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[Granulopoiesis: comparison of several methods for studying production and bone marrow cellularity (author's transl)].

Several methods measuring the granulocyte production have been compared in normal subjects, hypoplastic granulopenia, chronic leucopenia and acute leukemia: the granulocyte turnover-rate after injection of in vitro 51Cr labelled autologous granulocytes, the efficiency of 75Se-selenothionine in vivo labelling, the flow-out of the myelocyte compartment after in vitro flash-labelling with 3H-thymidine. The two first methods are correlated and measure the global effective production of granulocytes. The third method is a fractional measure of the bone marrow production and is not correlated with the former ones. The ratio between the granulocyte turnover-rate and the flow-out of the bone marrow proliferative pool is a measure of the bone marrow cellularity. Discrepancies between this measure and the granulocyte turnover-rate has been found only in leukaemic patients.

Autoradiography↗

[Comparison of the therapeutic efficacity of 2 induction protocols in acute myeloid leukemia using exact quantification of bone marrow cellularity].

Using a recently developed technique for the determination of the pure bone marrow cell count per mm3 bone marrow, two different induction regimens for AML were compared for their efficacy, i.e. the therapy induced cytoreduction. In both protocols cytosine arabinoside, daunorubicin and 6-thioguanine were applied at comparable doses but different schedules. In both regimens a blast cell reduction of more than 2.0 log10 within the first 5 to 6 days of therapy strongly correlated (p less than 0.001) with the achievement of an adequate blast clearance in the marrow and complete remission (n = 18), while an inadequate blast cell reduction was revealed in all patients with a cell kill of less than 2.0 log10 (n = 9). Total cytoreduction on day 5 or 6 of therapy was comparable for both protocols. However, on one protocol a continuous logarithmic blast cell reduction was found while the cell kill followed a biphasic function on the other regimen.

Antineoplastic Combined Chemotherapy Protocols↗

Bone marrow cellularity in normal and polycythemic mice estimated by DNA incorporation of 3H-TdR.

Nucleated bone marrow cell numbers in normal and polycythemic mice were determined using 3H-thymidine (3H-TdR). The cellularities were estimated by extrapolating the exponential disappearance of labeled cells after a single injection of 3H-TdR to the time of injection. Dermestid beetles (Anthrenus piceus) were used to prepare tissue-free skeletons labeled with 3H-TdR. The correlation between tritium activity in bone marrow DNA and tritium derived from the combusted skeleton was determined. The total skeletal cellularity determined by isotope dilution analysis in both normal and polycythemic mice was 2.6 x 10(8) cells/mouse or 17.6 x 10(9) cells/kg body weight. Although the red cell component of the marrow was reduced in the polycythemic mouse, the total numbers of nucleated cells in both types of animals were similar. The differential distribution of cells in the polycythemic animal showed a twofold increase in granulocytic cells, which may explain the identical nucleated cell count in normal and in polycythemic mice.

Animals↗

Bone marrow cellularity assessed by point-counting.

A simple method for rapid point-counting of bone marrow biopsies is described; the method gave an accurate assessment of cellularity in 100 aspiration biopsy specimens. Measurements of marrow cellularity by the visual point-counting technique correlated well with those obtained with a Quantimet 720 image-analysing computer.

Bone Marrow Cells↗

Avian immune capacity and bone marrow cellularity after in ovo treatment with cyclophosphamide.

Lymphoid tissue, immunity and erythropoiesis in bone marrow were studied in chickens which had received air cell applications of cyclophosphamide (Cy) between 16 and 18 days of their embryonic development. The bursae from the Cy-treated birds were reduced significantly in size, deficient in bursal follicles, and lacked lymphocytes. The agglutinin level of sheep red blood cells of birds treated with Cy (2 mg) as 16, 17 and 18-day embryos was significantly lower than controls. While these Cy-treated birds lacked IgG antibody to sheep red blood cells, about 50% of the Cy birds produced unspecific IgG. Cy treatment did not suppress the graft-versus-host response. Cy did not change the absolute number of lymphocytes, granulocytes or erythroid series of cells in the bone marrow but did eliminate plasma cells. Since some of the Cy-treated birds did not produce specific agglutinin but made Ig, one would have to conclude that the presence of the bursa was not obligatory for Ig synthesis, but that the bursal microenvironment may be a prerequisite for synthesis of specific antibody.

Age Factors↗

Histomorphometrical determination of bone marrow cellularity in iliac crest biopsies.

The point-count principle is an exact method of bone marrow quantitation but fairly good correlation was found between quantitated and estimated values of the cellularity in iliac crest biopsies, although the latter values were significantly lower. No intraspecimen variation was found, but the cellularity in the individual biopsies varied considerably from field to field, indicating that quantitation and estimation on small samples obtained by aspiration may be misleading. The correlation between the values from undecalcified and decalcified sections was high, but decalcification of the biopsies resulted in an underestimation of the amount of haemopoietic tissue.

Adolescent↗

Heterotopically induced bone marrow. I. Cellular composition of bone marrow derived from the heterotopic ossicles induced in mice by xenogeneic epithelia of human amnion and dog's transitional epithelium.

Following heterotopic osteogenesis by implantation of xenogeneic epithelia (FL and WISH cell line, transitional epithelium of dog) in mice a biogenesis of hemopoietic tissue among induced ossicles is observed. Precursors and mature forms of all types of blood cells are found in the induced bone marrow. The concentration of lymphocytes in the induced bone marrow is higher, and that of erythropoietic cells lower as compared with orthotopic femur bone marrow. The yield of myeloid cells varied from 0.14 to 3.61 x 10(6) cells per induced bone-containing nodule.

Amnion↗

Bone marrow cellularity in myeloid stem cell disorders: impact of age correction.

We have reviewed the initial diagnostic bone marrow aspirate and biopsy specimens performed on the same date on 92 patients with acute myeloid leukaemia (AML), 100 patients with myelodysplastic syndrome (MDS), 24 patients with chronic granulocytic leukaemia (CGL), 19 patients with polycythemia vera (PV) and essential thrombocythemia (ET). An excellent assessment of cellularity by aspirate and biopsy was found. The estimation of BM cellularity for each group was utilized with and without age adjustment based on normal marrow biopsies. Without correcting the BM cellularity for age it was observed that the median BM cellularity was > 50% in AML, CGL, PV and ET. In contrast, the median BM cellularity was estimated at 40% for MDS. In the age group 70 years and beyond the median BM cellularity was not changed in CGL, PV and ET, and only slightly decreased (35%) in MDS. However, a trend from hypercellularity to normocellularity was observed in patients with AML in this age group. By utilizing anatomic comparisons with normal age the corrected data disclosed that all patients with CGL, PV and ET, 63% of patients with AML and only 35% of patients with MDS had hypercellular BM according to their age, while only two patients with AML and seven patients with MDS were found to be truly hypocellular by age. The optimal cut-off value for definition of hypocellular AML and hypocellular MDS, and differences between MDS and other myeloid stem cell disorders in terms of BM cellularity have been discussed.

Adolescent↗

[The comparative characteristics of the bone marrow cellular composition in rats after the prolonged continuous or interrupted action of a low geomagnetic field].

Bone marrow cell composition in male Wistar rats exposed to long-term continuous (Run 1) or interrupted (Run 2) hypo-geomagnetic field (HGMF) with an attenuation coefficient of 172.5 generating in a permalloic chamber has been studied. When comparing the rat myelograms of the two test runs, a significant increase of lymphoid cell content, less pronounced during an interrupted exposure to HGMF by 10.1 and 6.5%, respectively, was noted. Analysis of myeloid cell response indicated that on a continuous exposure to HGMF the percentage of neutrophilic promyelocytes and myelocytes is somewhat declined. The levels of mature relating to stab and nuclear-segmental neutrophils in bone marrow during both modes of HGMF exposures practically remained unchanged. A certain decrease in cell fractions of erythroblastic shoot (chiefly at the cost of polychromatophilic normocytes), to a lesser extent manifested during an interrupted exposure to HGMF (by 5.8 and 2.4%, respectively) was noted. Long-term exposure of the animals to a weak terrestrial magnetic field causes a particular eosinophilia of bone marrow due to an increased fraction of mature eosinophils approximately similar on both HGMF profiles (by 2.1 and 2.0% respectively). On an interrupted HGMF exposure there was a significant myelogram elevation of the mast cell counts by 1.4%.

Animals↗

[Changes in bone marrow cellularity close to cancer metastases. Cyto-histologic study].

Before starting any therapy, we systematically studied by biopsy the bone marrow of 66 patients suffering from various cancers and suspect of marrow metastasis. Metastatic cells were thus found in 45 patients. Bone marrow composition was examined on histologic sections by granulometric method, while relative proportions and morphology of the various hematopoietic series were examined on cytologic prints. It then appeared that any important metastatic invasion goes together with deep alterations of the surrounding hematopoietic tissue, with frequent peri-metastatic collagenic fibrosis and hypoplasia of the various cell-lines; when metastatic growth is still moderate, hematopoietic tissue is, on the contrary, often hyperplastic, "irritative". These marrow alterations are not to be found far from the metastasis, and thus seem to be directly linked to the actual presence of cancerous cells.

Adenocarcinoma↗

Evaluation of bone marrow cellularity by magnetic resonance imaging in patients with myelodysplastic syndrome.

Magnetic resonance imaging (MRI) is a safe modality for examining the bone marrow and it is quite effective in revealing marrow involvement in hematological malignancies. MRI has been compared with needle marrow biopsy in 22 patients with myelodysplastic disorders. A fairly good concordance has been demonstrated in 79% of cases. However, in 5 patients MRI revealed that bone marrow hyperplasia was not generalized. Therefore in elderly patients with MDS, MRI of the spine allows the quantification of bone marrow hyperplasia with a greater accuracy than bone marrow biopsy and this may be useful for monitoring the effect of cytostatic treatment.

Adult↗

ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response.

The tyrosine kinase inhibitor STI571 (imatinib mesylate, Gleevec) is an effective treatment for chronic myeloid leukemia (CML). We examined bone marrow samples from 53 patients with CML who were receiving STI571 in 3 multicenter phase 2 trials to assess morphologic changes and cytogenetic response to this drug. In most patients with initially increased blasts, the bone marrow blast count rapidly decreased during STI571 therapy. Reductions in cellularity, the myeloid/erythroid ratio (commonly with relative erythroid hyperplasia), and reticulin fibrosis (if present pretreatment) also were seen in most patients, resulting in an appearance resembling normal marrow in many cases. Eighteen patients (34%) had some degree of cytogenetic response. Surprisingly, these striking morphologic changes occurred irrespective of any cytogenetic response to STI571. Thus, STI571 seems to affect the differentiation of CML cells in vivo, causing even extensively Philadelphia chromosome-positive hematopoiesis to exhibitfeatures resembling normal hematopoiesis.

Antineoplastic Agents↗