Randomized trial of peripheral blood progenitor cell vs bone marrow as hematopoietic support for high-dose chemotherapy in patients with non-Hodgkin’s lymphoma and Hodgkin’s disease: a clinical and molecular analysis

Abstract

Summary:Filgrastim (r-metHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) and unstimulated bone marrow (BM) were evaluated and compared for reconstitution after high-dose chemotherapy in patients with relapsed Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) with respect to engraftment, overall and relapsefree survival, and contamination by lymphoma cells using molecular analysis of immunoglobulin gene rearrangements. Forty-four patients with either NHL or HD underwent autologous transplantation after highdose chemotherapy. Patients were randomized to receive either Filgrastim-mobilized PBPC (n = 15) or unstimulated BM (n = 14). An additional 15 patients received PBPC without randomization because of a recent history of marrow involvement by lymphoma. Use of PBPC was associated with faster neutrophil engraftment than BM (11 vs 14 days to an absolute neutrophil count Ͼ0.5 × 10 9 /l, P = 0.04), but without any difference in platelet engraftment, infectious complications, or overall or event-free survival. Both BM (65%) and PBPC (73%) were frequently contaminated by tumor cells as assessed by CDR3 analysis. Patients with negative polymerase chain reaction analysis of a BM sample during the study had a trend towards an improved survival; however, BM involvement by disease had no impact on the ability to mobilize or collect PBPC. We conclude that PBPC are as effective as BM in reconstituting hematopoiesis after high-dose chemotherapy and that both products are frequently contaminated by sequences marking the malignant clone.

Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation

“…Molecular analysis for the presence of tumor-sequence DNA was based on the detection of clonal CDR3 regions from the immunoglobulin heavychain gene unique for a patient's tumor, using consensus PCR. 19,20 Bcl-2/immunoglobulin (Ig) H PCR was used if there was no predominant CDR3 clone, based on previously described methods.…”

“…DNA was extracted from paraffin-embedded tissue sections (3 ϫ 7 m) or Ficoll-Hypaque density-gradient purified mononuclear cells from PBCs, using standard methods as previously described. 20,22 Consensus IgH polymerase chain reaction. CDR3 region of the IgH gene was amplified using semi-nested PCR.…”

“…CDR3 region of the IgH gene was amplified using semi-nested PCR. 20 The first round consisted 30 cycles using consensus V H (V con ) and J H (LJ H2 ), 20 followed by a second round of 20 to 30 cycles using V con and the nested J H (J con ) primers. Cycling conditions were identical in both rounds of PCR.…”

“…The use of polymerase chain reaction (PCR) assay with primers to the framework 3 region and J chain of the immunoglobulin heavy-chain gene to detect clonal populations of B cells has been reported for patients with NHL. [19][20][21] To study the incidence of PBC tumor contamination, we conducted PCR analysis for the presence of tumor DNA sequences in both arms.…”

Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation

“…[1][2][3][4][5][6][7] In lymphoid malignancies, autologous stem cell transplantation (ASCT) is the treatment frequently employed in relapsed malignant lymphomas (ML) or in very high-risk ML. [2][3][4][5][6][7][8][9][10][11][12] The presence of HSCs in peripheral blood is usually extremely low before mobilizing procedures, and engraftment of CD34 þ peripheral blood stem cells (PBSC) depends on the infusion of an adequate number of CD34 þ stem cells to restore haemopoiesis. [13][14][15][16][17][18][19][20][21][22][23] Indeed, the number of CD34 þ cells is commonly used to predict the potential engraftment of harvested HSC.…”