Abstract
Register data suggest that patients with Hodgkin's disease (HD) given high-dose therapy (HDT) with peripheral blood progenitor cells (PBPC) have a less favourable prognosis as compared to those given bone marrow as stem cell support. Since this can be due to infusion of tumour cells contaminating the PBPC grafts, we initiated a feasibility study in which PBPC grafts from HD patients were purged by CD34+ cell enrichment. Controversy exists about whether the use of CD34+ enriched stem cells leads to a delayed haematological and immune reconstitution. We compared these parameters, including risk of infections and clinical outcome after HDT, in patients with HD given either selected CD34+ cells or unmanipulated PBPC as stem cell support. From October 1994 to May 2000, 40 HD patients with primary refractory disease or relapse were treated with HDT and supported with either selected CD34+ cells (n = 21) or unmanipulated PBPC (n = 19) as stem cell support. All patients had chemosensitive disease at the time of transplantation. A median of 5.8 (range 2.7–20.0) vs 4.5 (range 2.3–17.6) × 106 CD34+ cells per kilo were reinfused in the CD34+ group and PBPC group, respectively. No difference was observed between the two groups with regard to time to haematological engraftment, reconstitution of B cells, CD56+ cells and T cells at 3 and 12 months and infectious episodes after HDT. Two (5%) treatment-related deaths, one in each group, were observed. The overall survival at 4 years was 86% for the CD34+group and 74% for the PBPC group with a median follow-up of 37 months (range 1–61) and 46 months (range 4–82), respectively (P = 0.9). The results of this study demonstrate that the use of CD34+ cells is safe and has no adverse effects either with respect to haematological, immune reconstitution or to infections after HDT. Bone Marrow Transplantation (2001) 28, 849–857.
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References
Schmitz N, Linch DC, Dreger P et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients (see comments) (published erratum appears in Lancet 1996 Mar 30;347(9005):914) Lancet 1996 347: 353–357
Brugger W, Bross KJ, Glatt M et al. Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors (see comments) Blood 1994 83: 636–640
Dreger P, Viehmann K, von-Neuhoff N et al. Autografting of highly purified peripheral blood progenitor cells following myeloablative therapy in patients with lymphoma: a prospective study of the long-term effects on tumor eradication, reconstitution of hematopoiesis and immune recovery Bone Marrow Transplant 1999 24: 153–161
Kvalheim G, Erikstein B, Gilen E et al. The presence of micrometastases in bone marrow and blood in high-risk stage II breast cancer patients before and after high-dose therapy. In: Dicke KA, Keating A (eds) Autologous Blood and Marrow transplantation. Proceedings of the Ninth International Symposium, Arlington, Texas Carden Jennings Publishing: Charlottesville, VA 1999 pp 247–255
Voso MT, Hohaus S, Moos M et al. Autografting with CD34+ peripheral blood stem cells: retained engraftment capability and reduced tumour cell content Br J Haematol 1999 104: 382–391
Brenner MK, Rill DR, Moen RC et al. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation Lancet 1993 341: 85–86
Gribben JG, Freedman AS, Neuberg D et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma (see comments) New Engl J Med 1991 325: 1525–1533
Kvalheim G, Holte H, Jakobsen E et al. Immunomagnetic purging of lymphoma cells from autografts J Hematother 1996 5: 561–562
Majolino I, Pearce R, Taghipour G et al. Peripheral-blood stem-cell transplantation versus autologous bone marrow transplantation in Hodgkin's and non-Hodgkin's lymphomas: a new matched-pair analysis of the European Group for Blood and Marrow Transplantation Registry Data. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation J Clin Oncol 1997 15: 509–517
Wolf J, Kapp U, Bohlen H et al. Peripheral blood mononuclear cells of a patient with advanced Hodgkin's lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells Blood 1996 87: 3418–3428
Blystad AK, Torlakovic E, Holte H et al. Mobilised atypical CD30+ cells contaminating PBPC products in patients with relapsed Hodgkin's disease are efficiently removed by CD34+ cell selection Blood 1999 94: 142a (Abstr.)
Blystad AK, Torlakovic E, Holte H et al. CD34+ cell enrichment depletes atypical CD30+ cells from PBPC grafts in patients with HD Cytotherapy 2001 3: 295–305
Sharp JG, Kessinger A, Pirruccello SJ et al. Frequency of detection of suspected lymphoma cells in peripheral blood stem cell collections. In: Dicke KA, Armitage JO, Dicke-Evinger MJ (eds) Autologous Bone Marrow Transplantation University of Nebraska Medical Center: Omaha 1991 pp 801–810
Sharp JG, Mann SL, Murphy B et al. Culture methods for the detection of minimal tumor contamination of hematopoietic harvests: a review J Hematother 1995 4: 141–148
Sharp JG, Chan WC . Detection and relevance of minimal disease in lymphomas Cancer Metastas Rev 1999 18: 127–142
Mapara MY, Korner IJ, Hildebrandt M et al. Monitoring of tumor cell purging after highly efficient immunomagnetic selection of CD34 cells from leukapheresis products in breast cancer patients: comparison of immunocytochemical tumor cell staining and reverse transcriptase-polymerase chain reaction Blood 1997 89: 337–344
Schiller G, Vescio R, Freytes C et al. Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma Blood 1995 86: 390–397
Bomberger C, Singh JM, Rodey G et al. Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors Blood 1998 91: 2588–2600
Divine M, Boutolleau D, Delfau LM et al. Poor lymphocyte recovery following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma Br J Haematol 1999 105: 349–360
Holmberg LA, Boeckh M, Hooper H et al. Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation Blood 1999 94: 4029–4035
Rutella S, Rumi C, Laurenti L et al. Immune reconstitution after transplantation of autologous peripheral CD34+ cells: analysis of predictive factors and comparison with unselected progenitor transplants Br J Haematol 2000 108: 105–115
Peggs KS, Ings SJ, Kottaridis PD et al. Cytomegalovirus infection and disease after autologous CD34-selected peripheral blood stem cell transplantation for multiple myeloma: no evidence of increased incidence based on polymerase-chain-reaction monitoring (letter) Blood 2000 96: 369–370
Schulenburg A, Kalhs P, Worel N et al. Immunologic recovery of patients given CD34-selected peripheral blood progenitor cell transplantation for malignant diseases (letter) Bone Marrow Transplant 2000 25: 223–224
Vescio R, Schiller G, Stewart AK et al. Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma Blood 1999 93: 1858–1868
Poppema S, Potters M . Dysregulated immune response in Hodgkin's Disease. In: Mauch P, Armitage JO, Diehl V et al (eds) Hodgkin's Disease Lippincott Williams & Wilkins: Philadelphia 1999 pp 159–168
Harris NL, Jaffe ES, Stein H et al. A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group (see comments) Blood 1994 84: 1361–1392
Aurlien E, Holte H, Pharo A et al. Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G-CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's lymphoma Bone Marrow Transplant 1998 21: 873–878
Dreger P, Marquardt P, Haferlach T et al. Effective mobilisation of peripheral blood progenitor cells with ‘Dexa-BEAM’ and G-CSF: timing of harvesting and composition of the leukapheresis product Br J Cancer 1993 68: 950–957
Kvalheim G, Wang MY, Pharo A et al. Purging of tumor cells from leukapheresis products: experimental and clinical aspects J Hematother 1996 5: 427–436
Johnsen HE, Knudsen LM . Nordic flow cytometry standards for CD34+ cell enumeration in blood and leukapheresis products: report from the second Nordic Workshop. Nordic Stem Cell Laboratory Group (NSCL-G) J Hematother 1996 5: 237–245
Ahmed T, Kancherla R, Qureshi Z et al. High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome Bone Marrow Transplant 2000 25: 1041–1045
Brugger W, Henschler R, Heimfeld S et al. Positively selected autologous blood CD34+ cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose VP16, ifosfamide, carboplatin, and epirubicin Blood 1994 84: 1421–1426
Shpall EJ, LeMaistre CF, Holland K et al. A prospective randomized trial of buffy coat versus CD34-selected autologous bone marrow support in high-risk breast cancer patients receiving high-dose chemotherapy Blood 1997 90: 4313–4320
Hammarstrom V, Pauksen K, Svensson H et al. Serum immunoglobulin levels in relation to levels of specific antibodies in allogeneic and autologous bone marrow transplant recipients Transplantation 2000 69: 1582–1586
Mackall CL, Stein D, Fleisher TA et al. Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults Blood 2000 96: 754–762
Gaudernack G, Egeland T . Epitope mapping of 33 CD34 mAb, including the Fifth Workshop panel. In: Schlossman SF, Boumsell L, Gilks W et al (eds) Leukocyte Typing V Oxford University Press: Oxford 1995 pp 861–864
Berenson RJ, Bensinger WI, Hill RS et al. Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma Blood 1991 77: 1717–1722
Friedman J, Lazarus HM, Koc ON . Autologous CD34+ enriched peripheral blood progenitor cell (PBPC) transplantation is associated with higher morbidity in patients with lymphoma when compared to unmanipulated PBPC transplantation Bone Marrow Transplant 2000 26: 831–836
Holmberg LA, Bensinger WI . Increased incidence of cytomegalovirus infection and disease after autologous CD34-selected PBPC transplantation (letter) Blood 2000 96: 370
Acknowledgements
This work was supported by The Norwegian Cancer Society. We give special thanks to Erling Jacobsen, Leiv Rusten and the staff at the Clinical Stem Cell Laboratory and the Central Laboratory, Kari Hildrum at Department of Immunology for technical assistance, the staff at the transplantation unit and Eva Skovlund for assistance with the statistical analysis.
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Blystad, A., Holte, H., Kvaløy, S. et al. High-dose therapy in patients with Hodgkin's disease: the use of selected CD34+ cells is as safe as unmanipulated peripheral blood progenitor cells. Bone Marrow Transplant 28, 849–857 (2001). https://doi.org/10.1038/sj.bmt.1703244
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DOI: https://doi.org/10.1038/sj.bmt.1703244
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