Autologous transplantation of mobilized peripheral blood CD34+ cells selected by immunomagnetic procedures in patients with multiple myeloma

Abstract

Summary:In the use of autologous PBPC transplantation in patients with multiple myeloma, contamination of PBPC with myeloma cells is commonly observed. Enrichment for CD34 ؉ cells has been employed as a method of reducing this contamination. In this study the reduction of myeloma cells in PBPC was accomplished by the positive selection of CD34 ؉ cells using immunomagnetic bead separation (Isolex 300 system). PBPC were mobilized from 18 patients using cyclophosphamide (4.5 g/m 2 ) and G-CSF (10 g/kg/day). A median of two leukaphereses and one selection was performed per patient. The median number of mononuclear cells processed was 3.50 × 10 10 with a recovery of 1.11 × 10 8 cells after selection. The median recovery of CD34 ؉ cells was 48% (range 17-78) and purity was 90% (29-99). The median log depletion of CD19 ؉ cells was 3.0. IgH rearrangement, assessed by PCR, was undetectable in 13 of 24 evaluable CD34 ؉ enriched products. Patients received 200 mg/m 2 of melphalan followed by the infusion of a median of 2.91 × 10 6 /kg CD34 ؉ cells (1.00-16.30). The median time to absolute neutrophil count Ͼ0.5 × 10 9 /l was 11 days, and sustained platelet recovery of Ͼ20 × 10 9 /l was 14 days. We conclude that immunomagnetic-based enrichment of CD34 ؉ cells results in a marked reduction in myeloma cells without affecting engraftment kinetics. Keywords: CD34 selection; multiple myeloma; immunomagnetic separation; transplantation The use of standard-dose chemotherapy in the management of multiple myeloma yields unsatisfactory outcomes in terms of both complete response rate and overall survival. In contrast, high-dose chemotherapy and combination chemo-radiotherapy have significantly improved both the disease-free and overall survival rates of patients suffering from multiple myeloma. [1][2][3] This improvement has been seen in both refractory and newly diagnosed patients treated with high-dose chemotherapy and autologous peripheral blood stem cell support. [4][5][6][7] Nonetheless, the high rate of relapse in the setting of autologous transplantation continues to be a major problem. It has been speculated that some of these relapses, particularly early ones, result from the transplantation of clonogenic myeloma cells. 8,9 Indeed, several investigators have shown that peripheral blood progenitor cell (PBPC) products contain significant numbers of circulating clonogenic myeloma cells. [10][11][12][13] In order to reduce the risk of relapse due to the transfer of myeloma cells, several techniques that remove these cells from the transplanted products are being investigated. 14-17 One such technique is the positive selection of CD34 + cells, shown to contain the necessary precursors for both short-and long-term hematopoietic reconstitution. Since it is believed that the CD34 antigen is not expressed on clonal myeloma cells, selection of CD34 + cells from autologous mobilized peripheral blood progenitor cells may result in the reduction of myeloma contamination of these cells by several orders of magnitude. 18,19 We report here ...

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

“…A variety of approaches have been developed in an attempt to improve the outcome of high-dose therapy in multiple myeloma patients, including tandem highdose therapy, 25,26 reduced intensity allogeneic transplantation ,27,28 purging strategies based either on negative or positive selection, [29][30][31][32][33][34][35][36][37][38][39] and new approaches to conditioning. Although the present study used a combination of melphalan and TBI for conditioning, it has since been established that high dose melphalan alone is less toxic and at least as effective as regimens including total body irradiation.…”

Lack of benefit of CD34+ cell selected over non-selected peripheral blood stem cell transplantation in multiple myeloma: results of a single center study

“…In most previously published works, mobilization of stem cells was obtained with cyclophosphamide and G-CSF. [11][12][13][14]18 This myelosuppressive procedure potentially exposed patients to infectious complications and required hospitalization. Although the number of CD34 ϩ cells collected appears to be superior after priming with high-dose cyclophosphamide followed by G-CSF as compared to G-CSF alone, [19][20][21][22] G-CSF alone in steady-state allowed efficient stem cell mobilization especially when performed in slightly pretreated patients and with responsive disease at the time of mobilization.…”

“…Indeed, positive selection of CD34 ϩ cells reduces the contamination of myeloma cells from the apheresis products up to 2 to 4 logs and provides a progenitor cell suspension capable of restoring normal hematopoiesis. [8][9][10][11][12][13][14] In order to evaluate the clinical impact of CD34 ϩ cell selected peripheral blood stem cell autologous transplantation in MM, we performed a case controlled analysis. 21 …”

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma

“…4,13,18 Moreover, both G-CSF and GM-CSF appear to be equivalent when added to cyclophosphamide. 19 It has also been suggested that a combination of cyclophosphamide, etoposide and G-CSF is superior to either cyclophosphamide plus growth factor or G-CSF alone in patients with multiple myeloma. 10 We combined cyclophosphamide with etoposide and G-CSF and added paclitaxel because of its ability to mobilise PBSC in other malignancies.…”