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Published in: Annals of Hematology 7/2005

01-07-2005 | Original Article

Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment

Authors: D. Lysak, V. Koza, K. Steinerova, P. Jindra, V. Vozobulova, M. Schutzova

Published in: Annals of Hematology | Issue 7/2005

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Abstract

Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m2 and granulocyte colony-stimulating factor (G-CSF) 10 μg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was ≥2.0×106 CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3×106 CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.
Literature
1.
go back to reference Bensinger W, Appelbaum F, Rowley S, Storb R, Sanders J, Lilleby K, Gooley T, Demirer T, Schiffman K, Weaver C (1995) Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol 13:2547–2555PubMed Bensinger W, Appelbaum F, Rowley S, Storb R, Sanders J, Lilleby K, Gooley T, Demirer T, Schiffman K, Weaver C (1995) Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol 13:2547–2555PubMed
2.
go back to reference Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S, Rai KR (1996) National Cancer Institute-sponsored working group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87:4990–4997PubMed Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S, Rai KR (1996) National Cancer Institute-sponsored working group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87:4990–4997PubMed
3.
go back to reference Demirer T, Buckner CD, Bensinger WI (1996) Optimization of peripheral blood stem cell mobilization. Stem Cells 14:106–116 Demirer T, Buckner CD, Bensinger WI (1996) Optimization of peripheral blood stem cell mobilization. Stem Cells 14:106–116
4.
go back to reference Demirer T, Buckner CD, Gooley T, Appelbaum FR, Rowley S, Chauncey T, Lilleby K, Storb R, Bensinger WI (1996) Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant 17:937–941PubMed Demirer T, Buckner CD, Gooley T, Appelbaum FR, Rowley S, Chauncey T, Lilleby K, Storb R, Bensinger WI (1996) Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant 17:937–941PubMed
5.
go back to reference Dreger P, von Neuhoff N, Kuse R, Sonnen R, Glass B, Uharek L, Schoch R, Loffler H, Schmitz N (1998) Early stem cell transplantation for chronic lymphocytic leukemia: a chance for cure? Br J Cancer 77:2291–2297 Dreger P, von Neuhoff N, Kuse R, Sonnen R, Glass B, Uharek L, Schoch R, Loffler H, Schmitz N (1998) Early stem cell transplantation for chronic lymphocytic leukemia: a chance for cure? Br J Cancer 77:2291–2297
6.
go back to reference Dreger P, Michallet M, Schmitz N (2000) Stem-cell transplantation for chronic lymphocytic leukemia: the 1999 perspective. Ann Oncol 11:S49–S53 Dreger P, Michallet M, Schmitz N (2000) Stem-cell transplantation for chronic lymphocytic leukemia: the 1999 perspective. Ann Oncol 11:S49–S53
7.
go back to reference Dreger P, Montserrat E (2002) Autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia. Leukemia 16:985–992 Dreger P, Montserrat E (2002) Autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia. Leukemia 16:985–992
8.
go back to reference Flinn IW, Byrd JC, Morrison C, Jamison J, Diehl LF, Murphy T, Piantadosi S, Seifter E, Ambinder RF, Vogelsang G, Grever MR (2000) Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies. Blood 96:71–75 Flinn IW, Byrd JC, Morrison C, Jamison J, Diehl LF, Murphy T, Piantadosi S, Seifter E, Ambinder RF, Vogelsang G, Grever MR (2000) Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies. Blood 96:71–75
9.
go back to reference Fruehauf S, Seggewiss R (2003) It’s moving day: factors affecting peripheral blood stem mobilization and strategies for improvement. Br J Haematol 122:360–375 Fruehauf S, Seggewiss R (2003) It’s moving day: factors affecting peripheral blood stem mobilization and strategies for improvement. Br J Haematol 122:360–375
10.
go back to reference Itälä M, Pelliniemi T-T, Rajamäki A, Remes K (1997) Autologous blood cell transplantation in B-CLL: response to chemotherapy prior to mobilization predicts the stem cell yield. Bone Marrow Transplant 19:647–651 Itälä M, Pelliniemi T-T, Rajamäki A, Remes K (1997) Autologous blood cell transplantation in B-CLL: response to chemotherapy prior to mobilization predicts the stem cell yield. Bone Marrow Transplant 19:647–651
11.
go back to reference Johnson S, Smith AG, Loffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W (1996) Multicentre prospective randomized trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukemia. The French Cooperative Group on CLL. Lancet 347:1432–1438 Johnson S, Smith AG, Loffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W (1996) Multicentre prospective randomized trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukemia. The French Cooperative Group on CLL. Lancet 347:1432–1438
12.
go back to reference Ketterer N, Salles G, Moullet I, Dumontet C, ElJaafari-Corbin A, Tremisi P, Thieblemont C, Durand B, Neidhardt-Berard EM, Samaha H, Rigal D, Coiffier B (1998) Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies. Br J Haematol 103:235–242 Ketterer N, Salles G, Moullet I, Dumontet C, ElJaafari-Corbin A, Tremisi P, Thieblemont C, Durand B, Neidhardt-Berard EM, Samaha H, Rigal D, Coiffier B (1998) Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies. Br J Haematol 103:235–242
13.
go back to reference Laszlo D, Galieni P, Raspadori D, Scalia G, Bigazzi C, Bocchia M, Bucalossi A, Marotta G, Tozzi M, Lauria F (2000) Fludarabine containing-regimens may adversely affect peripheral blood stem cell collection in low-grade non Hodgkin lymphoma patients. Leuk Lymphoma 37:157–161 Laszlo D, Galieni P, Raspadori D, Scalia G, Bigazzi C, Bocchia M, Bucalossi A, Marotta G, Tozzi M, Lauria F (2000) Fludarabine containing-regimens may adversely affect peripheral blood stem cell collection in low-grade non Hodgkin lymphoma patients. Leuk Lymphoma 37:157–161
14.
go back to reference Lie AKW, Hui CH, Rawling T, Dyson PG, Thorp D, Benic J, Rawling CM, Toogood I, Horvath N, Simmons PJ, To LB (1998) Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who failed initial mobilization with chemotherapy and G-CSF. Bone Marrow Transplant 22:853–857 Lie AKW, Hui CH, Rawling T, Dyson PG, Thorp D, Benic J, Rawling CM, Toogood I, Horvath N, Simmons PJ, To LB (1998) Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who failed initial mobilization with chemotherapy and G-CSF. Bone Marrow Transplant 22:853–857
15.
go back to reference McQuaker I, Haznes A, Stainer C, Byrne J, Russell N (1999) Mobilization of peripheral blood stem cells with IVE and G-CSF improves CD34+ cell yields and engraftment in patients with non-Hodgkin’s lymphomas and Hodgkin’s disease. Bone Marrow Transplant 24:715–722 McQuaker I, Haznes A, Stainer C, Byrne J, Russell N (1999) Mobilization of peripheral blood stem cells with IVE and G-CSF improves CD34+ cell yields and engraftment in patients with non-Hodgkin’s lymphomas and Hodgkin’s disease. Bone Marrow Transplant 24:715–722
16.
go back to reference Micallef I, Apostolidis J, Rohatiner A, Wiggins C, Crawley CR, Foran JM, Leonhardt M, Bradburn M, Okukenu E, Salam A, Matthews J, Cavenagh JD, Gupta RK, Lister TA (2000) Factors which predict unsuccessful mobilization of peripheral blood progenitor cells following G-CSF alone in patients with non-Hodgkin’s lymphoma. Hematol J 1:367–373 Micallef I, Apostolidis J, Rohatiner A, Wiggins C, Crawley CR, Foran JM, Leonhardt M, Bradburn M, Okukenu E, Salam A, Matthews J, Cavenagh JD, Gupta RK, Lister TA (2000) Factors which predict unsuccessful mobilization of peripheral blood progenitor cells following G-CSF alone in patients with non-Hodgkin’s lymphoma. Hematol J 1:367–373
17.
go back to reference Michallet M, Thiébaut A, Dreger P, Remes K, Milpied N, Santini G, Hamon M, Björkstrand B, Kimby E, Belhabri A, Tanguy ML, Apperley JF (2000) Peripheral blood stem cell (PBSC) mobilization and transplantation after fludarabine therapy in chronic lymphocytic leukaemia (CLL): a report of the European Blood and Marrow Transplantation (EBMT) CLL subcommittee on behalf of the EBMT Chronic Leukaemias Working Party (CLWP). Br J Haematol 108:595–601 Michallet M, Thiébaut A, Dreger P, Remes K, Milpied N, Santini G, Hamon M, Björkstrand B, Kimby E, Belhabri A, Tanguy ML, Apperley JF (2000) Peripheral blood stem cell (PBSC) mobilization and transplantation after fludarabine therapy in chronic lymphocytic leukaemia (CLL): a report of the European Blood and Marrow Transplantation (EBMT) CLL subcommittee on behalf of the EBMT Chronic Leukaemias Working Party (CLWP). Br J Haematol 108:595–601
18.
go back to reference Montillo M, Tedeschi A, Rossi V, Cairoli R, Pungolino E, Intropido L, Cafro AM, D’Avanzo G, Farioli R, Brando B, Scarpati B, Veronese S, Morra E (2004) Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H. Leukemia 18:57–62 Montillo M, Tedeschi A, Rossi V, Cairoli R, Pungolino E, Intropido L, Cafro AM, D’Avanzo G, Farioli R, Brando B, Scarpati B, Veronese S, Morra E (2004) Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H. Leukemia 18:57–62
19.
go back to reference Provan D, Bartlett-Pandite L, Zwicky C, Neuberg D, Maddocks A, Corradini P, Soiffer R, Ritz J, Nadler LM, Gribben JG (1996) Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood 88:2228–2235 Provan D, Bartlett-Pandite L, Zwicky C, Neuberg D, Maddocks A, Corradini P, Soiffer R, Ritz J, Nadler LM, Gribben JG (1996) Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood 88:2228–2235
20.
go back to reference Reiser M, Josting A, Draube A, Mapara MY, Scheid C, Chemnitz J, Tesch H, Wolf J, Diehl V, Söhngen D, Engert A (1999) Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization. Bone Marrow Transplant 23:1223–1228 Reiser M, Josting A, Draube A, Mapara MY, Scheid C, Chemnitz J, Tesch H, Wolf J, Diehl V, Söhngen D, Engert A (1999) Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization. Bone Marrow Transplant 23:1223–1228
21.
go back to reference Scimè R, Indovina A, Santoro A, Musso M, Olivieri A, Tringali S, Crescimanno A, Montanari M, Felice R, Catania P, Mariani G, Leoni P, Majolino I (1998) PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia. Bone Marrow Transplant 22:1159–1165 Scimè R, Indovina A, Santoro A, Musso M, Olivieri A, Tringali S, Crescimanno A, Montanari M, Felice R, Catania P, Mariani G, Leoni P, Majolino I (1998) PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia. Bone Marrow Transplant 22:1159–1165
22.
go back to reference Tarella C, Zallio F, Caracciolo D, Cherasco C, Bondesan P, Gavarotti P, Corradini P, Tassi V, Pileri A (1999) Hemopoietic progenitor cell mobilization and harvest following an intensive chemotherapy debulking in indolent lymphoma patients. Stem Cells 17:55–61 Tarella C, Zallio F, Caracciolo D, Cherasco C, Bondesan P, Gavarotti P, Corradini P, Tassi V, Pileri A (1999) Hemopoietic progenitor cell mobilization and harvest following an intensive chemotherapy debulking in indolent lymphoma patients. Stem Cells 17:55–61
23.
go back to reference Tournilhac O, Cazin B, Leprètre S, Divinè M, Maloum K, Delmer A, Grosbois B, Feugier P, Maloisel F, Villard F, Villemagne B, Bastit D, Belhadj K, Azar N, Michallet M, Manhès G, Travade P (2004) Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 103:363–365 Tournilhac O, Cazin B, Leprètre S, Divinè M, Maloum K, Delmer A, Grosbois B, Feugier P, Maloisel F, Villard F, Villemagne B, Bastit D, Belhadj K, Azar N, Michallet M, Manhès G, Travade P (2004) Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 103:363–365
Metadata
Title
Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment
Authors
D. Lysak
V. Koza
K. Steinerova
P. Jindra
V. Vozobulova
M. Schutzova
Publication date
01-07-2005
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 7/2005
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-005-1008-6

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