Autotransplantation of B-cell purged peripheral blood progenitor cells in B-cell lymphoma

Straka, Christian; Drexler, Evi; Mitterer, Manfred; Langenmayer, Irmgard; Pfefferkorn, Ludwig; Stade, Barbara; Koll, Robert; Emmerich, Bertold

doi:10.1016/s0140-6736(95)90678-9

Cited by 13 publications

(5 citation statements)

References 3 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: 98%

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: 98%

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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“…Fortunately, various strategies using monoclonal antibodies, either with complement, immunomagnetic beads, or immunotoxins or other purging agents can eliminate several logs of malignant cell line cells, while sparing normal hematopoietic progenitors. 11,31,[33][34][35] This QC-PCR assay may be an appealing and easily reproducible approach to devise purging strategies to enhance the elimination of lymphoma cells.…”

Section: Number Of Lymphoma Cells In Progenitor Cell Graftsmentioning

confidence: 99%

Lymphoma Cell Burden in Progenitor Cell Grafts Measured by Competitive Polymerase Chain Reaction: Less Than One Log Difference Between Bone Marrow and Peripheral Blood Sources

Léonard

Hétu

Busque

et al. 1998

Blood

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A controversy persists in autologous transplantation as to which source of progenitor cells, bone marrow (BM) or peripheral blood (PB), contains the lowest number of contaminating lymphoma cells, and how mobilization procedures affect these numbers. To accurately measure the number of non-Hodgkin's lymphoma (NHL) cells harboring the bcl-2/immunoglobulin H (IgH) rearrangement in progenitor cell grafts, we developed a nested quantitative competitive polymerase chain reaction assay (QC-PCR). DNA from lymph nodes of four patients with NHL were cloned into the pSK(+) vectors to generate four internal controls (ICs) (two with major breakpoint region [MBR] and two with minor cluster region [mcr] rearrangements). The kinetics of amplification of ICs paralleled those of bcl-2/IgH rearranged genomic DNA. When used in a QC-PCR assay, these ICs were accurate at a 0.2-log level and provided reproducible results, as shown by low intrarun and interrun variability. An excellent correlation between predicted and observed lymphoma cell content (r = .99) was observed over a range of at least 5 logs of rearranged cells. This approach was used to measure involvement by NHL cells at the time of progenitor cell harvest in 37 autologous transplant patients. The number of bcl-2/IgH rearranged cells in BM, PB, and mobilized PB (mPB) was found to vary from 1 to 1.1 × 105 per million cells. The number of lymphoma cells present in BM was significantly higher than in PB (P = .0001), with a median difference in lymphoma cell content between BM and PB of 0.48 log of cells (range, −0.7 to 5 logs). In contrast, we found no difference in the concentration of bcl-2/IgH rearranged cells present in BM versus PB progenitor cells mobilized with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) (mPB) (P = .57). In conclusion, the QC-PCR assay described in this study could measure accurately and reproducibly the number of bcl-2/IgH rearranged cells among normal cells. Differences in levels of contamination by lymphoma cells between BM and PB were of less than one log (10-fold), and no differences in lymphoma cell concentrations were observed between BM and mobilized PB. As more cells are usually infused with mPB than with BM grafts, mPB progenitor cell grafts may actually be associated with higher levels of contamination by lymphoma cells. Furthermore, this QC-PCR assay should provide an important tool to assess the prognostic impact of lymphoma cell burden both in progenitor cell grafts and in vivo.

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“…Details of the methods of PBSC collection and of the transplantation protocol have been described elsewhere. [22][23][24] The titers of IgG antibodies specific for the viral capsid antigen (VCA) of EBV were determined for all patients before and after transplantation and were in the seropositive range (Ͼ1:10) in each case. HLA-typing of patient WH was carried out by the Laboratory for Immunogenetics at the Poliklinik, University of Munich (Dr Scholz, Professor Albert).…”

Section: Patientsmentioning

confidence: 99%

Assessment and characterization of the cytolytic T lymphocyte response against Epstein–Barr virus in patients with non-Hodgkin’s lymphoma after autologous peripheral blood stem cell transplantation

Nolte

Buhmann

Straka

et al. 1998

Bone Marrow Transplant

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Summary:The cytolytic T lymphocyte (CTL) response has often been used to assess the reconstitution of T cell function after allogeneic or autologous bone marrow transplantation (BMT). Less is known, however, about the reconstitution of the CTL response after peripheral blood stem cell transplantation (PBSCT). Therefore, we investigated the CTL response against Epstein-Barr virus (EBV) of patients undergoing autologous PBSCT. CTLs of six patients with relapsed non-Hodgkin's lymphoma and multiple myeloma were established before and at different times after PBSCT by in vitro stimulation of peripheral blood lymphocytes with autologous EBVtransformed lymphoblastoid cell lines (LCLs). The efficiency of T cell priming by LCLs was assessed at the time of initiation of CTL lines; the proliferative response was strongly reduced during the first 4 months and increased 5 months or more following PBSCT. Cytolytic activity was measured after three or four restimulations of CTLs. All patients investigated had a detectable EBV-specific CTL response which was poor during the first weeks after transplantation, accompanied by a strong non-MHC-restricted cytotoxic activity and a high proportion of CD56-positive T cells. Five or more months after PBSCT, a specific CTL response against EBV was seen which was similar to the situation prior to PBSCT, while the unspecific cytotoxic response decreased. Blocking experiments with monoclonal anti-CD3, anti-CD8 or anti-MHC I antibodies resulted in substantial inhibition of autologous LCL lysis, whereas anti-CD4 or anti-MHC II antibodies had no effect. Finally, autologous PHA blasts of a patient with the HLA haplotype A1/9+, B5/8+, Cw4/7+, were loaded with various EBNA-derived nonapeptides known to be presented by HLA B8 or A11, and exposed to autologous, EBV-directed In the last few years, autologous peripheral blood stem cell transplantation (PBSCT) has been established as a standard treatment for relapsed aggressive non-Hodgkin's lymphoma and has proven advantageous when compared with autologous or allogeneic bone marrow transplantation (BMT). 1-5 However, in contrast to autologous or allogeneic BMT, little information is available concerning the reconstitution of the immune system following autologous peripheral blood stem cell transplantation (PBSCT). As after BMT, the CD4/CD8 ratio seems to be inversed after PBSCT, but lymphocyte subpopulations and functions recover more rapidly, including the proliferative response to mitogens and the cytotoxic activity of lymphocytes after stimulation with high-dose IL-2 (lymphocyte-activated killer cells, LAK). [6][7][8][9][10] Previous investigations mainly examined non-specific lymphocyte functions in patients undergoing autologous PBSCT and the reconstitution of the antigen-specific cytolytic T lymphocyte (CTL) response has not been evaluated so far. Therefore, we examined the CTL response of these patients to Epstein-Barr virus (EBV), a widespread lymphotropic herpes virus. Most people are infected with EBV by adulthood, and the life-long persist...

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Autotransplantation of B-cell purged peripheral blood progenitor cells in B-cell lymphoma

Cited by 13 publications

References 3 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?

Lymphoma Cell Burden in Progenitor Cell Grafts Measured by Competitive Polymerase Chain Reaction: Less Than One Log Difference Between Bone Marrow and Peripheral Blood Sources

Assessment and characterization of the cytolytic T lymphocyte response against Epstein–Barr virus in patients with non-Hodgkin’s lymphoma after autologous peripheral blood stem cell transplantation

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