Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 4/2009

01-04-2009 | Original Paper

Contamination of autologous peripheral blood progenitor cell grafts predicts overall survival after high-dose chemotherapy in multiple myeloma

Authors: H. G. Kopp, S. Yildirim, K. C. Weisel, L. Kanz, W. Vogel

Published in: Journal of Cancer Research and Clinical Oncology | Issue 4/2009

Login to get access

Abstract

Background

Despite of the introduction of novel treatment modalities for multiple myeloma, high-dose chemotherapy with hematopoietic stem-cell rescue is still considered the standard of care for eligible patients <65 years of age. As we have previously reported, stem-cell grafts regularly contain quantities of plasma cells measurable by flow cytometry. However, the pathogenetic significance of this finding remains unknown.

Methods

Multiple myeloma patients (n = 60) were mobilized with chemotherapy and filgrastim. Peripheral blood stem cell grafts were obtained by standard leukapheresis, and the number of CD38++/CD138+ cells/kg was determined by flow cytometry. Plasma cell contamination above a threshold of 4.5 × 105 plasma cells/kg was considered “high”, whereas lower quantities of plasma cells or absent plasma cells in the graft were considered “low”.

Results

Progression-free survival: the median statistical progression-free survival was 33.5 months (range 11–99 months) in the high-contamination group (n = 16) versus 47 months (range 8–148 months) in the low-contamination group (n = 44). This difference turned out not to be statistically significant (P = 0.15). However, the difference was highly significant regarding overall survival with 53 months (range 11–119 months) in the high-contamination group and with 114 months (range 8–158 months) in the low-contamination group (P = 0.012).

Conclusions

Patients with >4.5 × 105 plasma cells/kg contaminating the peripheral blood stem cell graft received after high-dose chemotherapy have a significantly reduced overall survival. Whether high contamination of grafts with plasma cells might reflect residual in vivo tumor mass prior to stem cell transplantation and a generally more aggressive behavior of malignant myeloma cells in these patients, or whether reinfused plasma cells contribute to an unfavorable course of disease remains to be determined.
Literature
go back to reference Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 335:91–97PubMedCrossRef Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 335:91–97PubMedCrossRef
go back to reference Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502PubMedCrossRef Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502PubMedCrossRef
go back to reference Barbui AM, Galli M, Dotti G, Belli N, Borleri G, Gritti G, Bellavita P, Viero P, Comotti B, Barbui T, Rambaldi A (2002) Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma. Br J Haematol 116:202–210PubMedCrossRef Barbui AM, Galli M, Dotti G, Belli N, Borleri G, Gritti G, Bellavita P, Viero P, Comotti B, Barbui T, Rambaldi A (2002) Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma. Br J Haematol 116:202–210PubMedCrossRef
go back to reference Barlogie B, van Rhee F, Shaughnessy JD Jr, Anaissie E, Crowley J (2008) Making progress in treating multiple myeloma with total therapies: issue of complete remission and more. Leukemia 22(8):1633–1636 Barlogie B, van Rhee F, Shaughnessy JD Jr, Anaissie E, Crowley J (2008) Making progress in treating multiple myeloma with total therapies: issue of complete remission and more. Leukemia 22(8):1633–1636
go back to reference Bourhis JH, Bouko Y, Koscielny S, Bakkus M, Greinix H, Derigs G, Salles G, Feremans W, Apperley J, Samson D, Bjorkstrand B, Niederwieser D, Gahrton G, Pico JL, Goldschmidt H (2007) Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study. Haematologica 92:1083–1090PubMedCrossRef Bourhis JH, Bouko Y, Koscielny S, Bakkus M, Greinix H, Derigs G, Salles G, Feremans W, Apperley J, Samson D, Bjorkstrand B, Niederwieser D, Gahrton G, Pico JL, Goldschmidt H (2007) Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study. Haematologica 92:1083–1090PubMedCrossRef
go back to reference Dingli D, Nowakowski GS, Dispenzieri A, Lacy MQ, Hayman SR, Rajkumar SV, Greipp PR, Litzow MR, Gastineau DA, Witzig TE, Gertz MA (2006) Flow cytometric detection of circulating myeloma cells before transplantation in patients with multiple myeloma: a simple risk stratification system. Blood 107:3384–3388PubMedCrossRef Dingli D, Nowakowski GS, Dispenzieri A, Lacy MQ, Hayman SR, Rajkumar SV, Greipp PR, Litzow MR, Gastineau DA, Witzig TE, Gertz MA (2006) Flow cytometric detection of circulating myeloma cells before transplantation in patients with multiple myeloma: a simple risk stratification system. Blood 107:3384–3388PubMedCrossRef
go back to reference Einsele H, Bamberg M, Budach W, Schmidberger H, Hess CF, Wormann B, Meisner C, Straka C, Hebart H, Trumper L, Kroger N, Zander AR, Hegewisch-Becker S, Hossfeld DK, Schmidt H, Muller P, Schlimok G, Hertenstein B, Peest D, Metzner B, Frickhofen N, Kanz L, Bensinger WI (2003) A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma. Bone Marrow Transplant 32:593–599PubMedCrossRef Einsele H, Bamberg M, Budach W, Schmidberger H, Hess CF, Wormann B, Meisner C, Straka C, Hebart H, Trumper L, Kroger N, Zander AR, Hegewisch-Becker S, Hossfeld DK, Schmidt H, Muller P, Schlimok G, Hertenstein B, Peest D, Metzner B, Frickhofen N, Kanz L, Bensinger WI (2003) A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma. Bone Marrow Transplant 32:593–599PubMedCrossRef
go back to reference Gahrton G (2005) Progress in hematopoietic stem cell transplantation in multiple myeloma. Curr Opin Hematol 12:463–470PubMedCrossRef Gahrton G (2005) Progress in hematopoietic stem cell transplantation in multiple myeloma. Curr Opin Hematol 12:463–470PubMedCrossRef
go back to reference Gazitt Y, Reading CC, Hoffman R, Wickrema A, Vesole DH, Jagannath S, Condino J, Lee B, Barlogie B, Tricot G (1995) Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells. Blood 86:381–389PubMed Gazitt Y, Reading CC, Hoffman R, Wickrema A, Vesole DH, Jagannath S, Condino J, Lee B, Barlogie B, Tricot G (1995) Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells. Blood 86:381–389PubMed
go back to reference Gertz MA, Witzig TE, Pineda AA, Greipp PR, Kyle RA, Litzow MR (1997) Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation. Bone Marrow Transplant 19:337–342PubMedCrossRef Gertz MA, Witzig TE, Pineda AA, Greipp PR, Kyle RA, Litzow MR (1997) Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation. Bone Marrow Transplant 19:337–342PubMedCrossRef
go back to reference Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK (2006) High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma. Expert Rev Anticancer Ther 6:343–360PubMedCrossRef Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK (2006) High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma. Expert Rev Anticancer Ther 6:343–360PubMedCrossRef
go back to reference Lemoli RM, Cavo M, Fortuna A (1996) Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of patients with multiple myeloma. J Hematother 5:339–349PubMed Lemoli RM, Cavo M, Fortuna A (1996) Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of patients with multiple myeloma. J Hematother 5:339–349PubMed
go back to reference Lemoli RM, Martinelli G, Olivieri A, Motta MR, Rizzi S, Terragna C, Leopardi G, Benni M, Ronconi S, Cantori I, Rondelli D, Mangianti S, Leoni P, Montanari M, Cavo M, Tura S (1999) Selection and transplantation of autologous CD34+ B-lineage negative cells in advanced-phase multiple myeloma patients: a pilot study. Br J Haematol 107:419–428PubMedCrossRef Lemoli RM, Martinelli G, Olivieri A, Motta MR, Rizzi S, Terragna C, Leopardi G, Benni M, Ronconi S, Cantori I, Rondelli D, Mangianti S, Leoni P, Montanari M, Cavo M, Tura S (1999) Selection and transplantation of autologous CD34+ B-lineage negative cells in advanced-phase multiple myeloma patients: a pilot study. Br J Haematol 107:419–428PubMedCrossRef
go back to reference Lemoli RM, Martinelli G, Zamagni E, Motta MR, Rizzi S, Terragna C, Rondelli R, Ronconi S, Curti A, Bonifazi F, Tura S, Cavo M (2000) Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy. Blood 95:2234–2239PubMed Lemoli RM, Martinelli G, Zamagni E, Motta MR, Rizzi S, Terragna C, Rondelli R, Ronconi S, Curti A, Bonifazi F, Tura S, Cavo M (2000) Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy. Blood 95:2234–2239PubMed
go back to reference Ludwig H, Strasser-Weippl K, Schreder M, Zojer N (2007) Advances in the treatment of hematological malignancies: current treatment approaches in multiple myeloma. Ann Oncol 18:ix64–ix70PubMedCrossRef Ludwig H, Strasser-Weippl K, Schreder M, Zojer N (2007) Advances in the treatment of hematological malignancies: current treatment approaches in multiple myeloma. Ann Oncol 18:ix64–ix70PubMedCrossRef
go back to reference Michallet M, Philip T, Philip I, Godinot H, Sebban C, Salles G, Thiebaut A, Biron P, Lopez F, Mazars P, Roubi N, Leemhuis T, Hanania E, Reading C, Fine G, Atkinson K, Juttner C, Coiffier B, Fiere D, Archimbaud E (2000) Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution. Exp Hematol 28:858–870PubMedCrossRef Michallet M, Philip T, Philip I, Godinot H, Sebban C, Salles G, Thiebaut A, Biron P, Lopez F, Mazars P, Roubi N, Leemhuis T, Hanania E, Reading C, Fine G, Atkinson K, Juttner C, Coiffier B, Fiere D, Archimbaud E (2000) Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution. Exp Hematol 28:858–870PubMedCrossRef
go back to reference Nowakowski GS, Witzig TE, Dingli D, Tracz MJ, Gertz MA, Lacy MQ, Lust JA, Dispenzieri A, Greipp PR, Kyle RA, Rajkumar SV (2005) Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 106:2276–2279PubMedCrossRef Nowakowski GS, Witzig TE, Dingli D, Tracz MJ, Gertz MA, Lacy MQ, Lust JA, Dispenzieri A, Greipp PR, Kyle RA, Rajkumar SV (2005) Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 106:2276–2279PubMedCrossRef
go back to reference Schiller G, Vescio R, Freytes C, Spitzer G, Sahebi F, Lee M, Wu CH, Cao J, Lee JC, Hong CH (1995) Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma. Blood 86:390–397PubMed Schiller G, Vescio R, Freytes C, Spitzer G, Sahebi F, Lee M, Wu CH, Cao J, Lee JC, Hong CH (1995) Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma. Blood 86:390–397PubMed
go back to reference Stewart AK, Vescio R, Schiller G, Ballester O, Noga S, Rugo H, Freytes C, Stadtmauer E, Tarantolo S, Sahebi F, Stiff P, Meharchard J, Schlossman R, Brown R, Tully H, Benyunes M, Jacobs C, Berenson R, White M, DiPersio J, Anderson KC, Berenson J (2001) Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial. J Clin Oncol 19:3771–3779PubMed Stewart AK, Vescio R, Schiller G, Ballester O, Noga S, Rugo H, Freytes C, Stadtmauer E, Tarantolo S, Sahebi F, Stiff P, Meharchard J, Schlossman R, Brown R, Tully H, Benyunes M, Jacobs C, Berenson R, White M, DiPersio J, Anderson KC, Berenson J (2001) Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial. J Clin Oncol 19:3771–3779PubMed
go back to reference Thirukkumaran CM, Russell JA, Stewart DA, Morris DG (2007) Viral purging of haematological autografts: should we sneeze on the graft? Bone Marrow Transplant 40:1–12PubMedCrossRef Thirukkumaran CM, Russell JA, Stewart DA, Morris DG (2007) Viral purging of haematological autografts: should we sneeze on the graft? Bone Marrow Transplant 40:1–12PubMedCrossRef
go back to reference Vogel W, Kopp HG, Kanz L, Einsele H (2005) Myeloma cell contamination of peripheral blood stem-cell grafts can predict the outcome in multiple myeloma patients after high-dose chemotherapy and autologous stem-cell transplantation. J Cancer Res Clin Oncol 131:214–218PubMedCrossRef Vogel W, Kopp HG, Kanz L, Einsele H (2005) Myeloma cell contamination of peripheral blood stem-cell grafts can predict the outcome in multiple myeloma patients after high-dose chemotherapy and autologous stem-cell transplantation. J Cancer Res Clin Oncol 131:214–218PubMedCrossRef
Metadata
Title
Contamination of autologous peripheral blood progenitor cell grafts predicts overall survival after high-dose chemotherapy in multiple myeloma
Authors
H. G. Kopp
S. Yildirim
K. C. Weisel
L. Kanz
W. Vogel
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 4/2009
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0499-7

Other articles of this Issue 4/2009

Journal of Cancer Research and Clinical Oncology 4/2009 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine