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PubMed2004

Effects of organ-specific loss of insulin-like growth factor-I production on murine hematopoiesis.

To determine whether circulating insulin-like growth factor (IGF)-I has a role in hematopoiesis, we examined hematologic parameters in mice with markedly reduced serum levels resulting from a liver-specific inactivation of the IGF-I gene. These mice have normal postnatal growth and development, suggesting that local production of IGF-I can maintain anabolic effects. Liver-specific IGF-I-deficient (LID) mice were compared with control littermates with regard to hematopoietic parameters. Spleen cellularity was decreased in the LID mice compared with control mice. Spleen myeloid progenitors, as determined by colony-forming units-granulocyte/monocyte (CFU-GM) and colony-forming units-high proliferative potential (CFU-HPP), were significantly decreased in the LID mice. Immune parameters, as indicated by the absolute number of B and T cells, did not significantly differ between the knockout and control mice. In contrast to the decreased cellularity and myelopoiesis in the spleen, bone marrow cellularity was not different between the 2 groups, but the total femoral content of CFU-GM and CFU-HPP was significantly increased in the LID mice. The decrease in splenic myelopoiesis was not due to the inability of progenitors to exit the bone marrow, because CFU-GM and burst-forming units-erythroid were significantly increased in the blood of LID mice compared with normal littermates. Administration of exogenous IGF-I to the LID mice for 4 days partially restored myelopoietic parameters in the spleen. Liver production of IGF-I and, therefore, normal serum levels of this hormone, although not necessary for general organ growth and development, seems necessary for survival or transition of myeloid progenitors into the spleen.

Animals↗

PubMed1994

Marrow cellularity as a predictor of adequate cell yield for transplantation.

Clear correlations have not been established between bone marrow cellularity before or at marrow harvest and marrow cell yield for transplantation. The authors therefore retrospectively reviewed 204 marrow donations to ascertain whether biopsy cellularity was predictive of nucleated cell yield at harvest, as measured by final cell counts (FCC)/kg body weight. Preharvest and intraoperative biopsy cellularity were highly correlated with each other; moderate correlation was found between intraoperative biopsy cellularity and FCC. Mean cellularity was slightly but significantly higher in samples yielding an FCC greater than 2 x 10(8) nucleated cells/kg (P < 0.01). Biopsy cellularity less than 20%, seen in 4% of specimens, did not consistently correlate with low FCC, defined as less than 2 x 10(8) nucleated cells/kg. More than 2 x 10(8) cells/kg were consistently obtained only when biopsy cellularity was 65% or more. Marrow biopsies performed before harvest can be used to predict intraoperative cell counts at the time of marrow donation, although a cell yield of more than 2 x 10(8) nucleated cells/kg can be assured only with high marrow cellularity.

Adolescent↗

PubMed1981

The effects of calusterone on hemopoiesis in mice after busulfan-induced suppression of hemopoietic stem cells.

Studies were undertaken in mice to determine the effect of calusterone (a weakly androgenic steroid) on hemopoiesis. Animals were myelosuppressed with a single injection of the alkylating agent busulfan and subsequently treated with varying courses of calusterone. Simultaneous injection of calusterone did not prevent the rapid decline in CFU-S or CFU-C. Daily administration of calusterone for 12 to 14 days after busulfan had little influence on bone marrow cellularity; however, a twofold increase in peripheral blood neutrophils was observed. Bone marrow CFU-S and CFU-C were twofold to threefold higher after 8 to 14 days of treatment with calusterone, but there were no progressive increments in these hemopoietic stem cells during this time interval. In contrast to the granulocyte series, erythroid recovery was rapid after busulfan. Marrow erythroid precursors and CFU-E returned to normal levels by day 8. Daily treatment with calusterone accelerated recovery and led to an overshoot in these parameters of marrow erythropoiesis. Although an early course of calusterone treatment had only modest effects on CFU-S and CFU-C, delayed treatment was clearly stimulatory. A 10-day course of calusterone from days 14 to 24 after busulfan increased bone marrow CFU-S and CFU-C from 5% to 23% of controls to near normal values. Thus calusterone appears to stimulate all classes of hemopoietic progenitor cells. Its effects after busulfan are highly time-dependent, with greatest activity observed in those cellular compartments undergoing proliferative expansion.

Animals↗

PubMed1996

Prediction of bone marrow involvement in patients with malignant lymphoma by GM-CSF stimulation test.

Recently, a stimulation test with colony stimulation factors was found useful to predict bone marrow cellularity. We examined the usefulness of this test to predict the bone marrow involvement in patients with malignant lymphoma. A single dose of GM-CSF (5 micrograms/kg) was given subcutaneously to 12 patients with malignant lymphoma. Six patients had normocellular bone marrow. Five of these 6 patients showed an increase in neutrophils of more than 5 x 10(9)/l after GM-CSF administration. The remaining 6 patients who had bone marrow lymphoma involvement had a neutrophil count of less than 5 x 10(9)/l. Therefore, the change in neutrophil count with a cut-off value of 5 x 10(9)/l distinguished the marrow lymphoma involvement with a sensitivity and specificity of 83% and 100%, respectively. The nadir neutrophil count was significantly higher in patients with normal marrow than in patients with marrow involvement after chemotherapy (P < 0.02). In conclusion, the GM-CSF stimulation test is useful to predict the marrow involvement in patients with malignant lymphoma.

Adolescent↗

PubMed1999

The relative extent and propensity of CD34+ vs. CD34- cells to undergo apoptosis in myelodysplastic marrows.

The paradox of peripheral cytopenias despite cellular bone marrow (BM) observed in myelodysplastic syndromes (MDS) has been associated with excessive intramedullary apoptosis of hematopoietic cells. Since MDS is regarded as a stem cell disorder, the present studies were undertaken to examine the relative susceptibility and propensity of early progenitor CD34+ cells to undergo apoptosis as compared to more maturing/matured CD34- cells. Five serial studies were performed on 4 independent groups of 36 newly diagnosed MDS patients. First, in 2 separate groups of 16 and 8 patients each, measurement of the extent of apoptosis in CD34+ and CD34- fractions of the BM aspirate mononuclear cells was carried out using independent biparametric flow cytometry methods, CD34 labeling/terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) (n = 16), and CD34 labeling/reduced uptake of nucleic acid staining dye LDS751 (n = 8). The difference in the median degrees of apoptosis in CD34+ vs. CD34- cells was not statistically significant by either technique (P = 0.583 and P = 0.674 for TUNEL and LDS751, respectively). In the next group of 4 MDS patients, a double-labeling was performed on plastic embedded marrow biopsy sections, to detect CD34 antigen with specific monoclonal antibody and apoptosis by in situ end labeling (ISEL) of fragmented DNA. Despite high overall apoptosis (56.2% +/- 18.4%), only an occasional CD34+ cell was found to be simultaneously labeled with ISEL. Finally, in the last group of 8 MDS patients, CD34+ cells were separated from CD34- cells on affinity column and cultured in serum containing medium for 4 hours. At 0- and 4-hour time points, ISEL was carried out to label apoptotic cells. In addition, a fluorometric assay was employed to estimate the activity of a proapoptotic enzyme, Caspase 3. Both the net increase in % ISEL labeled cells (apoptotic index or AI) and Caspase-3 activity were significantly lower in CD34+ cells as compared to CD34- cells (AI, 0.87% +/- 0.5% vs. 3.97% +/- 1.4%, n = 6, P = 0.028 and Caspase-3 Units/mg protein, 46.9 +/- 25.0 vs. 71.7 +/- 23.03, n = 5, P = 0.042, respectively). We conclude that when estimated in a total population of mononuclear cells, CD34+ cells and CD34- cells show comparable degrees of apoptosis. However, once separated the CD34+ fraction demonstrates lower propensity to undergo apoptosis, thereby suggesting the CD34- fraction as being a possible source for proapoptotic signaling.

Aged↗

PubMed1978

[Ineffective erythropoiesis in myeloid splenomegaly: the 59Fe test, bone marrow histologic and cytologic data].

Eight patients presenting primary myelofibrosis or spent polycythemia were submitted to a ferrokinetic study, a triphine bone marrow biopsy and a bone marrow puncture. In all cases before treatment (splenic radiotherapy) ferrokinetic measurements demonstrated an ineffective erythropoiesis, the intensity of which was precised on bone marrow biopsies, in numbering the erythroblasts per surface unit. Bone marrow biopsies permitted also, through a semiquantitative estimate of the bone marrow cellularity, to evaluate an aplasia component not always expected with ferrokinetic study. Study of bone marrow allowed to precise the site of the erythroblastic abortion; cellular death might occur during the last nitosis of the erythroblastic series (transition from the polychromatophil erythroblasts to the acidophil erythroblasts). In order to delineate the general pattern of erythropoiesis before treatment and when assessing the results of a treatment, besides ferrokinetic measurements, the study of bone marrow biopsy and smears appears relevant.

Adult↗

PubMed1993

Failure of stem cell factor to ameliorate AZT-induced anemia in immunodeficient mice.

Recent attempts to reduce 3' azido-3' deoxythymidine (AZT)-induced anemia in AIDS patients have focused both on AZT dose reduction and on the use of recombinant cytokines. The newly cloned cytokine stem cell factor (SCF) is a potent regulator of hematopoietic progenitor cell proliferation. Therefore, we attempted to ameliorate AZT-induced anemia using stem cell factor (SCF) in the LP-BM5 murine leukemia virus-induced model of AIDS (MAIDS). SCF was administered with oral AZT for up to 1 month, and effects on erythropoiesis examined. SCF alone increased both splenic BFU-E and CFU-E. AZT alone also increased the number of splenic BFU-E and CFU-E. SCF, administered to AZT-treated MAIDS mice, did not further enhance these increases. SCF increased bone marrow cellularity in AZT-treated MAIDS mice. However, the total number of bone marrow BFU-E was unaffected. In contrast, AZT, SCF, and the combination significantly decreased bone marrow CFU-E. SCF alone increased the absolute numbers of peripheral blood reticulocytes in MAIDS mice, but did not increase reticulocyte numbers in AZT-treated mice. SCF did not significantly increase hematocrits in either control or AZT-treated mice. Further studies are needed to maximize the differentiating capacity of the enlarged erythroid progenitor cell pool induced by SCF.

Anemia↗

PubMed1996

Spatial mapping of the percentage cellularity in human bone marrow using magnetic resonance imaging.

A noninvasive assay for the spatial distribution of the percentage cellularity in human bone marrow is presented. Twelve individuals were studied using two magnetic resonance imaging techniques: (1) fast spin echo imaging with frequency selective presaturation, and (2) three-point chemical shift imaging. The data were compared to results obtained using a previously validated stimulated echo spectroscopic method. The results of this study demonstrate that a measure of the percentage cellularity in bone marrow is possible using magnetic resonance imaging techniques provided that high-quality water or lipid suppression is achieved across the region of interest. Since the method is applicable to bone marrow at any anatomic location, it may prove useful in dosimetric calculations during and after a course of internal or external beam radiotherapy.

Adult↗

PubMed1993

Blood neutrophil increment after a single injection of rhG-CSF or rhGM-CSF correlates with marrow cellularity and may predict the grade of neutropenia after chemotherapy.

The grade of neutropenia after chemotherapy seems to be correlated to the bone marrow cellularity as judged by biopsies. Prolonged blood neutropenia after sequential chemotherapy reduces dose intensity and increases the risk of severe infections. A predictive non-invasive test for marrow cellularity is needed in the attempt to predict chemotherapy-induced blood neutropenia. Thirty-one patients with haematological disorders were studied with measurements of blood absolute neutrophil counts (ANC) 24 h after a single subcutaneous injection of recombinant human granulocyte colony stimulating factor (rhG-CSF) or granulocyte-macrophage CSF (rhGM-CSF). Before cytokine administration all patients had bone marrow biopsies performed. The median increase in blood ANC 24 h after cytokine administration was 15.9 x 10(9)/l (range 3.7-34.2) in 18 patients with normo- or hypercellular marrows and only 0.4 x 10(9)/l (range 0.0-11.2) in 13 patients with hypocellular marrows (P < 0.00001). An increase in ANC or more than 5 x 10(9)/l was predictive for normo- or hypercellular bone marrows with a sensitivity and specificity of 94% and 84%, respectively. A subsequent pilot study in selected patients with prolonged neutropenia was performed. The ANC increment in 12 cases before chemotherapy correlated to the grade of neutropenia and may predict the risk of febrile neutropenia. It is suggested that blood responsiveness to myeloid growth factors correlates with marrow cellularity and may identify outpatients with risk for severe neutropenia after cyclic chemotherapy.

Adolescent↗

PubMed1985

Abnormalities of myeloid progenitor cells after "successful" bone marrow transplantation.

We studied recovery of peripheral blood- and bone marrow-derived myeloid progenitor cells (CFU-G,M) in 29 patients who received bone marrow transplants 2 mo to 8.5 yr previously. All patients had normal levels of peripheral blood neutrophils, normal bone marrow cellularity, and a normal myeloid-erythroid ratio. Both peripheral blood- and bone marrow-derived CFU-G,M were markedly reduced compared with normal controls and bone marrow donors [5 +/- 1/10(6) vs. 37 +/- 4/10(6) (P less than 0.001) and 23 +/- 5/2 x 10(5) vs. 170 +/- 21/2 x 10(5) (P less than 0.001)]. Five patients had no detectable CFU-G,M even when 10(6) bone marrow cels were plated. These abnormalities of CFU-G,M were unrelated to age, sex, diagnosis, conditioning regimen, dose of bone marrow cells transplanted, and presence or absence of graft-vs.-host disease. Patients who received either autotransplants or transplants from identical twins also had decreased or absent CFU-G,M indicating that allogeneic factors and posttransplant immune suppressor with methotrexate or corticosteroids were not major determinants of this abnormality. Co-culture of normal or donor peripheral blood or bone marrow mononuclear cells with recipients peripheral blood or bone marrow mononuclear cells, purified T cells, or serum failed to show any evidence of active CFU-G,M suppression. Furthermore, the abnormality of CFU-G,M could not be corrected by the addition of normal syngeneic (donor) hematopoietic cells or serum. Depletion of T-cells from recipient bone marrow by physical techniques resulted in marked increase in CFU-G,M (36 +/- 13 vs. 138 +/- 36; P less than 0.05). The abnormality could be reproduced in vitro by readdition of autologous T cells. In contrast to results with T cell depletion by physical techniques, T cell depletion with a monoclonal anti-T antibody (B7) and complement had no effect. These data indicate that most-transplant recipients have a marked abnormality in CFU-G,M when these cells are cultured in vitro. In at least some of these patients, the decreased cloning efficiency of CFU-G,M appears to be mediated by a suppressive effect of autologous T cells.

Adolescent↗

PubMedDate not supplied

One year of rHuEPO therapy prolongs RBC survival and may stabilize RBC membranes despite natural progression of chronic renal failure to uremia and need for dialysis.

rHuEPO was administered to eight patients with chronic renal failure (CRF) and uremia (U) for 1 year. Creatinine Clearance (GFR) averaged 14.3 (9-25) ml/min at an Hct of 28% (26-30). Baseline RBC survival by 51Cr T1/2 was highly correlated with GFR (r = 0.66), p less than 0.05 (2), average 21.6 days. Repeat 51Cr T1/2 at 3 months with GFR 10 ml/min at Hct 38% was prolonged by 7 days to 28.6 (p less than 0.005), and at 1 year remained increased to 28 days (p less than 0.001) with Hct 39%, despite further decreased GFR to less than 4 ml/min and need for dialysis. Reticulocytes varied from 1.6% to 7.4 (3-6 weeks) to 3.1 (3 months) and 1.5% (1 year). Bone marrow cellularity increased from 36% to 47% (3 months) and 44% (1 year). M:E ratio decreased from 3.9:1 to 1.7:1 (3 months) to 1.6:1 (1 year). Marrow iron decreased from 4.1/6 to 2.4/6 (3 months) to 1.8/6 (1 year). Doses of rHuEPO had to be reduced to avoid polycythemia. rHuEPO stimulates erythropoiesis in pts with progressive CRF and U for 1 year. The initial increase in hematocrit is due to the early peak of reticulocytes. At 3 months, rHuEPO maintains the increased hematocrit by three mechanisms: 1) increased reticulocytosis, 2) a trend to increased bone marrow erythroid cellularity, and 3) lengthened RBC survival. At 1 year of rHuEPO therapy, the trend to increased marrow cellularity persists, however, the maintenance of target hematocrit is via a lengthened RBC survival. Despite progression of CRF and U, rHuEPO produced RBCs with longer survival than expected. RBC membranes may have been stabilized by rHuEPO.

Adult↗

PubMed1988

Modulation of responsiveness of chronic myelogenous leukemia granulocyte-macrophage colony-forming cells to growth regulation following in vivo treatment with recombinant gamma-interferon.

A patient with Philadelphia chromosome (Ph) chronic myelogenous leukemia (CML), in chronic phase, was treated with recombinant gamma-interferon (r gamma-IFN) in a phase I clinical trial. Prior to treatment, analysis of in vitro agar culture parameters indicated hyporesponsiveness of granulocyte-macrophage colony-forming cells (CFU-GM) to inhibition by prostaglandin E and acidic isoferritins and diminished expression of class II major histocompatibility complex (MHC) antigens (HLA-DR). Treatment was associated with no change in bone marrow cellularity or in the percentage of Ph cells. However, in vitro cultures of bone marrow cells showed a return to normal levels of both expression of CFU-GM class II antigen and of sensitivity to inhibition by prostaglandin E and acidic isoferritins which predicted and/or confirmed clinical response. Throughout the course of interferon therapy, white blood cell counts (WBC) and the percentage of bone marrow blast cells were maintained at normal levels. Onset of aggressive-phase disease was associated with increased WBC, an increase in bone marrow blast cells, a secondary chromosomal abnormality, loss of CFU-GM sensitivity to inhibition by putative negative growth regulators, and markedly diminished MHC class II antigen expression. Following a bone marrow transplant from a matched sibling, all hematologic parameters studied were found to be normal. These findings indicate that treatment with r gamma-IFN can modulate some of the abnormal growth characteristics of CFU-GM observed in CML.

Adult↗

PubMed2005

Full-dose 90Y ibritumomab tiuxetan therapy is safe in patients with prior myeloablative chemotherapy.

PURPOSE: Targeted radioimmunotherapy with yttrium-90 (90Y)-labeled ibritumomab tiuxetan (Zevalin, IDEC-Biogen, San Diego, CA) has shown significant activity in the treatment of relapsed or refractory CD20+ non-Hodgkin's lymphoma. Eligibility criteria used in phase I trials, and adopted in phase II and III trials, excluded patients with prior myeloablative therapy. We treated eight patients with 90Y ibritumomab tiuxetan who had prior autologous stem cell transplant, but met all other treatment criteria. EXPERIMENTAL DESIGN: Eight patients with CD20+ non-Hodgkin's lymphoma had extensive prior therapy including myeloablative chemotherapy but did not receive total body irradiation. Each had bone marrow cellularity of >15%, platelet count of >100,000/mm3, and one had documented lymphomatous bone marrow involvement of <25%. The standard course of 0.3 to 0.4 mCi/kg of 90Y ibritumomab tiuxetan was administered to patients at full dose. 18-Flouro-deoxyglucose positron emission tomography/computed tomography scans were done at pretreatment and approximately 12 weeks after treatment to assess patient response. Maximum toxicities were monitored and classified according to the Common Terminology Criteria for Adverse Events (ver. 3.0). RESULTS: Toxicities observed included grade 4 thrombocytopenia in three of eight evaluable patients and grade 4 neutropenia in one of eight evaluable patients. One patient had a neutropenic fever; all patients were off blood product support 12 weeks post-zevalin. Complete response by 18-flouro-deoxyglucose positron emission tomography/computed tomography imaging occurred in one of seven evaluable patients and one patient treated as consolidation had no evidence of disease. CONCLUSION: Our experience suggests that 90Y ibritumomab tiuxetan treatment is safe for use in patients with prior myeloablative therapy when the general inclusion criteria are fulfilled. In this small series, the response rates, however, are limited. Nevertheless, 90Y ibritumomab tiuxetan treatment may provide clinical benefit in carefully selected extensively pretreated patients.

Adult↗

PubMed2002

Clinicohaematological profile in chronic renal failure.

OBJECTIVE: Aim of the study was to observe the clinicohaematological profile, bone marrow and serum iron indices of patients with chronic renal failure. METHOD: A total of 27 patients of chronic renal failure were selected, irrespective of their age, sex, clinical profile and etiology. These patients were not on dialysis, haematinics or erythropoietin therapy. They underwent series of biochemical and haematological investigation including bone marrow aspiration and also estimation of serum iron indices. RESULTS: The commonest cause of chronic renal failure in study group was diabetes mellitus (20%), glomerulonephritis (8%). Fifty percent of the patients on first presentation were in end-stage renal disease. Most patients presented with features of anaemia (94%), uraemia (63%) and fluid overload (96%). Severity of anaemia was correlating with degree of azotemia. Sixty percent of the patients had microcytic hypochromic anaemia, five percent had macrocytic anaemia while 30% had normocytic normochromic anaemia. The reticulocyte count was high in 46% of the patients. RDW-CV of greater than 14 was observed in 67%. Thrombocytopaenia was found in 52% of the patients. Leucocyte count was within normal range in 75%. In differential leucocyte count and absolute eosinophil count was high in 32% of the subject. In bone marrow examination 61% of the patients had normal bone marrow cellularity, 75% were having erythroid hyperplasia. Fifty seven percent of the cases had bone marrow iron store of zero, 37.8% had normal bone marrow iron store, 6.5% had increased bone marrow iron store. Serum ferritin was low in 62% and serum iron was below normal in 74% of the patients. CONCLUSION: Majority (65%) of patient had microcytic hypochronic anaemia because of iron deficiency and 33% of patient had parasitic infestation.

Adolescent↗

PubMed1989

Nonneoplastic hematopoietic myeloproliferative syndrome induced by dysregulated multi-CSF (IL-3) expression.

Post 5-fluorouracil-treated murine marrow cells were infected with a retroviral vector (MPZen) bearing a multi-potential colony stimulating factor (Multi-CSF) cDNA insert and then transplanted into lethally irradiated syngeneic recipients to study the effects of autocrine production of Multi-CSF in normal hematopoietic cells. Extremely high levels (14,000 U/mL) of Multi-CSF were detected in the sera and in media conditioned by various hematopoietic tissues of the transplanted animals. While spleen, peritoneal, and peripheral blood cellularity increased approximately 10-fold, 10-fold, and 50-fold, respectively, bone marrow cellularity decreased twofold. Progenitor numbers were depressed twofold in the bone marrow but elevated more than 100-fold in the spleen and peritoneum. The majority (80%) of transplanted mice died within 5 weeks of transplantation and showed extensive neutrophilic infiltration of the spleen, lung, liver, and muscle, often with mast cell foci; a phenomenon also seen in the skin and intestine. Neither the infected cells from hematopoietic tissues of the primary mice, nor autonomous mast cell-lines that grew from these cells in liquid culture produced any overt disease when transplanted into normal or sublethally irradiated secondary recipients. In contrast, injection into mice of autonomous FDC-P1 cells transformed by the same retroviral construct led to tumor formation in vivo within 4 weeks. Thus, dysregulated Multi-CSF expression by normal hematopoietic cells produces a fatal but nonneoplastic myeloproliferative syndrome.

Animals↗

PubMed1980

Changes in cellularity and/or weight of mouse hemopoietic tissues as a measure of acute radiation effects.

Simultaneous determinations of the spleen weight loss, and thymus and femoral bone marrow cell depletion of approx. 45 h after whole-body irradiation of mice have been demonstrated to be a simple, rapid, sensitive and economical way of quantitating radiation damage to the hemopoietic system. Within the dose range of 45 to 300 rad of 250 kV X-rays, for all three end-points the logarithm of the radiation effect has been found to be proportional to the logarithm of dose, with the extrapolated common threshold dose of 29 +/- 3 rad, and 50% decrease relative to control values following 330 (extrapolated), 54, and 109 rad in case of the spleen weight, and thymus and bone marrow cellularities, respectively.

Acute Disease↗

PubMed1988

Demonstration of residual bone marrow effect in mice exposed to ethylene glycol monomethyl ether.

Ethylene glycol monomethyl ether (EGMME) has been reported to cause hematopoietic abnormalities in man. We have shown that mice exposed to EGMME post-natally have suppressed bone marrow cellularity and progenitor cells 8 weeks post-exposure which returns to normal values by 16 weeks. Studies were designed to determine whether EGMME exposed mice that recovered had evidence of residual marrow stem cell injury. B6C3F1 mice were injected subcutaneously with EGMME on days 1-5 after birth at doses of 0, 100, 200 and 400 mg/kg per day, allowed to recover, and stressed with 200 rads whole body irradiation at 15 and 21 weeks post-exposure. Bone marrow functions were examined during the recovery period. Mice that had been exposed to EGMME were more sensitive to irradiation and recovery of marrow cellularity and progenitor cell numbers occurred more slowly than in unexposed controls. This indicates that EGMME can cause persistent residual damage of bone marrow progenitor cells in mice, an effect that would not be apparent with routine hematological techniques.

Animals↗

PubMed1993

Hematological effects of the new immunosuppressive drug 15-deoxyspergualin.

Since systematic hematological studies on blood and bone marrow changes after treatment with 15-Deoxyspergualin (DOS) are lacking, a quantitative assessment was performed fourteen or twenty eight days after intraperitoneal application of DOS to rats. Further observations done 7 and 14 days after discontinuation of DOS administration allowed analysis of bone marrow regeneration. DOS induced lymphocytopenia, granulocytopenia and anemia with a decrease of bone marrow cellularity due to suppression of cell maturation. The effect was dose-dependent and bone marrow as well as blood changes were observed in animals treated with doses from 0.5 to 10.0 mg/kg DOS. Within 14 days after termination of the treatment, rapid recovery with normalization of all hematological parameters was observed. In the light of our data, these hematological side effects may not be a major disadvantage, if DOS is used in doses below 2.5 mg/kg, and for a course of therapy which is limited to 7 to 14 days.

Animals↗