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Research Article | Volume 14 Issue: 2 (March-April, 2024) | Pages 1217 - 1222
A Single-Center Study Demonstrates the Diagnostic Value of Bone Marrow Aspiration Examination
1
(Ex. Sr. Consultant Hematologist, Head & Director, Apollo Group of Hospitals, Ahmedabad, India) (Ex Professor, Govt. Medical College, Govt of Gujarat, India)
Under a Creative Commons license
Open Access
PMID : 16359053
Received
April 9, 2024
Revised
April 30, 2024
Accepted
May 23, 2024
Published
June 27, 2024
Abstract

Background: Until the results of the bone marrow biopsy (BMB) are known, an early diagnosis can be determined using the morphological evaluation of a bone marrow aspiration (BMA). This makes it possible to begin treatment right away, particularly in cases of haematological malignancies where prompt treatment is necessary. The purpose of this investigation was to evaluate the value and sensitivity of bone marrow aspiration in the detection of haematological malignancies.

Methods: Between January 2023 and 2024, patients, who had bone marrow aspiration and bone marrow biopsy had their data retrospectively were examined. In all, 500 patients had BMA and BMB procedures done concurrently for the purpose of this study.

Results: In 270 (54%) of the patients, abnormalities in the total blood count were the reason for a bone marrow evaluation. Based on 475 (95%), the diagnosis was made based on the BMA examination. Of the 475 individuals, 456 (96%) had a diagnosis of BMA that was consistent with a BMB diagnosis. BMA was insufficient for the diagnosis of lymphoma and solid organ metastases, whereas BMB and BMA agreed 100% in cases of acute and chronic leukemia.

Conclusion:  our research demonstrated that the assessment of BMA exhibited a high degree of sensitivity in the identification of haematological malignancies, including multiple myeloma, acute leukemia, and chronic leukemia.

Keywords
INTRODUCTION

In addition to being the source of numerous haematological illnesses, the bone marrow is a huge organ mass that is also involved in some infections, solid organ metastases, and metabolic disorders.1. Clinical symptoms unique to the disease, lymphadenopathy, splenomegaly, and abnormal test findings are all signs of effects on the bone marrow.1.

 

Once the medical history, physical examination, blood count, and peripheral smear morphology have been evaluated, the investigation of bone marrow is a crucial diagnostic tool in many blood illnesses. When such circumstances arise, it is crucial to investigate utilizing the generally concurrent methods of bone marrow aspiration and bone marrow biopsy.2

 

The primary purpose of BMA is to examine bone marrow cells cytomorphologically. Additionally, it permits the collection of blood samples for various analyses, including immunophenotyping, molecular genetics, cytogenetics, flow cytometry, and microbiological testing.3.

 It just takes a few hours for the morphological evaluation of BMA to provide a reliable and timely diagnosis of certain haematological malignancies; BMB results are often reported in a span of 10–14 days. As a result, therapy can begin right away for illnesses that pose a serious risk to life and need rapid attention, such as multiple myeloma and acute and chronic leukemias. The purpose of this study was to assess the compatibility of BMA and BMB and investigate the sensitivity of BMA for the diagnosis of haematological malignancies.

METHODS:

The study included 500 patients who had BMA and BMB simultaneously between January 2023 and December 2023. Those who were at least eighteen years old were included. A retrospective analysis was conducted on the patient files and data, stored in the hospital's information system. For each patient, the bone marrow examination was conducted from the anterior superior and posterior superior iliac crests. At the initial aspirate, 0.5 ml of bone marrow blood was extracted for BMA testing. Furthermore, a bone marrow biopsy sample of ≥1 centimetre was obtained for BMB analysis. Examinations were conducted on the bone marrow aspiration, laboratory values of the patients, peripheral smear results, and biopsy indications.


Blood samples for flow cytometry and genetic mutation analysis were obtained from the site of BMA/BMB in patients with suspected haematological malignancies because of these first investigations. In formol, BMB material was delivered to the pathology laboratory from either a different location or the location where BMA had been done.

After spreading the bone marrow-derived blood onto slides and colouring it with May-Grunwald-Giemsa, the sample was seen under a microscope at magnifications of 10 and 100. In the BMA examination, cellularity and megakaryocytes were assessed at ten magnifications. By counting 400 cells and using the formulation, the morphology, maturation, and differentiation features of the cells at 100 magnifications were ascertained. Using flow cytometry as a tool, acute leukemias were subtyped. In situations where the BMA examination was insufficient, the BMB result served as the basis for the final diagnosis. The degree of agreement between the BMA and BMB diagnoses was evaluated.

 

Statistical Analysis: The mean ± standard deviation was used to express numerical data, and numbers and percentages (n, %) were used to express categorical variables. When evaluating BMA and BMB, a diagnosis of the same kind was accepted as the outcome; a diagnostic of a different kind between the two procedures was seen as inconsistent. A percentage was used to represent the degree of agreement between the two techniques. The statistical analysis was carried out utilizing SPSS version 25.0.

RESULTS:

The median age of the 500 patients that were part of the study was 51.52±16.88 (18-87) years,

with 274 (54.8%) males and 226 (45.2%) females. In 382 (76.4%) of the patients, a bone marrow examination was done for a diagnosis; in 118 (23.6%) of the patients, it was done to assess remission. Pancytopenia was the most frequent reason for a bone marrow examination (n = 83, 16.6%). Table I displays the remaining indications. Of the patients in the sample, 475 (or 95%) had BMA analysed, however in the remaining 25 patients (5%) it was not possible to evaluate BMA because of inadequate particle sampling or subpar staining. Haematological malignancies were the most frequently diagnosed conditions, per the BMA review.

 

Table 1: The outcomes of bone marrow examination for the patients.

Significance

 

n (%)

Laboratory findings

 

Pancytopenia

83 (16.6%)

Anemia + leukocytosis +

thrombocytopenia

57 (11.4%)

Anemia

40 (8%)

Anemia + thrombocytopenia

23 (4.6%)

Albumin/globulin inversion + Ig increase

23 (4.6%)

Anemia + leukocytosis

17 (3.4%)

Leukocytosis

16 (3.2%)

Thrombocytopenia

11(2.2%)

Anemia + leukopenia

10 (2%)

Polycythemia

7 (1.4%)

Thrombocytosis + leukocytosis

4 (0.8%)

Thrombocytopenia + leukopenia

6 (1.2%)

Clinical findings

 

Lymphoma staging

41 (8.2%)

Acute leukemia remission evaluation

69 (13.8%)

Multiple myeloma remission evaluation

37 (7.4%)

Chronic leukemia remission evaluation

12 (2.4%)

Splenomegaly

17 (3.4%)

Fever

4 (0.8%)

 

 

 

Table 2: Bone Marrow Aspiration Results.

Diagnosis

n (%)

Acute leukemia

99 (19.8%)

Remission evaluation:

 

In remission

79 (15.8%)

Not in remission

30 (6%)

Normal bone marrow

74 (14.8%)

MDS

39 (7.8%)

Multiple myeloma

44 (8.8%)

CLL

22 (4.4%)

CML

21 (4.2%)

Lymphoma infiltration

10 (2%)

MPN other than CML

14 (2.8%)

Hypocellular bone marrow

9 (1.8%)

Solid organ metastasis

9 (1.8%)

Hairy cell leukemia

6 (1.2%)

Megaloblastic anemia

6 (1.2%)

ITP

6 (1.2%)

Aplastic anemia

3 (0.6%

HLH

4 (0.8%)

 

 

Table 3 shows diagnostic agreement between BMA and BMB.

BMA Diagnosis

Agreement with BMB diagnosis

Acute leukemia

99/99 (100%)

Remission evaluation:

 

In remission

78/79 (98.7%)

Not in remission

30/30 (100%)

Normal bone marrow

69/74 (93.2%)

MDS

33/39 (84.6%)

CLL

22/22 (100%)

CML

21/21 (100%)

Lymphoma infiltration

10/10 (100%)

Solid organ metastasis

9/9 (100%)

Hypocellular bone marrow

5/9 (55.5%)

Megaloblastic anemia

6/6 (100%)

Hairy cell leukemia

6/6 (100%)

Aplastic anemia

3/3 (100%)

HLH

4/4 (100%)

 

 

Table 4 shows the findings for patients who were diagnosed with BMB but not BMA.

Diagnosis

44/500 (%8.8)

MDS

9 (%1.8)

Normal bone marrow

15 (%3)

Lymphoma infiltration

6 (%1.2)

Aplastic anemia

2 (%0.4)

Secondary metastasis

3 (%0.6)

CMML

2 (%0.4)

MPN other than CML

2 (%0.4)

Megaloblastic anemia

1 (%0.2)

LHH

1 (%0.2)

 

The outcomes of the BMA assessments for each patient are shown in Table II. Of the 475 patients having diagnoses based on the BMA review, 456 (96%) had diagnoses that agreed with the BMB report (Table-III). As indicated in Table-IV, the final diagnosis was determined based on the BMB results for a total of 44 (8.8%) cases, including 25 (5%) that could not be assessed with BMA and 19 in which the BMB result was inconsistent with the BMB report.

DISCUSSION

A BMA assessment is typically enough to diagnose acute and chronic leukemias because to their widespread involvement in bone marrow.2 The BMA can identify between AML and ALL based on the features of the blasts present. A morphological examination cannot always distinguish acute leukemias. Acute leukemias should be subtyped for therapy and follow-up purposes. To ensure accurate results, BMA blood samples should undergo flow cytometry for immunophenotyping.4

In our study, flow  Cytometry was used to diagnose both acute and chronic leukemia. Flow cytometry is helpful for diagnosing, differentiating, and monitoring plasma cell neoplasms. Our study used flow cytometry to differentiate between multiple myeloma and plasma cell leukemia in individuals. Eser A.'s study highlights the significance of flow cytometry in diagnosing and monitoring multiple myeloma, specifically in marrow blood samples collected during the first aspirate.5

The morphological appearance of bone marrow smears made it easier to detect CLL, CML, and multiple myeloma using BMA.

In a study by Bashawri, 1,813 individuals presenting to a university hospital were reviewed for bone marrow examination indications and common diseases. The link between BMA and BMB diagnoses was analyzed.

The study found that the most common reason for this examination was to diagnose and treat acute leukemia (n = 403, 22.2%). BMA is a valuable diagnostic tool for a variety of disorders, particularly hematological diseases.6
Our investigation found that the most common BMA diagnosis was acute leukemia (AML + ALL) in 99 (19.8%) individuals, which was consistent with the BMB report. Our study found 100% agreement between BMA and BMB diagnosis for patients with chronic leukemia.

A retrospective analysis by Calvet et al. found that BMA helped diagnose and treat 40 (20.7%) of 193 patients hospitalized to the intensive care unit. The authors concluded that BMA could help diagnose and treat patients admitted to the intensive care unit, regardless of hematological malignancy status.7 In our study, the BMA examination helped diagnose and treat 200 patients (40%), including 186 (37.2%) with malignant hematological diseases and 14 (2.8%) with benign hematological diseases. Gilotara et al. found 72.4% concordance between BMA and BMB assessment results in 100 instances.8

Toi et al. found that simulating BMA and BMA in 160 cases resulted in consistent results (61.25%).9 Puri et al. conducted a retrospective analysis of 300 simultaneous BMA and BMB results. This study found 77.1% agreement between BMA and BMB. Our investigation found significant agreement between BMA and BMB materials due to their high adequacy ratio. The study found significant concordance rates between BMA and BMB for CLL, CML, and acute leukemias, like our findings.10 Our study found a strong diagnostic correlation (91.2%) between BMA and BMB among participants.

Although cell morphologies were adequately evaluated with BMA, in malignancies with focal BMB is used to diagnose lymphoma and multiple myeloma when there are insufficient particles or diagnostic cells from aspiration.12,13 Our investigation found that BMA and BMB data accurately diagnosed 44 (8.8%) patients with multiple myeloma.
Three (0.8%) individuals with multiple myeloma were unable to be diagnosed with BMA due to localized involvement or inadequate particles, so BMB was used instead. In 10 (2%) lymphoma patients, lymphoma infiltration was seen in both BMA and BMB. However, three (0.6%) individuals exhibited lymphoma involvement only in BMB due to localized involvement or insufficient bone marrow in BMA. Phillips et al. discovered bone marrow involvement in 759 (62.5%) out of 1,215 lymphoma patients.14 In our study, 41 patients with a definitive lymphoma diagnosis underwent a bone marrow examination for staging purposes. Ten patients had bone marrow involvement in the BMA evaluation, while another six had bone marrow involvement in the BMB. Our study found that 16 (39%) of 41 individuals with lymphoma had bone marrow involvement and were classified as stage 4. The presence of non-hematological cells of the same type in a bone marrow examination indicates metastatic solid organ cancers.15 In the study,

CONCLUSION

Flow cytometry and genetic analysis can help the BMA examination in diagnosing most acute and chronic leukemias. BMB is not necessary for diagnosing acute or chronic leukemia, except when enough aspiration samples are not available for BMA assessment. For patients with pre-diagnosed lymphoma, multiple myeloma, or solid organ metastases, BMA should be conducted alongside BMB.

REFERENCES
  1. Licthman MA, Burns LJ. Clinical evaluation of the patient, ‘Williams Hematology’ (ninth edition), Kaushansky K & (and 6 other Eds), New York, United States. 2016;pp 1-9.
  2. Riley RS, Hogan TF, Pavot DR, Forysthe R, Massey D, Smith E, et al. A pathologist’s perspective on bone marrow aspiration and biopsy: I. performing a bone marrow examination. J Clin Lab Anal. 2004;18(2):70-90. doi: 10.1002/jcla.20008
  3. Lee SH, Erber WN, Porwit A, Tomonaga M, Peterson LC. International Council for Standardization In Hematology. ICSH guidelines for the standardization of bone marrow specimens and reports. Int J Lab Hematol. 2008;30(5):349-364. doi: 10.1111/j.1751- 553X.2008.01100.x
  4. Anna Porwit, Clinical flow cytometry, ‘Wintrobe’s Clinical Hematology’ (Fourteenth edition), Greer JP & (and 8 other Eds), PA: Wolters Kluwer, Philadelphia, United States. 2019;pp 232-303.
  5. Eser A. The importance of flow cytometry study with the first aspirate taken during bone marrow aspiration in the diagnosis of multiple myeloma and follow-up of minimal residual disease. Med Sci Discov. 2021;8(4):219-224.
  6. Bashawri LA. Bone marrow examination Indications and diagnostic value. Saudi Med J. 2002;23(2):191-196.
  7. Calvet L, Pereira B, Sapin A-F, Mareynat G, Lautrette A and Souweine B. Contribution to diagnosis and treatment of bone marrow aspirate results in critically ill patients undergoing bone marrow aspiration: a retrospective study of 193 consecutive patients. J Intens Care. 2017;5(1):67. doi: 10.1186/s40560-017-0263-7
  8. Gilotra M, Gupta M, Singh S, Sen R. Comparison of bone marrow aspiration cytology with bone marrow trephine biopsy histopathology: An observational study. J Lab Physicians. 2017;9(3):182-189. doi: 10.4103/JLP. JLP_117_16
  9. Toi CP, Varghese RG’B, Rai R. Comparative Evaluation of Simultaneous Bone Marrow Aspiration and Bone Marrow Biopsy: An Institutional Experience. Indian J Hematol Blood Transfus. 2010;26(2):41-44. doi: 10.1007/s12288-010-0010-x
  10. Puri V, Sharma P, Kotru M, Sikka M, Sharma S. Utility of simultaneous assessment of bone marrow aspirates and trephine biopsy sections in various haematological disorders. Iraqi J Hematol.2018;7(1):26-32. doi: 10.4103/ijh.ijh_33_17
  11. Management of Haematological Malignancy, ‘Hoffbrand’s Essential Haematology’ (Seventh edition), Hoffbrand AV & Moss P AH (Eds), Wiley Blackwell, West Sussex, UK. 2016;pp:135-144.
  12. Charles KS, Winfield DA, Angel C, Goepel J. Audit of bone marrow aspirates and trephine biopsies in multiple myeloma-a single centre study. Clin Lab Hematol. 2004;26(6):403-406. doi: 10.1111/j.1365- 2257.2004.00646.x
  13. Moid F, Depalma L. Comparison of relative value of bone marrow aspirates and bone marrow trephine biopsies in the diagnosis of solid tumour metastasis and Hodgkin Lymphoma. Arch Pathol Lab Med. 2005;129(4):497-501. doi: 10.1043/1543-2165(2005)129<497:CO RVOB>2.0.CO;2.
  14. Phillips L, Opie J. The utility of bone marrow sampling in the diagnosis and staging of lymphoma in South Africa. Int J Lab Hem. 2018;40(3): 276–283. doi: 10.1111/ijlh.12782.
  15. Ozkalemkas F, Ali R, Ozkocaman V, Oscelik T, Ozanu OH. The bone marrow aspirate and biopsy in the diagnosis of unsuspected non hematologic malignancy. A clinical study of 19 cases. BMC Cancer. 2005; 1(5), 144. doi: 10.1186/1471-2407-5-144.16
  16. Mansoor SN, Ali M, Mueez F, Nadeem SM, Nadeem W and Nadeem SM. Hematological Diagnosis in Children: Results of a 10 Year Long Cohort Based Upon Bone Marrow Examination. Pak J Med Health Sci. 2017;11(2): 664-667.
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