Применение препарата Сел-септ у апластиков...

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Коллеги может у кого естьинформация о применении препарата СЕЛ-СЕПТ(мофетиламинофенолат) у больных приобретенной апластической анемией после курса АТГ с частичным ответом на него

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так никто и не ответил

[Dr. Vad]

[4888] Reversal of Myelodysplastic Hematologic Features after Discontinuation of Mycophenolate Mofetil.

Christian P. Schultheis, Rama Balaraman, Nasir Shahab, Donald Doll. Hematology/Oncology, University of Missouri/Ellis Fischel Cancer Center, Columbia, MO, USA



A 72 yo white male underwent a cardiac transplant in 1994 for severe cardiomyopathy secondary to coronary artery disease. Routine blood counts were stable at regular interval follow-ups while receiving prednisone and cyclosporine as his immunosuppressive treatment. In May of 2002, his immunosuppression was changed to mycophenolate mofetil 1000 mg bid along with low dose prednisone. Four weeks later, he experienced new onset dyspnea. Blood counts revealed a Hgb of 8.1 g/dl, WBC of 4.7, and platelets of 190, 000. His peripheral blood smear revealed macrocytosis, dacrocytes, and nucleated red blood cells. A bone marrow aspiration and biopsy disclosed dyserythropoiesis with nuclear budding and occasional karyorrhexis, nuclear and cytoplasm dyssynchrony, and ringed sideroblasts consistent with a diagnosis of refractory anemia with ringed sideroblasts. Mycophenolate mofetil was discontinued and 4 weeks later his Hgb increased to 12.2 g/dl. His peripheral blood smear at that time was normal. The patient refused a repeat bone marrow examination. Nonetheless, the temporal association of the hematologic abnormalities after the initiation of mycophenolate mofetil and the disappearance of such findings after the drug was discontinued suggest that the hematologic findings were causally related to the medication.



[3495] Enhanced Response to Basiliximab in a Patient with Aplastic Anemia after Treatment with Standard Immunosuppression.

Jessica A. Berman, Kashyap Patel, Jaime Caro. Cardeza Foundation for Hematologic Research, Thomas Jefferson University Hospital, Philadelphia, PA, USA



Hepatitis-associated aplastic anemia is a well-defined entity that occurs less than three months after non-A, non-B, or non-C acute hepatitis. [Brown KE, et al,. Hepatitis-Associated Aplastic Anemia. NEJM 1997;336(15):1059-64.] The suspected viral agent is hypothesized to destroy the bone marrow by an immune-mediated mechanism involving the T lymphocytes. The mainstay of therapy for severe aplastic anemia eradicates the T lymphocytes with either direct immunosuppression combining antithymocyte globulin (ATG) and cyclosporin A (CyA), or ablation of the marrow with cytotoxic chemotherapy with stem cell support from HLA-identical sibling donors. We present a case of a 19 year-old Caucasian male who developed post-hepatitis aplastic anemia. He presented with jaundice, flank pain, and elevated LFT's, and was diagnosed with acute hepatitis. All laboratory tests for a causative agent were either negative or normal. A complete blood count (CBC) was within normal limits. 6 weeks later he became pancytopenic with a WBC of 100/mm3, absolute neutrophil count (ANC) of 10/mm3, hemoglobin (Hb) 7.7g/dL, platelets 4,000/mm3, and absolute reticulocyte count 11,100/mm3. A bone marrow biopsy showed an absence of normal hematopoietic elements, with 10% cellularity, which confirmed the diagnosis of severe aplastic anemia in the setting of recent acute hepatitis. The patient's only brother was not an HLA match. He was supported with daily platelet transfusions and frequent red cell transfusions.

Treatment was begun with ATG 40 mg/kg for 4 days, mycophenilate mofetil 1500 mg daily, and CyA 150 mg daily. Over the next 4 months, his CBC improved slightly, and he was no longer transfusion-dependent. Mycophenilate mofetil was discontinued 3.5 months later, but he remained on CyA. He had only achieved a partial response in his CBC, with ANC 660/mm3 and platelets 22,000/mm3.

Thus treatment was begun with basiliximab, the chimeric anti-IL-2 monoclonal antibody against T lymphocytes, of which he received two doses at 20 mg each, five days apart. [Jain A, et al. Liver Transplantation: Current Management, Immunosuppressive Therapy. Surgical Clinics of North America 1999;79(1):59-76.] 19 days later, his ANC was 1,008/mm3, and by 10 weeks his ANC was 2,100/mm3 with platelets of 48,000/mm3. At 6 months he had no evidence of aplastic anemia with ANC 2,843/mm3, Hb 13.1 g/dL, platelets 126,000/mm3. He has sustained a normal CBC for 24 months since the treatment with basiliximab to the current normal values of ANC 4,828/mm3, Hb 14.7 g/dL and platelet count 230,000/mm3. Enhanced suppression of the T lymphocytes accounts for the success of basiliximab. The IL-2 receptor on T lymphocytes is responsible for T cell activation, expansion, and viability. Blockade of this receptor reduces proliferation of T lymphocytes and the cytokines they produce, allowing full restoration of the normal bone marrow hematopoietic elements. [Tisdale JF, et al. Cyclophosphamide and other new agents for the treatment of severe aplastic anemia. Seminars in Hematology 2000;37(1):102-9.] We have demonstrated one patient with partial response to immunosuppression completely recover when treatment with basiliximab was initiated.Treatment was begun with ATG 40 mg/kg for 4 days, mycophenilate mofetil 1500 mg daily, and CyA 150 mg daily. Over the next 4 months, his CBC improved slightly, and he was no longer transfusion-dependent. Mycophenilate mofetil was discontinued 3.5 months later, but he remained on CyA. He had only achieved a partial response in his CBC, with ANC 660/mm3 and platelets 22,000/mm3.

[Dr. Vad]

А здесь уже в более положительных тонах:

Ann Hematol 2002 Dec;81(12):723-6

Myelodysplastic syndrome complicated by autoimmune hemolytic anemia: remission of refractory anemia following mycophenolate mofetil.

Lin JT, Wang WS, Yen CC, Chiou TJ, Liu JH, Hsiao LT, Yang MH, Chao TC, Tai CJ, Chen PM.

Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, #201, Sec. 2, Shi-Pai Road, Shi-Pai, Taipei, Taiwan and National Yang-Ming Medical University, Taipei, Taiwan.

Autoimmune hemolytic anemia (AIHA) rarely occurs in myelodysplastic syndrome (MDS). A 36-year-old Asian female was diagnosed with MDS (refractory cytopenia with multilineage dysplasia, RCMD) and complicated by AIHA 7 months later. Secondary myelofibrosis developed at the same time. Steroid therapy was ineffective and cyclosporin A (CsA) was discontinued due to its neurotoxicity with the development of leukoencephalopathy. However, the patient achieved a good hematological response after the use of mycophenolate mofetil (MMF, CellCept) with a dose of 1 g/day and prednisolone (15 mg/day). Prednisolone was tapered off over the next 3 weeks. The patient did not require any blood support 4 weeks after the use of MMF and has been hematologically stable for 4 months. To our knowledge, this is the first report of using MMF in treating MDS complicated by AIHA. MMF might be considered as a salvage therapy for patients with refractory anemia complicated by AIHA.



ASH'2001:[1854] Long-Term-Follow-Up of a Phase I-II Study of Myco- Phenolate-Mofetil (MMF) in Refractory Evans-Syndrome.

Christian Fibich, Robert Rohrberg, Helga Sommer, Heike Spohn, Axel Grothey, Hans-Joachim Schmoll, East German Study Group Hematology/Oncology (OSHO) (Intr. by Karen Valentine). Medicine, Tom-Baker-Cancer-Centre, University of Calgaryry, Calgary, AB, Canada; Onkologische Praxis, Halle, Germany; Innere Medizin, Klinikum Zwickau, Zwickau, Germany; Onkologische Praxis, Halle, Germany; Innere Medizin IV, Martin-Luther Universität, Halle, Germany



Introduction: Evans-Syndrome (ES) is the combination of autoimmune hemolysis and thrombocytopenia. As ES is a rare disease, data on the efficacy of different treatment-modalities in ES are lacking. Mycophenolate-Mofetil has been shown to be effective in steroid-refractory ITP and ES1. We here report on the follow-up of the ES-pts included in that trial. Patients and Methods: From 5-96 to 4-99 we enrolled 8 pts with refractory ES in a prospective, dose-escalation multicenter trial of MMF. 4 pts were male, 4 female, mean age was 41 years (range 24-60). The mean-number of prior therapies was 3.7 (range 2-7) and consisted of high dose corticosteroids (8/8), IVIG (8/8), Azathioprim (7/8), CsA (5/8). 4 pts had relapsed after splenectomy, one pt had splenic embolisation. Treatment-indication was isolated thrombocytopenia in 1 pt, hemolysis in 2 pts, and both in 5 pts. Drugs and dosage: The initial dose of MMF was 250 mg bid. After 2,4 and 6 weeks of treatment the dose of MMF was increased to 2x500 mg, 2x 1000 mg or 2x1500 mg respectively if not at least a minor response (MR) was achieved. In case of response, the pt was continued on the respective dose for 3 mth. In responding pts treatment was recommended for 6 mth after end of study, thereafter at the discretion of the physician. If present corticosteroid were tapered after onset of response. Results: 5 pt achieved a complete response (CR) at 1-16 mth of MMF, meaning normalization of all blood counts, 1 a partial response (PR), 1 a minor response consisting of amelioration of bleeding-symptoms with only marginal improvements in blood-counts and 1 pt a NC. Onset of response was between 48h and 34 days (mean day 11). At the current follow-up (5/01) all pts in the study are alive, no infectious complication>2, CTC have occurred, mean-duration of response is 19-39+ mth. 3 pts are in unmaintained complete remission for 9+ to 22+ mth (remission 19-39+ mth), 2 pt in remission on MMF (1CR, 1 PR) at 19 and 36 mth, 1 pt relapsed with steroid-sensitive-disease at 24 mth, 2 pts with NC/MR stopped MMF at 18 and 24 we. respectively. In all responding pts steroids could be tapered to below 10 mg prednisolone. Toxicity was mild, no pt discontinued MMF for toxicity. Conclusion: MMF is a save and potent drug in treating refractory ES with very promising long-term-results. Due to the favorable toxicity MMF may be considered an early treatment-option in steroid-refractory ES. As the study is now closed, we will continue to treat ES with phase-II MMF-protocol in analogy to the ITP-follow-up-trial.

[Dr. Vad]

Среди пробных методов после неудач с АТГ/ циклоспорином были успешно использованы (в единичных случаях!!!):

Талидомид (7мг/кг/сут) в 4 приема.

Ритуксимаб/Ритуксан 375мг/m2/нед. 4 раза.

Источники знаний на англ. языке могу выслать вам непосредственно на маил.

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Dr. Vad

Буду оч. признателен.

natusic@svitonline.com