Megakaryocytic Aplasia Research Articles

A Retrospective Multicenter Case Study Evaluating the Characteristics, Management and Outcome of Acquired Amegakaryocytic Thrombocytopenia

A Retrospective Multicenter Case Study Evaluating the Characteristics, Management and Outcome of Acquired Amegakaryocytic Thrombocytopenia

Acquired pure megakaryocytic aplasia successfully treated with cyclosporine.

Acquired pure megakaryocytic aplasia is a rare hematological disorder characterized by thrombocytopenia with absent or markedly reduced megakaryocytes in the bone marrow. We report a case of a 25-year-old male diagnosed as acquired pure megakaryocytic aplasia. Treatment with prednisone and intravenous immunoglobulin failed, but he was successfully treated with cyclosporine, with complete remission after 90 days and normal platelet count maintained thereafter.

Immune-mediated erythroid and megakaryocytic aplasia in a cat

A 6-month-old domestic shorthair cat was evaluated because of acute lethargy. Severe nonregenerative anemia and thrombocytopenia were identified. Cytologic examination of a bone marrow aspirate revealed selective erythroid and mega-karyocytic aplasia and a high number of apparently normal small lymphocytes. Infectious agents implicated in feline hematologic disorders were excluded on the basis of serologic tests or PCR amplification, including FeLV, Ehrlichia canis, Anaplasma phagocytophilum, Mycoplasma haemofelis, Candidatus Mycoplasma haemominutum, and Candidatus Myco-plasma turicensis. A 10-day course of prednisolone administration did not improve the hematologic disorder. Administration of human polyclonal immunoglobulins preceded increased reticulocyte count by 3 days. A second bone marrow examination confirmed restoration of erythroblasts and megakaryocytes. After 1 relapse, the disease was successfully controlled with prednisolone for > 3 years. Immune-mediated bone marrow aplasia is rare in cats and usually affects only erythrocyte progenitors. Concomitant involvement of erythroid and megakaryocytic cell lines can be successfully treated via immunosuppressive therapy. Human immunoglobulins seem to be well tolerated in cats; however, proof of a beneficial effect requires further study.

Acquired pure megakaryocytic aplasia: Report of a single case treated with mycophenolate mofetil

Acquired pure megakaryocytic aplasia (APMA) is a rare disorder in the field of hematological diseases. We report the case of a patient with APMA treated with mycophenolate mofetil and review the literature associated with this. Until today, very few cases of APMA have been reported and the disease etiology still seems to be unclear. There have been no reported cases of treatment of APMA treated with mycophenolate mofetil.

Acquired Pure Megakaryocytic Aplasia in a Patient with IgA Deficiency: A Rare Association.

Acquired Pure Megakaryocytic Aplasia in a Patient with IgA Deficiency: A Rare Association.

Clonal Gammopathies, Immune Cytopenias and Autoimmune Thyroid Dysfunction Following Alemtuzumab Containing Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation.

Reduced-intensity or “nonmyeloablative” conditioning (RIC) regimens, which include Alemtuzumab, results in stable donor hematopoietic and lymphoid engraftment with minimal graft versus host disease. At our institution 182 patients with myeloid and lymphoid malignancies have undergone RIC transplantation between March 1998 and March 2004. In order to ascertain whether the inclusion of Alemtuzumab affects post transplant immune reconstitution, we have assessed the incidence of clonal gammopathies and organ specific autoantibodies in all patients in whom information was available. We used 44 patients who had conventional nommyeloablative HSCT as our control group. In the RIC HSCT group 40(22%) developed clonal gammopathies. The median age at RIC HSCT was 55 years (range 24–66); the underlying dignosis was MDS(n=15), AML(n=15), NHL(n=8) and CML(n=2). A gammopathy was detected at a median of 19 weeks post RIC HSCT (range 8–44). Bone marrow aspiration and biopsy did not show increased numbers of plasma cells. Chimerism studies (unfractionated bone marrow and CD3+, CD15+, CD19+ and CD56+ peripheral blood fractions) showed that 18(45%) were fully donor, 18(45%) had mixed chimerism and it was not available for 4(10 %). By contrast clonal gammopathies were detected in only 4 of 44 patients who had conventional nonmyeloablative conditioning. There was a significant difference between two groups (P=0.05). 9 of 182 (5%) patients (AML=6, MDS=1, MCL=1) developed immune cytopenias at a median of 149 days(range 24–238 days). Those comprised of ITP(n=4), AIHA(n=3), Evans' syndrome(n=2), red cell and megakaryocytic aplasia(n=1). Chimerism studies (unfractionated bone marrow and CD3+, CD15+, CD19+ and CD56+ peripheral blood fractions) showed that 6(66%) patients were fully donor, 1(11%) was mixed chimeric and for 2(23%) patients chimerism studies were not available. One patient did not need any treatment; one patient with AIHA had a complete response to prednisolone. 2 patients (1 ITP and 1 Evans' syndrome) responded to IVIG. The five non-responders to IVIG (2 AIHA, 2 ITP, and 1 red cell aplasia and megakaryocytic aplasia) resonded to treatment with Rituximab 375mg/m2 weekly for 4 weeks with a maximal response at a mean of 30 days from commencing the treatment. 3 of 182(1.6%) patients developed autoimmune thyroid dysfunction. All patients had normal thyroid function tests and no antibodies to thyrotropin receptor before RIC HSCT. None of the patients, who had clonal gammopathy, immune cytopenia and autoimmune thyroid dysfunction, developed PTLD. We hypothesize that the RIC regimens incorporating monoclonal antibody Alemtuzumab causes clonal gammopathies, immune cytopenias and autoimmune thyroid dysfunction due to dysregulated B cell proliferation secondary to prolonged T cell recovery time.

Acquired pure megakaryocytic aplasia report of two cases with long‐term responses to antithymocyte globulin and cyclosporine

Acquired pure megakaryocytic aplasia report of two cases with long‐term responses to antithymocyte globulin and cyclosporine

Human serum megakaryocyte colony-stimulating activity appears to be distinct from interleukin-3, granulocyte-macrophage colony-stimulating factor, and lymphocyte-conditioned medium

Sera from patients with bone marrow megakaryocyte aplasia are a rich source of megakaryocyte colony-stimulating activity (Meg-CSA). Other biologic materials exhibiting Meg-CSA include phytohemagglutinin-stimulated human lymphocyte-conditioned medium (PHA-LCM), recombinant interleukin-3 (IL-3), and recombinant granulocyte macrophage colony-stimulating factor (GM-CSF). Neutralizing antisera to both recombinant IL-3 and GM-CSF were used to evaluate the relationship among these sources of Meg-CSA. Varying dilutions of IL-3 and GM-CSF antisera were tested in plasma clot cultures of normal human peripheral blood megakaryocyte progenitors optimally stimulated by either IL-3 (1 U/mL), GM-CSF (1 U/mL), PHA-LCM (2.5% to 5% vol/vol), or aplastic human serum (10% vol/vol). IL-3 antiserum at dilutions up to 1/2,000 totally abrogated megakaryocyte colony growth stimulated by IL-3. A 1/500 dilution of GM-CSF antiserum completely eliminated GM-CSF-induced megakaryocyte colony development. A combination of anti-IL-3 and anti-GM-CSF, each at a 1/500 dilution, inhibited all megakaryocyte colony growth stimulated by optimal concentrations of IL-3 and GM-CSF together. There was no neutralizing crossreactivity between the IL-3 and GM-CSF antisera. At maximally neutralizing concentrations, IL-3 antiserum inhibited 66% of the megakaryocyte colony growth stimulated by PHA-LCM. Residual megakaryocyte colony growth was eliminated by the addition of a 1/500 dilution of anti-GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Human Serum Megakaryocyte Colony-Stimulating Activity Appears To Be Distinct From Interleukin-3, Granulocyte-Macrophage Colony-Stimulating Factor, and Lymphocyte-Conditioned Medium

Abstract Sera from patients with bone marrow megakaryocyte aplasia are a rich source of megakaryocyte colony-stimulating activity (Meg-CSA). Other biologic materials exhibiting Meg-CSA include phytohemagglutinin- stimulated human lymphocyte-conditioned medium (PHA-LCM), recombinant interleukin-3 (IL-3), and recombinant granulocyte macrophage colony- stimulating factor (GM-CSF). Neutralizing antisera to both recombinant IL-3 and GM-CSF were used to evaluate the relationship among these sources of Meg-CSA. Varying dilutions of IL-3 and GM-CSF antisera were tested in plasma clot cultures of normal human peripheral blood megakaryocyte progenitors optimally stimulated by either IL-3 (1 U/mL), GM-CSF (1 U/mL), PHA-LCM (2.5% to 5% vol/vol), or aplastic human serum (10% vol/vol). IL-3 antiserum at dilutions up to 1/2,000 totally abrogated megakaryocyte colony growth stimulated by IL-3. A 1/500 dilution of GM-CSF antiserum completely eliminated GM-CSF-induced megakaryocyte colony development. A combination of anti-IL-3 and anti- GM-CSF, each at a 1/500 dilution, inhibited all megakaryocyte colony growth stimulated by optimal concentrations of IL-3 and GM-CSF together. There was no neutralizing crossreactivity between the IL-3 and GM-CSF antisera. At maximally neutralizing concentrations, IL-3 antiserum inhibited 66% of the megakaryocyte colony growth stimulated by PHA-LCM. Residual megakaryocyte colony growth was eliminated by the addition of a 1/500 dilution of anti-GM-CSF.

Immune disregulation of hematopoiesis.

In vitro coculture studies of normal T lymphocytes, natural killer (NK) cells, or monocytes with human hematopoietic progenitor cells (HPC) suggest a potential role for immune cells in the regulation of hematopoiesis. In some patients with severe aplastic anemia or selective pure red cell, white cell, or megakaryocyte aplasia, activated T cells, NK cells, or monocytes mediate marrow failure by suppressing growth of HPC. Immunosuppressive agents such as corticosteroids, antithymocyte globulin, cyclophosphamide, or cyclosporin A may dramatically improve blood cell production in patients with marrow failure by removing or modulating immune suppressor cells.

Immune Disregulation Of Hematopoiesis

In vitro coculture studies of normal T lymphocytes, natural killer (NK) cells, or monocytes with human hematopoietic progenitor cells (HPC) suggest a potential role for immune cells in the regulation ofhematopoiesis. In some patients with severe aplastic anemia or selective pure red cell, white cell, or megakaryocyte aplasia, activated T cells, NK cells, or mono­ cytes mediate marrow failure by suppressing growth of HPC. Immu­ nosuppressive agents such as corticosteroids, anti thymocyte globulin, cyclophosphamide ,

Marrow-suppressing factors in the blood in pure red-cell aplasia, thymoma and Hodgkin's disease.

1. A stem cell suppressing factor has been found in the serum of a patient with Hodgkin's disease, a thymic tumour and pure red‐cell aplasia. This factor disppeared when active erythropoiesis returned following radiotherapy to the tumour.2. The suppressing activity was assayed in mice by measuring the capacity of their bone marrow to restore erythropoiesis in heavily irradiated recipients.3. Failure to demonstrate a raised erythropoietin level, as well as the finding that IgA and IgM immunoglobulins were reduced, suggested that autoimmune processes might be involved. However, it appeared unlikely that the factor was an autoantibody since suppressing activity was destroyed by storage at −20° C.4. The sera of nine other patients, one with a thymoma associated with erythroid and megakaryocyte aplasia, three with anterior mediastinal tumours and five with secondary marrow aplasia, were assayed. Three of these showed mild suppressing activity, but this could have been due to non‐specific causes, the nature of which is discussed.