scholarly journals Granulocytic Sarcoma in a Nonleukemic Patient: Place of Radiotherapy and Systemic Therapies

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
C. Chargari ◽  
J. Jacob ◽  
O. Bauduceau ◽  
F. R. Ferrand ◽  
T. De Revel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Unusual Case ◽  
Granulocytic Sarcoma ◽  
Myeloproliferative Disorders ◽  
Therapeutic Strategies ◽  
Chronic Leukaemia ◽  
Acute Paraplegia ◽  
Spinal Epidural ◽  
Systemic Therapies

Granulocytic sarcoma is a rare extramedullary tumour, which most often occurs in the course of an acute or chronic leukaemia or myeloproliferative disorders. Rarely it is found before peripheral blood or bone marrow evidence of leukemia is present. We report an unusual case of acute paraplegia at first presentation of a spinal epidural granulocytic sarcoma without any haematological disorder. Therapeutic strategies are discussed in the light of the literature.

scholarly journals Detection of chromosome 20q deletions in bone marrow metaphases but not peripheral blood granulocytes in patients with myeloproliferative disorders or myelodysplastic syndromes

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1561-1570 ◽  
Author(s):  
FA Asimakopoulos ◽  
TL Holloway ◽  
EP Nacheva ◽  
MA Scott ◽  
P Fenaux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Myeloproliferative Disorders ◽  
Pcr Analysis ◽  
Multipotent Progenitors ◽  
The Common ◽  
Polymerase Chain ◽  
A Minor

Myeloproliferative disorders and myelodysplastic syndromes arise in multipotent progenitors and may be associated with chromosomal deletions that can be detected in peripheral blood granulocytes. We present here seven patients with myeloproliferative disorders or myelodysplastic syndromes in whom a deletion of the long arm of chromosome 20 was detectable by G-banding and/or fluorescence in situ hybridization in most or all bone marrow metaphases. However, in each case, microsatellite polymerase chain reaction (PCR) using 15 primer pairs spanning the common deleted region on 20q showed that the deletion was absent from most peripheral blood granulocytes. The human androgen receptor clonality assay was used to show that the vast majority of peripheral blood granulocytes were clonal in all four female patients. This represents the first demonstration that the 20q deletion can arise as a second event in patients with pre-existing clonal granulopoiesis. Microsatellite PCR analysis of whole bone marrow from two patients was consistent with cytogenetic studies, a result that suggests that cytogenetic analysis was not merely selecting for a minor subclone of cells carrying the deletion. Furthermore, in one patient, the deletion was present in both erythroid and granulocyte/monocyte colonies. This implies that the absence of the deletion in most peripheral blood granulocytes did not reflect lineage restriction of the progenitors carrying the deletion but may instead result from other selective influences such as preferential retention/destruction within the bone marrow of granulocytes carrying the deletion.

Dynamics of Telomere Length and Telomerase Activity in Ph1-Negative Chronic Myeloproliferative Disorders

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2789-2789
Author(s):  
Ioanna Bazdiara ◽  
Despina Pantelidou ◽  
Athanasios Anastasiadis ◽  
Vassilios Papadopoulos ◽  
Dimitrios Margaritis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Telomere Length ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Hematopoietic Cells ◽  
Myeloproliferative Disorders ◽  
Telomerase Activity ◽  
Secondary Leukemia ◽  
Chronic Myeloproliferative Disorders ◽  
Hematological Disorders

Abstract Evolving data demonstrate the pathogenetic significance of chromosomal ends telomeres and telomerase activity in the molecular pathogenesis of many hematological disorders. Furthermore, the presence of eroded telomeres and enhanced telomerase activity in hematopoietic cells has been associated with poor prognosis both in myeloid and lymphoid malignancies. The aim of the present study was to evaluate telomere length and telomerase activity in patients with Ph1-negative Chronic Myeloproliferative Disorders (Ph−-CMPD) either at diagnosis or during the course of the disease and to assess their possible clinical utility. Sixty-six bone marrow and 60 peripheral blood samples were obtained from 80 Ph−-CMPD patients (aged 58.57±16.42 years) and 18 healthy age-matched controls (aged 53.94±15.16 years). Thirty-six patients diagnosed suffering from Polycythemia Vera, 36 from Essential Thombocythemia, 4 from Idiopathic Myelofibrosis and 4 from Unclassified CMPD. Twenty-six samples were studied at diagnosis, whereas 54 during the course of the disease. Telomere length analysis of individual chromosome ends was performed on bone marrow metaphases using Telomere/Centromere Quantitative-Fluorescence In Situ Hybridization (T/C Q-FISH) (Dako A/S, Denmark). Telomerase activity was determined in bone marrow purified CD34(+) and CD20(+) cells as well as in peripheral blood CD3(+) T-lymphocytes and granulocytes with the PCR-based Telomeric Repeat Amplification Protocol (TRAP) assay (Roche, Germany). Gene expression of telomerase-associated proteins (hTERT, hTER, TEP1, TRF-1 and TRF-2) was assayed by Real-Time Multiplex PCR (Maximbio, USA). Ph−-CMPD patients showed significantly more eroded telomeres (P=0.010) and increased telomerase activity in CD34(+) cells (P=0.005) compared to healthy age-matched individuals. However, there was no statistical difference in telomere length (P=0.451) and enzyme activity (P=0.538) among different groups of Ph−-CMPD. Telomerase activity was not detected in the remaining hematopoietic cells both in patients and healthy controls, which was closely correlated with downregulation in hTERT mRNA expression. hTER, TEP1, TRF-1 and TRF-2 showed no apparent differential expression of mRNA in all hematopoietic cell fractions. Chromosomal aberrations (+8, +9, del13q14, del20q12) were found by FISH in 37% Ph−-CMPD patients with reduced telomere lengths (P=0.001) and enhanced telomerase activity (P=0.014), especially during the course of the disease (P=0.028). The patients with shortened telomeres displayed a higher incidence of having thrombotic or hemorrhagic events during follow-up (P=0.011), treatment failure (P=0.024) and disease progression to myelofibrosis, myelodysplastic syndromes, secondary leukemia or death (P=0.137). Nevertheless, telomerase expression was not correlated with the above complications. The event free survival (survival without complications, e.g. myelofibrosis, myelodysplastic syndromes, secondary leukemia and death) was significantly shorter in patients with reduced telomere lengths (Log Rank P=0.033), who demonstrated a 7,71-fold higher probability of having complications within five years from the initial diagnosis (95% CI=2,04–31,49 P<0.001). In conclusion, accelerated telomere shortening may not be prevented or restored by telomerase activity in most of the Ph−-CMPD myeloid cells. Loss of telomere stability seems to predispose to further genetic events such as chromosomal rearrangement and consequently to trigger off a multistage neoplastic transformation of these diseases. Moreover, the negative correlation between telomere length and survival probability of Ph−-CMPD patients is indicative that telomere dynamics may serve as a useful prognostic tool for these patients.

A Randomized Trial of Bone Marrow (BM) Versus Peripheral Blood (PB) Allogeneic Hemopoietic Stem Cell Transplants (HSCT) in Patients with Myeloproliferative Disorders.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2998-2998
Author(s):  
Andrea Bacigalupo ◽  
Maria Teresa van Lint ◽  
Attilio Olivieri ◽  
Marco Casini ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Randomized Trial ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Myeloproliferative Disorders ◽  
Hemopoietic Stem Cell ◽  
Term Survival

Abstract Background. Reduced intensity conditioning (RIC) regimens have been widely used over the past years with the aim of reducing transplant related mortality (TRM) of allogeneic hemopoietic stem cells transplants (HSCT). The preferred source is peripheral blood (PB) cells, although this source has not been prospectively compared with bone marrow (BM) iun the setting of RIC transplants. Aim of the study. To compare BM and PB allogeneic transplants following a RIC regimen in patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML) or idiopathic myelofibrosis (IM). Methods and patients. This is a prospective multicenter randomized trial: eligible were patients with AML, CML and IM, aged 45–60, with an HLA identical sibling, Conditioning regimen was thiotepa 5 mg/kgx2 and cyclophopshamide 50 mg/kgx2. Graft versus host disease (GvHD) prophylaxis was low dose cyclosporin and low dose methotrexate. Patients were randomized to receive unmanipulated BM (n=36) or unmanipulated PB (n=35), after stratification for disease phase (1st remission, n=47) or advanced disease (n=24). Median age was 51 in both groups and follow up of surviving patients 760 and 756 days respectively. Results. Engraftment was achieved in all but one patient who has autologous reconstitution. Acute GvHD grade III–IV accurred in 0% vs 12% of BM vs PB patients (p=0.03) and extensive chronic GvHD in 13% vs 37% respectively (p=0.03). Cumulative incidence (CI) of TRM at 5 years is 6% for BM and 9% for PB (p=0.6). Relapse of the original disease occurred in 61% vs 29% of BM and PB patients (p=0.007) and the CI of relapse related death (RRD) is 39% vs 19% respectively (p=0.07). Actuarial 5 year survival is 47% in BM vs 68% in PB paitents (p=0.3). A COX proportional step down analysis shows chronic GvHD to be a significant favourable factor for RRD and survival. Conclusions. In patients receiving a RIC allogeneic graftTRM is low and comparable in BM and PB transplanst;acute and chronic GvHD is more frequent in PB transplants,relapse is significantly decreased in PB transplants and RRD is also lower,there is a non significant survival advantage for PB patients andthe occurrence of chronic GvHD protects against relapse and favourably influences long term survival.

scholarly journals Nonleukemic Granulocytic Sarcoma of Knee: A Case Report

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Ibrahim Elghissassi ◽  
Hanane Inrhaoun ◽  
Hind Mrabti ◽  
Hassan Errihani
Keyword(s):  
Bone Marrow ◽  
Rare Condition ◽  
Granulocytic Sarcoma ◽  
Myeloproliferative Disorders ◽  
Left Knee ◽  
Pathological Analysis ◽  
Extramedullary Tumor ◽  
End Of Treatment ◽  
Immature Myeloid Cells ◽  
Knee Mass

Granulocytic sarcoma (GS) is a rare extramedullary tumor composed of immature myeloid cells. It is usually associated with leukemia or other myeloproliferative disorders. It occurs very rarely without overt hematologic diseases. A 19-year-old man presented with left knee mass. Biopsy with pathological analysis showed lymphoma aspect. Immunostains yielded the diagnosis of GS with myeloperoxidase and CD43 positivity. There was no systemic manifestation of leukemia, and bone marrow biopsiy was negative for neoplastic infiltration. Chemotherapy by CHOP was efficient, and the patient remaind alive and healthy 40 months after the end of treatment. The case is discussed in the framework of the existing literature about the diagnosis, treatment, and prognosis of this very rare condition.

scholarly journals Chloroma (granulocytic sarcoma) without evidence of leukemia: facilitated light microscopic diagnosis

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 104-108 ◽  
Author(s):  
KS Jr McCarty ◽  
J Wortman ◽  
J Daly ◽  
RW Rundles ◽  
JS Hanker
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Granulocytic Sarcoma ◽  
Histochemical Staining ◽  
Histologic Diagnosis ◽  
Sudan Black B ◽  
Poorly Differentiated ◽  
Microscopic Diagnosis ◽  
Immature Cells ◽  
Formalin Fixed

Abstract Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lacks the characteristic green color. The diagnostic difficulty may be further compounded when the granulocytic sarcoma develops before there is peripheral blood or bone marrow evidence of leukemia. Previous criteria for the diagnosis of chloroma have been ambiguous because of the capricious nature of the hydroperoxidase activity and the lack of definitive histochemical criteria. In this case, a combination of Sudan black B and myeloperoxidase histochemical staining and ultrastructural evaluation was applied. The light microscopic histochemical studies suggested the presence of Phi bodies and rods both in the formalin-fixed tumor and in the cells derived from the subsequent pleural effusion; this was confirmed by electron microscopy, which demonstrated the peridicity of the crystalline rod substructure. These observations show that light microscopic histochemical studies can facilitate the diagnosis of granulocytic sarcoma or chloroma in the absence of peripheral blood or bone marrow manifestations of leukemia.

scholarly journals Chloroma (granulocytic sarcoma) without evidence of leukemia: facilitated light microscopic diagnosis

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 104-108
Author(s):  
KS Jr McCarty ◽  
J Wortman ◽  
J Daly ◽  
RW Rundles ◽  
JS Hanker
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Granulocytic Sarcoma ◽  
Histochemical Staining ◽  
Histologic Diagnosis ◽  
Sudan Black B ◽  
Poorly Differentiated ◽  
Microscopic Diagnosis ◽  
Immature Cells ◽  
Formalin Fixed

Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lacks the characteristic green color. The diagnostic difficulty may be further compounded when the granulocytic sarcoma develops before there is peripheral blood or bone marrow evidence of leukemia. Previous criteria for the diagnosis of chloroma have been ambiguous because of the capricious nature of the hydroperoxidase activity and the lack of definitive histochemical criteria. In this case, a combination of Sudan black B and myeloperoxidase histochemical staining and ultrastructural evaluation was applied. The light microscopic histochemical studies suggested the presence of Phi bodies and rods both in the formalin-fixed tumor and in the cells derived from the subsequent pleural effusion; this was confirmed by electron microscopy, which demonstrated the peridicity of the crystalline rod substructure. These observations show that light microscopic histochemical studies can facilitate the diagnosis of granulocytic sarcoma or chloroma in the absence of peripheral blood or bone marrow manifestations of leukemia.

Assessment of Immature Platelet Fraction in Patients with Ph-Negative Myeloproliferative Disorders and Thrombocytosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4980-4980
Author(s):  
Ondrej Zapletal ◽  
Jan Blatny ◽  
Michaela Selingerova ◽  
Jiri Jarkovsky ◽  
Miroslav Penka
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Peripheral Blood ◽  
Myeloproliferative Disorders ◽  
Optical Channel ◽  
Polycythaemia Vera ◽  
Platelet Production ◽  
Platelet Counts ◽  
Immature Platelet Fraction ◽  
Immature Platelets

Abstract Abstract 4980 Background Myeloproliferative disorders (MPD) in general result from proliferation of a clone of myeloid cells derived from a neoplastic pluripotent precursor or from connective tissue elements in bone marrow. This leads to increased numbers in one or more blood cell lines in peripheral blood. Some MPDs can be associated with thrombocytosis (MPD-T): essential thrombocythaemia (ET), polycythaemia vera (PV) and early stages of chronic idiopathic myelofibrosis (CIMF). Usually in MPD-T the thrombocytosis is caused by increased platelet production from proliferating mature megakaryocytes, especially in ET. Elevated platelet counts in these patients are often associated with both thromboembolic events and bleeding. One of the goals of MPD treatment is the control of platelet count. Immature platelets mirror the platelet production in bone marrow. In certain automated blood count analyzers it is possible to measure Immature platelet fraction (IPF) from the routine CBC samples sent to haematology lab. Reference range for IPF parameter for method used in this study is 1,1-6,1%. Objective Measurement of IPF parameter by fully automated analyzer (XE-2100, Sysmex, Kobe, Japan) in optical channel and analyzing it ( software IPF Master) in patients treated for Ph-negative MPD. We enrolled 85 pts- 67 ET (79%), 10PV(12%) and 8 CIMF (9%) patients; 57 were women and 28 men; median age 56 years ranging from 20 up to 83 years. We analyzed and evaluated IPF in whole group as well as in subgroups depending on diagnosis, gender, age, JAK-2 mutation and platelet count. Results At the time of assessment the majority of our pts were already commenced on treatment for their MPD. Platelet counts (plt) in whole cohort ranged from 164 up to 2148 ×109/l, with median 374 ×109/l. Thirty eight pts (45%) had plt < 350 ×109/l. Plt <450 ×109/l (WHO 2008 recommended cut off level for thrombocytosis) were found in 59 pts (69%). IPF median in whole cohort was 5,9% (0,7-14,4%). When comparing IPF in subgroups mentioned above statistically significant differences (p<0,05) was found only between subgroups with normal and abnormal plt counts: IPF median 7,45% (0,8-14,4%) resp. 4,6% (0,7-11,9%), (p=0,002) and between subgroups with less and more than 450×109/l plt (IPF median 6,6% (0,8-14,4%) resp. 3,85% (0,7-9,6%), (p<0,001). Fact, that patients with higher plt had lower IPF and vice versa, was confirmed also by Spearman correlation coefficient. When correlating results of plt a IPF in the whole cohort, we found the trend to indirect dependence (rs= –0,386). Conclusions MPD-T patients in our cohort did not have marked elevation of IPF parameter, neither those with high platelet counts (so far untreated pts). Thus we can speculate, that increased number of Plts in peripheral blood is caused by increased number of mature megacaryocytes in bone marrow which produce adequate numbers of platelets without increase of immature fraction rather than increased number of immature platelets released from megacaryocytes appearing in normal numbers in bone marrow Thus it seems that negative feedback of increased Plt counts on releasing of Plts from megacaryocytes is maintained also in patients with MPD-T. Further assessment is needed and should further determine, what is the clinical relevance (if any) of measurement of IPF in patients treated for MPD-T. Disclosures Blatny: Sysmex, Czech Republic: Consultancy.

Fasudil, a Rho-Associated Protein Kinase (ROCK) Inhibitor, Decreases Disease Burden in a Cbl/Cbl-b Deficiency-Driven Murine Model for Myeloproliferative Disorders

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4569-4569
Author(s):  
Basem M. William ◽  
Dan Feng ◽  
Wei An ◽  
Scott Nadeau ◽  
Bhopal Mohapatra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Western Blot ◽  
Peripheral Blood ◽  
Bone Marrow Cells ◽  
Myeloproliferative Disorders ◽  
Rock Inhibitor ◽  
Average Life Span ◽  
Over Time ◽  
Marrow Cells

Abstract Myeloproliferative disorders (MPDs) are heterogeneous clonal diseases with variable clinical courses. Mutations in the Cbl family genes have been reported in multiple independent studies to be present in about 10% of patients with MPDs and these patients tend of have a poorer prognosis. We have previously demonstrated that Cbl-flox/flox, Cbl-b-null mice rendered Cbl/Cbl-b double knockout (DKO) in the hematopoietic compartment with MMTV-Cre develop a disease phenotypically similar to human MPDs. An in vitro kinase inhibitor screen identified fasudil, a ROCK inhibitor, with relatively selective anti-proliferative activity against Cbl/Cbl-b DKO vs. control murine bone marrow cells. We established a mouse model with a uniform time of MPD onset by transplanting Cbl/Cbl-b DKO bone marrow cells (2x106 per recipient) into 21 busulfan-conditioned NOD/SCID/gamma chain-deficient (NSG) mice. All recipients showed donor cell engraftment. Four weeks post-transplant, we treated 13 mice with 100 mg/kg fasudil daily by gavage. By two weeks of treatment, total white cell and monocyte counts were significantly lower in mice treated with fasudil (p=0.02 and 0.04 respectively). For the entire group, we observed a trend towards improved survival in fasudil-treated mice that didn't reach statistical significance (p=0.07). However, analysis of male recipients only (n=12) revealed a significant survival advantage in fasudil-treated group (p=0.04). The gender difference may stem from a currently unexplained more severe disease phenotype we observed in female recipients. Notably, while all untreated mice succumbed to MPD, prolonged survival was observed in 2 mice beyond 27 weeks, nearly twice the average life-span in the Cbl/Cbl-b DKO MPD model (16 weeks). The 2 long-term survivors had undetectable levels of myosin light chain (MLC), a downstream target of ROCK phosphorylation (figure) suggesting that inhibition of downstream signaling of ROCK is associated with improved disease control and survival. Taken together, our data suggest a therapeutic potential for fasudil in the treatment of MPDs or other mutant Cbl-driven myeloid disorders. Figure: Fasudil activity in mouse model of Cbl/Cbl-b DKO MPD. Total WBC (A) and monocyte (B) counts over time in untreated and fasudil-treated mice (mean+/-SEM), C: MLC levels by Western Blot in peripheral blood of control vs. fasudil-treated mice; those surviving longer than 27 weeks are indicated. Figure:. Fasudil activity in mouse model of Cbl/Cbl-b DKO MPD. Total WBC (A) and monocyte (B) counts over time in untreated and fasudil-treated mice (mean+/-SEM), C: MLC levels by Western Blot in peripheral blood of control vs. fasudil-treated mice; those surviving longer than 27 weeks are indicated. Disclosures No relevant conflicts of interest to declare.

RETICULOENDOTHELIOSIS AND MYELOPROLIFERATIVE DISORDERS

PEDIATRICS ◽  
1954 ◽  
Vol 14 (5) ◽  
pp. 495-504 ◽  
Author(s):  
HENRY K. SILVER
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Myeloproliferative Disorders ◽  
Red Cells ◽  
Moderate Increase ◽  
Monocytic Leukemia ◽  
Abnormal Cells

1. The case of a three-year-old boy is presented who had hepatosplenomegaly, bleeding manifestations, reticulocytosis, marked thrombocytopenia and leukocytosis and in whom abnormal cells of various types were found in the peripheral blood. These abnormal cells included nucleated red cells, young myeloid forms as well as immature monocytes. The bone marrow was characterized by a marked increase of nucleated red cells, in all stages of developments, as well as by a moderate increase of mature and immature monocytes. 2. This case appeared to be related clinically to: (1) erythroleukemia; (2) leukoerythroblastosis; (3) monocytic leukemia, both of the Naegeli type and (4) of the Schilling type with leukomoid reaction; (5) leukemic reticuloendotheliosis, and (6) patient No. VII of Downey. 3. The interrelationships between these disorders is discussed.

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