Abstract
Background
Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strateg for malignant lymphoproliferative disorder. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF.
Methods
A total of 69 patients (MM 25 patients, NHL 44 patients) with malignant lymphoproliferative disorder had been mobilizedwith chemotherapy and granulocyte colony-stimulating growth factor from January, 2003 to July, 2008. We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positve cells in the PB and their correlation with the yield of PBPCs collected from the mobilized patients.
Results
The total number of leukapheresis sessions was 134 (mean: 1.94 session per patient), and the mean number of harvested CD34 positive cell per patient was 12.47×106/kg. The number of harvested CD34 positive cells was correlated with the patient's height, the number of peripheral blood hematopoietic progenitor cells (HPC) and the number of PB CD34 positive cells at the harvest (P<0.05). But the number of PB CD34 positive cell was the only significant factor for the quantity of harvested CD34 positive cells on the linear regression analysis (P<0.05). More than 23.7/μL PB CD34 positive cells were needed to harvest 3×106/kg CD34 positive cells, according to the ROC curve (P<0.05).
References
1. Shipp MA, Abeloff MD, Antman KH, et al. International Consensus Conference On High-Dose Therapy With Hematopoietic Stem Cell Transplantation In Aggressive non-Hodgkin's lymphomas, report of the jury. J Clin Oncol. 1999; 17:423–9.
2. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myélome. N Engl J Med. 1996; 335:91–7.
3. Goldman JM. Autografting cryopreserved buffy coat cells for chronic granulocytic leukaemia in transformation. Exp Hematol. 1979; 7(5 Suppl):389–97.
4. Schwartzberg L, Birch R, Blanco R, et al. Rapid and sustained hematopoietic reconstitution by peripheral blood stem cell infusion alone following high-dose chemotherapy. Bone Marrow Transplant. 1993; 11:369–74.
5. Russell NH, Hunter A, Rogers S, Hanley J, Anderson D. Peripheral blood stem cells as an alternative to marrow for allogeneic transplantation. Lancet. 1993; 341:1482.
6. Rowley SD. Processing of hematopoietic stem cell components for transplantation: variations in current practice. Transfusion. 1998; 38:1–4.
7. Kessinger A, Armitage JO, Landmark JD, Smith DM, Weisenburger DD. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. Blood. 1988; 71:723–7.
8. Dicke KA, Hood D, Hanks S. Peripheral blood stem cell collection after mobilization with intensive chemotherapy and growth factors. J Hematother. 1994; 3:141–4.
9. Yang SM, Liu KY, Lu DP. Comparison of the effect of Cobe Spectra and Fenwal CS 3000 plus blood cell separators in collection of peripheral blood stem cell components. Zhongquo Shi Yan Xue Ye Xue Za Zhi. 2005; 13:245–9.
10. Demirer T, Buckner CD, Bensinger WI. Optimization of peripheral blood stem cell mobilization. Stem Cells. 1996; 14:106–16.
11. Bender JG, To LB, Williams S, Schwartzberg LS. Defining a therapeutic dose of peripheral blood stem cells. J Hematother. 1992; 1:329–41.
12. Sutherland HJ, Eaves CJ, Lansdorp PM, Phillips GL, Hogge DE. Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in auto-transplants. Blood. 1994; 83:3808–14.
13. Keung YK, Cobos E, Dunn D, et al. Determining factors for the outcome of peripheral blood progenitor cells harvests. J Clin Apher. 1996; 11:23–6.
14. Pérez-Simón JA, Caballero MD, Corral M, et al. Minimal number of circulating CD34+ cells to ensure successful leukapheresis and engraftment in autologous peripheral blood progenitor cell transplantation. Transfusion. 1998; 38:385–91.
15. Socinski MA, Cannistra SA, Elias A, Antman KH, S-chnipper L, Griffin JD. Granulocyte-macrophage colony stimulating factor expands the circulating haemopoietic progenitor cell compartment in man. Lancet. 1988; 1:1194–8.
16. Haas R, Hohaus S, Egerer G, Ehrhardt R, Witt B, Hunstein W. Recombinant human granulocyte-macrophage colonystimulating factor (rhGM-CSF) subsequent to chemotherapy improves collection of blood stem cells for autografting in patients not eligible for bone marrow harvest. Bone Marrow Transplant. 1992; 9:459–65.
17. Brugger W, Bross K, Frisch J, et al. Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte-macrophage colonystimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin. Blood. 1992; 79:1193–200.
18. Teshima T, Harada M, Takamatsu Y, et al. Granulocyte colonystimulating factor (G-CSF)-induced mobilization of circulating haemopoietic stem cells. Br J Haematol. 1993; 84:570–3.
19. Haas R, Mohle R, Frühauf S, et al. Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. Blood. 1994; 83:3787–94.
20. Kotasek D, Shepherd KM, Sage RE, et al. Factors affecting blood stem cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma and solid tumors. Bone Marrow Transplant. 1992; 9:11–7.
21. Schwella N, Siegert W, Beyer J, et al. Autografting with blood progenitor cells: predictive value of pre-apheresis blood cell counts on progenitor cell harvest and correlation of the reinfused cell dose with hematopoietic reconstitution. Ann Hematol. 1995; 71:227–34.
22. Hillyer CD, Tiegerman KO, Berkman EM. Increase in circulating colony-forming units-granulocyte-macrophage during large-volume leukapheresis: evaluation of a new cell separator. Transfusion. 1991; 31:32. 7–32.
23. Mohle R, Murea S, Pförsich M, Witt B, Haas R. Estimation of the progenitor cell yield in a leukapheresis product by previous measurement of CD34+ cells in the peripheral blood. Vox Sang. 1996; 71:90–6.
24. Remes K, Matinlauri I, Grenman S, et al. Daily measurements of blood CD34+ cells after stem cell mobilization predict stem cell yield and posttransplant hematopoietic recovery. J Hematother. 1997; 6:13–9.
25. Schots R, Van Riet I, Damiaens S, et al. The absolute number of circulating CD34+ cells predicts the number of hematopoietic stem cells that can be collected by apheresis. Bone Marrow Transplant. 1996; 17:509–15.
Table 1.
Table 2.
ESHAP‡ | Cyclophosphamide | Others | |
---|---|---|---|
Patients (%) | 31(44.9) | 32(46.8) | 6(8.5) |
Duration of G-CSF (days, mean) | 8.41 | 11.27 | 9.0 |
Route of G-CSF | |||
IV | 23 | 26 | 6 |
SC | 8 | 6 | 0 |
Dosage of G-CSF | |||
10 ug/kg per 24 hours (qd) | 31 | 16 | 3 |
5 ug/kg per 12 hours (bid) | 0 | 16 | 3 |
Harvested CD34+ cells (×106/kg, mean) | 10.6 | 14.92 | 9.0 |
Table 3.
Blood cells | Mean (range) |
---|---|
WBC (×103/μL) | 14.78 (1.32∼75.59) |
Neutrophil | 10.32 (0.56∼61.23) |
Lymphocyte | 0.87 (0.06∼4.5) |
Monocyte | 1.14 (0∼4.96) |
HPC† (/μL) | 60.85 (4∼304) |
CD34+ cell (/μL) | 99.76 (61∼763.5) |
Table 4.
Leukapheresis | Patients (%)† | Mean CD34+cells (×106/kg, range) |
---|---|---|
1st | 69 (100) | 7.54 (0∼27) |
2nd | 46 (66.67) | 6.39 (0.2∼34.8) |
3rd | 14 (20.29) | 2.87 (0.2∼14.8) |
4th | 3 (4.34) | 0.66 (0.3∼0.9) |
5th | 2 (2.9) | 1 (0.3∼1.7) |
Table 5.
Correlation coefficient for CD34+cell harvest | |||
---|---|---|---|
Pearson correlation coefficient | P-value | ||
Height | –0.297 | 0.014 | |
HPC | 0.419 | 0.010 | |
PB† CD34+cell | 0.266 | 0.038 | |
Linear regression for CD34+harvest (R2=0.485) | |||
Estimated coefficient (B) | Standard error | P-value | |
Height | –0.197 | 0.129 | 0.141 |
HPC | –0.010 | 0.026 | 0.698 |
PB CD34+cell | 0.058 | 0.020 | 0.008 |