Eero Niskanen

Treatment of advanced esthesioneuroblastoma with high‐dose chemotherapy and autologous bone marrow transplantation. A case report

A 46‐year‐old woman presented with an advanced unresectable esthesioneuroblastoma which failed to respond to radiation therapy and one course of chemotherapy. She underwent treatment with high‐dose chemotherapy (cyclophosphamide, doxorubicin, and vinblastine) followed by autologous bone marrow transplantation. The major toxicity from the regimen was severe oropharyngeal mucositis. A complete remission was achieved and the patient is free of disease and asymptomatic 3.5 years after treatment.

Physiological concentrations of atrial natriuretic factor stimulate human erythroid progenitors in vitro

Human alpha-ANF[1-28] potentiated erythroid colony formation up to four-fold in cultures containing erythropoietin. Both early and late erythroid precursor cells responded to alpha-ANF[1-28] [0.032 to 1 nM] in a dose dependent fashion. Removal of T lymphocytes and macrophages which have been shown to modulate erythropoiesis did not abolish the stimulatory effect. All major circulatory forms of ANF (alpha-ANF[1-28], alpha-ANF[4-28] and alpha-ANF[5-28]) had potent erythropoietic activity. These results indicate that concentrations of ANF reached during hypoxia stimulate erythroid progenitor cells in the presence of erythropoietin.

Hematopoietic Growth Factors in Clinical Hematology

Five primary hematopoietic growth factors have been extensively evaluated in trials in patients with inadequate blood cell formation. Results have convincingly demonstrated that various chronic anemias can be corrected with erythropoietin. Similarly, there is no doubt that granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) increase the number of leukocytes and improve the function of cells in patients with congenital and acquired leukopenias. Recent studies indicate that interleukin-3 (IL-3) and macrophage colony-stimulating factor (M-CSF) can also stimulate blood cell production in patients. As a result, morbidity and perhaps mortality associated with severe cytopenias can be reduced substantially.

Effect of cooling rate on human and murine hemopoietic precursor cell recovery

The effect of cooling rate on recovery of human and murine hemopoietic precursor cells was studied. In the presence of 10% Me2SO, a cooling rate of 7 degrees C/min from -4 to -30 degrees C was optimal for recovery of both human and murine precursor cells which give rise to colonies in diffusion chambers implanted in mice (CFU-DG). Cooling of human marrow at a rate between 3 and 7 degrees C/min resulted in the best CFU-C recovery, although no good correlation between the cooling rate and murine CFU-C recovery was demonstrated. These data suggest that recovery of the primitive hemopoietic precursor cells can be improved by changing the standard cryopreservation programs used presently. However, improved recovery of CFU-DG does not necessarily translate into faster reconstitution of hemopoiesis. No significant difference was observed in overall recovery of bone marrow cellularity in lethally irradiated mice following injection of untreated marrow and marrow cooled at a rate of 1 and 7 degrees C/min.

Diamine oxidase is important in assessment of polyamine effects on hemopoietic cell proliferation in vitro

SummaryA difference was observed in the effect of difluoromethlyornithine (DFMO), a specific inhibitor of ornithine decarboxylase, on human and murine granulocyte-macrophage precursor cell (CFU-C) proliferation in vitro, in the presence of fetal bovine serum (FBS) and horse serum (HS). A dose of DFMO which almost totally abolished CFU-C colonies in cultures containing FBS had no effect or very little effect on CFU-C in cultures supplemented with HS. This effect could be reversed by aminoguanidine reacting with diamine oxidase (DAO), which is present in FBS but not in HS. The importance of DAO in the assessment of polyamine effects is also suggested by decreased colony formation in cultures containing HS and DFMO only after the addition of this enzyme. Additionally, Mo T cell line cultures containing DFMO demonstrated a substantially lower intracellular concentration of putrescine in the presence of FBS rather than HS.

Haematological Cell Proliferation and Differentiation Responses to Perturbations of Polyamine Biosynthesis

Abstract. Combined administration of methylglyoxal‐bis‐guanylhydrazone (MGBG) (25 mg/kg) with difluoromethylornithine (DFMO), or MGBG alone at a higher dose (50 mg/kg), to mice resulted in a decreased white cell count (WBC) in the peripheral blood while DFMO or MGBG alone at a lower dose (25 mg/kg) had no effect. As expected, DFMO alone increased the number of colony forming units spleen (CFU‐s), colony forming units diffusion chamber granulocyte (CFU‐dg) and colony forming units culture (CFU‐c) in the bone marrow. MGBG treatment led to an increase in CFU‐dg alone. Combined treatment seemingly had no effect on marrow stem cells. Total tibial and differential counts were not affected by any of the treatments. Cell proliferation in diffusion chamber cultures, as judged by CFU‐dg colony formation, was impaired by MGBG alone or in combination with DFMO, at dose levels which had no effect or increased the precursor cell number in the bone marrow. This effect was partially reversed with either putrescine or spermidine. Determination of intra‐cellular polyamine concentrations, demonstrated decreased putrescine and spermidine levels after DFMO administration. As expected, MGBG treatment resulted in decreased spermidine and spermine levels, concomitant with an increase in putrescine. In mice which received both agents, rather than only MGBG, after 3 days higher intracellular polyamine concentrations were observed. After 11 days, however, there was no significant difference between the two groups.

Separation By Velocity Sedimentation of Human Haemopoietic Precursors Forming Colonies in vivo and in vitro Cultures

Cells which give rise to granulocyte‐macrophage colonies under the influence of peripheral blood white cells (CFU‐c (WBC)) and Mo T cell conditioned medium (CFU‐c (Mo)) sedimented at a faster rate than the cells which form mixed erythroid‐granulocytic colonies in methylcellulose in vitro (CFU‐mix) and granulocytic (CFU‐dg) and megakaryocytic (CFU‐dm) colonies in diffusion chambers in mice. Despite identical peak sedimentation rate for the two CFU‐c populations, sedimentation profiles suggest that they are heterogeneous with respect to size. A proportion of CFU‐c (Mo) may be identical with CFU‐dg and CFU‐mix. Sedimentation profiles for cells which give rise to mixed colonies in vitro (CFU‐mix) and to granulocytic colonies in diffusion chambers in cyclophosphamide pretreated mice (CFU‐dg (CY)) and in Mo conditioned medium treated mice (CFU‐dg (Mo)) were similar. On the average CFU‐dm sedimented somewhat slower than CFU‐dg. These and other observations suggesting a close relationship between CFU‐dg and multipotential haemopoietic precursors are discussed.