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Results for “bone marrow cellularity”

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PubMed2000

Low-dose melphalan induces favourable responses in elderly patients with high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia.

We treated 21 elderly patients with high-risk myelodysplasia (n = 14) or secondary acute myeloid leukaemia (n = 7) with 2 mg of melphalan orally once a day until a complete peripheral response was obtained or until there was evidence of treatment failure. We observed seven (30%) complete and two (10%) partial peripheral responses occurring within 4-16 weeks and lasting for 12 + to 55 weeks. In relapse, retreatment was successful in most of the patients. Responses were associated with the absence of complex cytogenetic abnormalities and with a normal or reduced bone marrow cellularity.

Acute Disease↗

PubMed2000

Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.

Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.

Adult↗

PubMed2003

HLA-DR4 predicts haematological response to cyclosporine in T-large granular lymphocyte lymphoproliferative disorders.

T-cell large granular lymphocytic lymphoproliferative disease (T-LGL) is often associated with life-threatening cytopenias. Twenty-five subjects with anaemia and/or neutropenia caused by T-LGL were treated with cyclosporin A (CSA) 5-10 mg/kg/d for at least 3 months. Eighteen patients survived between 35 and 77 months after starting treatment. Fourteen patients [56%; 95% confidence interval (CI) 35-76%] responded to CSA with sustained improvement in the neutrophil count or transfusion independence. Seven had complete normalization of blood counts, and four achieved a durable response only after the addition of erythropoietin. Sustained response required continued low-dose CSA. In a multivariate analysis, HLA-DR4 was highly predictive of CSA responsiveness (odds ratio 18; 95% CI 1.8-184). T-LGL subtype, LGL counts after therapy, lymphocytic marrow infiltration and bone marrow cellularity did not significantly affect the probability of response. We conclude that CSA is effective in inducing haematological responses in HLA-DR4-positive patients and that T-LGL is likely to have an immune pathogenesis.

Adult↗

PubMed2002

Apoptosis and prognostic factors in myelodysplastic syndromes.

Apoptosis↗

PubMed2003

Imbalance between apoptosis and telomerase activity in myelodysplastic syndromes: possible role in ineffective hemopoiesis.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. The heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is involved in pre-mRNA processing and binds to telomeric cDNA repeats. The hnRNP B1 is a marker for early cancer. The aim of our study was to clarify the relationships between prognosis and apoptosis, telomerase activity (TA) and hnRNP expression in the bone marrow. The subjects were 51 patients with MDS, including patients with refractory anemia (RA) (n = 32), refractory anemia with ringed sideroblasts (RARS) (n = 1), refractory anemia with excess blasts (RAEB) (n = 7), refractory anemia with excess blasts in transformation (RAEB-t) (n = 8) and chronic myelomonocytic leukemia (CMMoL) (n = 3). We also studied 6 cases with acute myelogenous leukemia (AML) arising from MDS (AML-MDS) and 10 control subjects. Bone marrow biopsies were stained immunohistochemically for caspase-3 (marker of apoptotic activity) and human telomerase reverse transcriptase (hTERT), and hnRNP B1. Fatal pancytopenia was the cause of death in 19 of the 51 patients. The caspase-3 positive cell rate was higher in MDS (16.3%) than in controls (4.4%) and AML-MDS (0.5%). The percentage of hnRNP B1-positive cells was higher in MDS (15.3%) and AML-MDS (56.3%) than in controls (5.6%). In MDS, hnRNP B1 levels were higher in RAEB and RAEB-t subtypes than in RA and RARS. The percentage of hTERT-positive cells was higher in AML-MDS (50.0%) than in controls (20.2%) and MDS (23.6%). Our findings suggest that activation of apoptosis occurs in MDS in the absence of hTERT expression, implicating high apoptosis in the absence of high TA with ineffective hematopoiesis. Poor prognosis correlated with higher caspase-3 and lower hTERT rates. In MDS, hnRNP B1 activity may be associated with leukemic transformation.

Adolescent↗

PubMedDate not supplied

Management of the hematologic complications of human immunodeficiency virus infection.

Replication of various strains of human immunodeficiency virus can be increased in vitro by certain colony-stimulating factors (CSFs), but the protective effect of zidovudine (AZT) on macrophages is not antagonized in the presence of those factors--specifically, in the presence of granulocyte-macrophage CSF (GM-CSF). In clinical studies, GM-CSF given alone dramatically increased counts of white cells, particularly neutrophils and band cells. Very small doses of GM-CSF, self-administered subcutaneously, restored white cell production in leukopenic patients with AIDS. Combination treatment with AZT and GM-CSF in AZT-intolerant patients allowed resumption of AZT treatment and increased bone marrow cellularity. Treatment of anemic patients who have AIDS or AIDS-related complex with recombinant human erythropoietin (r-HuEPO) produced promising results. After 12 weeks of treatment with r-HuEPO, the need for transfusions to maintain hematocrit values within the normal range was reduced significantly or eliminated in patients with low baseline levels of endogenous erythropoietin. Studies combining AIDS chemotherapy with CSF or erythropoietin treatment are proposed.

Anemia↗

PubMed1988

Remission of chronic idiopathic myelofibrosis to busulfan treatment.

Three patients with chronic idiopathic myelofibrosis have responded to busulfan treatment with an excellent hematologic remission and reversal of myelofibrosis and myeloid metaplasia. Four months after busulfan therapy all three patients showed an improvement of hematocrit and hemoglobin and reduction of the number of leukoerythroblasts. Cellular bone marrow was re-established in two patients. A decrease of hepatomegaly and splenomegaly also occurred and was well correlated with the hematologic response. In one patient, when busulfan was discontinued for about 2 years after achieving an excellent remission, hematologic relapse was accompanied by increase of hepatomegaly and splenomegaly. When busulfan treatment was resumed, hematologic response and decrease of hepatomegaly and splenomegaly reoccurred. This observation has demonstrated the beneficial effect of busulfan in chronic idiopathic myelofibrosis; therefore, the role of busulfan in the management of this disease should be further investigated.

Aged↗

PubMedDate not supplied

Aplastic anemia due to chemicals and drugs: a study of 108 patients.

To illustrate the etiologic role of drugs and chemicals in the development of aplastic anemia, we analyzed 108 cases of aplastic anemia among 3,715 hematologic patients during a ten-year period at the hematology section of Istanbul Medical School. Among these 3,715 patients, 695 had leukemia, a result indicating the relative rarity of aplastic anemia as compared with leukemia. Of the 108 patients, 58.3% were male and 41.7% were female. Their ages ranged from six months to 82 years. Pancytopenia was severe in 42.6% of the patients, and moderate or mild in 57.4%. Bone marrow was hypocellular in 84 patients, normocellular in 16, and hypercellular in eight. In 52 (48.1%) of the patients with aplastic anemia, the following etiologic factors were implicated: benzene (25 patients), antirheumatic drugs (ten), chloramphenicol (four), chloramphenicol plus hepatitis or chromosome anomalies (two), thiamphenicol plus sulfonamide (one), antituberculous drugs (three), daraprim (three), insecticides (two), hepatitis (one), and sulfonamide (one). Data indicate that the degree of bone-marrow cellularity is not always related to functional capacity, and numerous agents may have etiologic roles in the development of aplastic anemia.

Adolescent↗

PubMed1989

Small cell lung cancer in a patient with neutropenia due to Felty's syndrome.

A patient with severe neutropenia due to Felty's syndrome had limited stage small cell lung cancer, resulting in a therapeutic dilemma. Because he had a cellular bone marrow and no history of recurrent infection, we decided to administer full doses of cytotoxic chemotherapy with curative intent. A durable remission was achieved without complication, despite persistent severe peripheral neutropenia. It may be possible to administer aggressive chemotherapeutic regimens to selected patients with Felty's syndrome when there is the potential for cure of malignant disease.

Agranulocytosis↗

PubMed1989

Immunosuppressive activity, lymphocyte subset analysis, and acute toxicity of FK-506 in the rat. A comparative and combination study with cyclosporine.

The immunosuppressive and toxic properties of the recently discovered macrolide antibiotic FK506 were examined in comparison and in conjunction with cyclosporine administration in the rat. Male Sprague-Dawley rats were immunized systemically with sheep erythrocytes and received, from the same time, either FK506 (1 mg/kg/day) intramuscularly or CsA (25 mg/kg/day) by gavage, or both drugs in combination. Seven days after immunization, the splenic plaque-forming cell response and circulating antibody titers were reduced greater than 90% in animals receiving either FK506 or CsA and in the drug combination group. These immunosuppressive effects of FK506 and CsA were accompanied by significant increases in the incidences of splenic OX-8+ cells and by corresponding reductions in the W3/25+:OX-8+ ratio. No further changes in T cell populations were observed in animals given both drugs. A progressive monocytosis was found in response to CsA, but not in FK506-treated rats. Increases in plasma urea were observed in FK-506 and drug-combination or CsA-treated rats on day 7, whereas creatinine levels were raised only in the FK-506 groups. Elevated bilirubin levels and alterations in liver enzyme activities were observed in CsA-treated rats by day 4, whereas FK-506 alone produced no similar effects. CsA-treated rats also exhibited elevated blood and urinary glucose levels from day 4. No biochemical evidence of additive drug toxicity was detected. The only histological abnormalities observed were thymic medullary atrophy in all drug-treated animals, together with very minor reductions in bone marrow cellularity in a proportion of those rats given FK-506. These findings show that, at the dosage selected, the powerful immunosuppressive activities of FK-506 were associated with little evidence of acute toxicity and with no indications of additive toxicity with CsA.

Animals↗

PubMedDate not supplied

Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia.

PURPOSE: The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the correlation between in vitro and in vivo antileukemic response and long-term outcome were prospectively evaluated. PATIENTS AND METHODS: Two hundred fifty-one patients were randomized to receive 1 of 3 asparaginase preparations (Escherichia coli, Erwinia chrysanthemi [Erwinia], or pegaspargase). In vitro assessment of efficacy was expressed as the percent total cell kill (TCK), based on the number of viable cells found after 5 days of culture in the presence of asparaginase. In vivo leukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after treatment with a single dose of asparaginase. Acute toxicity was determined by clinical and laboratory assessment. RESULTS: There was equivalent cell kill with all three types of asparaginase. The mean in vitro TCKs for E. coli, Erwinia, and pegaspargase were 31%, 39%, and 36%, respectively (P = 0.63). The mean LCKs in marrow of patients exposed to E. coli, Erwinia, and pegaspargase were 69%, 74%, and 65%, respectively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leukemic events among 21 in vitro nonresponders; 57%, P < 0.001). There was no difference in acute toxicity among the three asparaginase preparations. CONCLUSIONS: All three asparaginase preparations produced equivalent LCKs in in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor.

Antineoplastic Agents↗

PubMed2004

Osteocutaneous flap prefabrication in rats.

Composite tissue defects may involve skin, mucosa, muscle, and bone together or in combinations of two or three of these tissues. Defects involving bone and skin are frequently encountered. Osteocutaneous flaps may be used to reconstruct these composite tissue defects. Sometimes, it is not possible to obtain a vascular osteocutaneous flap. Another way of producing an osteocutaneous flap that has the desired feature is prefabrication. Prefabrication of osteocutaneous flaps can be performed in two ways: (1) a vascularized osseous flap may be grafted with skin and (2) an osteocutaneous flap can be prefabricated by implanting an osseous graft into an axial island flap. There are many articles describing osteocutaneous flap prefabrication, but there is no comparison of both methods in the literature. As an experimental model for osteocutaneous flap prefabrication, rat tail bone was chosen. For the experiments, five groups were formed. Each group contained 10 rats. In the first experimental group, a vascularized osseous segment was skin grafted and an osteocutaneous flap was prefabricated. In the second experimental group, an osseous graft was implanted into an axial skin flap. To compare viability of skin and bone components of the two prefabrication groups, vascularized tail bone was elevated with overlying skin in the third group, a bone flap was elevated in the fourth group, and a skin flap that had been prefabricated by using vascular implantation was elevated in the fifth group. The authors examined five rats in each group by microangiography at the end of 4 weeks. On microangiographic analysis, all groups showed patency of vascular pedicles. There was no difference among the groups from the point of view of vascular patency and bone appearance. Bone scintigraphy was performed on the five rats in each group. On bone scintigraphic scans, the bone component of flaps was visualized in all groups except for group 5. The mean radioactivity value on the flap side was 10,362 +/- 541.1 in group 1, 10,241 +/- 1173 in group 2, 10,696 +/- 647.1 in group 3, and 10,696 +/- 647.1 in group 4. When the radioactivity values on the flap side were compared, no statistically significant difference among groups was seen, except for group 5 (p < 0.05). To evaluate bone metabolic activity, the bone component of flap and remaining last tail bone was harvested and the radioactivity of each specimen was measured with a well-type gamma counter. The parameter of percentage radioactivity in counts per minute per unit per gram of tissue was calculated. The value of the bone component of the flap side and the value of normal bone were estimated and results were compared. The mean result was 0.86 +/- 0.08 in group 1, 0.88 +/- 0.07 in group 2, 0.87 +/- 0.07 in group 3, and 0.81 +/- 0.04 in group 4. The difference among all groups was not statistically significant. Histologic examination was performed on all rats in each group and demonstrated that the bony component was viable, showing a cellular bone marrow, osteoblasts along bony trabeculae, and vascular channels in bone-containing groups. There were no significant microangiographic, histologic, or scintigraphic differences between the two experimental methods.

Angiography↗

PubMed1992

Human neutrophil gelatinase: a marker for circulating blood neutrophils. Purification and quantitation by enzyme linked immunosorbent assay.

Human neutrophil gelatinase was purified to apparent homogeneity. The N-terminal amino-acid sequence of the purified enzyme could be aligned to an internal part of the cDNA-derived amino-acid sequence of 92-kDa type IV collagenase from SV 40-transfected human lung fibroblasts and from a TPA differentiated monocytic cell line, U937. Total amino-acid composition of U937 and neutrophil gelatinases was identical. Gelatinase was susceptible to treatment with o- and n-glycanase, indicating that posttranslational addition of oligosaccharide side chains occurs. An enzyme-linked immunosorbent assay for gelatinase was developed using specific polyclonal rabbit antibodies. The assay was specific, sensitive, accurate, and reproducible. Ninety percent range for plasma gelatinase from normal subjects was 17.3 to 102.9 ng/ml. In patients treated with cytostatic agents for non-Hodgkin's lymphoma, there was a parallel drop in plasma gelatinase and peripheral granulocyte count. This indicates that plasma gelatinase is a marker for circulating neutrophils. Plasma gelatinase does not seem to reflect bone marrow cellularity.

Amino Acid Sequence↗

PubMed1985

Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications.

The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities.

Anemia, Refractory, with Excess of Blasts↗

PubMed1989

Alpha-2 antiplasmin in acute nonlymphoblastic leukemia.

The levels of alpha-2-antiplasmin (alpha 2-AP), antithrombin III (At III) and plasminogen were studied in 21 patients with acute nonlymphoblastic leukemia (ANLL) before and after induction chemotherapy and during bone marrow cellularity recovery after the postchemotherapy aplastic phase. In the patients with M2, M3 or M4 leukemia who had clinical and laboratory evidence of DIC, the alpha 2-AP levels were very low in the initial phase of the disease but improved significantly during recovery of marrow cellularity. At III and plasminogen values were in the normal range at disease onset and showed no significant modification during the course of leukemia. Proteolytic cleavage of alpha 2-AP by granulocyte proteases, rather than hyperfibrinolysis, may be responsible for the low levels of the inhibitor in the proliferative phase of ANLL. This alpha 2-AP deficiency may well contribute to hemorrhagic diathesis in ANLL independently of the presence or absence of hyperfibrinolysis or DIC. Moreover, the lower alpha 2-AP levels observed during the proliferative phase of ANLL may relate to disease activity.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

Myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) represent a group of syndromes having in common a defective production of one or more myeloid cell lines. They occur in patients which are more than 50 years old without any sex preponderance. The term MDS is replacing the obsolete and archaic term of 'preleukemia' and/or 'oligoblastic leukemia'. The more striking hematologic features are a discrepancy between a cellular bone marrow and a peripheral blood cytopenia. MDS may be idiopathic or secondary. Some of them precede or predispose to the subsequent development of an acute myeloid leukemia. A correct analysis of peripheral blood and bone marrow smears permits to classify MDS and to establish some prognostic features. Some syndromes are easily recognizable such as acquired idiopathic sideroblastic anemia, refractory anemia with excess of blasts, pure refractory cytopenia and acute myelodysplasia with myelofibrosis. Nevertheless this classification does not cover all these syndromes. Some of them with borderline features will be discussed separately. An analysis of a large series of MDS recently published in the literature will be presented as well as nosologic problems which arise. A conceptual effort should be made to recognize and evaluate the MDS.

Humans↗

PubMed1977

Acquired aplastic anaemia in adults. I. A retrospective analysis of 40 cases: single factors influencing the prognosis.

In a retrospective analysis of 40 aplastic anaemia patients, an attempt was made to determine prognostic parameters permitting discrimination between short survivors (less than 6 months) and long-term survivors (greater than 6 months). Short survival proved to be significantly associated with a persistently low reticulocyte index and progressive neutropenia. Other factors such as bone marrow cellularity, HBF level, aetiology, or presenting signs were not indicative. Chromosomal aberrations were found in one third of the cases examined, but none had developed into a leukaemic stage after an observation period of 2--5 years. None of the patients with cytogenetic aberrations showed complete restoration of haematopoiesis, in contrast to several of the patients without chromosomal abnormalities. In this series, drug-associated aplastic anaemia was found more often in the short-survival group. These clinical findings indicate that the term 'aplastic anaemia' covers a heterogenous group of disorders.

Adolescent↗

PubMedDate not supplied

Stem cell factor is a potent synergistic factor in hematopoiesis.

Stem cell factor (SCF), a ligand for c-kit, has a broad range of activities including effects on cells at or near the level of the multipotential stem cell as well as on committed cells. Preclinical studies show that SCF can protect against lethal irradiation, elicit multilineage responses in peripheral blood and bone marrow cellularity, and increase circulating peripheral blood progenitor cells (PBPC) in a dose-dependent manner. Recombinant human SCF has major clinical potential through its synergy with other factors, especially recombinant human granulocyte colony-stimulating factor, to enhance mobilization of PBPC.

Animals↗