, Hester J, Korbling M, Durett A, Men R, Berenson R, Heimfeld S, Hamer J, Calvert L, Tibbits P, Talpaz M, Kantarjian H, Champlin R, Reading C . Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukaemia (CML) contribute to relapse after autologous bone marrow in CML Blood 1994 83: 3068–3076

  14. 14

    Coulombel L, Kalousek DK, Eaves CJ, Gupta CM, Eaves AC . Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia New Engl J Med 1983 308: 1493–1498

  15. 15

    McGlave PB, Arthur D, Miller WJ, Lasky L, Kersey J . Autologous transplantation for CML using marrow treated ex vivo with recombinant human interferon gamma Bone Marrow Transplant 1990 6: 115–120

  16. 16

    Carlo-Stella C, Mangoni L, Piovani G, Almmici C, Garau D, Caramatti C, Rizzoli V . In vitro purging in chronic myelogenous leukemia: effect of mafosfamide and recombinant granulocyte-macrophage colony-stimulating factor Bone Marrow Transplant 1991 8: 265–272

  17. 17

    Barnett MJ, Eaves CJ, Phillips GL, Gascoyne RD, Hogge DE, Horsman DE, Humphries RK, Klingemann HG, Lansdorp PM, Nantel SH, Reece DE, Shepherd JD, Spinelli JJ, Sutherland HJ, Eaves AC . Autografting with cultured marrow in chronic myeloid leukemia: results of a pilot study Blood 1994 84: 724–732

  18. 18

    De Fabritiis P, Amadori S, Petti MC, Mancini M, Montefusco E, Picardi A, Geiser T, Camphbell K, Calabretta B, Mandelli F . In vitro purging with BCR-ABL antisense oligonucleotides does not prevent haematology reconstitution after autologous bone marrow transplantation Leukemia 1995 9: 662–664

  19. 19

    Ratajezak MZ, Hijia N, Catani L . Acute and chronic phase chronic myelogenous leukemia colony forming units are highly sensitive to the growth inhibitory effects of c-myb antisense oligodeoxynucleotides Blood 1992 79: 1956–1961

  20. 20

    Estrov Z, Markowitz AB, KuzrockR, Wetzler M, Kantarjian HM, Ferrajoli A, Guttermann JU, Talpaz M . Suppression of chronic myelogenous leukemia colony growth by IL-4 Leukemia 1993 7: 214–220

  21. 21

    Bhatia R, Verfaille CM . Autografting for chronic myelogenous leukemia Curr Opin Hematol 1995 2: 436–443

  22. 22

    Carella AM, Podesta M, Frassoni F, Raffo MR, Pollicardo N, Pungolino E, Vimercati R, Sessarego M, Parodi C, Rabitti C, Ferrero R, Benvenuto F, Figari O, Carlier P, Levcasic G, Valbonesi M, Vitale V, Giordano D, Pierluigi D, Nati S, Guerracio A, Rosso C, Saglio G . Collection of normal blood repopulating cells during early hematopoietic recovery after intensive conventional chemotherapy in chronic myelogenous leukemia Bone Marrow Transplant 1993 12: 267–271

  23. 23

    Carella AM, Simonsson B, Link H, Lennard A, Boogaerts M, Gorin NC, Thomas-Martinez JF, Dabouz-Harrouche F, Gautier L, Badri N . Mobilization of Philadelphia (Ph1)-negative peripheral blood progenitor cells with chemotherapy and rHuG-CSF in chronic myelogenous leukaemia patients with a poor response to interferon-alpha Br J Haematol 1998 101: 111–118

  24. 24

    Reiffers J, Taylor K, Gluckman E, Gorin NC, Mahon FX, Miclea JM, Destrée D, Gautier L . Collection of Ph-negative progenitor cells with granulocyte-colony stimulating factor in patients with chronic myeloid leukaemia who respond to recombinant alpha-interferon Br J Haematol 1998 102: 639–646

  25. 25

    Archimbaud E, Michallet M, Philip I, Charrin C, Clapisson G, Belhabri A, Guilhot F, Stryckmans P, Adeleine P, Fiere D . Granulocyte colony-stimulating factor given in addition to interferon-alpha to mobilize peripheral blood stem cells for autologous transplantation in chronic myeloid leukaemia Br J Haematol 1997 99: 678–684

  26. 26

    Kantarjian HM, Keating MJ, Smith TL, Talpaz M, McCredie KB . Proposal for a simple synthesis prognostic staging system in chronic myelogenous leukemia Am J Med 1990 88: 1–8

  27. 27

    Cortes J, Kantarjian H, O'Brien S, Kurzrock R, Keating M, Talpaz M . GM-CSF can improve the cytogenetic response obtained with interferon-alpha therapy in patients with chronic myelogenous leukemia Leukemia 1998 12: 860–864

  28. 28

    Neuman HA, Fauser AA . Effect of interferon on pluripotent hemopoietic progenitors (CFU-GEMM) derived from human bone marrow Exp Hematol 1982 10: 587–591

  29. 29

    Korbling M, Huh YO, Durett A, Mirza N, Miller P, Engel H, Anderlini P, van Besien K, Andreeff M, Przepiorka D, Deisseroth AB, Champlin R . Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy-1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease Blood 1995 86: 2842–2848

  30. 30

    Sheridan WP, Begley GC, Juttner C, Szer J, To LB, Maher D, McGrath KM, Morstyn G, Fox RM . Effects of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy Lancet 1992 339: 640–644

  31. 31

    Bedi A, Griffin CA, Barber JP, Vala MS, Hawkins AL, Sharkis SJ, Zehnbauer BA, Jones RJ . Growth factor-mediated terminal differentiation of chronic myeloid leukemia Cancer Res 1994 54: 5535–5538

  32. 32

    Giralt S, Escudier S, Kantarjian H, Deisseroth AB, Freireich EJ, Anderson BS, O'Brian S, Andreeff M, Fisher H, Cork A, Hirsch-Ginsberg C, Trujillo J, Stass S, Champlin R . Preliminary results of treatment with filgrastim for relapse of leukaemia and myelodysplasia after allogeneic bone marrow transplantation New Engl J Med 1993 329: 757–761

  33. 33

    Carreras E, Sierra J, Rovira M, Urbano-Ispiza A, Martinez C, Nomdedeu B, Cervantes F, Marin P, Rozman C, Monsterrat E . Successful autografting in chronic myelogenous leukaemia using Philadelphia-negative blood progenitor cells mobilized with rHuG-CSF alone in a patient responding to alpha-interferon Br J Haematol 1997 96: 421–423

  34. 34

    Carella AM, Cunningham I, Lerma E, Dejana A, Benvenuto F, Podseta M, Celesti L, Chimirri F, Abate M, Vassalo F, Figari O, Parodi C, Sessarego M, Valbinesi M, Carlier P, Prencipe E, Gatti AM, Van den Berg D, Hoffman R, Frassoni F . Mobilization and transplantation of Philadelphia-negative peripheral-blood progenitor cells early in chronic myelogenous leukaemia J Clin Oncol 1997 15: 1575–1582

  35. 35

    Carella AM, Frassoni F . ICE, mini-ICE or high-dose hydroxyurea to mobilize Philadelphia (Ph1)-negative PBPC in chronic myelogenous leukaemia (letter) Br J Haematol 1996 95: 213–215

  36. 36

    Gewirtz AM . Treatment of chronic myelogenous leukemia (CML) with c-myb antisense oligodeoxynucleotides Bone Marrow Transplant 1994 14: (Suppl. 3) S57-S61

  37. 37

    Verfaillie CM, Miller WJ, Boylan K, McGlave PB . Selection of benign primitive hematopoietic progenitors in chronic myelogenous leukemia on the basis of HLA-DR antigen expression Blood 1992 79: 1003–1010

  38. 38

    Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB . Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells Nature Med 1996 2: 561–566

  39. 39

    Carlo-Stella C, Mangoni L, Almici C, Caramatti C, Cottafavi L, Dotti GP, Rizzoli V . Autologous transplant for chronic myelogenous leukaemia using marrow treated ex vivo with mafosfamide Bone Marrow Transplant 1994 14: 425–432

  40. 40

    Gladstone DE, Bedi A, Miller CB, Noga SJ, Griffin CA, Piantadosi S, Cagnoni PJ, Brodsky RA, Smith BD, Douglas TT, Shpall EJ, Jones RJ . Philadelphia chromosome-negative engraftment after autologous transplantation with granulocyte–macrophage colony-stimulating factor for chronic myeloid leukemia Biol Blood Marrow Transplant 1999 5: 394–399

  41. 41

    Carlo-Stella C, Regazzi E, Andrizzi C, Savoldo B, Garau D, Montefusco E, Vignetti M, Mandelli F, Rizzoli V, Meloni G . Use of granulocyte–macrophage colony-stimulating factor (GM-CSF) in combination with hydroxyurea as post-transplant therapy in chronic myelogenous leukemia patients autografted with unmanipulated hematopoietic cells Haematologica 1997 82: 291–296

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Michallet, M., Thiébaut, A., Philip, I. et al. Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-α. Leukemia 14, 2064–2069 (2000) doi:10.1038/sj.leu.2401956

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  • late autotransplantation
  • PBPC
  • G-CSF
  • IFN-α
  • CML

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