New Insights In Hematology, Venice, Italy, May 1-4 1996: Selection and transplantation of autologous hematopoietic CD34+ cells for patients with multiple myeloma

Roberto M. Lemoli, Alessandra Fortuna, Donatella Raspadori, Maria Alessandra Ventura, Giovanni Martinelli, Alessandro Gozzetti, Giuliana Leopardi, Marina Ratta, Michele Cavo, Sante Tura

Research output: Contribution to journalArticle

Abstract

Here we review our recent experience addressing the issue of positive selection and transplantation of hematopoietic CD34+ cells to reduce neoplastic contamination in peripheral blood (PB) autografts from patients with multiple myeloma (MM). We evaluated PB samples from 30 pretreated MM patients following the administration of high dose cyclophosphamide (Cy; 7g/m2 or 4g/m2) and granulocyte-colony stimulating factor (G-CSF), for collection of circulating stem cells (PBSC) to support hematopoietic reconstitution following myeloablative radio-chemotherapy. Twenty six patients showed adequate mobilization of CD34+ progenitor cells and were submitted to PBSC collection. Circulating hematopoietic CD34+ cells were highly enriched by avidin-biotin immunoabsorption, cryopreserved, and used to reconstitute BM function after myeloablative therapy in 13 patients. The median purity of the enriched CD34+ cell population was 89.5% (range 51-94%) with a 75-fold increase compared to the pretreatment samples. The median overall recovery of CD34+ cells and CFU-GM was 58% (range 33-95%) and 45% (range 7-100%), respectively. Positive selection of CD34+ cells resulted in 2.5-3 log of plasma cells and CD 19+ B-lineage cells depletion as determined by immunofluorescence studies, although DNA analysis of CDR III region of IgH gene demonstrated the persistence of minimal residual disease (MRD) in 5 out of 6 patient samples studied. Myeloma patients were reinfused with enriched CD34+ cells after myeloablative therapy consisting of total body irradiation (TBI, 1000 cGy) and high dose Melphalan (140 mg/m2) or Melphalan (200 mg/m2) alone. They received a median of 5 x 106 CD34+ cells/kg and showed a rapid reconstitution of hematopoiesis: the median time to 0.5 x 109 neutrophils, 20 and 50 x 109 platelets/L of PB was 10, 11 and 12 days, respectively. When we analyzed the immunological reconstitution of this group of patients, we observed a rapid and full recovery of total lymphocyte and NK cell count, although the absolute CD4+ cell count was lower than pretreatment level. These results, as well as other clinically significant parameters, did not significantly differ from those of patients (= 13) receiving unmanipulated PBSC following the same pretransplant conditioning regimen. The results of this trial demonstrate that positive selection of CD34+ cells reduces the contamination of myeloma cells from the apheresis products up to 3 log and provides a cell suspension capable of restoring a normal hematopoiesis after a TBI-containing conditioning regimen. Based on this pilot trial, we have recently started a clinical study involving a double autotransplant, conditioned with melphalan 1200 mg/m2) followed by melphalan (140 mg/m2) and busulphan (14 mg/kg), supported by the reinfusion of highly purified CD34+ cells.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalLeukemia and Lymphoma
Volume26
Issue numberSUPPL. 1
Publication statusPublished - 1997

Fingerprint

Autologous Transplantation
Hematology
Multiple Myeloma
Italy
Melphalan
Hematopoiesis
Autografts
Stem Cells
Busulfan
Granulocyte-Macrophage Progenitor Cells
Blood Component Removal
Avidin
Whole-Body Irradiation
Residual Neoplasm
Granulocyte Colony-Stimulating Factor
CD4 Lymphocyte Count
Biotin
Plasma Cells
Radio
Natural Killer Cells

Keywords

  • Autologous transplantation
  • CD34 cells
  • Multiple myeloma

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

New Insights In Hematology, Venice, Italy, May 1-4 1996 : Selection and transplantation of autologous hematopoietic CD34+ cells for patients with multiple myeloma. / Lemoli, Roberto M.; Fortuna, Alessandra; Raspadori, Donatella; Ventura, Maria Alessandra; Martinelli, Giovanni; Gozzetti, Alessandro; Leopardi, Giuliana; Ratta, Marina; Cavo, Michele; Tura, Sante.

In: Leukemia and Lymphoma, Vol. 26, No. SUPPL. 1, 1997, p. 1-11.

Research output: Contribution to journalArticle

Lemoli, RM, Fortuna, A, Raspadori, D, Ventura, MA, Martinelli, G, Gozzetti, A, Leopardi, G, Ratta, M, Cavo, M & Tura, S 1997, 'New Insights In Hematology, Venice, Italy, May 1-4 1996: Selection and transplantation of autologous hematopoietic CD34+ cells for patients with multiple myeloma', Leukemia and Lymphoma, vol. 26, no. SUPPL. 1, pp. 1-11.
Lemoli, Roberto M. ; Fortuna, Alessandra ; Raspadori, Donatella ; Ventura, Maria Alessandra ; Martinelli, Giovanni ; Gozzetti, Alessandro ; Leopardi, Giuliana ; Ratta, Marina ; Cavo, Michele ; Tura, Sante. / New Insights In Hematology, Venice, Italy, May 1-4 1996 : Selection and transplantation of autologous hematopoietic CD34+ cells for patients with multiple myeloma. In: Leukemia and Lymphoma. 1997 ; Vol. 26, No. SUPPL. 1. pp. 1-11.
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T2 - Selection and transplantation of autologous hematopoietic CD34+ cells for patients with multiple myeloma

AU - Lemoli, Roberto M.

AU - Fortuna, Alessandra

AU - Raspadori, Donatella

AU - Ventura, Maria Alessandra

AU - Martinelli, Giovanni

AU - Gozzetti, Alessandro

AU - Leopardi, Giuliana

AU - Ratta, Marina

AU - Cavo, Michele

AU - Tura, Sante

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N2 - Here we review our recent experience addressing the issue of positive selection and transplantation of hematopoietic CD34+ cells to reduce neoplastic contamination in peripheral blood (PB) autografts from patients with multiple myeloma (MM). We evaluated PB samples from 30 pretreated MM patients following the administration of high dose cyclophosphamide (Cy; 7g/m2 or 4g/m2) and granulocyte-colony stimulating factor (G-CSF), for collection of circulating stem cells (PBSC) to support hematopoietic reconstitution following myeloablative radio-chemotherapy. Twenty six patients showed adequate mobilization of CD34+ progenitor cells and were submitted to PBSC collection. Circulating hematopoietic CD34+ cells were highly enriched by avidin-biotin immunoabsorption, cryopreserved, and used to reconstitute BM function after myeloablative therapy in 13 patients. The median purity of the enriched CD34+ cell population was 89.5% (range 51-94%) with a 75-fold increase compared to the pretreatment samples. The median overall recovery of CD34+ cells and CFU-GM was 58% (range 33-95%) and 45% (range 7-100%), respectively. Positive selection of CD34+ cells resulted in 2.5-3 log of plasma cells and CD 19+ B-lineage cells depletion as determined by immunofluorescence studies, although DNA analysis of CDR III region of IgH gene demonstrated the persistence of minimal residual disease (MRD) in 5 out of 6 patient samples studied. Myeloma patients were reinfused with enriched CD34+ cells after myeloablative therapy consisting of total body irradiation (TBI, 1000 cGy) and high dose Melphalan (140 mg/m2) or Melphalan (200 mg/m2) alone. They received a median of 5 x 106 CD34+ cells/kg and showed a rapid reconstitution of hematopoiesis: the median time to 0.5 x 109 neutrophils, 20 and 50 x 109 platelets/L of PB was 10, 11 and 12 days, respectively. When we analyzed the immunological reconstitution of this group of patients, we observed a rapid and full recovery of total lymphocyte and NK cell count, although the absolute CD4+ cell count was lower than pretreatment level. These results, as well as other clinically significant parameters, did not significantly differ from those of patients (= 13) receiving unmanipulated PBSC following the same pretransplant conditioning regimen. The results of this trial demonstrate that positive selection of CD34+ cells reduces the contamination of myeloma cells from the apheresis products up to 3 log and provides a cell suspension capable of restoring a normal hematopoiesis after a TBI-containing conditioning regimen. Based on this pilot trial, we have recently started a clinical study involving a double autotransplant, conditioned with melphalan 1200 mg/m2) followed by melphalan (140 mg/m2) and busulphan (14 mg/kg), supported by the reinfusion of highly purified CD34+ cells.

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