Experimental hematology
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Experimental hematology · Dec 1995
Hematopoietic growth factors after HLA-identical allogeneic bone marrow transplantation in patients treated with methotrexate-containing graft-vs.-host disease prophylaxis.
The use of hematopoietic growth factors (HGFs) in the allogeneic transplant setting has sometimes been avoided for fear of stimulating leukemic cell growth and intensifying graft-vs.-host disease (GVHD). However, neither an increase in relapse rate nor an aggravation of GVHD has been routinely described when HGFs are used after allogeneic bone marrow transplantation (allo-BMT). Early outcomes after HLA-matched allo-BMT in 26 patients with hematologic malignancies treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) from the day of transplantation were analyzed. ⋯ A decrease in the number of early deaths from fungal or bacterial infections was found in the cytokine-treated group (p = 0.05). These data suggest that the early use of rhG-CSF or rhGM-CSF after HLA-matched allo-BMT in hematologic malignancies accelerates engraftment, reduces hospitalization time, and improves outcome, without increasing acute GVHD or early relapse. Because MTX-based prophylaxis regimens are associated with prolonged neutropenia, the routine use of HGFs after transplantation may be particularly useful in regimens including MTX.
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Experimental hematology · Dec 1995
Proliferative response of human marrow myeloid progenitor cells to in vivo treatment with granulocyte colony-stimulating factor alone and in combination with interleukin-3 after autologous bone marrow transplantation.
We have recently reported that the hematologic recovery of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) undergoing autologous bone marrow transplantation (BMT) is significantly faster when recombinant human interleukin-3 (rhIL-3) is combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in comparison with patients receiving G-CSF alone. In this paper, we studied the kinetic response and concentration of BM progenitor cells of 17 patients with lymphoid malignancies submitted to autologous BMT and treated with the G-CSF/IL-3 combination. The results were compared with those of five lymphoma patients receiving the same pretransplant conditioning regimen followed by G-CSF alone. rhG-CSF was administered as a single subcutaneous (sc) injection at the dose of 5 micrograms/kg/d from day 1 after reinfusion of autologous stem cells; rhIL-3 was added from day 6 at the dose of 10 micrograms/kg/d sc (overlapping schedule). ⋯ Our results demonstrated that pretreatment with G-CSF modified the response of BM cells to subsequent stimulation with additional CSFs. The results presented in this paper indicate that in vivo administration of two cytokines increases the proliferative rate and concentration of BM progenitor cells to a greater degree than G-CSF alone. These results support the role of growth factor combinations for accelerating hematopoietic recovery after high-dose chemotherapy.
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Experimental hematology · Dec 1995
A mononuclear cell dose of 3 x 10(8)/kg predicts early multilineage recovery in patients with malignant lymphoma treated with carmustine, etoposide, Ara-C and melphalan (BEAM) and peripheral blood progenitor cell transplantation.
We have assessed the potential use of the mononuclear cell (MNC) content as the sole assessment of graft quality in 35 patients receiving BEAM (carmustine, etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma. PBPCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each patient underwent two (n = 20) or three (n = 15) apheresis procedures. Median cell yields were 5.08 x 10(8) MNC/kg (range 1.59-15.70 x 10(8)) and 73.10 x 10(4) CFU-GM/kg (range 0.09-346.72 x 10(4)). ⋯ All patients receiving an MNC dose of > or = 3 x 10(8)/kg achieved neutrophil and platelet recovery by days 12 and 24, respectively. These preliminary data demonstrate that for patients with lymphoma undergoing PBPC mobilization according to this protocol and treatment with BEAM chemotherapy, assessment of MNC dose alone is sufficient to predict early hematologic recovery. Additional assays such as CFU-GM or CD34+ cell counts may not be necessary if this MNC dose is reinfused.
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Experimental hematology · May 1995
Comparative Study Clinical Trial Controlled Clinical TrialInfluence of in vivo administration of GM-CSF and G-CSF on monocyte cytotoxicity.
The influence of colony-stimulating factors (CSFs) on the monocyte functions of 32 patients with refractory testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was tested. Eight patients were treated as a control group without CSF therapy, 12 patients received recombinant human granulocyte-macrophage-CSF (rhGM-CSF), and 12 patients received recombinant human granulocyte-CSF (rhG-CSF). For the assessment of monocyte activation induced by CSF expression of major histocompatibility complex (MHC) class I and II antigens, production of tumor necrosis factor (TNF) and monocyte-mediated cytotoxicity against tumor cell targets were chosen. ⋯ A significant increase in the expression of MHC class I was seen in monocytes from patients under G-CSF treatment, whereas no change of class II antigens was noticed. Production of TNF and monocyte-mediated cytotoxicity against U937 tumor cells was significantly increased in monocytes derived from patients receiving GM-CSF, as compared to those from the control group, while no effect was detectable in monocytes from patients with G-CSF therapy. However, after in vitro stimulation with interferon-gamma (IFN-gamma), monocytes derived from GM-CSF as well as from G-CSF treated patients responded with a significantly higher TNF-production and cytotoxicity than monocytes from control patients.
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Experimental hematology · May 1995
Comparative StudyDifferential effects of the hematopoietic inhibitors MIP-1 alpha, TGF-beta, and TNF-alpha on cytokine-induced proliferation of subpopulations of CD34+ cells purified from cord blood and fetal liver.
We have previously characterized the proliferative response of primitive CD34+ cells, purified from adult bone marrow, umbilical cord blood, and fetal liver, to a mixture of hematopoietic stimulators (steel factor [SF], interleukin-3 [IL-3], IL-6, and erythropoietin [Epo]) in serum-free liquid cultures. In the present study, we assessed the effects of the hematopoietic inhibitors, macrophage inflammatory protein-1 alpha (MIP-1 alpha), transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha), on the cytokine-induced proliferation of three different CD34+ cell subpopulations derived from cord blood and on total CD34+ cells derived from fetal liver. In cultures of cord blood cells, addition of MIP-1 alpha inhibited the numerical expansion of primitive CD34+ cells (CD34+ CD45RAlow CD71low cells) without inhibiting the proliferation of more mature subpopulations enriched for myeloid (CD34+ CD45RA+ CD71low cells) or erythroid (CD34+ CD45RAlow CD71+ cells) progenitors. ⋯ In keeping with the fact that the majority of the progenitors contained in these cells were erythroid progenitors, the inhibitory effects of the three cytokines were similar to those observed in cultures of CD34+ CD45RAlow CD71+ cord blood cells. The results of the present study demonstrate that MIP-1 alpha, TGF-beta, and TNF-alpha have the capacity to modulate cytokine-induced proliferation of cord blood and fetal liver progenitors. The differential effects of these three cytokines confirm their pleiotropic nature as regulators of hematopoiesis.