scholarly journals CX3CR1 expression and megakaryocytic series assessment on bone marrow biopsies in acquired aplastic anemia. Correlations with hematological parameters.

2015 ◽  
Vol 23 (4) ◽  
pp. 483-494
Author(s):  
Cosmina Ioana Gavrilut (Tomescu) ◽  
Cosmina Bondor ◽  
Bogdan Fetica ◽  
Annamaria Fulop ◽  
Laura Urian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Hematological Parameters ◽  
Immunosuppressive Treatment ◽  
Control Group ◽  
Case Group ◽  
Study Objective ◽  
Bone Marrow Biopsies ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity

Abstract The study objective was to examine the clinical and hematological significance of receptor CX3CR1 and megakaryocytes in patients with aplastic anemia. Method. 40 patients diagnosed with aplastic anemia and 10 case-control were included in the study. Were analyzed bone-marrow biopsies regarding cellularity, the presence of megakaryocytes and immunohistochemical expression of CX3CR1, CD4, CD8, CD45RO. We divided patients according to CX3CR1 intensity and the presence of megakaryocytes in 4 groups, which were analyzed comparatively. We realized the second division of patients in 4 groups, depending on the CX3CR1 intensity and cellularity of bone-marrow biopsy. Results. Statistically significant differences between the case group and the control group were observed in terms of the percentage of CD8, CD45RO positive cells and positivity for CX3CR1. In the lot of patients with aplastic anemia, we found statistically significant differences between groups with megakaryocytes present and absent, in terms of the number of lymphocytes, platelets, hemoglobin, ESR at 1 hour, ESR at 2 hours, bone marrow cellularity. Conclusions. CX3CR1 could be involved in the pathogenesis of aplastic anemia, influencing bone marrow cellularity. Megakaryocytes influence more hematological parameters, so we suggest using thrombopoietin receptor analogues as 1st line treatment along with the immunosuppressive treatment.

scholarly journals Bone marrow cellularity determination: comparison of the biopsy, aspirate, and buffy coat

Blood ◽  
1977 ◽  
Vol 49 (1) ◽  
pp. 29-31 ◽  
Author(s):  
RA Gruppo ◽  
BC Lampkin ◽  
S Granger
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Buffy Coat ◽  
Reliable Indicator ◽  
Volumetric Measurement ◽  
Bone Marrow Biopsies ◽  
Bone Marrow Cellularity ◽  
Volumetric Determination ◽  
Marrow Cellularity

Abstract Bone marrow biopsies (244) performed with a Jamshidi needle were evaluated in 53 children with leukemia or aplastic anemia. Adequate specimens were obtained in 85%. Results of cellularity estimated by biopsy were compared to the cellularity of the aspirate versus volumetric determination of the myeloid-erythroid layer (buffy coat). A wide discrepancy was noted between marrow cellularity confirmed by biopsy versus the aspirate or buffy coat. The greatest variance was seen in the hypercellular or normocellular marrows, as estimated by biopsy, in which 39% were misinterpreted as moderately or severely hypocellular by aspirate. Volumetric measurement of buffy coat was least acceptable for estimating cellularity. Thus the biopsy has proved to be an important and reliable indicator of bone marrow cellularity.

scholarly journals Bone marrow cellularity determination: comparison of the biopsy, aspirate, and buffy coat

Blood ◽  
1977 ◽  
Vol 49 (1) ◽  
pp. 29-31
Author(s):  
RA Gruppo ◽  
BC Lampkin ◽  
S Granger
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Buffy Coat ◽  
Reliable Indicator ◽  
Volumetric Measurement ◽  
Bone Marrow Biopsies ◽  
Bone Marrow Cellularity ◽  
Volumetric Determination ◽  
Marrow Cellularity

Bone marrow biopsies (244) performed with a Jamshidi needle were evaluated in 53 children with leukemia or aplastic anemia. Adequate specimens were obtained in 85%. Results of cellularity estimated by biopsy were compared to the cellularity of the aspirate versus volumetric determination of the myeloid-erythroid layer (buffy coat). A wide discrepancy was noted between marrow cellularity confirmed by biopsy versus the aspirate or buffy coat. The greatest variance was seen in the hypercellular or normocellular marrows, as estimated by biopsy, in which 39% were misinterpreted as moderately or severely hypocellular by aspirate. Volumetric measurement of buffy coat was least acceptable for estimating cellularity. Thus the biopsy has proved to be an important and reliable indicator of bone marrow cellularity.

scholarly journals Effects of a Novel Orally Bioavailable Small Molecule (Imidazolyl Ethanamide Pentandioic Acid) on Acute Radiation Syndrome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5089-5089
Author(s):  
Dirk Pleimes ◽  
Vivienne Bunker ◽  
Michael Meyer ◽  
Maciej Czajkowski
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Positive Control ◽  
Reduction Factor ◽  
Control Group ◽  
Therapeutic Treatment ◽  
Bone Marrow Cellularity ◽  
Kaplan Meier ◽  
Marrow Cellularity ◽  
The Impact

Abstract Introduction Acute radiation syndrome (ARS) develops within 24 hours of exposure to ionizing radiation. Leukocyte growth factors have been used to reduce mortality and mitigate the hematopoietic symptoms of ARS. Three subcutaneously applied radiomitigators G-CSF, Peg-G-CSF and GM-CSF have been approved by the FDA as medical countermeasures but few others are under development. Imidazolyl ethanamide pentandioic acid (IEPA, Myelo001) is a novel small molecule for the treatment of ARS. Preclinical and clinical studies have shown that IEPA applied orally or intraperitoneally was effective in reducing hematopoietic symptoms caused by radiation and chemotherapy. Objective To investigate the effects of IEPA as a radioprotector (prophylactic) and radiomitigator (therapeutic) for ARS and hematopoietic syndrome of ARS (H-ARS). Methods Multiple oral or intraperitoneal administrations of IEPA (25 or 50 mg/kg doses) and radiation levels of 5.8 Gy (estimated LD25/30) and 6.0 Gy (estimated LD50/30) on mortality, body weight and bone marrow cellularity were assessed in a mouse model. 205 C57BL/6 mice were subdivided into 1 unirradiated group, 6 groups exposed to 5.8 Gy, and 2 groups exposed to 6.0 Gy. Prophylactic treatment (25 or 50 mg/kg) was started 3 days before total-body irradiation, while therapeutic treatment (50 mg/kg) was begun 24 h post exposure. The 6 LD25/30 groups consisted of a vehicle control group (VL; 2), twice daily intraperitoneally administered IEPA (ML; 3), orally twice a day (ML; 4) or once a day (ML; 5), G-CSF positive control subcutaneously administered once a day (GL; 6) or in combination with IEPA (M/GL; 7). The 2 LD50/30 groups consisted of a vehicle control group (VH; 8) and a group administered IEPA orally once a day (MH; 9). The experiments assessed mortality using Kaplan-Meier estimator, body weight and bone marrow cellularity over the course of 30 days with prescheduled sacrifices of subgroups on days 7, 14 and 30. Results No significant benefit of prophylactic and therapeutic treatment on survival in the lower (5.8 Gy) irradiation group was detected. Groups ML; 3 and ML; 4 had a dose reduction factor (DFR) < 1 vs VL; 2 whereas ML; 5, GL; 6 and M/GL; 7 had a DRFs > 1. In the high radiation group (6.0 Gy), the Kaplan-Meier estimator revealed an increase in survival (85 %) after therapy compared to controls (56 %). The dose reduction factor in group MH; 9 compared to the controls (VH; 8) was 1.5. The highest protective effect on body weight was observed in the therapeutic regimen (MH; 9) used for 6.0 Gy exposure, which showed a positive effect on days 15, 21 and 30. Therapeutic IEPA treatment mitigated the impact of radiation on bone marrow cellularity. A pronounced effect on peripheral hematology was neither observed in the prophylactic, therapeutic IEPA nor the positive control G-CSF treated groups. Conclusions Different routes of administration and doses of IEPA in the prophylactic groups did not alter ARS symptoms. However, therapeutic treatment in the LD25/30 setting with IEPA and G-CSF, and the LD50/30 setting with IEPA at a dose of 50 mg/kg showed a reduction in mortality and weight loss compared to the controls. Additionally, IEPA treatment mitigated the impact of radiation on bone marrow cellularity. Analysis of peripheral blood did not reveal significant differences across the treatment groups probably due to no optimal time point analysis. Limitations included the small size of the prophylactically treated groups exposed to a low radiation dose. Disclosures Pleimes: Bayer: Consultancy, Equity Ownership; Myelo Therapeutics: Employment, Equity Ownership. Bunker:Myelo Therapeutics: Other: Contract Research via SNBL USA on behalf and in account of Myelo Therapeutics GmbH; SNBL USA: Employment. Meyer:Myelo Therapeutics GmbH: Consultancy. Czajkowski:Myelo Therapeutics GmbH: Employment.

scholarly journals Bone Marrow Lymphoid Infiltrates and Aplasia after CD19-Directed CAR T Cell Therapy in Pediatric B-Lymphoblastic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2839-2839
Author(s):  
Jared McFerran ◽  
Andrew Lytle ◽  
Kirubel Gebre ◽  
Vinodh Pillai
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Aplastic Anemia ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Cellularity ◽  
Car T Cell ◽  
Car T ◽  
Marrow Cellularity ◽  
The Impact

Abstract Introduction Chimeric Antigen Receptor (CAR) T cell therapy is used to treated relapsed/refractory B-Acute Lymphoblastic Leukemia (B-ALL) patients. Long term side effects include B cell aplasia and cytopenia that are treated with supportive therapy. Prolonged cytopenia is seen in 16% of CAR T-cell treated B-ALL patients. The etiology of cytopenia is not clear, and could be attributed to the impact of chemotherapy, CAR T cells and disease or patient-specific factors. The impact of CAR T cell infusion on bone marrow cellularity, lymphocyte compartment and its correlation with cytopenia has not been investigated. Methods We analyzed pre- and post-CAR bone marrow biopsies in 178 B-ALL patients who received a CD19-directed CAR T-cell product between 2012-2017 and followed for at least 12 months. Responses were categorized into sustained responders, non-responders, CD19-positive relapses and CD19-negative relapses as previously described. Bone Marrow biopsy (BMB) overall cellularity, complete blood counts (CBC) in a 12-month post infusion period were analyzed. BMB were considered mildly, moderately and severely hypocellular based on cellularity of 50, 25 and 5% respectively. Hypocellularity was further stratified by CBC per aplastic anemia (AA) classification guidelines: Non-Severe Aplastic Anemia (NSAA) and Very Severe Aplastic Anemia (VSAA). Immunohistochemistry (IHC) for CD3, CD4, CD8, CD163, granzyme and perforin were performed on pre- and post-CAR BMB. CD3 IHC was digitally scanned and analyzed quantitatively (Leica Aperio ImageScope) and qualitatively. Targeted RNA sequencing-based gene expression profiling (EdgeSeq Immuno-Oncology Panel, HTG Diagnostics) was performed on pre-and post-treatment biopsies, with differential expression assessed by DESeq2 within HTG Reveal software. RNAseq gene expression was deconvoluted to impute relative expression of immune cell subsets. Results 31% of patients were mildly hypocellular but none were severely hypocellular at baseline pre-CAR timepoints. The highest proportion of hypocellularity was at the 1-month time point. 81% of patients were mildly hypocellular (≤50%), 42% were markedly hypocellular (≤25%), and 13% were severely hypocellular (≤5%) at the 1-month time point. By month 12, the proportion of mildly hypocellular patients was 74%, markedly hypocellular patients was 26%, and severely hypocellular patients was 7% (Figure 1). The proportion of NSAA and VSAA was 57% and 10% in moderately hypocellular BMB. The proportion of NSAA and VSAA was 64% and 18% in severely hypocellular BMB. Severely hypocellular patients had a higher average day minus 1 disease burden (33% involvement) compared to their moderate (24%) and non-hypocellular patients (16%). VSAA patients had a lower baseline BMB cellularity (47%) compared to NSAA patients (71%) and those without AA (60%) Increased CD3+ T cells were noted in the post-CAR BMB compared to the pre-CAR BMB (Figure 1B). Lymphocyte were singly scattered or formed loose aggregates and tight lymphohistiocytic clusters. IHC and RNAseq analysis showed increased CD8+ granzyme+ cells in the post-CAR BMB compared to pre-CAR BMB. Sustained responders showed higher T cell infiltration compared to other categories of patients (Figure 1C and D). Lymphoid infiltrates did not correlate with hypocellularity or cytopenia. Conclusion We describe for the first time the changes in bone marrow cellularity and lymphocyte compartment after CD19-directed CAR T-cell infusion in B-ALL. A subset of patients were moderately or severely hypocellular and met criteria for aplastic anemia. However, most of them recovered bone marrow cellularity and CBC. Hypocellularity and AA were correlated with pre-CAR disease burden and baseline cellularity rather than post-CAR lymphocyte infiltration. We also show for the first time that sustained responders to CD19-CAR showed increased CD3+ CD8+ T cell infiltrates compared to CD19-positive relapses and non-responders. Figure 1. A. Bone marrow hypocellularity post-CAR T-cell infusion. Proportion of patients who were mildly hypocellular, markedly hypocellular, and severely hypocellular in the 12month follow up period. B. Increased CD3+ T cells and aggregates after CAR T cell infusion. C and D. Sustained responders show significantly greater CD3+ T cells after CAR T cell infusion compared to other categories. *P&lt;0.05. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 132
Author(s):  
Bruno Fattizzo ◽  
Fabio Serpenti ◽  
Wilma Barcellini ◽  
Chiara Caprioli
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Clonal Selection ◽  
Cytotoxic T Cells ◽  
Immunosuppressive Treatment ◽  
Young Patients ◽  
Suppressor Cells ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Increased Risk

Myelodysplasias with hypocellular bone marrow (hMDS) represent about 10–15% of MDS and are defined by reduced bone marrow cellularity (i.e., <25% or an inappropriately reduced cellularity for their age in young patients). Their diagnosis is still an object of debate and has not been clearly established in the recent WHO classification. Clinical and morphological overlaps with both normo/hypercellular MDS and aplastic anemia include cytopenias, the presence of marrow hypocellularity and dysplasia, and cytogenetic and molecular alterations. Activation of the immune system against the hematopoietic precursors, typical of aplastic anemia, is reckoned even in hMDS and may account for the response to immunosuppressive treatment. Finally, the hMDS outcome seems more favorable than that of normo/hypercellular MDS patients. In this review, we analyze the available literature on hMDS, focusing on clinical, immunological, and molecular features. We show that hMDS pathogenesis and clinical presentation are peculiar, albeit in-between aplastic anemia (AA) and normo/hypercellular MDS. Two different hMDS phenotypes may be encountered: one featured by inflammation and immune activation, with increased cytotoxic T cells, increased T and B regulatory cells, and better response to immunosuppression; and the other, resembling MDS, where T and B regulatory/suppressor cells prevail, leading to genetic clonal selection and an increased risk of leukemic evolution. The identification of the prevailing hMDS phenotype might assist treatment choice, inform prognosis, and suggest personalized monitoring.

Morphologic Examination of Sequential Bone Marrow Biopsies after Nonmyeloablative Stem Cell Transplantation Complements Molecular Studies of Donor Engraftment

2006 ◽  
Vol 130 (10) ◽  
pp. 1479-1488
Author(s):  
Anand S. Lagoo ◽  
Jerald Z. Gong ◽  
Timothy T. Stenzel ◽  
Barbara K. Goodman ◽  
Patrick J. Buckley ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Early Recurrence ◽  
Bone Marrow Biopsies ◽  
Additional Information ◽  
Nonmyeloablative Stem Cell Transplantation ◽  
Marrow Cellularity ◽  
Atypical Localization

Abstract Context.—Nonmyeloablative stem cell transplantation (NMSCT) is a mode of immunotherapy increasingly employed in treating hematologic, lymphoid, and solid tumors. Patients are monitored principally by molecular analysis of donor engraftment. Objective.—To determine the role of morphologic examination of bone marrow after NMSCT. Design.—Seventy-three patients undergoing NMSCT under the Campath 1H (humanized anti-CD52 antibody) protocol were studied. Pretransplant and sequential posttransplant bone marrow specimens were evaluated and the findings were correlated with corresponding engraftment data. Results.—Pretransplant bone marrow specimens from 43% of the patients were involved by disease, and these marrow specimens were significantly more cellular than those that were free of disease. Morphologically detectable disease was still present in day 14 posttransplant marrow specimens in more than one half of these patients, but there was no difference in engraftment in those with or without marrow disease. Early posttransplant marrow in nearly one half of the patients showed myeloid hyperplasia and atypical localization of immature myeloid precursors. Marrow cellularity for the first 2 months after NMSCT was significantly lower in those patients receiving stem cells mismatched at 1 to 3 loci as compared with those who received fully matched grafts (mean cellularity, 38.1% vs 54.1% at day 14). Marrow failure without recurrent disease at 3 to 6 months after transplant was detected by engraftment study in only approximately 15% of cases. Similarly, early recurrence of disease was detected first by morphologic examination in 4 of 13 cases before a decline in donor engraftment occurred. Conclusion.—Morphologic examination of bone marrow provides additional information that is complementary to donor engraftment analysis for optimal management after NMSCT.

scholarly journals Direct effects of thyroid hormones on bone marrow erythroid cells of rats

Blood ◽  
1975 ◽  
Vol 45 (5) ◽  
pp. 671-679 ◽  
Author(s):  
LA Malgor ◽  
CC Blanc ◽  
E Klainer ◽  
SE Irizar ◽  
PR Torales ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Thyroid Hormones ◽  
Rabbit Antiserum ◽  
Cell Types ◽  
Progressive Increase ◽  
Erythroid Cell ◽  
Control Group ◽  
Erythroid Cells ◽  
Intravenous Infusions ◽  
Marrow Cellularity

Abstract A stimulatory effect on bone marrow cellularity was observed in normal and nephrectomized rats continuously infused with T3 and T4. Results of bone marrow studies are expressed in absolute numbers of total nucleated erythroid cells per milligram of femoral marrow at the beginning and after 8 hr of continuous intravenous infusions. Administration of T3 and T4 to nephrectomized rats produced a marked and significant increase in total erythroid cells counted. After differential analyses of the nucleated erythroid elements, a significant increase in all erythroid cell types was also observed. Similar results were seen in a control group of rats in which both ureters have been previously ligated and in groups of nephrectomized rats receiving rabbit antiserum against erythropoietin before starting the intravenous infusions of T3 and T4. These results indicate that stimulation of marrow erythropoiesis produced by thyroid hormones in our system is not dependent on renal or extra-renal production of erythropoietin. The progressive introduction of T3 and T4 into the circulation of rats with bilateral nephrectomy or ureter-ligated normal rats, may overload the mechanism of transport of these hormones in plasma. As a consequence, a progressive increase in free active forms of T3 and T4 in plasma may occur. Our interpretation of the present findings is that thyroid hormones stimulate directly bone marrow erythropoiesis. This stimulation is clearly evident when high levels of free active forms of thyroid hormones are present in plasma.

scholarly journals Erratum

2018 ◽  
Vol 46 (6) ◽  
pp. 722-722
Keyword(s):  
Bone Marrow ◽  
Image Analysis ◽  
Automated Image Analysis ◽  
Proof Of Concept ◽  
Analysis Method ◽  
Image Analysis Method ◽  
Bone Marrow Cellularity ◽  
Marrow Cellularity ◽  
Rat Bone

Kozlowski, C., Brumm, J., and Cain, G. (2018). An Automated Image Analysis Method to Quantify Veterinary Bone Marrow Cellularity on H&E Sections. Tox Path46, 324–335. (Original DOI: 10.1177/0192623318766457). Kozlowski, C., Fullerton, A., Cain, G., Katavolos, P., Bravo, J., and Tarrant, J. M. (2018). Proof of Concept for an Automated Image Analysis Method to Quantify Rat Bone Marrow Hematopoietic Lineages on H&E Sections. Tox Path46, 336–347. (Oringinal DOI: 10.1177/0192623318766458). In the print issue and initial version of the online issue, the figures for Kozlowski, Brumm, and Cain were mistakenly placed into Kozlowski, Fullerton, et al., and vice versa. The online versions of both articles have been updated to display the appropriate figures.

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