mycophenolic-acid and Purpura--Thrombocytopenic--Idiopathic

Immune thrombocytopenia (ITP) is a common hematological manifestation of systemic lupus erythematosus (SLE). The heterogeneity of its clinical characteristics and therapeutic responses reflects a complex pathogenesis. A better understanding of its pathophysiological mechanisms and employing an optimal treatment regimen is therefore important to improve the response rate and prognosis, and avoid unwanted outcomes. Besides glucocorticoids, traditional immunosuppressants (i.e. cyclosporine, mycophenolate mofetil) and intravenous immunoglobulins, new therapies are emerging and promising for the treatment of intractable SLE-ITP, such as thrombopoietin receptor agonists (TPO-RAs), platelet desialylation inhibitors(i.e. oseltamivir), B-cell targeting therapy(i.e. rituximab, belimumab), neonatal Fc receptor(FcRn) inhibitor, spleen tyrosine kinase(Syk) inhibitor and Bruton tyrosine kinase(BTK) inhibitor et al., although more rigorous randomized controlled trials are needed to substantiate their efficacy. In this review, we update our current knowledge on the pathogenesis and treatment of SLE-ITP.

Topics: Humans; Immunoglobulins, Intravenous; Infant, Newborn; Lupus Erythematosus, Systemic; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Autoantibodies; Azathioprine; Calcineurin Inhibitors; Cardiovascular Diseases; Cyclophosphamide; Disease Management; Female; Glucocorticoids; Heart Valve Diseases; Humans; Hydroxychloroquine; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Lupus Vasculitis, Central Nervous System; Macrophage Activation Syndrome; Methotrexate; Mycophenolic Acid; Myocarditis; Outcome Assessment, Health Care; Pericarditis; Phenotype; Pregnancy; Pregnancy Complications; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Recurrence; Rituximab; Severity of Illness Index; Survival Rate; Uterine Cervical Neoplasms

Mycophenolate mofetil (MMF) has been shown to be effective in children with immune thrombocytopenia (ITP) and Evans syndrome (ES), but data from larger series and details on the timing of the response are lacking. We evaluated 56 children treated with MMF for ITP (n = 40) or ES (n = 16), which was primary or secondary to autoimmune lymphoproliferative syndrome -related syndrome (ARS). Thirty-five of the 54 evaluable patients (65%) achieved a partial (18%) or complete (46%) response after a median (range) of 20 (7-137) and 37 (7-192) d, respectively. ITP and ES patients responded in 58% and 81% of cases (P = not significant, ns), with complete response in 32% and 81% (P = 0·01), respectively. 60% and 73% of children with primary disease and ARS responded (P = ns) with complete response in 34% and 68% of cases (P = 0·01), respectively. Six of 35 (17%) children relapsed after a median of 283 d (range 189-1036). Limited toxicity was observed in four patients. The median durations of treatment and follow-up were seven and 12·7 months, respectively. This is the largest reported cohort of patients treated with MMF for ITP/ES. The results show that MMF is effective and safe and provides a relatively quick response, suggesting that it has a potential role as an alternative to more aggressive and expensive second/further-line treatments.

Topics: Adolescent; Anemia, Hemolytic, Autoimmune; Antibiotics, Antineoplastic; Child; Child, Preschool; Disease Progression; Female; Humans; Infant; Italy; Male; Mycophenolic Acid; Odds Ratio; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Retreatment; Retrospective Studies; Thrombocytopenia; Treatment Outcome

Immune thrombocytopenia is a rare autoimmune disorder with associated bleeding risk and fatigue. Recommended first-line treatment for immune thrombocytopenia is high-dose glucocorticoids, but side effects, variable responses, and high relapse rates are serious drawbacks.. In this multicenter, open-label, randomized, controlled trial conducted in the United Kingdom, we assigned adult patients with immune thrombocytopenia, in a 1:1 ratio, to first-line treatment with a glucocorticoid only (standard care) or combined glucocorticoid and mycophenolate mofetil. The primary efficacy outcome was treatment failure, defined as a platelet count of less than 30×10. A total of 120 patients with immune thrombocytopenia underwent randomization (52.4% male; mean age, 54 years [range 17 to 87]; mean platelet level, 7×10. The addition of mycophenolate mofetil to a glucocorticoid for first-line treatment of immune thrombocytopenia resulted in greater response and a lower risk of refractory or relapsed immune thrombocytopenia, but with somewhat decreased quality of life. (Funded by the U.K. National Institute for Health Research; FLIGHT ClinicalTrials.gov number, NCT03156452; EudraCT number, 2017-001171-23.).

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Fatigue; Female; Glucocorticoids; Hemorrhage; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Young Adult

Treatment options are limited in patients with chronic immune thrombocytopenic purpura (ITP) which has been unresponsive to corticosteroids and/or splenectomy. Mycophenolate mophetil (MMF) is effective in many autoimmune disorders including severe and refractory ITP through its targeting of T-cell and B-cell lymphocytes. We report on the efficacy of MMF (1.5-2 g/day) in 16 adults with severe steroid-resistant ITP. MMF was administered for at least 12 weeks (median 37 weeks, range 14-64 weeks). Patients comprised of 10 females and six males, with median pre-treatment platelet counts of 8 × 10(9)/L, median age of 55 years, median ITP duration of 58 months and a median of four prior treatments (range 3-8); nine had been previously splenectomized. Eleven patients (69%) responded after 12 weeks of MMF: 6 (55%) achieving complete remission (CR) and five (45%) achieved partial remission (PR). MMF therapeutic responses were better in those patients who had had fewer prior treatments (p<0.05), and were independent of patient age, sex, disease duration, and splenectomy status (p>0.05). Five of the 11 responders (45%; 3CR/2PR) had sustained remissions; however, six responders (55%; 3CR/3PR) relapsed after median of 14 weeks (range 9-20). Three of the six relapsing patients responded to MMF reinstitution achieving stabile PRs; three were left untreated as none had further bleeding and their platelets remained at "safe" levels (median 30 × 10(9)/L). The MMF treatment was well tolerated; one heavily pretreated patient developed a bronchopneumonia and a second had an episode of diarrhea. MMF used as a second-line agent can produce a sustained response in severe ITP which has been unresponsive to steroid and/or splenectomy without major toxicity.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Chronic Disease; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Treatment Outcome; Young Adult

Treatment options for patients with chronic refractory immune thrombocytopenic purpura (ITP) are limited. Because combination immunosuppressant therapy appeared to be effective in ITP and other disorders, we used this approach in patients with particularly severe and refractory ITP. In this retrospective, observational study, we determined the response (platelet count above 30 x 10(9)/L and doubling of baseline) among 19 refractory ITP patients. Treatment consisted of azathioprine, mycophenolate mofetil, and cyclosporine. The patients had failed a median of 6 prior treatments, including splenectomy (in all except 1). Of 19 patients, 14 (73.7%) achieved a response lasting a median of 24 months, after which time 8 (57.1%) relapsed. Of the 8 relapsing patients, 6 responded to additional treatments. Of the 14 patients who achieved an initial response, 2 (14.3%) remained in remission after eventually stopping all medications. Severe adverse events did not occur. Combination immunosuppressant therapy can produce a rise in the platelet count that is sometimes sustained in refractory ITP patients.

Topics: Azathioprine; Chronic Disease; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Recurrence

Refractory disease occurs in 25% or more of adults with idiopathic (immune) thrombocytopenic purpura (ITP). Therapy to elevate the platelet count may be required in a proportion of these patients. Immunosuppressive agents such as prednisone, azathioprine, cyclophosphamide, and cyclosporin have been shown to be effective treatments in a proportion of patients with refractory ITP. A newer immunosuppressive medication, mycophenolate mofetil (MMF), has been used successfully with acceptable toxicity in solid organ transplant patients to reduce the risk of organ rejection. The goal of this study was to determine whether MMF is an effective treatment for refractory ITP. Efficacy, defined as a sustained platelet increase to a level greater than 50 x 10(9)/L, was seen in 7 of 18 patients with refractory ITP. Three of these 7 patients have had intermittent thrombocytopenic episodes while continuing the medication. No severe toxicity was seen, although two of the 18 patients discontinued MMF within the first month of treatment because of side effects, i.e., headache. In summary, MMF may be a useful component of a combination protocol but does not appear to be highly effective as sole therapy in patients with refractory ITP. The data suggests that response rates to MMF may be higher in patients who have had a shorter duration of their ITP.

Topics: Adolescent; Adult; Aged; Child, Preschool; Disease-Free Survival; Drug Combinations; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Organ Transplantation; Pilot Projects; Purpura, Thrombocytopenic, Idiopathic; Risk Factors

Treatment of auto-immune cytopenia refractory to front line therapy with intravenous immunoglobulins and steroids is a matter of concern. We assessed the efficacy and safety of mycophenolate mofetil in a prospective open preliminary study.. Adult patients with steroid refractory auto-immune cytopenias were included. Mycophenolate mofetil (MMF) was added to treatment given at the time of inclusion, and efficacy was evaluated in term of improvement of platelet/haemoglobin levels and in term of reduction of previously given drugs, if any. All auto-immune thrombocytopenic purpura (AITP) patients had serologic assessment for associated auto-antibodies at the time of inclusion. Cytopenias associated with other auto-immune diseases, lymphoproliferative diseases or HIV infection were excluded.. From November 1999 through November 2003, 13 patients were included (nine AITP, three auto-immune haemolytic anaemia (AIHA), one Evans' syndrome; four males, nine females; age: 35-72 yr). For AITP patients, an overall response of 78% was observed. Retrospective analysis showed no significant difference between patients having a short disease duration (<1 yr) and longer disease duration; between patients who previously received more or less than three treatments; and between patients for whom MMF was started as monotherapy or in association with prednisone, However, all AITP patients presenting associated auto-antibodies responded to MMF, while only 50% of patients without associated antibodies were responders. All patients presenting AIHA and Evans' syndrome were responders. The drug was well tolerated, with no significant side effects reported. The cumulative data suggest a potential place for MMF in the treatment arsenal of refractory cytopenias.

Topics: Adult; Aged; Autoantibodies; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.

Topics: Adult; Aged; Autoantibodies; Drug Resistance; Female; Humans; Immunosuppressive Agents; Leukocytes; Male; Middle Aged; Mycophenolic Acid; Platelet Glycoprotein GPIIb-IIIa Complex; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Remission Induction; Splenectomy

Most children treated for immune thrombocytopenia remit during the first year following diagnosis. For the ∼40% who develop persistent or chronic disease, second-line treatment options include immunomodulation and thrombomimetic agents. While immunomodulators target the underlying mechanism, prolonged immunosuppression may increase the risk of infection. We report the use of the reversible immunomodulating agent mycophenolate mofetil (MMF) in 16 pediatric patients with immune thrombocytopenia refractory to first-line treatment. Using escalating doses up to 2400 mg/m 2 /d, MMF treatment resulted in a 73% response rate. Adverse events were mostly mild and tolerable. Complete responders have been successfully tapered off MMF with sustained responses.

Topics: Child; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

We report on the presentation and outcome of a 28-year-old female who developed red cell aplasia following alemtuzumab therapy for relapsing remitting multiple sclerosis. The patient also developed synchronous immune thrombocytopenia and immune neutropenia, but not aplastic anemia. This patient received high dose steroids, intravenous immunoglobulin (iv.Ig), rituximab, red cell transfusions, vincristine, G-CSF, cyclosporin and mycophenolate to treat the combination of cytopenias over a period of 6 months with subsequent improvement in bone marrow function. While alemtuzumab has several recognized autoimmune complications, little is known about the potential hematological side effects. The combination of red cell aplasia, immune thrombocytic purpura and autoimmune neutropenia has not previously been described in the literature following alemtuzumab immunotherapy and highlights the importance of monthly blood monitoring post alemtuzumab administration.. Lay abstract We report a case of 28-year-old women with relapsing remitting multiple sclerosis who was treated with alemtuzumab and subsequently developed a series of autoimmune complications. Several months after completing her second course of alemtuzumab the patient became breathless and noticed bruising on her legs. On investigation she was found to be anemic and had a low platelet level (which predisposed her to bruising). In addition, her immune system was also impaired meaning she was more prone to developing opportunistic infections. The patient was treated with a variety of different medications and required blood transfusions for several months before she recovered. Despite the multiple complications the patient developed from alemtuzumab her multiple sclerosis remains stable with no new relapses 3 years following treatment.

Topics: Adrenal Cortex Hormones; Adult; Alemtuzumab; Antineoplastic Agents, Immunological; Cyclosporine; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Multiple Sclerosis, Relapsing-Remitting; Mycophenolic Acid; Neutropenia; Purpura, Thrombocytopenic, Idiopathic; Red-Cell Aplasia, Pure; Rituximab; Treatment Outcome; Vincristine

Topics: Autoimmunity; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Topics: Autoimmunity; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Topics: Autoimmunity; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Topics: Autoimmunity; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

We report a case of a 56-year-old woman with a history of idiopathic thrombocytopenic purpura (ITP) following splenectomy on mycophenolate mofetil (MMF), who developed moderate bleeding after stopping MMF. Her laboratory testing suggested the presence of an abnormal circulating heparin-like anticoagulant with demonstrable anti-Xa activity. She was initially treated with antifibrinolytic therapy and was subsequently started on MMF alongside intravenous immunoglobulin, which significantly improved her bleeding symptoms. The presence of abnormal circulating heparin-like anticoagulants is a rare cause of coagulopathy. Few cases exist in the literature, with nearly all occurring in the setting of hematologic or solid-organ malignancy. The mechanism by which these endogenous anticoagulants develop is unclear. Clinical manifestations range from mild bleeding and bruising to life-threatening hemorrhage refractory to conventional therapy. Diagnosis of a heparin-like anticoagulant is based on coagulation testing as well as exclusion of other exogenous anticoagulants, acquired inhibitors, and/or factor deficiencies.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Hemorrhage; Heparin; Humans; Hypothyroidism; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Splenectomy

Thrombocytopenia (TP) is a common complication of childhood-onset systemic lupus erythematosus (SLE), and can range from mild to life-threatening. However, severe TP with multiple hemorrhagic complications is very rare and often predicts a poor prognosis. We describe a 12-year-old Chinese girl who had a history of idiopathic thrombocytopenic purpura who developed SLE that presented as subdural hemorrhage and retinal hemorrhage because of severe TP.. A 12-year-old girl was admitted into our hospital because of fever, purpura, and gum bleeding lasting for 12 days. She had a history of idiopathic thrombocytopenic purpura 2 years ago previously.. SLE was diagnosed according to American College of Rheumatology classification criteria. Subdural hemorrhage and retinal hemorrhage were diagnosed based on brain MRI and funduscopy. Severe TP was defined as platelet count <20 × 109/L.. She was treated first with intravenous immunoglobulin, but it was not efficacious. High-dose methylprednisolone showed short-term efficacy. Then, she was given a glucocorticoid and cyclosporine A plus mycophenolate mofetil.. Fever, purpura, and gum bleeding were resolved before hospital discharge. Subdural hemorrhage and left hemorrhagic retinopathy were improved remarkably. She had a durable response to refractory TP with no adverse effects during >1-year follow-up.. Isolated TP may be an early symptom of childhood-onset SLE . A child with severe TP is prone to develop life-threatening hemorrhagic complications. Glucocorticoids and combined immunosuppressive drugs had a durable response to refractory TP in this patient with no adverse effects.

Topics: Child; Cyclosporine; Female; Glucocorticoids; Hematoma, Subdural; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methylprednisolone; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Retinal Hemorrhage

Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Male; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Salvage Therapy; Sirolimus; TOR Serine-Threonine Kinases; Treatment Outcome; Young Adult

Immune thrombocytopenia (ITP) is an autoimmune condition that may cause thrombocytopenia-related bleeding. Current first-line ITP treatment is with high-dose corticosteroids but frequent side effects, heterogeneous responses and high relapse rates are significant problems with only 20% remaining in sustained remission with this approach. Mycophenolate mofetil (MMF) is often used as the next treatment with efficacy in 50%-80% of patients and good tolerability but can take up to 2 months to work.. To test the hypothesis that MMF combined with corticosteroid is a more effective first-line treatment for immune thrombocytopenia (ITP) than current standard of corticosteroid alone.. DesignMulticentre, UK-based, open-label, randomised controlled trial.. Haematology departments in secondary care.. Side effects, bleeding events, remission rates, time to relapse, time to next therapy, cumulative corticosteroid dose, rescue therapy, splenectomy, socioeconomic costs, patient-reported outcomes (quality of life, fatigue, impact of bleeding, care costs).. The sample size of 120 achieves a 91.5% power to detect a doubling of the median time to treatment failure from 5 to 10 months. This will be expressed as an HR with 95% CI, median time to event if more than 50% have had an event and illustrated with Kaplan-Meier curves. Cost-effectiveness will be based on the first 12 months from diagnosis.. Ethical approval from NRES Committee South West (IRAS number 225959). EudraCT Number: 2017-001171-23. Results will be submitted for publication in peer-reviewed journals.. NCT03156452.

Topics: Adrenal Cortex Hormones; Adult; Clinical Trial Protocols as Topic; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Multicenter Studies as Topic; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Randomized Controlled Trials as Topic; Research Design

Successful treatment of both pediatric autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), specifically those that are refractory to first-line therapies, remains unsatisfactory in terms of long-term remission and medication side effects. Here, we propose a novel combination therapy of mycophenolate mofetil (MMF), an adjunct immunosuppressive, and short-term corticosteroids for the treatment of persistent or chronic autoimmune cytopenias in children. This combination may allow for rapid decrease of steroid usage as well as prolonged count stabilization with minimal toxicity to the patient.. Prospective case series of nine patients, six with persistent or chronic ITP and three with persistent or chronic AIHA, between the ages of 5 and 19 years who are being treated with combination therapy consisting of corticosteroids and MMF.. Our results are very promising, as MMF appears to be an effective and well-tolerated adjunct immunosuppressant that allows for rapid weaning of steroid usage, minimal adverse side effects to the patients, and long-term stabilization of counts, a goal that has not been achieved successfully with other secondary treatment modalities. Therefore, this novel combination therapy may be an excellent alternative for the treatment of persistent or chronic autoimmune cytopenias in the pediatric population.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Antibiotics, Antineoplastic; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Immunomodulation; Male; Mycophenolic Acid; Prognosis; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Remission Induction; Young Adult

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

Topics: Adolescent; Blood Platelets; Child; Child, Preschool; Chronic Disease; Cyclosporine; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Mycophenolic Acid; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Remission Induction; Retrospective Studies; Rituximab; Splenectomy; Treatment Outcome

Severe immune thrombocytopenia purpura (ITP) presents a clinical challenge. Second-line treatment options are variable without a precise protocol. We present 46 severe ITP patients treated with mycophenolate mofetil (MMF), retrospectively identified from three London teaching hospitals. Data was collected on patient demographics, co-morbidities and previous treatment strategies. Our key interest was whether there was a sustained response in platelet count to MMF. Patients included 27 males and 19 females whose ages ranged from 19 to 93 years old (median 52·5 years). Twenty-nine had primary ITP and 17 had secondary ITP, a third of whom had viral-associated disease. The standard dose of MMF was 1 g/day. Twenty-four patients (52%) responded with 15 (33%) achieving a complete response. No active viral-associated ITP patients demonstrated a response to MMF, although numbers were small (n = 4). We were not able to demonstrate a difference between responders and non-responders based on gender, age, previous therapies or time since diagnosis of ITP. Three of four previously splenectomized patients responded, two achieving complete response. We conclude that MMF is a useful steroid-sparing immunosuppressant to be considered in the second-line or later treatment of ITP.

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Comorbidity; Drug Evaluation; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Remission Induction; Retrospective Studies; Salvage Therapy; Splenectomy; Virus Diseases; Young Adult

A patient presented with erysipelas and developed deep venous thrombosis (DVT) and later idiopatic thrombocytopenic purpura (ITP). In the literature we find no reports of ITP following DVT. It is well known that patients can develop HIT after DVT or DVT after ITP, both caused by the medicine used for treatment. Patients have developed ITP after heparin-induced thrombocytopenia (HIT). Cases are also described in which heparin antibodies are found, but in which the final diagnosis was ITP. The diagnosis of the patient in our case story could be ITP based on DVT, but with no history of HIT. Alternatively, he could have developed two complications to an infection.

Topics: Aged; Anti-Bacterial Agents; Anticoagulants; Dexamethasone; Erysipelas; Heparin; Humans; Male; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Treatment Outcome; Venous Thrombosis

Topics: Antineoplastic Agents; Child; Genetic Diseases, X-Linked; Humans; Male; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic

Topics: Anemia, Hemolytic, Congenital; Child; Female; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Syndrome

Rituximab and mycophenolate mofetil are used in the treatment of resistant immune thrombocytopenic purpura (ITP). Both therapeutic approaches can induce responses in subsets of patients, but these responses are usually of limited duration and often lasting for less than one year. Mycophenolate mofetil 250 mg twice daily was insufficient to induce a prolonged response. In this article, we describe a patient with severe chronic ITP that was treated with rituximab. The platelet count started to decrease 5 months after rituximab therapy, low dose therapy with mycophenolate mofetil 250 mg twice daily was then started and peripheral blood platelet counts then stabilized between 70 and 100 x 10(9)/l. Mycophenolate mofetil could later be reduced to 250 mg once daily, and the patient has now had stable platelet counts for more than 4 years. Thus, the previous mycophenolate mofetil treatment that was insufficient to induce a prolonged response could maintain a prolonged response after rituximab therapy. This observation suggests that mycophenolate mofetil can be used to prolong responses after rituximab therapy for ITP.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Rituximab

Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy.. Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005.. Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made.. We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.

Topics: Adult; Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Autoimmune Diseases; Bone Marrow; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphocyte Activation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pancreas Transplantation; Pilot Projects; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Red-Cell Aplasia, Pure; Retrospective Studies; T-Lymphocytes

To determine whether mycophenolate mofetil (MMF) has beneficial effects on refractory idiopathic thrombocytopenic purpura (ITP) and the corresponding cellular mechanism.. Twenty refractory ITP patients resistant to corticosteroid and/or splenectomy and chemical therapy were given MMF 1.5-2.0 g/d orally for a 2 to 4-month period. Serum immunoglobulin was detected by rate nephelometry. Platelet-associated antibodies (PAIgG) were assayed by enzyme-linked immunosorbant assay. The immunophenotypic analysis was performed on a flow cytometer and cell apoptosis was detected with transferase mediated dUTP biotin nick end labeling (TUNEL) method.. Sixteen of the 20 (80%) patients had responses to MMF treatment; 9 (45%) achieved a complete response, 4 (20%) achieved a partial response, and 3 (15%) achieved a minor response. The therapeutic effects were found to be better in male patients than female patients. The number of CD3+ peripheral blood cells (PBCs) and CD4+ PBCs increased and the number of CD8+ PBCs decreased. The plasma level of IgG, IgM, IgA and platelet associated IgG (PAIgG) decreased in 86% of the patients. TUNEL assay showed that mycophenolate acid (MPA) 0.1 mmol/L induced apoptosis of peripheral blood mononuclear cells isolated from refractory ITP patients. The apoptosis rate was increased in male patients after treatment with MPA, but was unchanged in female patients.. Therapy for a period of 8 to 16 weeks with median-dose of MMF was valuable for the treatment of refractory ITP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis; Blood Platelets; CD4-CD8 Ratio; Child; Female; Humans; Immunosuppressive Agents; Leukocytes, Mononuclear; Male; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Sex Factors

Immune thrombocytopenia (IT) is a common manifestation of systemic lupus erythematosus (SLE). Although severe IT (<20 x 10(9)/L) occurs in about 5-10% of patients, usually in the context of active disease, the absence of randomized controlled trials has not allowed the development of evidence-based guidelines for managing this condition. Conventionally, high-dose glucocorticoids are considered first-line therapy. Adjunctive medical and surgical treatments for patients with an absent or partial response to glucocorticoids have met with varying degrees of success. We describe an SLE patient with IT refractory to high-dose corticosteroids, pulse methylprednisolone and intravenous immunoglobulin therapy, whose platelet counts normalized during therapy with mycophenolate mofetil (MMF). Pending further controlled studies to confirm this observation, we suggest that MMF may be considered as a therapeutic option in the treatment of glucocorticoid-refractory immune thrombocytopenia in SLE.

Topics: Adrenal Cortex Hormones; Adult; Antibodies, Antiphospholipid; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Methylprednisolone; Mycophenolic Acid; Platelet Count; Purpura, Thrombocytopenic, Idiopathic

The treatment of both auto-immune haemolytic anaemia (AIHA) and auto-immune thromobocytopenic purpura (AITP) remains unsatisfactory in those refractory to first-line management. Mycophenolate mofetil (MMF) is an immunosuppressive agent originally used to prevent acute rejection of solid organ transplants and used more recently in the management of auto-immune conditions. We report its use in four patients with AIHA and six patients with AITP. All four patients with AIHA and five of the six patients with AITP showed a complete or good partial response to treatment with MMF, confirming a possible role in the treatment of these conditions.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Female; Hemoglobins; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic