Epimedium Polysaccharide Ameliorates Benzene-Induced Aplastic Anemia in Mice

Benzene (BZ) is an important occupational and environmental pollutant. Exposure to BZ may cause aplastic anemia which is characterized as bone marrow hematopoietic failure. In order to reduce the harmful effects of this pollutant, it is necessary to identify additional preventative measures. In this study, we investigated the protective effects of epimedium polysaccharide (EPS), a natural compound with antioxidant and immune-enhancing potency, on aplastic anemia induced by benzene exposure in mice. Male CD-1 mice were randomly divided into five groups including control, BZ (880 mg/kg), LE (EPS low-dose, 20 mg/kg + BZ), ME (EPS middle-dose, 100 mg/kg + BZ), and HE (EPS high-dose, 200 mg/kg + BZ) groups. Animals were exposed to BZ by subcutaneous injection in the presence or absence of EPS via oral administration. All mice were treated 3 times a week for 8 consecutive weeks to develop a mouse model of benzene-induced aplastic anemia (BIAA). Results showed that BZ induced a significant decrease in both white and red blood cells, platelet counts, and hemoglobin level compared with that in the control group (p<0.01). Treatment of EPS led to a protective effect against these changes particularly in the highest-dose group (HE, p<0.01). EPS also recovered the decreased number of nucleated cells in peripheral blood cell smears and femur biopsies by BZ exposure. The increased level of reactive oxygen species (ROS) in bone marrow mononuclear cells (BMMNCs) in mice from the BZ group was significantly lower (p<0.01) in the mice from the highest concentration of EPS (HE) group when compared with that from the control group. In addition, BZ exposure led to a significant increase in the apoptosis rate in BMMNCs which was prevented by EPS in a dose-dependent manner (p<0.01). The antiapoptosis effect of EPS was through reversing apoptotic proteins such as BAX, Caspase-9 and Caspase-3, and Bcl-2. Finally, EPS treatment partially restored the levels of T cells and the different subtypes except CD80+ and CD86+ compared with the BZ group (HE, p<0.05). These results suggest that EPS has protective effects against BIAA via antioxidative stress, immune modulation, and antiapoptosis mechanisms.

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Dose-dependent facilitation of peripheral nerve regeneration by bone marrow–derived mononuclear cells: a randomized controlled study

Journal of Neurosurgery ◽

10.3171/2012.8.jns111446 ◽

2012 ◽

Vol 117 (6) ◽

pp. 1170-1181 ◽

Cited By ~ 15

Author(s):

Amol Raheja ◽

Vaishali Suri ◽

Ashish Suri ◽

Chitra Sarkar ◽

Arti Srivastava ◽

...

Keyword(s):

Bone Marrow ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Mononuclear Cells ◽

Peripheral Nerve Regeneration ◽

Control Group ◽

High Dose ◽

Myelin Thickness ◽

Dose Dependent

Object Bone marrow–derived stem cells enhance the rate of regeneration of neuronal cells leading to clinical improvement in nerve injury, spinal cord injury, and brain infarction. Recent experiments in the local application of bone marrow–derived mononuclear cells (BM-MNCs) in models of sciatic nerve transection in rats have suggested their beneficial role in nerve regeneration, although the effects of variable doses of stem cells on peripheral nerve regeneration have never been specifically evaluated in the literature. In this paper, the authors evaluated the dose-dependent role of BM-MNCs in peripheral nerve regeneration in a model of sciatic nerve transection in rats. Methods The right sciatic nerve of 60 adult female Wistar rats (randomized into 2 test groups and 1 control group, 20 rats in each group) underwent transection under an operating microscope. The cut ends of the nerve were approximated using 2 epineural microsutures. The gap was filled with low-dose (5 million BM-MNCs/100 μl phosphate-buffered saline [PBS]) rat BM-MNCs in one group, high-dose (10 million BM-MNCs/100 μl PBS) rat BM-MNCs in another group, and only PBS in the control group, and the approximated nerve ends were sealed using fibrin glue. Histological assessment was performed after 30 days by using semiquantitative and morphometric analyses and was done to assess axonal regeneration, percentage of myelinated fibers, axonal diameter, fiber diameter, and myelin thickness at distal-most sites (10 mm from site of repair), intermediate distal sites (5 mm distal to the repair site), and site of repair. Results The recovery of nerve cell architecture after nerve anastomosis was far better in the high-dose BM-MNC group than in the low-dose BM-MNC and control groups, and it was most evident (p < 0.02 in the majority of the parameters [3 of 4]) at the distal-most site. Overall, the improvement in myelin thickness was most significant with incremental dosage of BM-MNCs, and was evident at the repair, intermediate distal, and distal-most sites (p = 0.001). Conclusions This study emphasizes the role of BM-MNCs, which can be isolated easily from bone marrow aspirates, in peripheral nerve injury and highlights their dose-dependent facilitation of nerve regeneration.

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Telomerase Enzyme Activity In Egyptian Children With Bone Marrow Failure

Blood ◽

10.1182/blood.v122.21.4662.4662 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4662-4662

Author(s):

Amal M. El-Beshlawy ◽

Mona Mohamed Hamdy ◽

Amina Abd El Salam ◽

Mervet El Ansary ◽

Nelly Abulata ◽

...

Keyword(s):

Bone Marrow ◽

Aplastic Anemia ◽

Immunosuppressive Therapy ◽

Mononuclear Cells ◽

Conflicts Of Interest ◽

Bone Marrow Failure ◽

Telomerase Activity ◽

Telomere Maintenance ◽

Control Group ◽

Egyptian Children

Background Telomeres are structural elements that seal the ends of chromosomes protecting them from recombination and end to end fusion. Maintenance of the integrity of telomeres requires the telomerase ribonucleoprotein complex. Abnormal telomere maintenance is a feature of a variety of human diseases including constitutional aplastic anemia. Predisposition to the development of marrow failure has been conferred by genetic alternations results in low telomerase activity. Short telomeres in leukocytes and reduced hematopoietic function. Aim To evaluate the telomerase functional activity in Egyptian children with inherited and acquired bone marrow failure and its relation to the phenotypic features of the acquired disease and its response to immunosuppressive therapy. Patients and Methods This was a case-control study conducted on unrelated children (n=40) with bone marrow failure syndromes and forty healthy subjects age and sex-matched as controls. The diagnosis of bone marrow failure was based on the bone marrow biopsy and blood-count results. Patients with acquired aplastic anemia (AAA) were considered severe if at least 2 of the following were noted: neutrophil count < 0.5×109/L; platelet count < 20×109/L with hypocellular marrow. Response to immunosuppressive therapy (IST) was evaluated after 6 months of initiation of therapy. Assessment of Telomerase Activity Telomerase activity was measured in mononuclear cells utilizing the Telomeric Repeat Amplification Protocol (TRAP )using the TeloTAGGG Telomerase PCR ELISA. Results Forty patients were included in the study (30 AAA , 6 Fanconi Anemia (FA), 2 Pure Red Cell Aplasia (PRCA), one case with Dyskeratosis Congenita (DCK) and one case with constitutional aplastic anemia. The Mean age was 11.1±4.9 years (range 3.5 to 18 years, median 11 years ) and the duration of follow-up mean; 5.14 (±3.84) years (range 1-13 years). Patients with AAA (n=30) received treatment with cyclosporine A( n =27) and ATG( n=3). Telomerase level The median telomerase level was significantly lower in inherited BMF syndromes when compared to controls [5.05 (4.60 – 8.70 IQR) Vs 11.15 (5.90-16.60 IQR), p=0.04]. In AAA the median telomerase level was insignificantly lower than controls [5.4 (2.3 – 21.0 IQR) Vs 11.15 (5.90-16.60 IQR), p=0.228]. A good inverse correlation was detected between the telomerase level and age of the patients (r=-0.39, p=0.026). No correlation was found between the telomerase level and disease duration in hereditary or AAA (r= -0.303, p=0.111 and r=0.305, p=0.156 respectively). Telomerase activity and clinical variables We classified our cases into two groups according to the median value of the control group (11.5): Low telomerase level group: (n=27): included 18 AAA (66.7%) and 9 hereditary aplastic Anemia (33.3%). Cases with AAA 14/18 (77.8%) with low telomerase activity were severe cases with bone marrow cellularity less than 10 % Vs 6/12 (50%) with normal telomerase. Fifty per cent of cases (9/18) with low telomerase responded partially or completely to IST Vs. 83.4% of the normal telomerase (10/12) group. Patients of AAA who received cyclosporine therapy (n=27), 19 cases (70.4%) were responders versus zero % of patients who received ATG (n=3). The median telomerase of responders was 16.5 + 4.7 Vs 11.6 + 3.8 of none responders. Conclusion • Telomerase activity was affected in hereditary and acquired bone marrow failure. • Evaluation of telomerase activity is essential for therapeutic and prognostic aspects of these diseases. Cyclosporin A can be used as a monotherapy in the treatment of acquired aplastic anemia even in the presence of decreased telomerase activity Disclosures: No relevant conflicts of interest to declare.

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Evaluation of protective effects of propolis against aluminium silicate toxicity in rats

Genetika ◽

10.2298/gensr1901299a ◽

2019 ◽

Vol 51 (1) ◽

pp. 299-312

Author(s):

El-Aziz Abd ◽

Ali Abu-Almaaty ◽

Nahed Omar ◽

Ahmed Abdeen ◽

Mahmmoud Zakaria

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Chromosomal Aberrations ◽

Harmful Effect ◽

Antioxidant Property ◽

Aluminum Silicate ◽

Control Group ◽

Albino Rats ◽

High Dose ◽

Protective Effects

Objective of the study was evaluation of the harmful effect induced by aluminum silicate in bone marrow chromosomes and liver tissues. Also, how could prevents this toxicity. 60 Adult male albino rats weighing 100-120 g were used for our experiments. The animals were divided into six equal groups: first normal healthy control group, second group was given 200 ml propolis/Kg day after day by stomach gavage, third group received low dose of aluminum silicate (5 mg/kg; intra peritoneal) twice a week, forth group injected with high dose of aluminum silicate (20 mg/kg; intra peritoneal) twice a week, fifth group received propolis and aluminum silicate with similar doses as that of second & third groups and sixth group received propolis and aluminum silicate with similar doses as that of second & forth groups. At the end of 8 weeks for each rat, bone marrow was aspirated and liver was removed for lab examinations. The results showed that rats exposed to aluminum silicate had severe chromosomal aberrations and changes in CYP gene expression. It caused significantly increased in the frequency of chromosomal aberrations such as polyploidy, hypoploidy, deletions, fragments, chromatid breaks, chromosome breaks, double minutes, ring, gap and translocation were also observed. Gene expression of CYPs was increased with exposure to aluminum silicate and was down regulated in treatment with propolis while Bcl-2 and BAX were decreased in exposure to aluminum silicate and up regulated by the treatment. Propolis has a curative effect against aluminum silicate toxicity owing to its antioxidant property.

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Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

International Journal of Molecular Sciences ◽

10.3390/ijms22010176 ◽

2020 ◽

Vol 22 (1) ◽

pp. 176

Author(s):

Toshiaki Iba ◽

Jerrold H. Levy ◽

Koichiro Aihara ◽

Katsuhiko Kadota ◽

Hiroshi Tanaka ◽

...

Keyword(s):

Dose Group ◽

Low Dose ◽

Leukocyte Adhesion ◽

Endothelial Glycocalyx ◽

High Dose Group ◽

Control Group ◽

High Dose ◽

Protective Effects ◽

Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

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Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

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Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

The American Journal of Chinese Medicine ◽

10.1142/s0192415x12500929 ◽

2012 ◽

Vol 40 (06) ◽

pp. 1241-1255 ◽

Cited By ~ 9

Author(s):

Sae-Kang Ku ◽

Jae-Soo Kim ◽

Young-Bae Seo ◽

Yong-Ung Kim ◽

Seung-Lark Hwang ◽

...

Keyword(s):

Reflux Esophagitis ◽

Group Treatment ◽

Control Group ◽

Esophageal Mucosa ◽

Dependent Manner ◽

Protective Effects ◽

Model Group ◽

Curculigo Orchioides ◽

Intact Group ◽

Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

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Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor.

Molecular and Cellular Biology ◽

10.1128/mcb.15.6.3147 ◽

1995 ◽

Vol 15 (6) ◽

pp. 3147-3153 ◽

Cited By ~ 88

Author(s):

G A Blobel ◽

C A Sieff ◽

S H Orkin

Keyword(s):

Bone Marrow ◽

Estrogen Receptor ◽

Transcription Factor ◽

Progenitor Cells ◽

Erythroid Cell ◽

High Dose ◽

Dependent Manner ◽

Erythroid Progenitor ◽

Erythroid Progenitor Cells

High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5. We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures. To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen. ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1. GATA-1 and ER bind to each other in vitro in the absence of DNA. In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner. Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1. We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. Interference with GATA-binding proteins may be one mechanism by which steroid hormones modulate cellular differentiation.

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Abstract 239: Stem Cell Therapy Improves Critical Limb Ischemia

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a239 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Alaa Marzouk

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Embryonic Stem ◽

Limb Ischemia ◽

Control Group ◽

Chronic Limb Ischemia

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.

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Effects of glutamine on the immune system: influence of muscular exercise and HIV infection

Journal of Applied Physiology ◽

10.1152/jappl.1995.79.1.146 ◽

1995 ◽

Vol 79 (1) ◽

pp. 146-150 ◽

Cited By ~ 38

Author(s):

T. Rohde ◽

H. Ullum ◽

J. P. Rasmussen ◽

J. H. Kristensen ◽

E. Newsholme ◽

...

Keyword(s):

Proliferative Response ◽

Mononuclear Cells ◽

Natural Killer Cell Activity ◽

Killer Cell ◽

Cell Activity ◽

Control Group ◽

Dependent Manner ◽

Killer Cell Activity ◽

Hiv Seropositive

Glutamine increased the proliferative response and the lymphokine-activated killer cell activity of blood mononuclear cells isolated from normal healthy subjects (n = 6) in a dose-dependent manner, with optimum at 0.3–1.0 mM. The relative fraction of CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells was not changed by glutamine at a concentration of 0.6 mM, except in the phytohemagglutinin-stimulated proliferation experiment where the fraction of CD4+, and therefore CD3+ cells, increased. The natural killer cell activity was not influenced by glutamine. Human immunodeficiency virus (HIV)-seropositive subjects (n = 8) who performed concentric bicycle exercise for 1 h at 75% of maximal O2 consumption had an overall lower phytohemagglutinin-stimulated proliferative response, compared with the HIV-seronegative control group (n = 7). The proliferation during exercise was lower in both the HIV-seropositive and the HIV-seronegative group. Addition of glutamine in vitro did not normalize the lower proliferation in the HIV-seropositive group or the attenuated proliferation seen during exercise in both groups.

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Low-risk intensive therapy for multiple myeloma with combined autologous bone marrow and blood stem cell support

Blood ◽

10.1182/blood.v80.7.1666.bloodjournal8071666 ◽

1992 ◽

Vol 80 (7) ◽

pp. 1666-1672

Author(s):

S Jagannath ◽

DH Vesole ◽

L Glenn ◽

J Crowley ◽

B Barlogie

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mononuclear Cells ◽

Intensive Therapy ◽

Autologous Bone Marrow ◽

Blood Stem Cell ◽

High Dose ◽

Platelet Recovery ◽

Gm Csf ◽

Autologous Bone

To improve the safety of autotransplantation for myeloma, peripheral blood stem cell (PBSC) collection was attempted in 75 previously treated patients after the administration of high-dose cyclophosphamide (HD-CTX; 6 g/m2) with or without granulocyte-macrophage colony- stimulating factor (GM-CSF). Sixty patients subsequently received melphalan 200 mg/m2 (57 patients) or melphalan 140 mg/m2 and total body irradiation (850 cGy) (3 patients) supported by both autologous bone marrow and PBSC; 38 patients received GM-CSF posttransplantation. Among 72 patients undergoing PBSC apheresis, “good” mobilization (greater than 50 colony-forming units granulocyte-macrophage [CFU-GM] per 10(5) mononuclear cells) was achieved when prior chemotherapy did not exceed 1 year and when GM-CSF was used post-HD-CTX; similarly, rapid platelet recovery to 50,000/microL within 2 weeks was associated with “good” PBSC mobilization. These same variables also predicted for rapid engraftment after autotransplantation, so that hematologic recovery (granulocytes greater than 500/microL and platelets greater than 50,000/microL) proceeded within 2 weeks among the 37 patients with “good” PBSC collection. As a result of rapid neutrophil recovery (greater than 500/microL) within a median of 2 weeks, infectious complications both post-HD-CTX and posttransplant were readily manageable, resulting in only one treatment-related death post-HD-CTX. The cumulative response rate (greater than or equal to 75% cytoreduction) for all 75 patients was 68%, with 12-month event-free and overall survival projections of about 85%. Using both bone marrow and PBSC together with GM-CSF, autotransplants are safe and appear effective in myeloma, especially when prior therapy had been limited to less than 1 year. More than 80% of transplanted patients achieved complete hematologic recovery within a median of 1 month posttransplant (granulocytes greater than 1,500/microL; platelets greater than 100,000/microL; hemoglobin greater than 10 g%), thus providing sufficient hematopoietic reserve for further chemotherapy in the event of posttransplant relapse.

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