Skip to main content
Top
Published in: Annals of Hematology 8/2007

01-08-2007 | Original Article

Viable CD34+/CD133+ blood progenitor cell dose as a predictor of haematopoietic engraftment in multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation

Authors: C. Hicks, R. Wong, A. Manoharan, Y. L. Kwan

Published in: Annals of Hematology | Issue 8/2007

Login to get access

Abstract

Both CD34 (cluster of differentiation 34) and the more recently described CD133 are markers of primitive stem cells with haematopoietic repopulating ability. Most transplanting centres use a minimum number of CD34+ cells as the requirement for a transplant and consider this a predictor of haematopoietic engraftment. However, transplanted CD34+ cell dose does not always give a close correlation with time to engraftment nor explain delayed engraftment in some patients. We have retrospectively evaluated the potential of measuring viable CD133+ cell numbers in the autograft as an alternative predictor of haematological engraftment after autologous stem-cell transplantation in a cohort of patients with multiple myeloma (MM). We found an average 32% loss of viability of CD34+ cells in the post-thaw sample compared with the fresh sample. Of the original estimated CD34+ cell numbers transplanted per kg, 43% of the thawed samples were double positive for CD34+/CD133+. In this patient group, the CD34+/CD133+ subset gave the closest statistical correlation with time to neutrophil engraftment (p < 0.05), particularly for patients given above median (1.8 × 106/kg) dose of the double-positive cells. The CD34+/CD133+ population was the only parameter to give a significant correlation with white cell engraftment in this patient cohort (p < 0.05). There was no significant correlation between CD34+, viable CD34+ or viable CD34+/CD133+ cells/kilogram with platelet engraftment. Determination of viable CD34+/CD133+ progenitor cell dose in the autograft may be a useful tool to predict neutrophil recovery after autologous transplantation than conventional assessment of CD34+ numbers. These results warrant further investigation of the role of CD133 in haematopoietic engraftment.
Literature
1.
go back to reference To LB, Haycock DN, Simmons PJ, Juttner CA (1997) The biology and clinical uses of blood stem cells. Blood 89:2233–2258PubMed To LB, Haycock DN, Simmons PJ, Juttner CA (1997) The biology and clinical uses of blood stem cells. Blood 89:2233–2258PubMed
2.
go back to reference Bender JG, To LB, Williams S, Schwartzberg LS (1992) Defining a therapeutic dose of peripheral blood stem cells. J Hematother 1:329–341PubMed Bender JG, To LB, Williams S, Schwartzberg LS (1992) Defining a therapeutic dose of peripheral blood stem cells. J Hematother 1:329–341PubMed
3.
go back to reference Villalon L, Odriozola J, Larana JG, Zamora C, Perez de Oteyza J, Jodra MH et al (2000) Autologous peripheral blood progenitor cell transplantation with <2 × 10(6) CD34 (+)/kg: an analysis of variables concerning mobilisation and engraftment. Hematol J 1:374–381PubMedCrossRef Villalon L, Odriozola J, Larana JG, Zamora C, Perez de Oteyza J, Jodra MH et al (2000) Autologous peripheral blood progenitor cell transplantation with <2 × 10(6) CD34 (+)/kg: an analysis of variables concerning mobilisation and engraftment. Hematol J 1:374–381PubMedCrossRef
4.
go back to reference Shpall EJ, Champlin R, Glaspy JA (1998) Effect of CD34+ peripheral blood progenitor cell dose on haematopoietic recovery. Biol Blood Marrow Transplant 4:84–92PubMedCrossRef Shpall EJ, Champlin R, Glaspy JA (1998) Effect of CD34+ peripheral blood progenitor cell dose on haematopoietic recovery. Biol Blood Marrow Transplant 4:84–92PubMedCrossRef
5.
go back to reference Sator M, Antonenas V, Garvan F, Webb M, Bradstock KF (2005) Recovery of viable CD34+ cells from cryopreserved hemopoietic progenitor cell products. Bone Marrow Transplant 36:199–204CrossRef Sator M, Antonenas V, Garvan F, Webb M, Bradstock KF (2005) Recovery of viable CD34+ cells from cryopreserved hemopoietic progenitor cell products. Bone Marrow Transplant 36:199–204CrossRef
6.
go back to reference Abrahamsen JF, Wentzel-Larsen T and Bruserud O (2004) Autologous transplantation: the viable transplanted CD34+ cell dose measured post-thaw does not predict engraftment kinetics better than the total CD34+ cell dose measured pre-freeze in patients that receive more than 2 × 10(6) CD34+ cells/kg. Cytotherapy 6:356–362 Abrahamsen JF, Wentzel-Larsen T and Bruserud O (2004) Autologous transplantation: the viable transplanted CD34+ cell dose measured post-thaw does not predict engraftment kinetics better than the total CD34+ cell dose measured pre-freeze in patients that receive more than 2 × 10(6) CD34+ cells/kg. Cytotherapy 6:356–362
7.
go back to reference Allan DS, Keeney M, Howson-Jan K, Popma J, Weir K, Bhatia M, Sutherland DR et al (2002) Number of viable CD34+ cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 29:967–972PubMedCrossRef Allan DS, Keeney M, Howson-Jan K, Popma J, Weir K, Bhatia M, Sutherland DR et al (2002) Number of viable CD34+ cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 29:967–972PubMedCrossRef
8.
go back to reference Pecora AL, Preti RA, Gleim GW, Jennis A, Zahos K, Cantwell S et al (1998) CD34+CD33− cells influence days to engraftment and transfusion requirements in autologous blood stem-cell recipients. J Clin Oncol 16:2093–2104PubMed Pecora AL, Preti RA, Gleim GW, Jennis A, Zahos K, Cantwell S et al (1998) CD34+CD33− cells influence days to engraftment and transfusion requirements in autologous blood stem-cell recipients. J Clin Oncol 16:2093–2104PubMed
9.
go back to reference Watanabe T, Dave B, Heimann DG, Jackson JD, Kessinger A, Talmadge JE (1998) Cell adhesion molecule expression on CD34+ cells in grafts and time to myeloid and platelet recovery after autologous stem cell transplantation. Exp Hematol 26:10–18PubMed Watanabe T, Dave B, Heimann DG, Jackson JD, Kessinger A, Talmadge JE (1998) Cell adhesion molecule expression on CD34+ cells in grafts and time to myeloid and platelet recovery after autologous stem cell transplantation. Exp Hematol 26:10–18PubMed
10.
go back to reference Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG et al (1997) AC133, a novel marker for human haematopoietic stem and progenitor cells. Blood 90:5002–5012PubMed Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG et al (1997) AC133, a novel marker for human haematopoietic stem and progenitor cells. Blood 90:5002–5012PubMed
11.
go back to reference Pasino M, Lanza T, Marotta F, Scarso L, De Biasio P, Amato S et al (2000) Flow cytometric and functional characterisation of AC133(+) cells from human umbilical cord blood. Br J Haematol 108:793–800PubMedCrossRef Pasino M, Lanza T, Marotta F, Scarso L, De Biasio P, Amato S et al (2000) Flow cytometric and functional characterisation of AC133(+) cells from human umbilical cord blood. Br J Haematol 108:793–800PubMedCrossRef
12.
go back to reference Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT et al (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterisation and molecular cloning. Blood 90:5013–5021PubMed Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT et al (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterisation and molecular cloning. Blood 90:5013–5021PubMed
13.
go back to reference Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M et al (2000) Expression of VEGFR-2 and AC133 by circulating human CD 34 (+) cells identifies a population of functional endothelial precursors. Blood 95:952–958PubMed Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M et al (2000) Expression of VEGFR-2 and AC133 by circulating human CD 34 (+) cells identifies a population of functional endothelial precursors. Blood 95:952–958PubMed
14.
go back to reference Padovan CS, Jahn K, Birnbaum T, Reich P, Sostak P, Strupp M et al (2003) Expression of neuronal markers in differentiated marrow stromal cells and CD133+ stem-like cells. Cell Transplant 12:839–848PubMed Padovan CS, Jahn K, Birnbaum T, Reich P, Sostak P, Strupp M et al (2003) Expression of neuronal markers in differentiated marrow stromal cells and CD133+ stem-like cells. Cell Transplant 12:839–848PubMed
15.
go back to reference Bitan M, Shapira MY, Resnick IB, Zilberman I, Miron S, Samuel S et al (2005) Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133+ purified stem cells. Exp Hematol 33:713–718PubMedCrossRef Bitan M, Shapira MY, Resnick IB, Zilberman I, Miron S, Samuel S et al (2005) Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133+ purified stem cells. Exp Hematol 33:713–718PubMedCrossRef
16.
go back to reference Lang P, Bader P, Schumm M, Feuchtinger T, Einsele H, Fuhrer M et al (2004) Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors. Br J Hematother Stem Cell Res 12:23–32 Lang P, Bader P, Schumm M, Feuchtinger T, Einsele H, Fuhrer M et al (2004) Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors. Br J Hematother Stem Cell Res 12:23–32
17.
go back to reference Trickett AE, Smith S, Kwan YL (2001) Accurate calculation of blood volume to be processed by aphaeresis to achieve target CD34+ cell numbers or PBPC transplantation. Cytotherapy 3:5–10PubMedCrossRef Trickett AE, Smith S, Kwan YL (2001) Accurate calculation of blood volume to be processed by aphaeresis to achieve target CD34+ cell numbers or PBPC transplantation. Cytotherapy 3:5–10PubMedCrossRef
18.
go back to reference Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR (1998) Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 34:61–70PubMedCrossRef Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR (1998) Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 34:61–70PubMedCrossRef
19.
go back to reference Sasaki DT, Dumas SE, Engleman EG (1987) Discrimination of viable and non-viable cells using propidium iodide in two color immunofluorescence. Cytometry 8:213–420 Sasaki DT, Dumas SE, Engleman EG (1987) Discrimination of viable and non-viable cells using propidium iodide in two color immunofluorescence. Cytometry 8:213–420
20.
go back to reference Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al (1995) An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myoablative chemotherapy. Blood 86:3961–3969PubMed Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al (1995) An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myoablative chemotherapy. Blood 86:3961–3969PubMed
21.
go back to reference Besinger W, Applebaum F, Rowley S, Storb R, Sanders J, Lilleby K et al (1995) Factors that influence collection and engraftment of autologous peripheral blood stem cells. J Clin Oncol 13:2547–2555 Besinger W, Applebaum F, Rowley S, Storb R, Sanders J, Lilleby K et al (1995) Factors that influence collection and engraftment of autologous peripheral blood stem cells. J Clin Oncol 13:2547–2555
22.
go back to reference Haas R, Witt B, Mohle R, Goldschmidt H, Hohaus S, Fruehauf S et al (1995) Sustained long-term haematopoiesis after myeloablative therapy with peripheral blood progenitor support. Blood 85:3754–3761PubMed Haas R, Witt B, Mohle R, Goldschmidt H, Hohaus S, Fruehauf S et al (1995) Sustained long-term haematopoiesis after myeloablative therapy with peripheral blood progenitor support. Blood 85:3754–3761PubMed
23.
go back to reference Ketterer N, Salles G, Raba M, Espinouse D, Sonet A, Tremisi P et al (1998) High CD34(+) counts decrease hematological toxicity of autologous peripheral blood progenitor cell transplantation. Blood 91:3148–3155PubMed Ketterer N, Salles G, Raba M, Espinouse D, Sonet A, Tremisi P et al (1998) High CD34(+) counts decrease hematological toxicity of autologous peripheral blood progenitor cell transplantation. Blood 91:3148–3155PubMed
24.
go back to reference Jansen J, Thompson JM, Dugan MJ, Nolan P, Weimann MC, Birhiray R et al (2002) Peripheral blood progenitor cell transplantation. Ther Apher 6:5–14PubMedCrossRef Jansen J, Thompson JM, Dugan MJ, Nolan P, Weimann MC, Birhiray R et al (2002) Peripheral blood progenitor cell transplantation. Ther Apher 6:5–14PubMedCrossRef
25.
go back to reference Olivieri A, Offidani M, Montanari M, Ciniero L, Ombrosi L, Masia CM et al (1998) Factors affecting haemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: a single center experience. Haematologica 83:329–337PubMed Olivieri A, Offidani M, Montanari M, Ciniero L, Ombrosi L, Masia CM et al (1998) Factors affecting haemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: a single center experience. Haematologica 83:329–337PubMed
26.
go back to reference Tricot G, Jagannath D, Nelson J, Tindle S, Miller L, Cheson B et al (1995) Peripheral blood stem cell transplants for multiple myeloma: identification of favourable variables for rapid engraftment in 225 patients. Blood 85:588–596PubMed Tricot G, Jagannath D, Nelson J, Tindle S, Miller L, Cheson B et al (1995) Peripheral blood stem cell transplants for multiple myeloma: identification of favourable variables for rapid engraftment in 225 patients. Blood 85:588–596PubMed
27.
go back to reference Yang H, Acker JP, Cabuhat M, Letcher B, Larratt L, McGann LE (2005) Association of post-thaw viable CD34+cells and CFU-GM with time to haematopoietic engraftment. Bone Marrow Transplant 35:881–887PubMedCrossRef Yang H, Acker JP, Cabuhat M, Letcher B, Larratt L, McGann LE (2005) Association of post-thaw viable CD34+cells and CFU-GM with time to haematopoietic engraftment. Bone Marrow Transplant 35:881–887PubMedCrossRef
28.
go back to reference Matsumoto K, Yasui K, Yamashita N, Horie Y, Yamada T, Tani Y et al (2000) In vitro proliferation potential of AC133 positive cells in peripheral blood. Stem Cells 18:196–203PubMedCrossRef Matsumoto K, Yasui K, Yamashita N, Horie Y, Yamada T, Tani Y et al (2000) In vitro proliferation potential of AC133 positive cells in peripheral blood. Stem Cells 18:196–203PubMedCrossRef
29.
go back to reference Kuci S, Wessels JT, Buhring HJ, Schilbach K, Schumm M, Seitz G et al (2003) Identification of a novel class of human adherent CD34-stem cells that give rise to SCID-repopulating cells. Blood 101:869–876PubMedCrossRef Kuci S, Wessels JT, Buhring HJ, Schilbach K, Schumm M, Seitz G et al (2003) Identification of a novel class of human adherent CD34-stem cells that give rise to SCID-repopulating cells. Blood 101:869–876PubMedCrossRef
30.
go back to reference Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R et al (2006) Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoeitic stem cells. Blood 107:2162–2169PubMedCrossRef Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R et al (2006) Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoeitic stem cells. Blood 107:2162–2169PubMedCrossRef
31.
go back to reference Lefrere F, Delarue R, Levy V, Damaj G, Tu A, Porcher R et al (2002) High dose-CD34+cells are not clinically relevant in reducing cytopenia and blood component consumption following myeloablative therapy and peripheral blood progenitor cell transplantation as compared with standard dose. Transfusion 42:443–450PubMedCrossRef Lefrere F, Delarue R, Levy V, Damaj G, Tu A, Porcher R et al (2002) High dose-CD34+cells are not clinically relevant in reducing cytopenia and blood component consumption following myeloablative therapy and peripheral blood progenitor cell transplantation as compared with standard dose. Transfusion 42:443–450PubMedCrossRef
32.
go back to reference Hass R, Mohle R, Fruhauf S et al (1994) Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. Blood 83:3787–3794 Hass R, Mohle R, Fruhauf S et al (1994) Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. Blood 83:3787–3794
Metadata
Title
Viable CD34+/CD133+ blood progenitor cell dose as a predictor of haematopoietic engraftment in multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation
Authors
C. Hicks
R. Wong
A. Manoharan
Y. L. Kwan
Publication date
01-08-2007
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 8/2007
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-007-0297-3

Other articles of this Issue 8/2007

Annals of Hematology 8/2007 Go to the issue
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

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.