Predicting the Diagnosis of a Myelodysplastic Syndrome Using Complete Blood Count and Cell Population Data Prior to Bone Marrow Biopsy

Abstract X-linked thrombocytopenia with thalass emia (XLTT)(OMIM 314050)was first described by Thompson in 1977(Thompson et al. J Blood 1977 50(2):303-16). This rare inherent disorder was caused by a nucleotide change G>A at position 647, which leads to an amino acid substitution of arginine to glutamine (R216Q) in the gene of GATA-1 on the band p11-12 ohuman X chromosome(Raskind et al. Blood 2000, 95(7):2262-8 ;Yu et al.J Blood 2002,100(6): 2040-2045). GATA-1, belonging to the GATA family of transcription factors plays a crucial role in the development of several hematopoietic cell lines ( Ferreira et al. J Mol Cell Biol 2005,25(4): 1215-1227) . The missense mutation(R216Q) in XLTT affects GATA-1 binding to palindromic DNA sites (Yu et al.J Blood 2002,100(6): 2040-2045). The clinical characteristics of XLTT are mild thrombocytopenia, splenomegaly, reticulocytosis, hemolytic anemia and unbalanced hemoglobin (Hb) chain synthesis resembling ¦Â-thalassemia (Raskind et al. Blood 2000, 95(7):2262-8 ; Balduini et al. J Thromb Haemost 2004, Jan;91(1):129-40). About 7 families of XLTT were reported before (Millikan et al.J Semin Thromb Hemost 2011,37(6): 682-689; Danielsson et al. J Lakartidningen 2012 ,109(34-35): 1474-1477).Bone marrow fibrosis is described only in tow Swedish families ( Danielsson et al. J Lakartidningen 2012 ,109(34-35): 1474-1477).But there is limited data about the treament and prognosis of the diesase. Here we describe the full clinical characteristics of a boy of XLTT who was treated by splenectomy. The patient was first admitted at the age of 1year and 8 months in 2011.The chief complain was skin petechia and pale for more than one month. The boy had lower weight but no visible malformation. Feeding difficult and lag of language development were also complained.His Liver was 2.3cm below the right ribs and spleen was 3.2cm below the left. Peripheral blood count showed hemoglobin 8 g/dL, MCV76.7fl, MCH21.8 pg,MCHC284 g/L and reticulocyte count 0.1764¡Á1012/L. Peripheral blood smear demonstrated marked anisopoikilocytosis, polychromasia and nucleated RBCs.Platelet count was 64¡Á109/L with normal morphology.Wight blood cell was normal in number and morphology.elevated to 0.226(normal range 0-0.025) while HBA2 and hemoglobin electrophoresis was normal. Bone marrow biopsy and aspirate smear revealed a hypercellular marrow with dysplasia of erythrocyte series and megakaryoblasts (Figure 1 A). Polynuclear erythroblast ,micromegakaryocytes and hypolobated megakaryocytes could be easily seen (Figure 1 B). Fibrosis proliferation was obvious (Figure 1 A). Genetic analysis discovered a mutantion of GATA-1(R216Q)and excluded mutations of hemoglobin gnens and JAK-2. Patient was treated with dexamethasone and thalidomide which got little effect. The baseline hemoglobin was 6-8 g/dL.Platelet count ranged from 30 to 70¡Á109/L. Splenectomy was done at the age of 5years and 4 months because of constantly RBC transfusion and splenomegaly. Fibrosis proliferation and extramedullary hematopoiesis in spleen were proved by biopsy (Figure 1 C,D).The boy's complete blood count was recovered 4 months after splenectomy. Hemoglobin rose to11.6 g/dL and platelet count was 337¡Á109/L. HBF was still high at 0.226. Multifocal fibrosis proliferation still existed in bone marrow biopsy but with no myelodysplasia (Figure 1 E,F). Hepatomegaly didn't progress. He has good quality of life,and normal growth and intelligence development. Splenectomy can be a therapeutic strategy of X-linked thrombocytopenia with thalassemia. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Complete blood count and cell population data parameters from the Abbott Alinity hq analyzer are useful in differentiating myelodysplastic syndromes from other forms of cytopenia

International Journal of Laboratory Hematology ◽

10.1111/ijlh.13777 ◽

2021 ◽

Author(s):

Sang Mee Hwang ◽

Youngwon Nam

Keyword(s):

Cell Population ◽

Myelodysplastic Syndromes ◽

Blood Count ◽

Complete Blood Count ◽

Population Data

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Audit of bone marrow biopsy reports submitted to a myelodysplastic syndrome registry

Pathology ◽

10.1016/j.pathol.2021.06.094 ◽

2021 ◽

Vol 53 ◽

pp. S45-S46

Author(s):

Marsali Maclean ◽

Linda Saravanan

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndrome ◽

Bone Marrow Biopsy

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Follicular Lymphoma in Staging Bone Marrow Specimens: Correlation of Histologic Findings With the Results of Flow Cytometry Immunophenotypic Analysis

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-282-flisbm ◽

2007 ◽

Vol 131 (2) ◽

pp. 282-287

Author(s):

Dan Iancu ◽

Suyang Hao ◽

Pei Lin ◽

S. Keith Anderson ◽

Jeffrey L. Jorgensen ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

B Cell ◽

Bone Marrow Biopsy ◽

Cell Population ◽

Color Flow ◽

Flow Cytometric Immunophenotyping ◽

Histologic Evidence ◽

Flow Cytometric ◽

Biopsy Specimens

Abstract Context.—Bone marrow (BM) examination is part of the staging workup of lymphoma patients. Few studies have compared BM histologic findings with results of flow cytometric immunophenotyping analysis in follicular lymphoma (FL) patients. Objective.—To correlate histologic findings with immunophenotypic data in staging BM biopsy and aspiration specimens of FL patients. Design.—Bone marrow biopsy specimens of untreated FL patients were reviewed. Histologic findings were correlated with 3-color flow cytometric immunophenotyping results on corresponding BM aspirates. Results.—Bone marrow biopsy specimens (with or without aspirates) of 114 patients with histologic evidence of FL in BM were reviewed. There were 76 bilateral and 38 unilateral biopsies performed, resulting in 190 specimens: 187 involved by FL and 3 negative (in patients with a positive contralateral specimen). The extent of BM involvement was <5% in 32 (17.1%), ≥5% and ≤25% in 102 (54.6%), >25% and ≤50% in 27 (14.4%), and >50% in 26 (13.9%) specimens. The pattern of involvement was purely paratrabecular in 81 (43.3%), mixed in 80 (42.8%), and purely nonparatrabecular in 26 (13.9%). Immunophenotyping was only performed unilaterally, on BM aspirates of 92 patients, and was positive for a monoclonal B-cell population in 53 (57.6%) patients. Immunophenotyping was more often negative when biopsy specimens showed FL with a purely paratrabecular pattern. For comparison, we assessed 163 FL patients without histologic evidence of FL in BM also analyzed by flow cytometric immunophenotyping. A monoclonal B-cell population was identified in 5 patients (3%). Conclusions.—Our data suggest that 3-color flow cytometric immunophenotyping adds little information to the evaluation of staging BM specimens of FL patients.

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Usefulness of Unicel DxH 800 Cell Population Data in the Detection of Plasmacell Leukemia: 2 Cases Report

Blood ◽

10.1182/blood.v118.21.4915.4915 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4915-4915

Author(s):

Donatella Raspadori ◽

Santina Sirianni ◽

Alessandro Gozzetti ◽

Francesco Lauria ◽

Claudio Fogli ◽

...

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

Cell Population ◽

Blood Smear ◽

Normal Values ◽

Population Data ◽

Morphological Features ◽

Short Report ◽

Lymphocyte Population ◽

Literature Report

Abstract Abstract 4915 Introduction and methods. Lymphoproliferative disorders (LD) are characterized and described by lymphocyte population with heterogeneous morphological features both in optical microscopy revision and in flow cytometry. Several literature report the clinical usefulness of Cell Population Data (CPD) provided by Beckman Coulter hematology analyzers. Abnormal values of CPD correlate with morphological abnormalities of leukocytes. In this work we present a case report of a plasmacell leukemia analyzed with UniCel DxH800 device. DxH800 performs leukocytes differential with the Flow Cytometric Digital Morphology (FCDM) technology, based on the measurements of Volume (V), Conductivity (C) and 5-angle Scatter light laser (MALS, UMALS, LMALS, LALS, AL2) on cells in their native state. Mean and standard deviation of FCDM measurements are collected in 56 CPD. Normal CPD values were computed from a 42 normal samples. Results. A 47-years old woman, referring continuous asthenia, was addressed to our lab with clinical suspect of LD with leukocytosis (WBC=17190/μl, LY#=3800). DxH800 analysis confirmed WBC count adding some important comments. WBC histogram showed a big peak in lymphocyte population. Differential values reported neutrophilia and lymphocytosis while scatterplot showed a lymphocyte cluster very close to the neutrophil one. CPD suggested a heterogeneous neutrophil population with low volume and low scatters (MALS, UMALS, LMALS, LALS, AL2 in arbitrary units) respectively of 106, 90, 112, 62, 75 vs normal values of 144, 137, 143, 158, 159. Examination of blood smear showed a lot of lymphocyte with nuclear immaturity and plasmoblast features. Immunophenotype revealed that 63% of the WBC were CD138+/CD38+, CD56+ CD200-, CD27- CD20-. Bone marrow biopsy confirmed the plasmacell leukemia diagnosis. A 65-years old man was admitted to our department for a light lymphocytosis associated with a IgGk monoclonal component. Immunophenotipic analysis showed a NK proliferation (CD3 50%, CD4 38%, CD8 34%, CD2 92%, CD7 92%, CD16 45%, CD56 48%, CD57 54%). DxH800 analysis reported LY#=3.6/μl and MO#=1,6/μl. LY CPD indicate cells with light signals of degranulation (MALS=56, UMALS=60, LMALS=63 vs normal values of 66, 60 and 63 ) together with abnormal monocyte CPD such as MV=157, MC=136, MALS=79, UMALS=80, LALS=75 vs normal values of 164, 129, 85, 80 and 75 respectively. All this data induced us to look for a mononuclear population different both from lymphocytes and monocytes in the peripheral blood smear. Bone marrow microscopy analysis showed morphologically abnormal cells that were classified as plasmacells after immunophenotyping (CD138+/CD38+, CD56+, CD45-, CD117+, CD20-, CD27-, CD200+. Further immunophenotypic analysis showed in PB 14% of plasmacells CD138+/CD38+/CD45-. Conclusion. We presented 2 cases report of a plasmacell leukemia whose diagnosis were supported by the useful information of the CPD provided by DxH 800. CPD abnormal values for lymphocytes and monocytes were known to correlate with morphological abnormalites of the cells. For this reason we were triggered to deeply investigate the blood smear of the two patient and we performed the immunophenotyping. This short report confirm the usefulness of CPD provided by UniCel DxH800 as the first check point for the diagnostic route. Moreover we confirm that morphological features in the PB smear discovered during the diagnosis, supported by flow-cytometry data, were properly correlated with CPD values. Disclosures: Fogli: Instrumentation Laboratory: Employment. Di Gaetano:Instrumentation Laboratory: Employment.

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Deletion of Cellular Prion Protein (PrPC) Results in Peripheral Lymphocytosis and Larger Platelets

Blood ◽

10.1182/blood.v126.23.4619.4619 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4619-4619

Author(s):

Yan Zheng ◽

Guangyuan Li ◽

Menglei Zhu ◽

Yu Li ◽

Howard Meyerson ◽

...

Keyword(s):

Bone Marrow ◽

Blood Cell ◽

Lymph Nodes ◽

Peripheral Blood ◽

Blood Count ◽

Complete Blood Count ◽

Absolute Lymphocyte Count ◽

Cellular Prion Protein ◽

Platelet Volume ◽

Spleen And Lymph Nodes

Abstract Cellular prion protein (PrPC) is a GPI-anchored cell surface glycoprotein that is expressed in the brain, blood, bone marrow (BM), and lymphoid tissue. PrPC can be converted post-translationally into scrapie-PrP (PrPSc), which is involved in the pathogenesis of neurodegenerative diseases including Creutzfeldt-Jakob disease, Kuru disease in humans, and scrapie and bovine spongiform encephalopathy in animals. However, the biological function of PrPSc has yet to be conclusively elucidated. In order to understand the role of PrPC in the hematopoietic system, we compared bone marrow, lymphoid organs and peripheral blood of PrPC knockout mice (KO) to age and sex-matched transgenic mice used as background controls (WT) expressing human PrPC under the control of a mouse PrPC promoter with a slightly augmented expression (2-fold) of PrPC. Complete blood count (CBC) showed a significant increase of WBC in KO mice (KO 9.03 ± 5.16 x109/L vs. WT 4.13 ± 1.87 x109/L, p = 0.0405; Table 1 and Figure 1). Further analysis of WBC differential revealed that the elevated number of WBC in KO mice was due to lymphocytosis. Specifically, KO mice had a 3-fold increase in the absolute lymphocyte count (KO 7.59 ± 4.63 x109/L vs. WT 2.90 ± 1.32 x109/L, p = 0.0303), as well as a higher lymphocyte percentage (KO 82.47 ± 4.20% vs. WT 70.19 ± 4.44%, p = 0.0011) compared to controls. KO mice also had a trend toward higher hemoglobin (KO 12.00 ± 4.40 g/dL vs. WT 9.84 ± 4.83 g/dL), RBC (KO 8.01 ± 2.87 x1012/L vs. WT 6.25 ± 3.11 x1012/L), and hematocrit (KO 43.94 ± 17.00 % vs. WT 36.04 ± 18.07 %) compared to WT mice. Additionally, platelet count in KO mice was higher than control mice (KO 762.20 ± 138.61 x 109/L vs. WT 661.80 ± 230.20 x 109/L). Of interest, the mean platelet volume (platelet size) was significantly increased in KO mice compared to controls (KO 6.00 ± 0.29 fL vs. WT 5.24 ± 0.56 fL, p =0.0140). Thus, absence of PrPC resulted in significant leukocytosis and specifically higher absolute count and percentage of lymphocytes, as well as larger platelets in peripheral blood. To further analyze if the observed lymphocytosis is due to abnormalities in hematopoiesis or lymphopoiesis, bone marrow (BM), thymus, spleen and lymph nodes from WT and KO mice were isolated and examined by flow cytometry using a comprehensive panel of fluorochrome-conjugated antibodies specific for all hematologic cell precursors/lineages. Analysis of all cell populations in each of these organs revealed no significant differences in the numbers of RBC and megakaryocyte in BM, and of lymphocytes in the thymus, spleen and lymph nodes (data no shown). Additionally, histological analysis of BM, thymus, spleen and lymph nodes tissue from KO and WT animals failed to show morphological differences between the two groups (data not shown). Therefore, lack of PrPC does not appear to affect hematopoiesis and lymphopoiesis. In summary, our findings indicate that PrPC deficiency translates into a significant increase in the number of lymphocytes in peripheral blood; however, development and maturation of lymphocytes in KO mice appeared normal. Therefore, PrPC might be critical in the survival and trafficking of lymphocytes in peripheral blood. The molecular mechanisms underlying the observed changes in lymphocytes and platelets, and whether there are any related changes in the functions of lymphocytes and platelets will be subject of future studies. Table 1. Complete blood count (CBC) of PrPC WT and KO mice WT KO p value Mean ± SD Mean ± SD WBC (109/L) 4.13 ± 1.87 9.03 ± 5.16 0.0405 Absolute lymphocyte count (109/L) 2.90 ± 1.32 7.59 ± 4.63 0.0303 Lymphocyte (%) 70.19 ± 4.44 82.47 ± 4.20 0.0011 RBC (1012/L) 6.25 ± 3.11 8.01 ± 2.87 0.1898 HB (g/dL) 9.84 ± 4.83 12.00 ± 4.40 0.2404 HCT (%) 36.04 ± 18.07 43.94 ± 17.00 0.2618 PLT (109/L) 661.80 ± 230.20 762.20 ± 138.61 0.2138 MPV (fL) 5.24 ± 0.56 6.00 ± 0.29 0.0140 SD: Standard deviation; WBC: White blood cell; RBC: Red blood cell; HB: Hemoglobin; HCT: Hematocrit; RDW: Red cell distribution width; PLT: Platelet; MPV: Mean platelet volume Figure 1. PrPC deficiency results in lymphocytosis in peripheral blood. Figure 1. PrPC deficiency results in lymphocytosis in peripheral blood. Disclosures No relevant conflicts of interest to declare.

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Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome with Isolated Del(5q) with Lenalidomide, Bortezomib, and Dexamethasone

Blood ◽

10.1182/blood-2020-140532 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 17-18

Author(s):

Nyomi Washington ◽

Eugen A Shippey ◽

Michael B Osswald

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Partial Response ◽

Myelodysplastic Syndrome ◽

Bone Marrow Biopsy ◽

Induction Therapy ◽

Successful Treatment ◽

Light Chain ◽

Plasma Cells ◽

Bone Marrow Blasts

Lenalidomide is known to be an effective therapy for multiple myeloma (MM) and for myelodysplastic syndrome with isolated del(5q). However, there have been very few reports of treatment of both conditions using lenalidomide when they are diagnosed concurrently. A review of the literature revealed two reports of MM and del(5q) MDS treated with lenalidomide. We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide. The patient is a 74 year old female who was referred to hematology for worsening chronic macrocytic anemia with a hemoglobin of 9.4 g/dL. A serum protein electrophoresis (SPEP) was obtained during her workup and demonstrated an IgG kappa monoclonal spike of 4.7 g/dL. Free light chain analysis demonstrated a kappa/lambda ratio of 36.7. The patient was mildly hypercalcemic at 10.6 g/dL but had no renal insufficiency. Platelet and white blood cell counts were normal. There were no osteolytic lesions on skeletal survey and a whole body PET scan identified no bony disease or plasmacytomas. A β-2 microglobulin level was 3.7 mg/L and albumin was 3.3 g/dL. Bone marrow biopsy revealed 60% plasma cells in a 70% cellular marrow. Granulocytic and megakaryocytic dysplasia was identified. Fluorescence in situ hybridization returned showing a 4:14 translocation in 72% of analyzed nuclei and monosomy 13 in 61% of nuclei analyzed consistent with an unfavorable risk profile. Chromosome analysis also revealed a 5q deletion in 15 of 20 analyzed cells. Bone marrow blasts were measured at 1%. Therefore, the patient concurrently met diagnostic criteria for stage II IgG kappa multiple myeloma per the International Staging System and low risk myelodysplastic syndrome with isolated del(5q) per the 2016 WHO classification of MDS with a Revised International Prognostic Scoring System Score (IPSS-R) of 2. She was started on lenalidomide 25 mg daily, bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 and dexamethasone 20 mg on days 1, 8, and 15 of a 21 day cycle. After 3 cycles of therapy, serum immunofixation electrophoresis showed an unquantifiably low IgG kappa monoclonal spike and the patient's kappa/gamma light chain ratio had normalized to 1.1. Hemoglobin and calcium returned to normal. On repeat bone marrow biopsy, there was normocellular marrow with 4% polytypic plasma cells by kappa/lambda immunohistochemistry. No dysplasia was identified and bone marrow blasts were 1.5%. Therefore, the patient achieved a very good partial response (VGPR) to therapy for multiple myeloma according to International Myeloma Working Group criteria within 3 months. She met National Comprehensive Cancer Network criteria for response of her MDS to lenalidomide by normalization of hemoglobin. The patient's case demonstrates successful treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) using lenalidomide. Among the two other similar cases we discovered in the literature, one patient was treated with low-dose lenalidomide and dexamethasone [Nolte, et al. Eur J Haematol. 2017 Mar;98(3):302-310.], and the other patient was treated with high-dose lenalidomide and dexamethasone, achieving a partial response [Ortega, et al. Leuk Res. 2013 Oct;37(10):1248-50.]. Neither patient received a proteasome inhibitor. In our case, the patient was treated with higher intensity induction therapy for multiple myeloma and achieved a VGPR. She did not have worsening cytopenias during therapy, and in fact experienced normalization of her blood counts. Therefore, it is reasonable to treat patients simultaneously diagnosed with MM and MDS with isolated del(5q) with standard three-drug induction therapy for multiple myeloma. While our approach makes sense in the abstract, hematology/oncologists should be aware that it works in practice. Disclosures No relevant conflicts of interest to declare.

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Two Cases of Severe Hypertension in JAK2 Mutation-Positive Myeloproliferative Neoplasms

Case Reports in Vascular Medicine ◽

10.1155/2020/8887423 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Raunak Rao ◽

Spoorthy Kulkarni ◽

Ian B. Wilkinson

Keyword(s):

Bone Marrow ◽

Renal Artery ◽

Renal Artery Stenosis ◽

Bone Marrow Biopsy ◽

Blood Count ◽

Severe Hypertension ◽

Myeloproliferative Neoplasms ◽

Artery Stenosis ◽

Full Blood Count ◽

Jak2 Mutation

Background. Myeloproliferative neoplasms are a heterogeneous group of disorders resulting from the abnormal proliferation of one or more terminal myeloid cells—established complications include thrombosis and haemorrhagic events; however, there is limited evidence to suggest an association with arterial hypertension. Herein, we report two independent cases of severe hypertension in JAK2 mutation-positive myeloproliferative neoplasms. Case Presentations. Case 1: a 39-year-old male was referred to our specialist hypertension unit with high blood pressure (BP) (200/120 mmHg), erythromelalgia, and headaches. We recorded elevated serum creatinine levels (146 μM) and panmyelosis. Bone marrow biopsy confirmed JAK2-mutation-positive polycythaemia vera. Renal imaging revealed renal artery stenosis. Aspirin, long-acting nifedipine, interferon-alpha 2A, and renal artery angioplasty were employed in management. BP reached below target levels to an average of 119/88 mmHg. Renal parameters normalised gradually alongside BP. Case 2: a 45-year-old male presented with high BP (208/131 mmHg), acrocyanosis, (vasculitic) skin rashes, and nonhealing ulcers. Fundoscopy showed optic disc blurring in the left eye and full blood count revealed thrombocytosis. Bone marrow biopsy confirmed JAK2-mutation-positive essential thrombocytosis. No renal artery stenosis was found. Cardiac output was measured at 5 L/min using an inert gas rebreathing method, providing an estimated peripheral vascular resistance of 1840 dynes/s/cm5. BP was well-controlled (reaching 130/70 mmHg) with CCBs. Conclusions. These presentations highlight the utility of full blood count analysis in patients with severe hypertension. Hyperviscosity and constitutive JAK-STAT activation are amongst the proposed pathophysiology linking myeloproliferative neoplasms and hypertension. Further experimental and clinical research is necessary to identify and understand possible interactions between BP and myeloproliferative neoplasms.

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