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

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.

Download Full-text

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

Blood ◽

10.1182/blood.v49.1.29.29 ◽

1977 ◽

Vol 49 (1) ◽

pp. 29-31 ◽

Cited By ~ 18

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.

Download Full-text

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

Revista Romana de Medicina de Laborator ◽

10.1515/rrlm-2015-0040 ◽

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.

Download Full-text

Histomorphometrical Determination of Bone Marrow Cellularity in Iliac Crest Biopsies

Scandinavian Journal of Haematology ◽

10.1111/j.1600-0609.1980.tb02353.x ◽

2009 ◽

Vol 24 (2) ◽

pp. 110-114 ◽

Cited By ~ 24

Author(s):

G. Kerndrup ◽

G. Pallesen ◽

F. Melsen ◽

L. Mosekilde

Keyword(s):

Bone Marrow ◽

Iliac Crest ◽

Bone Marrow Cellularity ◽

Marrow Cellularity

Download Full-text

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

Blood ◽

10.1182/blood-2021-148466 ◽

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<0.05. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

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

Archives of Pathology & Laboratory Medicine ◽

10.5858/2006-130-1479-meosbm ◽

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.

Download Full-text

Significance of p53 overexpression in bone marrow biopsies from patients with bone marrow failure: aplastic anemia, hypocellular refractory anemia, and hypercellular refractory anemia

Annals of Hematology ◽

10.1007/s002770050455 ◽

1998 ◽

Vol 77 (6) ◽

pp. 261-264 ◽

Cited By ~ 19

Author(s):

M. T. Elghetany ◽

S. Vyas ◽

G. Yuoh

Keyword(s):

Bone Marrow ◽

Aplastic Anemia ◽

Bone Marrow Failure ◽

Refractory Anemia ◽

P53 Overexpression ◽

Bone Marrow Biopsies

Download Full-text

Erratum

Toxicologic Pathology ◽

10.1177/0192623318794946 ◽

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.

Download Full-text

STI571 (Imatinib Mesylate) Reduces Bone Marrow Cellularity and Normalizes Morphologic Features Irrespective of Cytogenetic Response

American Journal of Clinical Pathology ◽

10.1309/nr81-vcu0-ckw1-4ht9 ◽

2002 ◽

Vol 117 (3) ◽

pp. 360-367 ◽

Cited By ~ 48

Author(s):

Robert P. Hasserjian ◽

Federica Boecklin ◽

Sally Parker ◽

Andy Chase ◽

Sunanda Dhar ◽

...

Keyword(s):

Bone Marrow ◽

Imatinib Mesylate ◽

Cytogenetic Response ◽

Bone Marrow Cellularity ◽

Marrow Cellularity

Download Full-text

Qnantitation of Femoral Bone Marrow Cellularity of Rats with Acute Chloroleukemia

Blood ◽

10.1182/blood.v26.3.309.309 ◽

1965 ◽

Vol 26 (3) ◽

pp. 309-316 ◽

Cited By ~ 3

Author(s):

EVELYN E. VARSA ◽

EUGENE S. HANDLER ◽

ALBERT S. GORDON

Keyword(s):

Bone Marrow ◽

Leukemic Cells ◽

Femoral Bone ◽

Progressive Decrease ◽

Cell Numbers ◽

Bone Marrow Cellularity ◽

Acute Form ◽

Long Evans ◽

Marrow Cellularity ◽

Femoral Bone Marrow

Abstract Procedures of bone marrow quantitation have been applied to the study of the pathogenesis of a leukemia in rats. Mature Long-Evans rats developed an acute form of the Shay Chloroleukemia after intravenous administration of leukemic cells. Assessment of total nucleated cell numbers (normal and leukemic) per mg. of femoral bone marrow was made during the course of the pathogenesis (20 days). Reductions in the numbers of normal marrow elements were observed prior to significant increases in chloroleukemic cells. A progressive decrease in total marrow cellularity was noted in all subsequent stages. In animals surviving 17-20 days, the total number of hemic cells in the femoral marrow was found to be approximately 40 per cent of that seen in normal animals. The leukemia developed more rapidly in young than in adult animals. Using total and differential bone marrow cellularity as a criterion for the stage of pathogenesis, standardized leukemic rats can be prepared for experimentation.

Download Full-text