Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment.

Shpall, Elizabeth J.; Jones, Roy B.; Bearman, Scott I.; Franklin, Wilbur A.; Archer, Philip G.; Curiel, Tyler J.; Bitter, Mitchell A.; Claman, Henry N.; Stemmer, Salomon M.; Purdy, Malcolm

doi:10.1200/jco.1994.12.1.28

Cited by 384 publications

(196 citation statements)

References 25 publications

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“…Although these observations certainly provide no clear-cut evidence, ex vivo purging appears to be essential in patients with CLL. In contrast to marrow grafts, PBPC collection products have the advantage that their engraftment potential is not or only slightly reduced by immunological purging (Brugger et al, 1994;Shpall et al, 1994;Dreger et al, 1995a;Straka et al, 1995). During the course of this study, our B-cell depletion procedures were steadily refined.…”

Section: Discussionmentioning

confidence: 99%

Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure?

Dreger

Neuhoff²,

Kuse³

et al. 1998

Br J Cancer

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Summary B-cell chronic lymphocytic leukaemia (CLL) cannot be cured by conventional therapy. To improve the prognosis of patients with CLL, we have designed a sequential treatment strategy that comprises intensive chemotherapy for mobilization of peripheral blood progenitor cells (PBPCs) and induction of minimal disease, followed by high-dose radiochemotherapy with stem cell reinfusion and post-transplant molecular monitoring by polymerase chain reaction (PCR) amplification of the complementary determining region IlIl Thirteen patients having achieved minimal disease were reinfused with purged autologous stem cells (ASC) after preparation with total body irradiation and cyclophosphamide. Engraftment was delayed in patients receiving BM (n = 3) but prompt [neutrophils >0.5 x 109 1-after 10 (9-13) days, platelets >20 x 109 1-after 11 (9-214) days] in patients restored with PBPCs (n = 10). Procedure-related deaths did not occur. Although the results of CDRIII PCR suggest persistence or recurrence of the leukaemic clone in at least three cases, to date only one patient has relapsed, whereas all others survive without clinical evidence of disease with a maximum follow-up of 48 months. We conclude that sequential high-dose therapy using Dexa-BEAM and autologous stem cell transplantation is a safe and highly effective treatment for patients with CLL. However, a longer follow-up is needed to assess whether definite cures can be achieved using this strategy.

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Section: Discussionmentioning

confidence: 99%

Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure?

Dreger

Neuhoff²,

Kuse³

et al. 1998

Br J Cancer

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“…Earlier studies showed engraftment with enriched CD34 + cell fractions, [4][5][6][7][8][9][10][11][12] but these components were only 42-73% CD34 + cells. With more highly purified CD34 + cell fractions, it is necessary to assess whether or not a required accessory cell (or cells) is depleted from the components.…”

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confidence: 99%

Isolation of CD34+ cells from blood stem cell components using the Baxter Isolex system

Rowley

Loken²,

Radich

et al. 1998

Bone Marrow Transplant

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Summary:The CD34 antigen is expressed by human hematopoietic progenitor and stem cells. These cells are capable of reconstituting marrow function after marrow-ablative chemo-radiotherapy. Several different technologies have been developed for the separation of CD34 ؉ cells from bone marrow or peripheral blood stem cell (PBSC) components. We used an immunomagnetic separation technique to enrich CD34 ؉ cells from PBSC components in anticipation of autologous transplantation for patients with B lymphoid malignancies. Twenty-nine patients enrolled on this study and received mobilization chemotherapy followed by G-CSF. Of these, 21 achieved a peripheral blood CD34 ؉ cell level of at least 2.0 ؋ 10 4 /l required by protocol for separation of the stem cell components. A median of three components per patient was collected for processing. The average CD34 ؉ cell concentration in the components after apheresis was 1.0 ؎ 1.2%. After the CD34 ؉ cell selection, the enriched components contained 0.6 ± 0.6% of the starting nucleated cells. The recovery of CD34 ؉ cells, however, averaged 58.4 ؎ 19.2% of the starting cell number, with a purity of 90.8 ؎ 6.5%. Overall depletion of CD34 ؊ cells was 99.96 ؎ 0.06%. Nineteen patients were treated with marrow-ablative conditioning regimens and received an average of 6.2 ؎ 2.0 ؋ 10 6 CD34 ؉ cells/kg body weight. These patients recovered to an ANC >0.5 ؋ 10 9 /l at a median of 11 days (range 8-14), and platelet transfusion independence at a median of 9 days (range 5-13). Four patients died of transplant-related complications or relapse before 100 days after transplantation. No patient required infusion of unseparated cells because of failure of sustained bone marrow function. These data demonstrate that peripheral blood-derived CD34 ؉ cells enriched by use of an immunomagnetic separation technique are capable of rapid engraftment after autologous transplantation.

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“…However, the major rationale for CD34-positive cell selection in autologous marrow and stem cell transplantation is a reduction or removal of contaminating tumour cells accidentally coharvested during leukapheresis to avoid their reinfusion after high-dose therapy. 19,20 In this report we compare CD34 + cell enrichment, CD34 + cell recovery, and the efficacy of purging of experimentally seeded breast cancer cells from bone marrow and G-CSF-mobilised peripheral blood stem cell collections between three devices using immunoaffinity and magnetic microbeads for separation of anti-CD34 antibody-labelled CD34 + cells. We show that CD34 + enrichment leads to a decrease in the total number of contaminating tumour cells up to 4.3 log steps with reasonably high recovery of CD34-positive progenitor cells.…”

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confidence: 99%

Purging and haemopoietic progenitor cell selection by CD34+ cell separation

Krüger

Gruber

et al. 1998

Bone Marrow Transplant

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The median tumour cell reductions in log steps were 3.7 (2.9-4.3) (n ‫؍‬ 13) (Isolex-50), 3.5 (2.6-4.3) (n ‫؍‬ 13) (MiniMACS) and 1.5 (0.9-2.9) (n ‫؍‬ 17) (Ceprate-LC). Results were compared statistically by univariate analysis. Purity was significantly (P Ͻ 0.05) better after Mini-MACS selection. Recovery rates were significantly different between all devices tested. Tumour cell purging was superior after immunomagnetic separation (P Ͻ 0.001). Tumour cell purging is a main objective of CD34 + selection in the autologous setting. High-dose chemotherapy supported by autologous stem cell reinfusion for treatment of metastatic and high-risk female breast cancer is currently under investigation in several American and European studies. 1,2,3 Tumour cell contamination of autologous stem cell products has been described using immunocytochemistry, reverse transcriptase PCR and cell culture techniques in approximately one third of harvests with a range from 0% to 100%. [4][5][6][7] The clonogenic and metastatic potential of tumour cells isolated from blood and autografts was demonstrated in cell culture assays and in nude mice. [8][9][10] The metastatic potential of accidentally retransplanted tumour cells could be investigated by gene marking of autografts prior to infusion followed by the detection of marked cells after relapse. 11 However, due to the poor transduction efficacy of epithelial cancer cells by gene transfer, a negative result would not exclude the possibility of relapse induction by accidentally reinfused tumour cells. Different approaches have been described to purge autografts of tumour cells. 12 A major problem of purging procedures using cytotoxic agents is the damage to haemopoietic progenitor cells with subsequent delay of engraftment, an increased incidence of severe infections due to prolonged neutropenia and bleeding complications due to thrombocytopenia. [13][14][15] Haemopoietic cells necessary for recovery after highdose therapy and progenitor support express the CD34 antigen on their surface. 16 These cells can easily be enriched by immunological methods using anti-CD34 antibodies and separation by biotin-streptavidin immunoaffinity or magnetic separation with paramagnetic microbeads. Rapid and safe engraftment after reinfusion of enriched CD34 + cell fractions has been described by several investigators after allogeneic and autologous transplantation. 17,18 The immunologic selection of CD34-positive cells has no toxic side-effects on haemopoietic stem cells and progenitors without prolongation of cytopenia after reinfusion.Furthermore, CD34 positive-cell selection is a promising approach to reducing the incidence or mitigating the severity of graft-versus-host-disease in the allogeneic setting by adjusted or nearly complete T cell depletion. However, the major rationale for CD34-positive cell selection in autologous marrow and stem cell transplantation is a reduction or removal of contaminating tumour cells accidentally coharvested during leukapheresis to avoid their reinfusion after high-d...

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Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment.

Abstract: CD34+ marrow and/or PBPCs provide reliable and timely hematopoietic reconstitution in breast cancer patients receiving high-dose chemotherapy. Contamination of both marrow and PBPCs with breast cancer cells was reduced using this positive selection technique.

Cited by 384 publications

References 25 publications

Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure?

Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure?

Isolation of CD34+ cells from blood stem cell components using the Baxter Isolex system

Purging and haemopoietic progenitor cell selection by CD34+ cell separation

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