UK Single Instituition Experience of Mastocytosis: Guys and St Thomas' NHS Foundation Trust

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5052-5052
Author(s):  
Nandini Sadasivam ◽  
Mufaddal Moonim ◽  
Clive Grattan ◽  
Jonathan White ◽  
Bridget Wilkins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Clinical Symptoms ◽  
Systemic Mastocytosis ◽  
Symptom Control ◽  
Alpha Interferon ◽  
Treatment Needs ◽  
Self Administration ◽  
Bone Marrow Biopsies ◽  
Kit D816v

Abstract Abstract 5052 Introduction: Systemic mastocytosis(SM) is diagnosed when clonal, neoplastic mast cells are demonstrated in extracutaneous tissues. SM is a heterogeneous disorder ranging from indolent disease to aggressive multisystem involvement. We have an established mastocytosis working group in our Trust which was registered with the European Competence Network of Mastocytosis(ECNM) in 2005. We present data prospectively collected using an ECNM algorithm for the management of SM patients over 5 years. Methods: 120 cases of cutaneous mastocytosis have been discussed at 3 monthly multidisciplinary meetings with dermatology colleagues. Full blood counts, liver, bone profile and DEXA scans are reviewed with clinical symptoms and treatments. Patients with a tryptase level of >20ng/ml are offered haematology review and bone marrow investigation. In addition patients referred directly to haematology for a second opinion have their cases and bone marrows reviewed. Bone marrow samples are sent for c-kit D816V mutation analysis. Results: Classification of SM patients. 59/120 (46%) patients were offered bone marrow biopsies. Tryptase levels for these ranged from 15.1–760ng/ml (median 51.5ng/ml).4 patients declined biopsy.5/55 had normal biopsies and were c-kit negative.50 patients had SM.47/50(94%) met the WHO major criteria and 3/50(6%) minor criteria. These were subclassified-38/50(76%) had Indolent Systemic Mastocytosis(ISM);1/50 (2%) had Smouldering Systemic Mastocytosis(SSM);5/50(10%) had Aggressive Systemic Mastocytosis and 6/50(12%) had Systemic Mastocytosis with associated haematologiocal non-mast cell lineage disorder(SM-AHNMD). The bone marrow trephine disease burden was variable:ASM (range 5–100%), SSM 20%, ISM (5-45%) and AHNMD (5-100%). Tryptase levels reflected total disease bulk including cutaneous burden. C-KIT D816V mutation 44 patients with SM had samples analysed for the D816V mutation. 35 were positive (80%) and 9 negative (20%). Clinical Symptoms: 11/59 (19%) patients were asymptomatic (10 had ISM and 1 SSM).36/59 (61%) patients had urticarial symptoms needing symptomatic treatment (2 normal marrow, 2 AHNMD, 2 ASM and 30 ISM).16/59 (27%) patients had allergic symptoms ranging from mild allergies to anaphylaxis.(3 normal marrows, 13 ISM).13/59(22%) had gastrointestinal symptoms ranging from loose motions to severe colitis(1 normal marrow,1 ASM and 11 ISM). DEXA results:36/59(61%) patients had reported DEXA scans at our Trust, the rest reviewed locally. 6/36 (16%) had osteoporosis and required treatment. One 63yr old female patient has SM-AHNMD(MPD). 5 patients had ISM. 3 were females (age range 45–65yrs; tryptase levels 42.9, 49.1 and 60.5ng/ml)) and 2 male (both 45yrs: tryptase levels 31.2 and 47.8ng/ml). After 1 year of treatment with bisphophonates one of the male patients showed an improvement in his osteoporosis indices.7/36(19%) had osteopaenia reported all with a diagnosis of ISM.5 were male and 2 female (tryptase range 21.1–174ng/ml:median 40.3ng/ml).23/36(64%) patients had normal DEXA scans. Management: Treatment regimes in patients with SM are for symptom control. Antihistamines, anti-inflammatory agents, anti-leucotriene agents, mast cells stabilising agents, bisphosphonates and steroids are used. In severe anaphylactic patients self administration of adrenaline is taught. Patients with ASM have been treated with various modalities e.g. Cladrabine, Alpha Interferon, Dasatinib, Imatinib (D816V negative patients) and Midostaurine with variable partial responses.2 patients with ASM have died due to rapidly progressive disease.2 AHNMD patients have an associated MPD (1 Jak 2 postive) and are being treated with pegylated alpha interferon and venesection.2 AHNMD patients died as a result progressive acute myeloid leukaemia and Non Hodgkins Lymphoma.2 AHNMD patients (MDS/MGUS) are being monitored. Conclusions: Our data reflects the heterogeneous nature of this disorder both clinically and in the histological classification. Patients with ISM can have severe clinical manifestations and treatment needs to be tailored to the individual's symptoms. Assessment and surveillence for osteoporosis is vital for all patients. ASM patients have limited treatment options with variable and unsustained responses. Further development of evidence based novel therapies requires multicentred trials in this rare group of patients. Disclosures: Harrison: Incyte: Honoraria; Novartis: Honoraria.

Kit Signaling Regulates Mitf Expression in Mastocytosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3601-3601
Author(s):  
Youl-Nam Lee ◽  
Pierre Noel ◽  
Amir Shahlaee ◽  
Melody Carter ◽  
Reuben Kapur ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Tyrosine Kinase Receptor ◽  
Bone Marrow Biopsies ◽  
Activating Mutations ◽  
Cell Assays ◽  
Mast Cell Disease ◽  
Mitf Expression

Abstract Mastocytosis is a heterogeneous disease arising from abnormal proliferation of mast cells. Activating mutations in codon D816 of the tyrosine kinase receptor, c-kit, are found in the majority of adult patients with systemic mastocytosis, an aggressive form of the disease. Constitutive activation of the Kit signaling pathway is critical to the transformed phenotype, and thus understanding how this pathway regulates downstream events is of great importance. A number of transcription factors are also essential to mast cell development, including the Microphthalmia-associated transcription factor (Mitf). We examined Mitf expression in bone marrow biopsies from nine patients with systemic mastocytosis by immunohistochemistry; we found that Mitf is highly expressed in all cases with the D816V mutation. In contrast, Mitf is not highly expressed in non-malignant mast cells in the bone marrow from patients with aplastic anemia and leukemia, suggesting thatMitf expression is regulated by Kit-dependent signalsMitf may play a role in the transformed phenotype of mastocytosis.We show that in normal mast cells, Kit signaling markedly upregulates Mitf expression. In both normal and malignant mast cells, pharmacologic inhibitors of Kit, and the downstream kinase, PI3K, block Mitf expression. To examine whether Mitf is required for transformed phenotype from constitutive Kit signaling in mast cells, we have used a shRNA-expressing lentivirus to knockdown Mitf expression in mastocytosis cell lines. We found that silencing of Mitf markedly impaired growth in proliferation and colony forming cell assays. This work demonstrates a link between two critical factors, Kit and Mitf, in the development of malignant mast cell disease.

Change In Mast Cell Bone Marrow Burden and In Serum Tryptase Level Are Not Accurate Markers of Response In Patients with Systemic Mastocytosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3073-3073
Author(s):  
Alfonso QuintÁs-Cardama, ◽  
Matjaz Sever ◽  
Jorge E. Cortes ◽  
Hagop M. Kantarjian ◽  
Srdan Verstovsek
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Median Number ◽  
Response To Therapy ◽  
Serum Tryptase ◽  
Bone Marrow Biopsies ◽  
Tryptase Level ◽  
Bone Marrow Mast Cell

Abstract Abstract 3073 Background: Bone marrow involvement, with or without cutaneous or visceral involvement, is almost universal in patients with systemic mastocytosis (SM). The KITD816V mutation is present in most patients with SM, thus confirming its clonal nature. Patients with ASM are usually managed with cytoreductive agents such as hydroxyurea (HU), cladribine (2CDA), or interferon-alpha (IFN-α), although the activity of these therapies is limited as they do not target specifically the malignant clone. Response assessment in SM relies on symptom improvement and reduction in serum tryptase levels and visceral and/or bone marrow mast cell burden (percent mast cell involvement). We contend that the later two relatively objective metrics may not be appropriate markers of response because serum tryptase levels may vary significantly at different time-points in the same patient in the absence of intervention, do not correlate accurately with mast cell burden, and bone marrow mast cell burden determination is subject to sampling bias given the patchy infiltration observed in many cases of SM. Objectives: To assess the utility of bone marrow mast cell burden reduction and serum tryptase level reduction as criteria for response in patients with SM. Patients and Therapy: We studied a cohort of 50 patients with SM for whom at least 2 sequential bone marrow biopsies and 2 serum tryptase level determinations were available at our center. The KITD816V mutation was present in 20 (59%) of 34 assessable patients. No patient carried the JAK2V617F mutation or the FIP1L1-PDGFRA rearrangement. Patients had a diagnosis of indolent SM (ISM, n=25), aggressive SM (ASM, n=16), or SM-AHNMD (n=9). All but 1 patient received SM-directed therapy (median number of therapies 2, range 1–5), including: imatinib (n=16), dasatinib (n=23), RAD001 (n=8), denileukin diftitox (n=7). The median number of bone marrow biopsies available per patient was 4 (range, 2–14) and the median number of tryptase measurements was 6 (range, 2–18), which were obtained both on and off SM-directed therapies. Results: Four patients had a bone marrow complete response: 1 with imatinib, 2 with dasatinib, and 1 with decitabine (with SM-MDS). However none of the responders normalized their tryptase levels. We used the coefficient of variation (CV) as a normalized measure of dispersion of a probability distribution for the percentage of mast cells in bone marrow biopsies and serum tryptase levels. In this manner, the CV summarizes/describes the variation in tryptase levels and bone marrow mast cell percentage from the baseline (first recorded value) in the patients evaluated. We found that among the 49 treated patients, the percentage of bone marrow mast cells varied significantly with a CV ranging from 6 – 173% and an average of 65%. Forty-four percent of patients had a CV equal or higher to the average. Similar results were observed regarding tryptase levels, with an average CV of 19% that ranged from 0 to 96%. Thirty-six percent of patients had a CV higher than average. Conclusion: While most patients fail to respond to currently available SM-directed therapies, sequential bone marrow biopsies and tryptase level determinations exhibit remarkable variation both during and in the absence of SM-directed therapy. Therefore, it seems that single time point measurements of these values do not represent proper tools to assess accurately response to therapy. Disclosures: No relevant conflicts of interest to declare.

Aggressive Systemic Mastocytosis Is Associated with a High Kit D816V Allele Burden in Peripheral Blood.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2899-2899
Author(s):  
Philipp Erben ◽  
Georg Bolz ◽  
Juliana Popa ◽  
Georgia Metzgeroth ◽  
Martin C Müller ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Detection Limit ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Peripheral Blood ◽  
Kinase Inhibitors ◽  
Systemic Mastocytosis ◽  
Allele Burden ◽  
Minor Criteria ◽  
Kit D816v

Abstract Abstract 2899 Poster Board II-875 According to 2008 WHO definitions, diagnosis of systemic mastocytosis (SM) is based on the presence of one major criteria (multifocal dense infiltrates of mast cells in bone marrow or organ biopsies) and at least one of the following minor criteria (i) >25% are atypical cells on bone marrow smears or are spindle-shaped in mast cell infiltrates of visceral organs, ii) KIT point mutation at codon 816 in the bone marrow or other extracutaneous organs, iii) mast cells express CD2 and/or CD25, iv) baseline serum tryptase concentration >20 ng/mL) or the presence of at least three minor criteria. Patients with aggressive SM (ASM) have to present with one or more C-findings (i) neutrophils <1,000/μL, Hb <10g/dL, or platelets <100,000/μL, ii) hepatomegaly with impaired liver function – elevated transaminases and/or bilirubin levels and/or hypoalbuminemia, iii) palpable splenomegaly with signs of hypersplenism, iv) malabsorption with significant hypoalbuminemia and/or significant loss. ASM and MCL are clearly associated with an inferior survival. The activating KIT D816V point mutation is thought to be pivotal for pathogenesis and potential targeted therapy with novel tyrosine kinase inhibitors. However, conventional sequencing (CS) of RNA/DNA extracted from bone marrow (BM) samples of SM patients reveals the mutation in less than 50-60% of patients while peripheral blood (PB) samples are frequently negative as consequence of low numbers of malignant cells and poor assay sensitivity. For better qualitative and additional quantitative assessment of the KIT D816V allele burden (expressed as ratio KIT D816V vs. KIT wildtype), we sought to establish (i) a D-HPLC (denaturing-high performance liquid chromatography) assay combined with direct sequencing in case of a positive D-HPLC signal and (ii) a LightCyclerTM based quantitative PCR (RQ-PCR). The assay sensitivities were calculated through serial cell (KIT D816V positive HMC-1 cells in NB4 cells) and RNA dilutions. The detection limit was estimated between 0.1 and 0.5% for both assays which was thus significantly improved in comparison to the detection limit of CS which was at 10–15%. Patient material was available from BM (n=134) and PB (n=93) from 173 patients (88 m, 85 f, median age 54 years) with diagnosis of SM including 10 patients with confirmed ASM (n=9) or aleukemic variant of MCL (n=1) according to WHO definitions. At diagnosis, D-HPLC, RQ-PCR and CS were positive in 78% (104/134), 84% (112/134) and 60% (80/134) of BM samples, respectively. Two patients had a KIT D816H and one patient had a KIT D816L mutation. In 54 cases with contemporaneously collected BM and PB samples, the KIT D816V mutation was found in PB of BM positive patients by D-HPLC, RQ-PCR and CS in 47% (22/46), 55% (27/49) and 38% (14/37) of cases, respectively. This information allowed the detection of the KIT D816V mutation in an additional 27 of 39 (69%) patients without available bone marrow biopsies. All ASM patients were KIT D816V positive in PB with a median KIT D816V allele burden of 36% (range 26–98%) vs. 7.8% (range 0.1–61%) in other stages of SM (p=0.0021). Eleven of 124 (8.9%) SM patients with a KIT D816V allele burden >20% are currently explored for the potential diagnosis of ASM or MCL. In conclusion, D-HPLC is a reliable and sensitive method for the screening of variable KIT mutations in BM and PB of SM patients and is clearly superior to CS. Application of RQ-PCR assays for the most common D816V mutation may overlook rare mutations but allows quantification of the KIT D816V allele burden which may be useful for diagnosis of ASM and monitoring of residual disease during treatment with novel tyrosine kinase inhibitors, e.g. midostaurin or dasatinib. Disclosures: No relevant conflicts of interest to declare.

scholarly journals P5: SYSTEMIC MASTOCYTOSIS PRESENTING AS CARDIAC TAMPONADE WITH CD25+ PERICARDIAL MAST CELLS

2016 ◽  
Vol 64 (3) ◽  
pp. 819.1-819
Author(s):  
VK Sukrithan ◽  
JN Salamon ◽  
G Berulava ◽  
NE Sibinga ◽  
AK Verma
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Mast Cells ◽  
Pericardial Effusion ◽  
Systemic Mastocytosis ◽  
Maculopapular Rash ◽  
Epinephrine Infusion ◽  
Pericardial Window ◽  
Bone Marrow Biopsies ◽  
Large Pericardial Effusion

Purpose of StudyCase.Methods UsedDescriptive.Summary of ResultsA 59 year old man with a history of lymphadenopathy, presented with shortness of breath and pleuritic chest pain since three days. A hyperpigmented maculopapular rash with urticaria was present along with multiple syncopal episodes and chronic diarrhea. CT scan of the abdomen in 2006 revealed lymphadenopathy, hepatosplenomegaly, and osteosclerosis. Inguinal and cervical lymph node biopsies in 2006 and 2012, and two bone marrow biopsies in 2012 were negative for malignancy. In 2009, he was diagnosed with non-ischemic cardiomyopathy with an ejection fraction of 40%. Peripheral blood, lymph node, and bone marrow flow cytometry were also unrevealing. On admission, the eosinophil count on admission was 500/µL. Echocardiography showed a large pericardial effusion with impaired right ventricular filling and significant respiratory variation in transmitral flow velocity. A pericardial window was placed, with drainage of approximately 1 liter of exudative fluid. During the surgery, the patient suffered sudden hypotension requiring epinephrine infusion. Tryptase levels drawn were 115 and 154 ng/ml. Pericardial tissue showed scattered c-Kit+ and CD25+ mast cells and blood PCR showed D816V mutation in the c-KIT gene. Re-stained stomach biopsy specimens from 2006 showed two clusters of c-Kit+ and CD25+ mast cells. A bone marrow biopsy showed aggregates of c-Kit+, tryptase+, CD25+ mast cells consistent with Systemic Mastocytosis. The transient hypotension was likely due to distributive shock from mast cell degranulation. Hyperactive mast cells may have served as mediators of the inflammatory response, contributing to production of the pericardial effusion leading to tamponade.ConclusionsSM with tamponade.Abstract P5 Figure 1

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

Blood ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 752-759 ◽  
Author(s):  
Karoline V. Gleixner ◽  
Matthias Mayerhofer ◽  
Karl J. Aichberger ◽  
Sophia Derdak ◽  
Karoline Sonneck ◽  
...  
Keyword(s):  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Drug Effects ◽  
Kit Mutation ◽  
Growth Inhibitory ◽  
Ic50 Values ◽  
Tk Inhibitors ◽  
Mast Cell Leukemia ◽  
Kit D816v

AbstractIn most patients with systemic mastocytosis (SM), including aggressive SM and mast cell leukemia (MCL), neoplastic cells express the oncogenic KIT mutation D816V. KIT D816V is associated with constitutive tyrosine kinase (TK) activity and thus represents an attractive drug target. However, imatinib and most other TK inhibitors fail to block the TK activity of KIT D816V. We show that the novel TK-targeting drugs PKC412 and AMN107 counteract TK activity of D816V KIT and inhibit the growth of Ba/F3 cells with doxycycline-inducible expression of KIT D816V as well as the growth of primary neoplastic mast cells and HMC-1 cells harboring this KIT mutation. PKC412 was a superior agent with median inhibitory concentration (IC50) values of 50 to 250 nM without differences seen between HMC-1 cells exhibiting or lacking KIT D816V. By contrast, AMN107 exhibited more potent effects in KIT D816V- HMC-1 cells. Corresponding results were obtained with Ba/F3 cells exhibiting wild-type or D816V-mutated KIT. The growth-inhibitory effects of PKC412 and AMN107 on HMC-1 cells were associated with induction of apoptosis and down-regulation of CD2 and CD63. PKC412 was found to cooperate with AMN107, imatinib, and cladribine (2CdA) in producing growth inhibition in HMC-1, but synergistic drug interactions were observed only in cells lacking KIT D816V. Together, PKC412 and AMN107 represent promising novel agents for targeted therapy of SM. (Blood. 2006;107: 752-759)

Vascular Endothelial Growth Factors and Angiopoietins As New Players in Mastocytosis

2021 ◽  
Author(s):  
Simone Marcella ◽  
Angelica Petraroli ◽  
Mariantonia Braile ◽  
Roberta Parente ◽  
Anne Lise Ferrara ◽  
...  
Keyword(s):  
Growth Factors ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Serum Concentrations ◽  
Kit Receptor ◽  
Clinical Variants ◽  
Endothelial Growth Factors ◽  
Kit D816v

Abstract Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSAKIT WT and ROSA KIT D816V and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSAKIT WT, ROSAKIT D816V and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients.

scholarly journals MDS with 5q deletion and rare cKIT positive mastocytosis: a diagnostic and therapeutic challenge

2019 ◽  
Vol 12 (4) ◽  
pp. e227768
Author(s):  
Daniel Steven Sanders ◽  
Thomas Fennell ◽  
Mohammad Muhsin Chisti
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Case Report ◽  
Systemic Mastocytosis ◽  
Molecular Testing ◽  
Bone Marrow Biopsies ◽  
Haematological Response ◽  
Clonal Origin ◽  
Mast Cell Population ◽  
5Q Deletion

A patient with a diagnosis of myelodysplastic syndrome (MDS) with isolated 5q deletion underwent repeat bone marrow biopsy to assess haematological response after 6 months of initial lenalidomide therapy. Subsequent bone marrow biopsies revealed persistent MDS with del(5q) in addition to a small atypical mast cell population with >25% of mast cells with spindle-shaped morphology and immunohistochemistry characteristics consistent with mastocytosis. Molecular testing on the bone marrow was positive for cKIT D816V and the patient was diagnosed with systemic mastocytosis (SM) with an associated haematological neoplasm. MDS with SM is well known to be associated; however, to the best of our knowledge, only one prior case report identifies MDS with del(5q) and associated cKIT D816V positive mastocytosis. While the exact clonal origin of both chromosomal aberrations is unclear, this case illustrates the therapeutic efficacy of lenalidomide in a patient with MDS with del(5q) and rarely associated cKIT positive SM.

scholarly journals Systemic Mastocytosis and Essential Thrombocythemia: Case Report and Literature Overview

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 528
Author(s):  
Mauro Cancian ◽  
Elisabetta Cosi ◽  
Marco Pizzi ◽  
Sandro Giannini ◽  
Irene Bertozzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Systemic Mastocytosis ◽  
Inflammatory Reactions ◽  
Zolendronic Acid ◽  
Literature Overview ◽  
Dose Aspirin ◽  
Low Dose Aspirin

Mastocytosis is a rare disease in which heightened amounts of mast cells accumulate in the skin, bone marrow, and other visceral organs. Upon activation, mast cells release a wide variety of preformed or newly synthesized mediators which can induce allergic symptoms and inflammatory reactions. Mastocytosis is diagnosed by biopsy and can be divided into cutaneous and systemic mastocytosis (SM). The first one affects the skin and is relatively benign, whilst SM, which involves bone marrow and other organs, may be aggressive and associate with both myelodisplastic and myeloproliferative diseases. Here we present a case of SM associated with essential thrombocythemia and complicated by severe osteoporosis, successfully treated with hydroxyurea, low-dose aspirin and zolendronic acid.

scholarly journals Treatment of hairy cell leukemia with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 817-820 ◽  
Author(s):  
G Flandrin ◽  
F Sigaux ◽  
S Castaigne ◽  
C Billard ◽  
M Aguet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hairy Cell Leukemia ◽  
Alpha Interferon ◽  
Initial Increase ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies ◽  
Biopsy Specimens ◽  
Hairy Cells ◽  
Normal Controls

Abstract Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 patients. Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of thrombocytopenia often appeared within 2 months and usually preceded improvement of anemia, monocytopenia, and neutropenia. Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 patients by the fourth month and in 3 of 8 additional patients by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

Systemic Mastocytosis in a Goat

1995 ◽  
Vol 32 (6) ◽  
pp. 719-721 ◽  
Author(s):  
K. N. M. Khan ◽  
J. E. Sagartz ◽  
G. Koenig ◽  
K. Tanaka
Keyword(s):  
Electron Microscopy ◽  
Bone Marrow ◽  
Transmission Electron Microscopy ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Periodic Acid ◽  
Hypochromic Anemia ◽  
Postmortem Examination ◽  
Periodic Acid Schiff ◽  
Transmission Electron

Systemic mastocytosis was diagnosed in a 4-year-old, female Nubian goat. Clinically, the animal was depressed and had severe macrocytic hypochromic anemia and leukopenia. Postmortem examination revealed neoplastic mast cells invading the heart, lung, liver, spleen, lymph nodes, and bone marrow. Eosinophils were frequently admixed with infiltrating mast cells in all organs. Using routine light microscopy, histochemistry, and transmission electron microscopy, metachromatic and periodic acid—Schiff–positive granules were identified within the cytoplasm of neoplastic mast cells. Erythrophagocytosis was observed in some neoplastic cells, although its contribution to the anemia was not clear. This report represents the first description of mast cell neoplasia in the goat.

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