Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging

Gorin, NC; Aegerter, Philippe; Auvert, B; Meloni, G.; Goldstone, AH; Burnett, Alan Kenneth; Carella, Angelo Michele; Körbling, Martin; Hervé, P.; Maraninchi, D

doi:10.1182/blood.v75.8.1606.bloodjournal7581606

Cited by 31 publications

(37 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have demonstrated that mafosfamidepurged autografts, although deprived of cycling progenitors, are capable of reconstituting hematopoietic function due to the property of mafosfamide to spare noncycling stem cells [25,26]. The addition of SCF to a growth factor combination including G-CSF, GM-CSF, IL-3 and EPO has been found to be critical for in vitro proliferation of quiescent primitive progenitors surviving marrow purging with mafosfamide [13,14].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Growth of Mobilized Peripheral Blood Progenitor Cells is Significantly Enhanced by Stem Cell Factor

et al. 1997

View full text Add to dashboard Cite

The existence of primitive hematopoietic progenitors in mobilized peripheral blood is suggested by clinical, phenotypic and in vitro cell culture evidences. In order to quantify primitive progenitors, 32 leukaphereses from 15 patients with lymphoid malignancies were investigated for the growth of multilineage colony-forming units (CFU-Mix), erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM) in the absence or presence of recombinant stem cell factor (SCF), a cytokine which selectively controls stem cell self-renewal, proliferation and differentiation. Primitive progenitors were also quantitated by means of a long-term assay which allows the growth of cells capable of initiating and sustaining hematopoiesis in long-term culture (LTC-IC). Addition of SCF (50 ng/ml) to methylcellulose cultures stimulated with maximal concentrations of G-CSF, GM-CSF, interleukin 3 and erythropoietin significantly increased the growth (mean ± SE) of CFU-Mix (7.7 ± 1.7 versus 2.4 ± 0.6, p ≤ 0.0001), BFU-E (47 ± 10 versus 32 ± 6, p ≤ 0.002) and CFU-GM (173 ± 31 versus 112 ± 20, p ≤ 0.0001). Mean (± SE) percentages of SCF-dependent CFU-Mix, BFU-E and CFU-GM were 60 ± 5%, 19 ± 5%, and 33 ± 4%, respectively. Mean (± SE) LTC-IC growth per 2 × 10 6 nucleated cells was 221 ± 53 (range, 2 to 704). Linear regression analysis demonstrated a statistically significant correlation (r = .87; p ≤ 0.0001) between LTC-IC and SCF-dependent progenitors. In conclusion, our data suggest that: A) the optimal quantification of mobilized progenitors requires supplementation of methylcellulose cultures with SCF, and B) in vitro detection of SCF-dependent progenitors might represent a reliable and technically simple method to assess the primitive progenitor cell content of blood cell autografts. Such in vitro evaluation of immature hematopoietic progenitors might be clinically relevant for predicting the reconstituting potential of autografts.

show abstract

Section: Discussionmentioning

confidence: 99%

In Vitro Growth of Mobilized Peripheral Blood Progenitor Cells is Significantly Enhanced by Stem Cell Factor

et al. 1997

View full text Add to dashboard Cite

show abstract

“…High-dose therapy with autologous stem cell transplantation (ASCT) is an effective treatment option for selected patients with haemopoietic malignancies and solid tumours (Gorin et al, 1990;Coiffier et al, 1993). An obstacle to this approach is that the reinfusion of clonogenic tumour cells contained in the autograft could contribute to relapse of disease (Brenner et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Effect of the protein tyrosine kinase inhibitor genistein on normal and leukaemic haemopoietic progenitor cells

Carlo‐Stella¹,

Regazzi²,

Garau³

et al. 1996

Br J Haematol

View full text Add to dashboard Cite

Receptor and nonreceptor protein tyrosine kinases (PTKs) play a key role in the control of normal and neoplastic cell growth. The availability of PTK inhibitors prompted us to evaluate the effects of genistein, a natural inhibitor of PTKs, on in vitro colony formation by normal multilineage colony-forming units (CFU-Mix), erythroid bursts (BFU-E), granulocyte-macrophage colony-forming units (CFU-GM), long-term culture-initiating cells (LTC-IC) and acute myelogenous leukaemia colony-forming units (CFU-AML). Continuous exposure of normal marrow and blood mononuclear non-adherent cells, blood CD34+CD45RA- cells, and leukaemic blasts to increasing doses of genistein (1-100 microM) resulted in a statistically significant (P < or = 0.05) dose-dependent suppression of CFU-Mix, BFU-E, CFU-GM and CFU-AML growth. Regression analysis showed that growth inhibition was linearly related to genistein concentration. Genistein dose causing 50% inhibition (ID50) of CFU-AML was significantly lower compared to CFU-GM ID50 for marrow (19 v 32 microM, P < or = 0.017), unseparated blood (19 v 44 microM, P < or = 0.028) or CD34+CD45RA- blood (19 v 36, P < or = 0.04). Preincubation of leukaemic blasts with genistein (200 microM) for 1-2h confirmed that CFU-AML were significantly more sensitive than normal marrow and blood CFU-GM to genistein. Preincubation conditions which maximally suppressed leukaemic and normal colony growth spared a substantial percentage of marrow (29 +/- 4%) and blood (40 +/- 3%) LTC-IC. In conclusion, our data demonstrate that: (a) genistein strongly inhibits the growth of normal and leukaemic haemopoietic progenitors; (b) growth inhibition is dose- and time-dependent; (c) leukaemic progenitors are more sensitive than normal progenitors to genistein-induced growth inhibition; (d) genistein exerts a direct toxic effect on haemopoietic cells while sparing a substantial proportion of LTC-IC. The potent CFU-AML growth inhibition associated with the relative resistance of normal LTC-IC strongly supports the use of genistein for marrow purging.

show abstract

“…Over 70% of patients with follicular lymphoma have an aberrant translocation chromosome, t(14;18)(q32;q21) harboring the bcl-2 gene in juxtaposition to the immunoglobulin heavy chain (IgH) locus, a rearrangement detectable at diagnosis by polymerase chain reaction (PCR) [5][6][7]. Immunologic and pharmacologic purging of harvested bone marrow sufficient for delivery of PCRnegative progenitor cells has been shown to increase relapse-free survival [8,9]. Unless these additional treatment options are instituted, such occult lymphoma cells may subsequently contribute to disease relapse, especially in patients with advanced follicular lymphomas in whom overt marrow infiltration is commonly seen [10,11].…”

Section: Introductionmentioning

confidence: 99%

Occult lymphoma cells prevalent in autologous marrow from non‐Hodgkin's diffuse lymphoma

et al. 2003

View full text Add to dashboard Cite

The most effective treatment for recurrent non-Hodgkin's lymphoma (NHL) appears to be a high-dose cytotoxic chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT). However, it has been suggested that the presence of occult lymphoma cells in harvested marrow may be responsible for a significant fraction of treatment failures after HDC/ABMT. The present study examined randomly accrued NHL patients, independent of their cytogenic grades, for the presence of cells bearing bcl-2/ immunoglobulin heavy chain (IgH) gene rearrangements in lymph node (LN) biopsies and the bone marrow by polymerase chain reaction (PCR) and Southern blot hybridization combined with a classical culturing technique. Among 41 NHL patients examined, bcl-2/ IgH translocations were evident in LN biopsies and marrow from each of 10 follicular lymphoma patients, but not in any samples from 31 newly diagnosed diffuse lymphoma patients. Marrow aspirates from several patients that were cultured using a one-week "triggering culture" followed by an extended period of conventional culture resulted in emergence of a monoclonal, IgH-rearranged, bcl-2-normal lymphoid cell population. Such outgrowth was specifically seen in cultures of diffuse lymphoma marrow (7 of 28 evaluable patients). Southern analysis for IgH rearrangement within LN biopsies and of cells cultured from marrow of individual diffuse lymphoma patients produced identical patterns, suggesting that the occult lymphoma cells present in harvested marrow were derived from the predominant lymphoma cell population represented within involved lymph nodes. The culture of histologically occult lymphoma from diagnostic marrow and analysis of the derived cells by Southern blot hybridization can be used to detect potentially aggressive lymphoma cells within harvested marrow, despite their lack of bcl-2 gene rearrangement. Am.

show abstract

Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging

Cited by 31 publications

References 1 publication

In Vitro Growth of Mobilized Peripheral Blood Progenitor Cells is Significantly Enhanced by Stem Cell Factor

In Vitro Growth of Mobilized Peripheral Blood Progenitor Cells is Significantly Enhanced by Stem Cell Factor

Effect of the protein tyrosine kinase inhibitor genistein on normal and leukaemic haemopoietic progenitor cells

Occult lymphoma cells prevalent in autologous marrow from non‐Hodgkin's diffuse lymphoma

Contact Info

Product

Resources

About