Successful treatment with cyclosporin A for myelodysplastic syndrome with erythroid hypoplasia associated with T‐cell receptor gene rearrangements

Satō, Takashi; Iguchi, Tomotaka; Ando, Kotoji; Katagiri, Tomoko; Tauchi, Tetsuzo; Yaguchi, Makoto; Miyazawa, Kenji; Kimura, Yukihiko; Masuda, Michihiko; Mizoguchi, Hideaki; Ohyashiki, Kazuma

doi:10.1046/j.1365-2141.2001.02925.x

Cited by 35 publications

(26 citation statements)

References 13 publications

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“…Since the involvement of Tcells in MDS seems to be similar to PRCA, a good response to immunosuppressive therapy (CyA, ATG) point to the fact that erythroblastopenia can be mediated by an autoimmune T-cell subset [8,9,21]. In the review of the literature, well-documented cases of MDS with erythroid hypoplasia/aplasia had morphological evidence of myelodysplasia [2][3][4]8]. These patients were predominantly elderly at presentation, all requiring regular blood transfusion, and with an unfavorable prognosis because of the high risk of blastic transformation.…”

Section: Discussionmentioning

confidence: 99%

“…Although current treatment options for patients with MDS remain limited, immunosuppressive therapy with antithymocyte globulin (ATG) [5][6][7] and Cyclosporin A (CyA) [8,9], given either singly or in combination [10], and recombinent human erythropoietin (r-HuEPO) [3] are used with success in MDS. However, most patients have a poor prognosis and require repeated blood transfusion.…”

Section: Introductionmentioning

confidence: 99%

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A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1)

Dınçol¹,

Öztürk²,

Palandüz³

et al. 2006

Am. J. Hematol.

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Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report here a 20-year-old woman with severe transfusion-dependent anemia and reticulocytopenia. White blood cells and platelet counts were normal. Bone marrow examination showed a low percentage of erythroid precursors (6%) and a marked dyserythropoiesis and dysmegakaryopoiesis. A diagnosis of MDS (refractory anemia according to the FAB classification) with erythroid hypoplasia was made. Cytogenetic analysis of the bone marrow and peripheral blood revealed a 46,XX,t(3;14)(p21.1;q24.1) translocation, which was confirmed by fluorescence in situ hybridization analysis. This translocation was detected in the apparently healthy younger brother, father, and aunt (father's sister) of the patient. Clonality of T cells in the patient was not confirmed by the polymerase chain reaction and heteroduplex temperature-gradient gel electrophoresis. IgM serology for B19 parvovirus was negative. Other conditions known to be associated with erythroid hypoplasia, such as thymoma, were not present. The patient failed to respond to immunosuppressive therapy (antithymocyte globulin and cyclosporin A). Administration of recombinant human erythropoietin improved her anemia. To our knowledge, this balanced translocation, namely t(3;14)(p21.1;q24.1), which is present both in the patient with MDS with erythroid hypoplasia and in the healthy members of the family, has not been defined previously. Am. J. Hematol. 81:883-887, 2006. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1)

Dınçol¹,

Öztürk²,

Palandüz³

et al. 2006

Am. J. Hematol.

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“…PRCA in MDS is assumed to be the result of defective hemopoiesis in that hematopoietic stem cells are unable to differentiate along the erythroid pathway or erythroid precursors undergo excessive apoptosis (12). An immune-mediated pathogenetic mechanism is proposed because of the presence of monoclonal or oligoclonal T cells in the majority of cases analyzed (12,13). Immunosuppressive therapy including prednisolone is suggested to be a beneficial treatment modality because CyA has achieved an excellent response in some cases (12,13).…”

Section: Discussionmentioning

confidence: 99%

“…MDS with PRCA is a rare form of MDS that has been proposed to represent a novel and distinct entity (12)(13)(14)(15). PRCA in MDS is assumed to be the result of defective hemopoiesis in that hematopoietic stem cells are unable to differentiate along the erythroid pathway or erythroid precursors undergo excessive apoptosis (12).…”

Section: Discussionmentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy in Myelodysplastic Syndrome Involving Pure Red Cell Aplasia

et al. 2010

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Progressive multifocal leukoencephalopathy (PML) is a rare and fatal demyelinating disease of the central nervous system caused by JC polyomavirus (JCV) reactivation in an immunocompromized host. We describe a case of PML in a 76-year-old woman with myelodysplastic syndrome, who had been treated with azathioprine for a pure red cell aplasia-like condition. PML was diagnosed based on the neurologic symptoms, the magnetic resonance imaging patterns and the detection of JCV DNA in the cerebrospinal fluid. She died ten months after the diagnosis. An autopsy confirmed the diagnosis, and JCV DNA was detected in the cerebrum. Azathioprine might have triggered PML.

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“…Responses were unrelated to marrow cellularity or the presence of blasts; among 6 patients with abnormal karyotype, 3 responded (all were 5q-). Four of 8 Japanese MDS patients improved with cyclosporine 81 and another 4 cases, whose MDS included erythroid hypoplasia and evidence of T cell clonal expansion, became transfusion-independent with cyclosporine treatment; 85 in another patient, however, cyclosporine treatment was associated with seeming leukemic progression, which was reversed with drug discontinuation. …”

Section: Cyclosporinementioning

confidence: 99%

Myelodysplastic Syndromes

Greenberg¹,

Young²,

Gattermann³

2002

Hematology

122

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The myelodysplastic syndromes (MDS) are characterized by hemopoietic insufficiency associated with cytopenias leading to serious morbidity plus the additional risk of leukemic transformation. Therapeutic dilemmas exist in MDS because of the disease's multifactorial pathogenetic features, heterogeneous stages, and the patients' generally elderly ages. Underlying the cytopenias and evolutionary potential in MDS are innate stem cell lesions, cellular/cytokine-mediated stromal defects, and immunologic derangements. This article reviews the developing understanding of biologic and molecular lesions in MDS and recently available biospecific drugs that are potentially capable of abrogating these abnormalities.Dr. Peter Greenberg's discussion centers on decision-making approaches for these therapeutic options, considering the patient's clinical factors and risk-based prognostic category.One mechanism underlying the marrow failure present in a portion of MDS patients is immunologic attack on the hemopoietic stem cells. Considerable overlap exists between aplastic anemia, paroxysmal nocturnal hemoglobinuria, and subsets of MDS. Common or intersecting pathophysiologic mechanisms appear to underlie hemopoietic cell destruction and genetic instability, which are characteristic of these diseases. Treatment results and new therapeutic strategies using immune modulation, as well as the role of the immune system in possible mechanisms responsible for genetic instability in MDS, will be the subject of discussion by Dr. Neal Young.A common morphological change found within MDS marrow cells, most sensitively demonstrated by electron microscopy, is the presence of ringed sideroblasts. Such assessment shows that this abnormal mitochondrial iron accumulation is not confined to the refractory anemia with ring sideroblast (RARS) subtype of MDS and may also contribute to numerous underlying MDS pathophysiological processes. Generation of abnormal sideroblast formation appears to be due to malfunction of the mitochondrial respiratory chain, attributable to mutations of mitochondrial DNA, to which aged individuals are most vulnerable. Such dysfunction leads to accumulation of toxic ferric iron in the mitochondrial matrix.

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Successful treatment with cyclosporin A for myelodysplastic syndrome with erythroid hypoplasia associated with T‐cell receptor gene rearrangements

Cited by 35 publications

References 13 publications

A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1)

A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1)

Progressive Multifocal Leukoencephalopathy in Myelodysplastic Syndrome Involving Pure Red Cell Aplasia

Myelodysplastic Syndromes

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