Severe aplastic anemia in a patient with rheumatoid arthritis after introduction of etanercept

Open Medicine ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. 650-654
Author(s):  
Yoshiro Horai ◽  
Tomoya Miyamura ◽  
Karin Shimada ◽  
Motoko Ishida ◽  
Soichiro Takahama ◽  
...  

AbstractA 73-year-old female, diagnosed with rheumatoid arthritis (RA), complicated with severe levels of joint destruction, started etanercept (ETN) because of high persistent RA disease activity. Although her articular symptoms dramatically improved, she developed marked pancytopenia after the introduction of ETN. Bone marrow aspirate specimen revealed hypocellular marrow in three hematopoietic series without atypical findings, which was compatible with aplastic anemia (AA). This is a rare case of severe pancytopenia due to AA presumably induced by ETN.

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4874-4874
Author(s):  
Enkhtsetseg Purev ◽  
Bogdan Dumitriu ◽  
Neal S. Young ◽  
Danielle Townsley

Abstract Translocation of 8;21 (q22;q22), generating a fusion of RUNX1 and AML1 genes is considered leukemia-defining and typically presents as an unequivocal acute myeloid leukemia (AML) with peripheral blood blasts and a hypercellular marrow, although it has been reported in patients with Fanconi anemia and myelodysplastic syndrome (MDS) (Quentin S et al. Blood 2011 Apr 14;117(15)). Aplastic anemia is a rare disease characterized by severe pancytopenia and a hypocellular marrow. A few cytogenetic abnormalities, namely trisomy 8 and monosomy 7, are associated with particularly refractory aplastic anemia, and monosomy 7 is associated with clonal evolution to MDS and rapid progression to AML. We describe a case of newly-acquired severe aplastic anemia in a 23 year old woman. Laboratory studies at presentation showed white blood cells 1.38 k/uL, absolute neutrophil count 0 k/uL, hemoglobin 7.4 g/dL, absolute reticulocyte count 5 k/uL, and platelets 38 k/uL. Bone marrow biopsy was 5% cellular with trilineage hematopoiesis and absolutely no dysplasia, even on repeated review. Initial cytogenetic analysis performed outside the NIH at presentation was normal. The patient was transferred to our institution and promptly received standard immunosuppressive therapy given the severity of neutropenia. However, a repeat bone marrow analysis performed immediately prior to immunosuppression showed t(8:21) (q22;q22) by standard cytogenetics in 3 out of 20 metaphases, with confirmation by fluorescence in situ hybridization (FISH). Blasts were not identified despite multiple repeat bone marrow aspirations utilizing immunohistochemistry and flow cytometry. Testing for Fanconi anemia was negative and leukocyte telomere length was normal for age. She remained severely pancytopenic and transfusion dependent for many months. Chemotherapy for AML was withheld given the severe pancytopenia and absence of blasts, and a search for a bone marrow transplant donor was initiated. Progression to frank leukemia with circulating blasts occurred 8 months following initial presentation, just prior to unrelated donor allogeneic stem cell transplantation. To our knowledge, this is the first reported case of acquired severe aplastic anemia, profound marrow hypocellularity, hypocellular MDS or hypocellular AML occurring in association with the t(8;21)(q22;q22). This unusual case prompted us to perform comparative genomic hybridization (CGH) using the single nucleotide polymorphism (SNP) based CytoScan high density microarrays on DNA from the patient’s bone marrow mononuclear cells. We detected multiple, large regions of copy neutral loss of heterozygosity (also referred to as uniparental disomy) in the patient’s marrow, ranging in size from 3 to 29 Mbp on multiple chromosomes. We hypothesized that the copy-neutral loss of heterozygosity observed in this case would not be present in other patients with acquired aplastic anemia at diagnosis or in normal controls. CGH did not demonstrate any large regions of copy neutral loss of heterozygosity in 10 patients with acquired severe aplastic anemia and normal cytogenetics at diagnosis, nor in 35 healthy controls. Emerging data show that SNP arrays can detect abundant copy neutral loss of heterozygosity amongst select hematologic malignancies and are associated with the duplication of oncogenic mutations. In our patient, copy neutral loss of heterozygosity possibly provided a second lesion, in addition to the RUNX1/AML1 abnormality, that facilitated initiation or progression to leukemia. These results suggest SNP based CGH arrays may be useful in distinguishing hypocellular AML from aplastic anemia and further studies utilizing this technology are warranted. Disclosures: No relevant conflicts of interest to declare.


2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 645.1-645
Author(s):  
K. Katayama ◽  
K. Yujiro ◽  
T. Okubo ◽  
R. Fukai ◽  
T. Sato ◽  
...  

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared


1987 ◽  
Vol 54 (3) ◽  
pp. 137-146 ◽  
Author(s):  
W. Hinterberger ◽  
H. Gadner ◽  
P. H�cker ◽  
A. Hajek-Rosenmayr ◽  
W. Graninger ◽  
...  

2011 ◽  
Vol 38 (11) ◽  
pp. 2301-2308 ◽  
Author(s):  
YING-QIAN MO ◽  
LIE DAI ◽  
DONG-HUI ZHENG ◽  
LANG-JING ZHU ◽  
XIU-NING WEI ◽  
...  

Objective.The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.Methods.Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).Results.Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman’s rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.Conclusion.Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Huaquan Wang ◽  
Qi’e Dong ◽  
Rong Fu ◽  
Wen Qu ◽  
Erbao Ruan ◽  
...  

Objective. To assess the effectiveness of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients receiving immunosuppressive therapy (IST).Methods. Eighty-eight SAA patients receiving IST from January 2007 to December 2012 were included in this retrospective analysis. Of these, 40 subjects received rhTPO treatment (15000 U, subcutaneously, three times a week). rhTPO treatment was discontinued when the platelet count returned to normal range. Hematologic response, bone marrow megakaryocyte recovery, and time to transfusion independence were compared.Results. Hematologic response was achieved in 42.5%, 62.5%, and 67.5% of patients receiving rhTPO and 22.9%, 41.6%, and 47.9% of patients not receiving rhTPO at 3, 6, and 9 months after treatment, respectively (P= 0.0665,P= 0.0579, andP= 0.0847, resp.). Subjects receiving rhTPO presented an elevated number of megakaryocytes at 3, 6, and 9 months when compared with those without treatment (P= 0.025,P= 0.021, andP= 0.011, resp.). The time to platelet and red blood cell transfusion independence was shorter in patients who received rhTPO than in those without rhTPO treatment. Overall survival rate presented no differences between the two groups.Conclusion. rhTPO could improve hematologic response and promote bone marrow recovery in SAA patients receiving IST.


2018 ◽  
Vol 159 (42) ◽  
pp. 1710-1719
Author(s):  
Krisztián Kállay ◽  
Judit Csomor ◽  
Emma Ádám ◽  
Csaba Bödör ◽  
Csaba Kassa ◽  
...  

Abstract: Introduction: Acquired bone marrow failures are rare but fatal diseases in childhood. Since 2013, Hungary has been participating as a full member in the work of the European Working Group on uniform diagnostics and therapy in patients with acquired bone marrow failure syndromes. Hypocellular refractory cytopenia of childhood has been emphasized as a frequent entity, transplanted by reduced intensity conditioning with excellent outcomes. Aim: To analyse and compare the results of treatment before and after our joining. Method: A total of 55 patients have been treated in the 8 centres of the Hungarian Pediatric Oncology Network during 5 years between 2013 and 2017 (severe aplastic anemia: 9, myelodysplastic syndrome: 41, juvenile myelomonocytic leukemia: 5 patients). Allogeneic hematopoietic stem cell transplantation was performed in severe aplastic anemia in 7 cases, while antithymocyte globulin was administered in one case and one patient died before diagnosis. In patients with myelodysplastic syndromes, watch and wait strategy was applied in 4, while transplantation in 37 cases. Reduced intensity conditioning was used in 54 percent of these cases. Transplantation was the treatment of choice in all 5 patients with juvenile myelomonocytic leukemia. Results: In the whole patient cohort, the time from diagnosis to treatment was median 92 (3–393) days, while in severe aplastic anemia median 28 (3–327) days only. Grade II–IV acute graft versus host disease occurred in 22.6%, grade III–IV in 6.8% and chronic in 11.2%. All the patients treated with severe aplastic anemia are alive and in complete remission (100%). The overall estimated survival rate is 85.1% in myelodysplastic syndrome, while 75% in juvenile myelomonocytic leukemia. The median follow-up was 30.4 (1.1–62.5) months. There was a remarkable increase in overall survival comparing the data before (1992–2012) and after (2013) joining the international group, 70% vs. 100% (p = 0.133) in severe aplastic anemia and 31.3% vs. 85.1% (p = 0.000026) in myelodysplastic syndrome. Conclusion: Due to a change in the paradigm of the conditioning regimen in hypocellular refractory cytopenia of childhood, the overall survival rate has significantly increased. Orv Hetil. 2018; 159(42): 1710–1719.


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