scholarly journals Romiplostim: Successful treatment of a pregnant woman with refractory immune thrombocytopenia

2018 ◽  
Vol 5 (8) ◽  
pp. 2565-2571
Author(s):  
Mehrdad Payandeh ◽  
Afshin Karami ◽  
Noorodin Karami ◽  
Jafar Barati Masgareh
Keyword(s):  
Platelet Count ◽  
Pregnant Woman ◽  
Successful Treatment ◽  
Immune Thrombocytopenia ◽  
Response To Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Fetal Complications ◽  
Adults And Children

Immune thrombocytopenia is characterized by reduced platelet count. This condition occurs in both adults and children. The most common form of thrombocytopenia is primary ITP and autoantibodies are involved in its development. In this study, our patient was a pregnant woman with ITP who showed refractory to prednisolone and splenectomy as first and second line treatment, respectively, but the response to treatment with Romiplostim and platelet count was favorable, and delivery was reported without fetal complications.

Splenectomy or Rituximab in Steroid-Refractory Immune Thrombocytopenia (ITP): The Mayo Clinic Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3735-3735 ◽  
Author(s):  
William A. Hammond ◽  
Elisa M. Rodriguez ◽  
Zhuo Li ◽  
Bhagirathbhai Dholaria ◽  
Amanda Shreders ◽  
...  
Keyword(s):  
Medical History ◽  
Mayo Clinic ◽  
Immune Thrombocytopenia ◽  
Response To Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Consensus Guidelines ◽  
Line Therapy ◽  
Steroid Refractory

Abstract Introduction Immune thrombocytopenia (ITP) is an acquired disorder characterized by immune-mediated platelet destruction along with decreased platelet production. Adults with ITP are treated initially with glucocorticoids, intravenous immunoglobulin, and/or anti-D, but as many as 80% of patients (pts) will eventually relapse and become steroid-refractory. There is no universally agreed upon 2nd line therapy for ITP and consensus guidelines recommend either rituximab (R) or splenectomy (S) as acceptable, potentially curative options. Long-term responses to 2nd line S have been reported around 60%, and around 25% for R. It is unknown whether long-term outcome in the 3rd line setting is influenced by sequence of therapy. We evaluated the impact of sequence of 2nd and 3rdline therapy with R and/or S. Methods We identified all pts with ITP treated from 1990 through 2015 at the three Mayo Clinic (Arizona, Florida, and Minnesota) sites that were treated with R and/or S. Patients were excluded who were <18 years of age at the time of second-line treatment. Those with secondary ITP that received specific treatment for an infectious, autoimmune, or malignant condition causing thrombocytopenia were excluded. Patients with Evan's syndrome were included if the treatment was for thrombocytopenia, and not primarily for hemolytic anemia. For this analysis, secondary ITP was defined as ITP associated with hematologic malignancy. Hematologic malignancies did not require specific therapy at the time of treatment for ITP. Patients with uncontrolled infections or uncontrolled autoimmune disorders were excluded from analysis. We collected data from medical records regarding demographics, medical history, treatment history, response to treatment, and relapse. Medical history was captured for all concurrent diagnoses that could be considered associated with ITP including infectious and autoimmune conditions. Primary end-points were freedom from relapse after 2nd and 3rd line treatment with R or S. We used Kaplan-Meier method to estimate freedom from relapse after 2nd and 3rd line treatments. We also evaluated response to treatment, as defined by a platelet count >30,000/mm3 according to consensus guidelines. We performed three separate analyses for the entire cohort, primary ITP, and secondary ITP (separating out those with a concurrent diagnosis of malignancy). Results We identified 222 patients with a diagnosis of ITP, of which 191 had primary and 31 had secondary ITP. Treatment characteristics were similar in all groups except that pts treated initially with S were younger at diagnosis than pts treated with R (49 vs 60 years, P=0.003) and at time of 2ndline treatment (51.5 vs 61 years, P=0.018). For the overall cohort, patients treated with S as second-line therapy were more likely to achieve CR (86.6% vs 44%, P<0.0001), and had a significantly higher freedom from relapse at 5y (53.57% v. 14.96%, P<0.0001). Patients treated with S followed by R (S to R) had a trend towards higher 2y freedom from relapse than those treated with R followed by S (R to S) (69.48% v. 58.43%, P=0.3264). These data remained similar when primary ITP and secondary ITP were separated (data not shown). Conclusions These data support that S provides superior FFR at 5 years compared to R as second line treatment and suggests that, when needed, splenectomy followed by rituximab as opposed to rituximab followed by splenectomy might have a slight advantage. Disclosures No relevant conflicts of interest to declare.

Evidence-Based Mini-Review: Is Indium-Labeled Autologous Platelet Scanning Predictive of Response to Splenectomy in Patients With Chronic Immune Thrombocytopenia?

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 385-386 ◽  
Author(s):  
Adam Cuker ◽  
Douglas B. Cines
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Treatment Options ◽  
Evidence Based ◽  
Clinical Scenario ◽  
Line Treatment ◽  
Second Line ◽  
Primary Immune Thrombocytopenia ◽  
Autologous Platelet ◽  
Chronic Immune Thrombocytopenia

Abstract Clinical scenario: An otherwise healthy 25-year-old woman returns to your office for management of chronic primary immune thrombocytopenia. She was diagnosed 6 months earlier and continues to require prednisone 15 mg daily and periodic infusions of intravenous immunoglobulin to maintain a hemostatic platelet count. You discuss second-line treatment options, including splenectomy. The patient asks if there are any means by which to predict likelihood of response to splenectomy. You have heard about the use of indium-labeled autologous platelet scanning for this purpose and wonder what the evidence shows.

Primary Immune Thrombocytopenia in Elderly Patients: Clinical Profile, Efficacy and Safety of Treatment Protocols

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4196-4196 ◽  
Author(s):  
Maria Cristina Moragues Martinez ◽  
Kati Hurst ◽  
Maria Eva Mingot Castellano ◽  
Ana Isabel Heiniger Mazo
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Elderly Patients ◽  
Major Bleeding ◽  
Immune Thrombocytopenia ◽  
Rescue Therapy ◽  
Charlson Score ◽  
Line Treatment ◽  
Second Line ◽  
Primary Immune Thrombocytopenia

Abstract Introduction: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by accelerated platelet destruction and inadequate platelet production mediated by autoantibodies. As there are no specific diagnostic tests, the diagnosis of ITP remains one of exclusion. Although the incidence of ITP increases with age, there are no practice guidelines for elderly patients and few studies have been conducted. Compared with younger patients, older patients have a higher incidence of serious bleeding complications and increased related mortality. Therefore we propose to describe our experience in the management of ITP in patients over 65 years old. Methods: We conducted a retrospective study of 44 patients over 65 years old at the moment of the ITP diagnosis, treated in our center from January 1995 to March 2014. Variables analyzed were age, Charlson score, clinical manifestations and platelet count at diagnosis, type of treatment, response to treatment and adverse events. Results: The median current age is 77 years (IQR, 70-84 years), with a median age at diagnosis of 69 years (IQR, 65-75 years). The ratio of males to females was 0.91. Eighteen (40.9%) patients had a Charlson score greater than or equal to 2. The comorbilities were 27.8% diabetes with damage to target organs; 11.4% coronary disease; 9.8% solid metastatic tumor, 9.8% peripheral vascular disease, 9.8% chronic pulmonary disease; 5% congestive heart failure, 5% peptic ulcer, 5% cerebrovascular disease, 5% moderate-severe liver disease, 5% moderate-severe renal disease y 1.6% connective tissue disease, 1.6% dementia, 1.6% hemiplegia and 1.6% leukemia. The mean platelet count at diagnosis was 28x109 / L (IQR, 8-74x109 / L). Initial presentation was thrombocytopenia on a routine blood count in 43% of patients while the rest presented bleeding symptoms. Fourteen patients (31.8%) required admission on diagnosis. 18.8% showed major bleeding: 6 (13.63%) gastrointestinal haemorrhages, 1 (2.2%) hematuria and 47.7% minor bleeding: 8 (18.18%) bruising, 7 (15.9%) mucosal bleeding and 7 (15.89%) purpura and epistaxis. Regarding treatment, observation was used in 11 patients (25%), all of whom subsequently acheived spontaneous remission. Corticosteroid therapy (prednisone 0.5-1mg/kg), was the initial treatment used in 13 patients (29.5%), 15.9% received intravenous inmunoglobulins (1gr/kg x 2 days) and 18.2% combination therapy. A response was obtained in 75.6% of patients (35.6% CR, 40% R). Seven (16%) subjects received second-line treatment (1 splenectomy, 3 romiplostim, 1 eltrombopag, 1 rituximab, 1 Imurel). The patient that underwent splenectomy obtained CR. Of the 3 patients treated with romiplostim, 2 achieved CR directly, and the third required rescue therapy with eltrombopag to reach CR. The patient that received second line treatment with eltrombopag obtained R and the patient treated with Rituximab failed and needed rescue therapy with romiplostim. Finally the patient treated with azathioprine is in CR but still on treatment. At present we have an 84.1% response rate after a median follow up of 66 months (IQR, 27-100 months). During treatment we observed a single vascular event in the form of deep vein thrombosis with associated pulmonary embolism in a subject with additional thromboembolic risk factors. We found no infections, hyperglycemia or hypertensive crisis which required hospital admission or special monitoring. Five patients (11.4%) developed neoplasms (hepatocellular carcinoma, rectal neoplasm, pancreatic adenocarcinoma and Hürthle cell carcinoma), none of which were haematological. Three patients died: 2 due to neoplasm progression and 1 to acute renal failure. Conclusions: Low and intermediate doses of corticosteroids are a good first line treatment option in elderly patients. Close monitoring of the patient is advisable to ensure the early detection and treatment of adverse events and possible underlying diseases that could justify the thrombocytopenia. In our series the incidence of major bleeding in over 65s with ITP is clearly superior to that reported in younger subjects. Therefore, it is essential to optimize the intensity and duration of treatment in these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Late-line treatment in metastatic gastric cancer: today and tomorrow

2019 ◽  
Vol 11 ◽  
pp. 175883591986752 ◽  
Author(s):  
Elizabeth C. Smyth ◽  
Markus Moehler
Keyword(s):  
Gastric Cancer ◽  
Asian Population ◽  
Phase Iii ◽  
Response To Treatment ◽  
Evidence Based ◽  
Line Treatment ◽  
Second Line ◽  
Specific Patient ◽  
Line Therapy ◽  
Third Line

Survival for patients with unresectable advanced or recurrent gastric cancer (GC) remains poor and the historical lack of evidence-based therapeutic options after second-line therapy is reflected in current clinical guidelines for this condition. Despite uncertainty about optimal therapeutic strategies, further treatment is appropriate for some patients after failure of second line and may prolong survival. This approach has been reported in clinical trials and is becoming more common in real-world clinical settings. Several prognostic factors may increase the likelihood that a patient will be eligible for treatment in the third-line setting, including geographic location, status at diagnosis and response to treatment. There has been little progress over the last decade until the results from two large phase III randomized controlled trials completed in the last year: the ATTRACTION-2 trial with the programmed cell death-1 (PD-1) inhibitor, nivolumab, in an Asian population; and the TAGS trial with the oral chemotherapy trifluridine/tipiracil in a global population. Both ATTRACTION-2 and TAGS reported positive results in third-line treatment in advanced GC in specific patient groups. A further recently reported study, KEYNOTE-059, which was a single-arm phase II trial of the PD-1 inhibitor pembrolizumab in a mainly non-Asian population, has provided evidence supporting the use of this immunotherapy in patients with advanced GC. As further third-line options become available, more GC patients are expected to benefit from an individualized evidence-based approach to later-line therapy, with a common goal of extending survival and improving outcomes for their refractory disease.

Eltrombopag and High-Dose Dexamethasone As First Line Treatment For ITP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3544-3544
Author(s):  
David Gomez-Almaguer ◽  
Miguel Angel Herrera-Rojas ◽  
Andres Gomez-de Leon ◽  
Olga Graciela Cantú-Rodríguez ◽  
Cesar H Gutiérrez-Aguirre ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Line Therapy ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that involves antibody and cell mediated destruction of platelets as well as suppression of their production. Prednisone is the initial standard therapy in adults1. High-dose dexamethasone as front-line therapy given as pulses of 40 mg per day for 4 consecutive days, was effective in 85% of patients, nevertheless, 50% relapsed within six months2. The prices of ITP drugs for 1 month of treatment in an adult range from prednisone; $16, eltrombopag; $5,934, intravenous immune globulin (IVIG) (80 g); $9,648, to rituximab (2 g); $15,5963. Only prednisone/dexamethasone and eltrombopag are available in oral presentation, for this reason, ambulatory treatment is an alternative for these patients. The trombopoietin receptor agonists are effective for the treatment of patients with chronic ITP, although response is dependent on continued administration. Eltrombopag is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of thrombopoietin. This drug effectively raises the platelet count in adult patients (aged 18 years and over) as second/third line therapy, that is for patients refractory to corticosteroids and IVIG who have had their spleen removed or when splenectomy is not an option4. Our group, as well as others, has previously sought to improve response rates in these patients, particularly with the use of rituximab5, 6. To our knowledge neither eltrombopag nor romiplostim have been used as front line therapy in ITP, therefore the purpose of this study was to assess the efficacy of eltrombopag and dexamethasone in this setting. Patients and Methods This was a prospective, phase 2 study, using the combination of eltrombopag (50 mg PO once a day for 4 weeks) and high-dose dexamethasone (40 mg PO days 1,2,3,4) in untreated adult patients with immune thrombocytopenia or in patients with less than 7 days of treatment with corticosteroids. Complete response (CR) was defined as an increase in platelet count >100×109/L. Partial response (PR) was defined as an increase in the platelet count greater to 30 ×109/L according to standard criteria. Duration of response was considered from the day of initial administration to the first time of relapse (platelet count <30×109/L). Results Twelve consecutive patients were enrolled from June 2012 to June 2013, 6 women and 6 men. The median age at diagnosis was 50 years (range, 20 - 80 years). The median platelet count at diagnosis was 7 x 109/L (range, 2 - 29 x 109/L). Patients were followed for a median of 2.5 months (range 1.1 - 13). After steroid treatment at day +5, ten patients had responded (83.3%), five had achieved CR (41.7%), and five PR. After completing treatment with eltrombopag at day +34, all patients responded (100%), nine patients achieved CR (75%) and three PR (25%). Two patients relapsed in a median time of 39.5 days (range, 30.1 - 49), both regaining CR after treatment with another high-dose dexamethasone course and low-dose rituximab (4 doses of 100 mg every week). At 3 months follow-up 66.7% remained in CR and 33.3% in PR (n=6). At 6 months follow-up two patients remained in CR and two in PR (n=4). Time to best response achieved was 34 days from diagnosis (range, 19 – 64.1). At the end of follow-up 9 patients (75%) remained in CR and 3 patients in PR (25%). Total treatment cost per patient was $1,640 approximately. Conclusion Currently the initial treatment of ITP patients is based on prednisone or high dose dexamethasone with or without IVIG. This approach is associated with high cost and high relapse rate. The results from our pilot study suggest that high dose dexamethasone and eltrombopag are very effective as first line treatment for acute ITP in adults. This treatment is ambulatory, affordable and well tolerated; however, we still don't know if this approach will have a favorable impact on the relapse rate of this disease. Disclosures: Off Label Use: Eltrombopag as first line treatment for ITP.

Four Cases of Lenalidomide-Associated Immune Thrombocytopenia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4927-4927 ◽  
Author(s):  
Alessandra Pompa ◽  
Francesca Guidotti ◽  
Anna Ines Gregorini ◽  
Maria Cecilia Goldaniga ◽  
Francesca Gaia Rossi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Steroid Therapy ◽  
Partial Remission ◽  
Immune Thrombocytopenia ◽  
Line Treatment ◽  
The Third ◽  
Bone Marrow Evaluation ◽  
Grade 3 ◽  
D 20

Abstract Introduction Hematologic neoplasms are associated with an increased incidence of autoimmune events, particularly evident in non‐Hodgkin lymphomas (NHL) and especially chronic lymphocytic leukemia (CLL); until now only few cases have been described in patients affected by multiple myeloma (MM) and other plasma cell disorders. The introduction of new drugs, in particular immunomodulatory drugs (IMiDs), could increase the risk of these complications. Herein we describe four cases of immune thrombocytopenia (ITP) occurred during Lenalidomide (LEN) therapy in 3 patients affected by MM and 1 with light‐chain amyloidosis. Case reports Case 1. A 66‐year old woman with relapsed IgGk MM started 2th line treatment with LEN/DEX 25 mg/d-20 mg/w. During the first 5 cycles she presented moderate hematologic toxicity which resolved after dose reduction (LEN 15 mg/d). A severe and isolated thrombocytopenia appeared after 5th cycle with patient in good partial remission (PR) for MM. A bone marrow evaluation showed absence of plasma cells and abundant megakaryocytes leading to a diagnosis of ITP. LEN was interrupted and steroid therapy (prednisone 1 mg/Kg) and IV Ig infusion administered, obtaining a transient good response (from 17 to 114 x 109/l). LEN was then restarted at lower dosage but a month after, while myeloma still was in good response, ITP relapsed complicated by intracranial hemorrhage and was successfully treated with IV Ig; Len was definitely interrupted. At the third relapse Rituximab (750 mg/w x 4 weeks) was administered with only minimal increase of platelet count (Fig 1). Afterwards, the patient died due to rapid MM progression. Case 2. A 76‐year old woman with relapsed IgGλ MM started 2th line treatment with LEN 15 mg. After the 3rd cycle, having obtained a very good partial remission (VGPR), she presented with grade 3 thrombocytopenia which did not ameliorate with LEN suspension and resolved only after introduction of steroid, thus supporting ITP diagnosis. She underwent a 4th cycle of LEN/DEX maintaining a normal platelet count but then LEN was interrupted due to rapid MM progression. (Fig 2). Case 3. A 78‐year old woman with renal amyloidosis in IgAλ gammopathy started a 2nd line treatment with LEN/DEX 15 mg/d-20 mg/w with a significant reduction in proteinuria. During the 6th cycle she presented with diffuse purpura and a platelet count of 18x109/L. She received platelet transfusion and bone marrow evaluation showed abundant megakaryocytes supporting the diagnosis of ITP. Furthermore anti‐platelet antibodies search resulted positive. Steroid therapy was started with partial response on platelet count but the patient remained steroid‐therapy dependent. Case 4. A 66‐year‐old woman affected by MM started a 2th‐line treatment with LEN‐DEX 25 mg/d-20 mg/w. After the third cycle, being the patient in PR, a isolated grade 3 thrombocytopenia developed, persisting despite discontinuation of LEN. Viral infections were excluded and antiplatelet antibodies search resulted positive. Therefore she started steroid therapy (prednisone 1 mg/Kg) with an progressive increase of platelet count from 44 to 80x109/L after a month of therapy, that is ongoing. Lenalidomide has not yet been restarted. Discussion We report four cases of ITP developing during LEN therapy with the characteristics of ITP. None of these patients had a history of previous autoimmune events, the decline of platelet count was rapid and other causes of thrombocytopenia were excluded or unlikely in all the cases. Furthermore diagnosis was supported by consistent bone marrow evaluation in two cases. Considering the temporal association in these four cases, the ITP mechanism may be related to the immunomodulation and T‐cell activation caused by LEN. Even if further other studies are needed, it seems reasonable to consider a possible association between LEN and autoimmune phenomena, in particular ITP. Disclosures No relevant conflicts of interest to declare.

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