CD34+ selection of autologous peripheral blood stem cells for transplantation following sequential cycles of high-dose therapy and mobilisation in multiple myeloma

Abstract

Summary:A potential problem of autologous transplantation in the treatment of multiple myeloma (MM) is the infusion of tumor cells. CD34 + selection has been used to purge autografts in MM and it is also possible to reduce tumour cell contamination of autografts by cytotoxic drug therapy prior to peripheral blood stem cell (PBSC) collection. To evaluate the effectiveness of a protocol combining multiple cycles of high-dose therapy and CD34 + selection to reduce tumour contamination of PBSC autografts, 34 MM patients were entered on a treatment schedule comprising two sequential cycles of mobilisation, CD34 + selection, and transplantation following high-dose therapy. In the second cycle of mobilisation there was a five-fold reduction in tumour contamination of the stem cell harvest (0.5 × 10 6 /kg) compared with the first cycle (2.5 × 10 6 /kg). In the 97 CD34 + selection procedures performed a median of 185 × 10 8 mononuclear cells (MNC) were processed yielding a median of 0.98 × 10 8 CD34 + -enriched cells. CD34 + cells were enriched 68-fold from 1.3% to 88.6%. The median yield of CD34 + cells was 42.2%. Following CD34 + selection the tumour cell contamination of the leukapheresis product was reduced by a median of 2.7 logs. This study demonstrates that in multiple myeloma a significant reduction in the malignant contamination of stem cell autografts can be achieved by combining the in vivo purging effect of cytotoxic therapy with in vitro purging by CD34 + selection. Bone Marrow Transplantation (2000) 25, 1175-1184.

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

“…However, since myeloma cells do not express the CD34 antigen, 9,10,11 positive selection of CD34 + hematopoietic progenitor cells 12,13,14 has been used as a means of myeloma cell "purging" in ASCT. 11,15,16 In 1995, we initiated a European Group for Blood and Marrow Transplantation (EBMT) centre phase III randomized study to assess the safety and efficacy of CD34+ selection compared to unselected PBPC in patients with myeloma undergoing autologous transplantation. A similar study was initiated at around the same time in the United States, the preliminary results of which suggested that at a median follow-up of 12 months there was no clinical benefit from CD34 + selection.…”

Transplantation for multiple myeloma: who, when, how often?

“…No quality-of-life benefit was apparent during the first 2 years, and after 2.5 years, there was a trend only. 31 The MRC trial has just been published, comparing standard therapy consisting of ABCM (doxorubicin, BCNU, cyclophosphamide, melphalan) every 6 weeks or C-VAMP (cyclophosphamide, vincristine, doxorubicin, methylprednisolone) every 3 weeks followed by mobilization with cyclophosphamide 2 to 4 g/m 2 For personal use only. on April 29, 2019.…”

“…In an attempt to reduce tumor cell contamination, various CD34 ϩ selection methodologies have been reported. [29][30][31]79 None of these trials have demonstrated an improvement in PFS or OS. Allotransplantation provides 2 distinct advantages: absence of contaminating tumor cells in the autograft and the benefit of alloreactive donor T lymphocytes producing a GVM effect.…”

“…The sensitivity to initial treatment accurately predicts the probability of CR. 28,29 CD34 ϩ selection results in a significant reduction in myeloma cell contamination of the apheresis product and in rapid and sustained engraftment [30][31][32][33][34] without improvement in EFS and OS.…”

NK-cell purging of leukemia: superior antitumor effects of NK cells H2 allogeneic to the tumor and augmentation with inhibitory receptor blockade

“…46,47 Different physical, clinical, and immunologic means have been used to purge the contaminating tumor cells ex vivo, including the use of activated autologous NK cells to overcome relapse. [48][49][50][51][52] In our previous report investigating the possibility of syngeneic NK cells as purging agents in a murine leukemia model, we demonstrated that blocking inhibitory receptors specific for class I on a subset of syngeneic NK cells during ex vivo purging of C1498 murine leukemia contaminating the bone marrow graft significantly increased the extent of tumor cell elimination by syngeneic NK cells. 53 We also demonstrated that transplanting tumorcontaminating BMCs purged with syngeneic NK cells with inhibitory receptor blockade resulted in an increased proportion of long-term survivors without affecting hematopoietic cell recovery.…”