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Chronic Lymphocytic Leukemia

Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H

Leukemia volume 18, pages 57–62 (2004)Cite this article

Abstract

Chronic lymphocytic leukemia (CLL) cells could be undetectable by flow cytometry or polymerase chain reaction after sequential treatment with fludarabine and Campath-1H. Concern has been raised regarding the ability to mobilize sufficient peripheral blood progenitor cells (PBPCs) for autografting after purine analogues, and there are few data about PBPC collection after Campath-1H. In all, 16 CLL patients responding to sequential chemo-immunotherapy entered the study. In 10, mobilization regimen consisted of granulocyte colony-stimulating factor (G-CSF) 5–10 μg/kg/die. Patients failing mobilization or not achieving the target of 2.5 × 106 CD34+ cells/kg underwent a second attempt using intermediate-dose (ID) Ara-C, 800 mg/m2 every 12 h for six doses+G-CSF. PBPC collection after G-CSF alone was successful in two out of 10 patients. An adequate number of CD34+ cells were collected after ID Ara-C+G-CSF in eight patients failing the mobilization with G-CSF alone and in five out of six who did not receive G-CSF before. Greater yields of PBPCs were collected with Ara-C+G-CSF compared with G-CSF alone (13.8 vs 3.3). The extrahematologic toxicity was manageable. In conclusion, PBPC collection is feasible in CLL patients treated with sequential therapy including fludarabine and Campath-1H. Excellent yields were obtained in 92.8% of patients primed with ID Ara-C+G-CSF.

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References

  1. Gratwhol A, Passweg J, Baldomero H, Hermans J . Blood and marrow transplantation activity in Europe 1997. European Group for blood and marrow transplantation (EBMT). Bone Marrow Transplant 1999; 24: 231–245.

    Article  Google Scholar 

  2. Provan D, Bartlett-Pandite L, Zwicky C, Neuberg D, Maddocks A, Corradini P et al. Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood 1996; 88: 2228–2235.

    CAS  PubMed  Google Scholar 

  3. Hale G, Xia MQ, Tighe HP, Dyer MJ, Waldmann H . The CAMPATH 1-H antigen (CDw52). Tissue Antigens 1990; 35: 118–127.

    Article  CAS  PubMed  Google Scholar 

  4. Treumann A, Lifely MR, Schneider P, Ferguson MA . Primary structure of CD52. J Biol Chem 1995; 270: 6088–6099.

    Article  CAS  PubMed  Google Scholar 

  5. Montillo M, Cafro AM, Tedeschi A, Brando B, Oreste PL, Veronese S et al. Safety and efficacy of subcutaneous Campath-1H for treating residual disease in patients with chronic lymphocytic leukemia responding to fludarabine. Haematologica 2002; 87: 695–700.

    CAS  PubMed  Google Scholar 

  6. Dreger P, von Neuhoff N, Kuse R, Sonnen R, Glass B, Uharek L et al. Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure? Br J Cancer 1998; 77: 2291–2297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ketterer N, Salles G, Moullet I, Dumontet C, ElJaafari-Corbin A, Tremisi P et al. Factors associated with successful mobilisation of peripheral blood progenitor cells in 200 patients with lymphoid malignancies. Br J Haematol 1998; 103: 235–242.

    Article  CAS  PubMed  Google Scholar 

  8. Flinn IW, Byrd JC, Morrison C, Jamison J, Diehl LF, Murphy T et al. and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies. Blood 2000; 96: 71–75.

    CAS  PubMed  Google Scholar 

  9. Dyer MJ, Kelsey SM, Mackay HJ, Emmett E, Thornton P, Hale G et al. In vivo ‘purging’ of residual disease in CLL with CAMPATH 1-H. Br J Haematol 1997; 97: 669–672.

    Article  CAS  PubMed  Google Scholar 

  10. Demirer T, Buckner CD, Bensinger WI . Optimization of peripheral blood stem cells mobilisation. Stem Cells 1996; 14: 106–116.

    Article  CAS  PubMed  Google Scholar 

  11. Bensinger W, Appelbaum F, Rowley S, Storb R, Sanders J, Lilleby K et al. Factors that influence collection and engraftment of autologous peripheral blood stem cells. J Clin Oncol 1995; 13: 2547–2555.

    Article  CAS  PubMed  Google Scholar 

  12. Dreger P, Michallet M, Schmitz N . Stem-cell transplantation for chronic lymphocytic leukemia: the 1999 perspective. Ann Oncol 2000; 11: 49–53.

    Article  PubMed  Google Scholar 

  13. de la Rubia J, Sanz MA . Autologous peripheral blood stem cell transplantation for acute leukaemias. Baillieres Best Pract Res Clin Haematol 1999; 12: 139–150.

    Article  CAS  PubMed  Google Scholar 

  14. Magni M, Di Nicola M, Devizzi L, Matteucci P, Lombardi F, Gandola R et al. Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion. Blood 2000; 96: 864–869.

    CAS  PubMed  Google Scholar 

  15. Keating MJ, Scouros M, Murphy S, Kantarjian H, Hester J, McCredie KB et al. Multiple agent chemotherapy (POACH) in previously treated and untreated patients with chronic lymphocytic leukemia. Leukemia 1988; 2: 157–164.

    CAS  PubMed  Google Scholar 

  16. Robertson LE, Hall R, Keating MJ, Estey E, Kantajian H, McLaughlin P et al. High-dose cytosine arabinoside in chronic lymphocytic leukemia: a clinical and pharmacologic analysis. Leukemia Lymphoma 1993; 10: 43–48.

    Article  CAS  PubMed  Google Scholar 

  17. Mauro FR, Foa R, Meloni G, Gentile M, Giammartini E, Giannarelli D et al. Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients. Haematologica 2002; 87: 926–933.

    CAS  PubMed  Google Scholar 

  18. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S et al. National Cancer Institute-Sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–4997.

    CAS  PubMed  Google Scholar 

  19. Hallek M, Schmitt B, Wilhelm M, Busch R, Krober A, Fostitsch HP et al. German Chronic Lymphocytic Leukaemia Study Group. Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study Group. Br J Haematol 2001; 114: 342–348.

    Article  CAS  PubMed  Google Scholar 

  20. Bowen AL, Zomas A, Emmett E, Matutes E, Dyer MJS, Catovsky D . Subcutaneous CAMPATH-1H in fludarabine-resistant/relapsed chronic lymphocytic and B-prolymphocytic leukaemia. Br J Haematol 1997; 96: 617–619.

    Article  CAS  PubMed  Google Scholar 

  21. Rawstron AC, Kennedy B, Evans PAS, Davies FE, Richards SJ, Haynes AP et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 2001; 98: 29–35.

    Article  CAS  PubMed  Google Scholar 

  22. Diss TC, Peng H, Wotherspoon A, Isaacson PG, Pan L . Detection of monoclonality in low-grade B-cell lymphomas using the polymerase chain reaction is dependent on primer selection and lymphoma type. J Pathol 1993; 169: 291–295.

    Article  CAS  PubMed  Google Scholar 

  23. Simon RM . Clinical trials in cancer. In: DeVita VT, Hellman S, Rosenberg S (eds). Cancer: Principles and Practices of Oncology, 5th edn. Philadelphia: Lippincott-Raven Publishers, 1997, 513.

    Google Scholar 

  24. Gratama JW, Sutherland DR, Keeney M, Papa S . Flow cytometric enumeration and immunophenotyping of hematopoietic stem and progenitor cells. J Biol Regul Homeostasis Agents 2001; 15: 14–22.

    CAS  Google Scholar 

  25. Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1750–1757.

    Article  CAS  PubMed  Google Scholar 

  26. Johnson S, Smith AG Loffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ et al. Multicentre prospective randomized trial of fludarabine vs cyclophosphamide, doxorubicin and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukemia. The French Co-operative Group on CLL. Lancet 1996; 347: 1432–1438.

    Article  CAS  PubMed  Google Scholar 

  27. Keating MJ, O'Brien S, Kantarjian H, Estey E, Koller C, Beran M et al. Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent. Blood 1993; 81: 2878–2884.

    CAS  PubMed  Google Scholar 

  28. Keating MJ, O'Brien S, Lerner S, Koller C, Beran M, Robertson LE et al. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood 1998; 92: 1165–1171.

    CAS  PubMed  Google Scholar 

  29. Narayanasami U, Kanteti R, Morelli J, Klekar A, Al-Olama A, Keating C et al. Randomized trial of filgrastim vs chemotherapy and filgrastim mobilisation of hematopoietic progenitor cells for rescue in autologous transplantation. Blood 2001; 98: 2059–2064.

    Article  CAS  PubMed  Google Scholar 

  30. Siena S, Schiavo R, Pedrazzoli P, Carlo-Stella C . Therapeutic relevance of CD34 cell dose in blood cell transplantation for cancer therapy. J Clin Oncol 2000; 18: 1360–1377.

    Article  CAS  PubMed  Google Scholar 

  31. Vescio R, Berenson J . Autologous transplantation purging and the impact of minimal residual disease. Hematol Oncol Clin N Am 1999; 13: 969–986.

    Article  CAS  Google Scholar 

  32. Lemoli RM, Fortuna A, Motta MR, Rizzi S, Giudice V, Nannetti A et al. Concomitant mobilisation of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: positive selection and transplantation of enriched CD34+ cells to remove circulating tumor cells. Blood 1996; 87: 1625–1634.

    CAS  PubMed  Google Scholar 

  33. Meloni G, Proia A, Mauro FR, Amaranto P, Capria S, Cimino G et al. Unmanipulated peripheral blood stem cell autograft in chronic lymphocytic leukaemia: clinical findings and biological monitoring. Haematologica 2000; 85: 952–960.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Salvatore Siena (Milano, Italy) for helpful discussion and critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Hematology, Niguarda Ca’Granda Hospital, Milano, Italy

    M Montillo, A Tedeschi, V Rossi, R Cairoli, E Pungolino, L Intropido, A M Cafro, G D'Avanzo, R Farioli & E Morra

  2. Laboratory of Flow Citometry, Trasfusion Medicin Service, Niguarda Ca'Granda Hospital, Milano, Italy

    B Brando & B Scarpati

  3. Department of Pathology, Niguarda Ca’Granda Hospital, Milano, Italy

    S Veronese

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  1. M Montillo
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Correspondence to M Montillo.

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Montillo, M., Tedeschi, A., Rossi, V. et al. 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 (2004). https://doi.org/10.1038/sj.leu.2403190

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