Identification of Self-Limiting Pediatric Immune Thrombocytopenia at Diagnosis

Abstract Introduction In childhood immune thrombocytopenia (ITP), intravenous immunoglobulins (IVIG) treatment shortens the duration of thrombocytopenia and bleeding symptoms but does not prevent the development of chronic ITP (Heitink-Pollé et al. Blood 2018). This suggests that IVIG is efficacious in patients who would otherwise recover spontaneously. Thirty percent of children show no response to IVIG. We aim to target IVIG treatment to those who benefit most. We hypothesized that IVIG responders can be distinguished from non-responders by a specific immune profile. Methods To predict treatment responses to IVIG, a secondary analysis was performed in IVIG-treated children of the Treatment with or without IVIG for Kids with ITP(TIKI) randomized controlled trial. Children with newly diagnosed ITP, a platelet count <20x109/L, non-severe bleeding and an age below 7 years were included in this analysis (N=80). Patients were systematically profiled at diagnosis before treatment with IVIG, including clinical data, targeted genotyping, immunophenotyping of lymphocyte subsets and testing for antigen-specific platelet autoantibodies. A complete sustained platelet response was defined as a platelet count >100x109/L at week 1 and 4 after IVIG treatment. From an input of 46 variables, supervised statistical learning (Elastic net) was used to select predictors of absence of a sustained platelet response after IVIG administration. Results In total 32/80 patients (40%) did not show a sustained platelet response to IVIG; 23 patients showed no one-week platelet response and 9 relapsed from an initial response. Non-response to IVIG was associated with a large deletion in the Fc-gamma receptor locus (copy number region 1, encompassing FCGR2Cand FCGR3B), Buchanan bleeding Score > 1, lower hemoglobin levels, insidious disease onset and absence of anti-platelet IgG autoantibodies. Together, these five variables achieved a reasonable discrimination between IVIG-responders and non-responders with a receiver-operator-characteristic AUC of 0.81. Non-responders were classified with a sensitivity of 0.98 and a low specificity of 0.54. All children that were predicted to have a complete sustained response had favorable disease outcomes. Misclassifications occurred mostly in patients who showed a partial response to IVIG. When we used this set of predictors in children below 7 years of age that were included in the observation arm of the trial (N=67), children with persistent thrombocytopenia during follow-up were distinguished (6-month non-response, AUC 0.78; 12-month non-response, AUC 0.85), suggesting that children with persistent ITP showed similar disease characteristics as patients who did not respond to IVIG. Furthermore, this independently validated the association of the identified variables with prolonged ITP disease trajectories in patients who were not included during the statistical identification of the variables. Conclusions In children below 7 years of age with newly diagnosed ITP, patients with persistent thrombocytopenia and IVIG non-responders were distinguished with high sensitivity by a limited set of clinical and immune variables. Our data strongly support the hypothesis that IVIG is efficacious in patients who would otherwise recover spontaneously. While we will continue to investigate the underlying immune phenomena, these findings potentially allow the design of a model to predict responses to IVIG at diagnosis. Due to the low specificity, the current set of variables cannot yet be used to withhold IVIG therapy. However, based on the high sensitivity, we conclude that a group of children with self-limiting ITP and a complete sustained response to IVIG can be accurately identified. Disclosures Porcelijn: Sanquin Blood Supply Foundation: Employment. De Haas:Sanquin Blood Supply Foundation: Employment.

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Successful Discontinuation of Eltrombopag after Complete Remission in Patients with Primary Immune Thrombocytopenia

Blood ◽

10.1182/blood.v124.21.1465.1465 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1465-1465

Author(s):

Tomás José González-López ◽

Cristina Pascual ◽

María Teresa Álvarez-Román ◽

Fernando Fernández-Fuertes ◽

Blanca Sánchez-González ◽

...

Keyword(s):

Platelet Count ◽

Complete Remission ◽

Median Time ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Sustained Response ◽

Adult Patients ◽

Newly Diagnosed ◽

Platelet Response

Abstract Background: Eltrombopag is effective and safe for treating chronic immune thrombocytopenia (ITP) patients who have not responded to previous therapy. Interestingly, some patients in whom hemostatic platelet counts are achieved with eltrombopag may sustain the platelet response when eltrombopag ceases to be administered. However, the frequency of sustained responses after discontinuing eltrombopag without additional therapy for ITP is largely unknown. Methods: A total of 260 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry were retrospectively evaluated. The study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age was 62 [range, 18–93] years. There were 165 women and 95 men. According to the standard definition, patients were allocated to newly diagnosed (n=29), persistent (n=36) and chronic (n=195) ITP groups. The median time from diagnosis to eltrombopag initiation was 24 [range, 1–480] months. The median number of previous therapies was 3 [range, 0–10], including splenectomy (22%), rituximab (23%) and romiplostim (19%). The initial response rate to eltrombopag was 231/260 (89%), including 77% (n=201) cases of complete remission (platelet count ≥100 x 109/L). The median duration of eltrombopag treatment was 6 [range, 1–54] months. Eltrombopag was discontinued in 80 out of 201 (39.8%) patients who achieved CR. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=33), platelet count >400x109/L (n=29), patient’s request (n=5), aspartate aminotransferase elevation (n=3), diarrhea (n=3), thrombosis (n=3) and other reasons (n=4). For analysis of discontinuation, patients with follow-up < 6 months (n=15), newly diagnosed ITP (n=11) or patients who received concomitant or previous (6 months before) treatments at the start of eltrombopag use (n=5) were excluded. Of the 49 evaluable patients, 22 (45%) had an immediate relapse after stopping eltrombopag. One patient with sustained response after stopping treatment relapsed at 10 months. A total of 26 patients (53%) showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 [range, 6–25] months. These patients were characterized by a median time since ITP diagnosis of 46.5±114.1 months, with 4/26 having ITP <1 year. Eleven patients (42%) were male and their median age was 59 [range, 18-88] years. They had received a median of four previous treatment lines [range: 0–9 lines] and 11 (42%) were splenectomized. The median platelet count before starting eltrombopag was 22 x 109/L and that before eltrombopag withdrawal was 269 x 109/L. The main characteristics (age, gender, duration of ITP, prior anti-ITP lines, prior splenectomy, prior rituximab, prior romiplostim, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 26 patients with sustained response after stopping eltrombopag were compared with those of the 23 patients relapsing after eltrombopag withdrawal. No predictive factors of sustained response after eltrombopag withdrawal could be identified. Conclusion: Platelet response following eltrombopag cessation may be sustained in nearly half of adult patients with primary ITP after CR with eltrombopag. However, reliable markers for predicting which patients will have this response are lacking. Disclosures No relevant conflicts of interest to declare.

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Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial

Blood ◽

10.1182/blood-2018-02-830844 ◽

2018 ◽

Vol 132 (9) ◽

pp. 883-891 ◽

Cited By ~ 26

Author(s):

Katja M. J. Heitink-Pollé ◽

Cuno S. P. M. Uiterwaal ◽

Leendert Porcelijn ◽

Rienk Y. J. Tamminga ◽

Frans J. Smiers ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Intravenous Immunoglobulin ◽

Immune Thrombocytopenia ◽

Controlled Trial ◽

Ivig Treatment ◽

Severe Bleeding ◽

Newly Diagnosed ◽

Bleeding Events ◽

Randomized Controlled ◽

Key Points

Key Points In children with newly diagnosed ITP, IVIg treatment at diagnosis does not result in a lower rate of chronic ITP. Upfront treatment with IVIg led to faster recovery and less severe bleeding events.

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A Phase 3 Study of Eltrombopag Vs. Standard First-Line Management for Newly Diagnosed Immune Thrombocytopenia in Children

Blood ◽

10.1182/blood-2019-125487 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2369-2369

Author(s):

Kristin A. Shimano ◽

Rachael F. Grace ◽

Carolyn M. Bennett ◽

Robert J Klaassen ◽

Cindy Neunert ◽

...

Keyword(s):

Platelet Count ◽

Treatment Failure ◽

Standard Therapy ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Newly Diagnosed ◽

Platelet Response ◽

First Line ◽

Chronic Itp ◽

Thrombopoietin Receptor

Background: Immune thrombocytopenia (ITP) is the most common autoimmune cytopenia diagnosed in children, typically causing a severely low platelet count, variable bleeding symptoms, and reductions in health-related quality of life (HRQoL). Eltrombopag is an established therapy for pediatric patients with chronic ITP. Favorable safety and efficacy were shown in the PETIT and PETIT2 trials leading to FDA-approval for children with chronic ITP in 2015. Off-label use of eltrombopag for adults with newly diagnosed ITP has been described in two small single-center trials. Gomez-Almaguer et al. reported 100% response (platelets >30 x 109/L) at completion of therapy and 66.7% relapse-free survival at 1 year in a single-arm study of dexamethasone in combination with 4 weeks of eltrombopag upfront in adult patients with newly diagnosed ITP, better outcomes than expected for comparable patients treated with steroids alone. In a second study, Tripathi et al. found 76% of steroid-nonresponsive patients had a durable response to eltrombopag after 3 months of therapy. Pediatric hematologists are already using thrombopoietin receptor agonists (TPO-RAs) in some cases of newly diagnosed ITP, according to a retrospective study by Neunert et al. TPO-RAs may be an efficacious first-line therapy for newly diagnosed ITP patients who require treatment. Study Design and Methods: The PINES (Pediatric ITP Newly diagnosed patients Eltrombopag vs Standard therapy) Study, NCT03939637, is an investigator-initiated prospective, open label, randomized, multi-center trial sponsored by the ITP Consortium of North America (ICON) and funded by Novartis. The primary objective is to determine if the proportion of patients with a platelet response, defined as ≥ 6 of 8 weeks with platelets >50 x109/L during weeks 5-12 of therapy without rescue treatment, is significantly greater in patients with newly diagnosed ITP treated with eltrombopag than in those treated with standard first-line treatments. This is a primary outcome used in a previous pediatric study of eltrombopag in chronic ITP (PETIT2) and is a clinically relevant outcome measuring a sustained, rather than transient, platelet response. Patients (n=156) from 20 ICON centers will be randomized 2:1 to receive the experimental treatment, eltrombopag, or investigator's choice of 3 standard front-line therapies: prednisone, intravenous immune globulin, or anti-D globulin at protocol-specified doses (Figure). Eligible patients are ages 1 to <18 with primary ITP, within 3 months of diagnosis, with platelet count <30 x109/L who require pharmacologic treatment from the perspective of the treating clinician. There are 2 treatment groups: 1) upfront treatment, defined as patients within 10 days of ITP diagnosis with no prior treatment, and 2) treatment failure, defined as patients previously managed with observation or a first-line standard agent. Patients are excluded if they have severe bleeding, defined by Buchanan Overall Grade 4 or 5 bleeding or bleeding requiring emergent treatment in the opinion of the provider. Patients will be followed for 1 year. Patients may receive prednisone, intravenous immune globulin, or anti-D globulin as rescue treatments beyond their study-assigned treatment in the first 12 weeks of the study. Patients randomized to the eltrombopag arm may continue this treatment throughout the 1-year duration of study participation if needed, with guidelines given for dose adjustments. Treatment after the first 12 weeks of study in the standard therapy arm or for patients originally assigned to eltrombopag who do not respond is at the discretion of the treating physician. Randomization is stratified by age and treatment status (upfront treatment vs. treatment failure). A one-sided z-test, at alpha=0.025, will be used to compare the proportion of patients who have a platelet response between the two arms. All randomized patients will be analyzed in the intention-to-treat analysis. Secondary objectives include comparison of bleeding scores (WHO Bleeding Scale and Modified Buchanan Score), changes in HRQoL (measured by the Kids ITP Tool, Hockenberry Fatigue Scale, PROMIS, and Global Change Scale), and changes in percentage of CD4+25+Foxp3+ regulatory T cells. Samples will be banked for optional future biology studies. Site activation and enrollment began in May 2019, and updated enrollment data will be presented at the meeting. Figure Disclosures Shimano: Novartis: Research Funding; Pfizer: Research Funding; Daiichi Sankyo: Research Funding. Grace:Novartis: Research Funding; Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bennett:Novartis: Research Funding. Neufeld:Octapharma, Shire Pharmaceuticals (Baxalta), Novo Nordisk, Celgene, NHLBI/NIH: Research Funding; Octapharma, Agios, Acceleron, Grifols, Pfizer, CSL Behring, Shire Pharmaceuticals (Baxalta), Novo Nordisk, ApoPharma, Genentech, Novartis, Bayer Healthcare: Consultancy; Octapharma: Other: study investigator, NuProtect study (Octapharma-sponsored). London:United Therapeutics: Consultancy; ArQule, Inc: Consultancy. Despotovic:Novartis: Research Funding; Amgen: Research Funding; Dova: Honoraria. OffLabel Disclosure: Eltrombopag is a thrombopoietin receptor agonist FDA-approved for use in chronic ITP.

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Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽

10.1182/blood-2019-129274 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2352-2352

Author(s):

Tomas Jose Gonzalez-Lopez ◽

Fernando Fernandez-Fuertes ◽

Maria Cristina Pascual Izquierdo ◽

Isabel Caparros ◽

Silvia Bernat ◽

...

Keyword(s):

Platelet Count ◽

Median Time ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Previous Treatment ◽

Complete Response ◽

Platelet Response ◽

Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

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Hypovitaminosis D Influences the Clinical Presentation of Immune Thrombocytopenia in Children with Newly Diagnosed Disease

Journal of Clinical Medicine ◽

10.3390/jcm8111861 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1861

Author(s):

Petrovic ◽

Benzon ◽

Batinic ◽

Culic ◽

Roganovic ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Clinical Presentation ◽

Coastal Region ◽

Autoimmune Disorder ◽

Hypovitaminosis D ◽

Severe Bleeding ◽

Newly Diagnosed ◽

Randomized Controlled Studies ◽

Bleeding Score ◽

D Values

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia defined as platelet count in peripheral blood <100 × 109/L. Hypovitaminosis D is very common in children with autoimmune diseases. To analyze whether hypovitaminosis D is associated with the clinical presentation of ITP in children, medical records of 45 pediatric patients with newly diagnosed immune thrombocytopenia in the coastal region of Croatia were evaluated. The severity of bleeding was assessed using two bleeding scores. Children with lower 25-hydroxyvitamin D (25(OH)D) values had higher values of the skin-mucosa-organ-gradation (SMOG) bleeding score and respectively more severe bleeding on diagnosis of ITP. With further analysis of the main domains of that score, we found that patients with a lower 25(OH)D value had more severe bleeding in the skin and organs. When 25(OH)D and ITP Bleeding Scale (IBLS) score were analyzed, a negative correlation was found, but it was not significant. Our findings suggest that hypovitaminosis D influences the severity of the clinical presentation of ITP in children on initial diagnosis of the disease. Therefore, therapy with 25(OH)D could be a new potential option for treatment of ITP. To investigate the connection between 25(OH)D and the incidence and severity of ITP, further studies, especially randomized controlled studies, are needed.

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How I Manage cyclic thrombocytopenia

Blood ◽

10.1182/blood.2020008218 ◽

2020 ◽

Author(s):

Paul A Kyrle ◽

Sabine Eichinger

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Hematological Malignancies ◽

Severe Bleeding ◽

Typical Pattern ◽

Periodic Fluctuation ◽

Thrombopoietin Receptor ◽

Primary Immune Thrombocytopenia ◽

Platelet Count Monitoring ◽

Mucocutaneous Bleeding

Cyclic thrombocytopenia (CTP) is a rare disease, which is characterized by periodic fluctuation of the platelet count. The pathogenesis of CTP is unknown and most likely heterogeneous. Patients with CTP are almost always misdiagnosed as having primary immune thrombocytopenia (ITP). The interval between ITP and CTP diagnosis can be many years. CTP patients often receive ITP-specific therapies including corticosteroids, thrombopoietin receptor agonists, rituximab and splenectomy which are followed by a transient increase in platelet count that is wrongly attributed to treatment effect with inevitable "relapse". CTP can be diagnosed by frequent platelet count monitoring which reveals a typical pattern of periodic platelet cycling. An early diagnosis of CTP will prevent these patients from being exposed to possibly harmful therapies. The bleeding phenotype is usually mild and consists of mucocutaneous bleeding at the time when the platelet count is at its nadir. Severe bleeding from other sites can occur but is rare. Some patients respond to cyclosporine A or to danazol, but most patients do not respond to any therapy. CTP can be associated with hematological malignancies or disorders of the thyroid gland. Nevertheless, spontaneous remissions can occur, even after many years.

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Use of Post-Treatment Clinical Data To Predict Response to Decitabine.

Blood ◽

10.1182/blood.v110.11.1448.1448 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1448-1448

Author(s):

Elihu Estey ◽

J.-P. Issa ◽

Guillermo Garcia-Manero ◽

Stefan Faderl ◽

Hagop Kantarjian

Keyword(s):

Platelet Count ◽

Clinical Data ◽

Neutrophil Count ◽

Median Number ◽

Post Treatment ◽

Newly Diagnosed ◽

Platelet Response ◽

Best Response ◽

Blast Count ◽

To Receive

Abstract Best response of AML or MDS to decitabine (DAC) may require > 3 courses. Identification of pts whose response to initial courses suggests they are unlikely to respond further to subsequent courses would allow such pts to receive other therapies more expeditiously. 104 pts, median age 69, received DAC (20 mg/m2 IV daily × 5 days every 5 weeks) for newly- diagnosed MDS (80, 76 IPSS int-2 or high) or AML (24) from 9/00-5/07. After 3 courses, 33 of the 104 were in CR, 6 were dead, and 32 had been removed from study, with the remaining 32 receiving more DAC. The probability of CR decreased to < 10% on all courses after the 5th: Course# Pts Receiving CR Deaths/Off Study Received Next Course after course Course 1 104 7 (7%) 2/15 80 2 80 16 (20%) 4/12 48 3 48 10 (21%) 0/6 32 4 32 5 (16%) 0/5 22 5 22 3 (14%) 0/3 16 6 16 1 (6%) 1/3 11 7–15 11 1 (9%) 1/9 0 Results were qualitatively similar for AML and MDS. We divided the 32 pts who received ≥ 4 courses according to whether after course 3 their: marrow showed a response, defined as a p < 0.05 difference between the pre-Rx and post course 3 blast count, platelet count increased > 30, 000 if < 100,000 pre-Rx, or neutrophil count increased > 500 if < 500 pre Rx; criteria 2 and 3 were adapted from those of the IWG. 8/14 pts with vs. 1/11 without a marrow response after course 3 entered CR on subsequent courses (p = .02, 6/10 vs. 1/10 considering only MDS). The corresponding figure for platelet response/no response was 5/8 vs. 2/11 (3/5 vs. 2/9 for MDS). The median number of courses after the 3rd given pts with marrow response was 2 (range 1–10) vs. 3 (range 1–12) for pts without marrow response. Our data suggest that if CR is the goal, pts should not receive more than 5 courses of DAC and no more than 3 if marrow response has not occurred after the 3rd.

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Effect of Pregnancy in Women with a History of Primary Immune Thrombocytopenia Considered As Cured

Blood ◽

10.1182/blood.v128.22.2552.2552 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2552-2552

Author(s):

Thibault Comont ◽

Guillaume Moulis ◽

Karen Delavigne ◽

Pierre Cougoul ◽

Olivier Parant ◽

...

Keyword(s):

Platelet Count ◽

Complete Remission ◽

Epidural Analgesia ◽

Pregnant Women ◽

Immune Thrombocytopenia ◽

Specific Treatment ◽

Severe Bleeding ◽

Adult Women ◽

History Of ◽

The Impact

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease that occurs in young women. Pregnancy is a well-known risk factor for developing newly diagnosed ITP as well as for inducing disease flares in patients with current ITP. However, the impact of pregnancy in women with an old history of ITP, considered as cured, has not been assessed. The aim of this study was to describe the course of ITP in pregnant women with an ITP in complete remission (platelets count >100x109/L and absence of bleeding symptoms) for at least 5 years without any ITP treatment. We retrospectively selected all pregnant women with delivery at Toulouse University Hospital, South of France, between 2010 and 2015 with a hospital discharge code of ITP (international classification of diseases; version 10 code D69.3). This code has a sensitivity of 81.2% and a positive predictive value of 89.8% in this database. All medical charts were reviewed to confirm the diagnosis of ITP. We included adult women (≥18 years) with a diagnosis of primary ITP according to French guidelines (platelet count <150 x 109 /L and exclusion of other causes of thrombocytopenia, especially other causes of thrombocytopenia during pregnancy) in complete remission for at least 5 years. We identified 50 pregnancies in 39 ITP patients during the study period. Eleven pregnancies occurred in 10 patients in long-term complete remission of ITP at the time of pregnancy onset. Baseline characteristics were: median age at ITP diagnosis: 21 years (range: 4-29); median age at pregnancy onset:32 years (range: 26-34; history of ITP during a previous pregnancy: 1; history of bleeding: 4 (36.4%); previous treatment for ITP: 8 (72.7%), corticosteroids-CS (5), CS and intravenously immunoglobulin-IVIg (3), splenectomy (4), dapsone (1); last median platelet count before pregnancy: 170x109/L (range: 118-363). Platelets count decreased below 100x109/L in 3 pregnancies (27.2%) from the first trimester for one patient, from the second trimester for one other and from the third trimester for the last one, with a nadir of 3, 39 and 87 (x109/L) respectively. One of them experienced a severe bleeding (grade 3 according to the International Working Group bleeding classification). All thrombocytopenic patients required treatment during pregnancy: CS+IVIg for 2 (one for bleeding and one to allow epidural analgesia) and IVIg for the other (to allow epidural analgesia). For these 3 women, the median platelet count at delivery was 128 (range: 38-159) and consequently only 2 of them could have epidural analgesia. No bleeding during delivery was observed. Transient thrombocytopenia occurred in 2 newborns. Primary ITP considered as cured may relapse during pregnancy and may induce severe bleeding requiring specific treatment. A tight monitoring should be proposed to all pregnant women with a history of primary ITP, even after several years of complete remission. Disclosures Récher: Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Maternal and fetal outcomes of primary immune thrombocytopenia during pregnancy: A retrospective study

Obstetric Medicine ◽

10.1177/1753495x17727408 ◽

2017 ◽

Vol 11 (1) ◽

pp. 12-16 ◽

Cited By ~ 4

Author(s):

KS Gilmore ◽

C McLintock

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Post Partum ◽

Bleeding Complications ◽

Platelet Response ◽

Thrombocytopenic Purpura ◽

Primary Immune Thrombocytopenia ◽

Secondary Outcomes ◽

Post Partum Haemorrhage ◽

Auckland Hospital

Objective We reviewed outcomes of 52 pregnancies in 45 women with immune thrombocytopenic purpura who delivered at Auckland Hospital with an antenatal platelet count of <100 × 109/L. Outcome measures Primary outcomes were maternal platelet count at delivery and treatment response. Secondary outcomes included post-partum haemorrhage (PPH). Results Most women had thrombocytopenia at delivery. Treatment with prednisone was given in 14 (27%) pregnancies with responses considered safe for delivery in 11 pregnancies (79%). Women in eight pregnancies also received intravenous immunoglobulin; in five pregnancies (63%) a platelet response acceptable for delivery was achieved. Seventeen pregnancies (33%) were complicated by a PPH ≥500 mL. Ten pregnancies (19%) were complicated by a PPH ≥1000 mL. PPH was reported in all women with a platelet count <50 × 109/L at delivery. Conclusions There were no antenatal bleeding complications but PPH was common among women with platelet counts <50 × 109/L at the time of birth.

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Management of newly diagnosed immune thrombocytopenia: can we change outcomes?

Blood Advances ◽

10.1182/bloodadvances.2017009860 ◽

2017 ◽

Vol 1 (24) ◽

pp. 2295-2301 ◽

Cited By ~ 16

Author(s):

Cindy E. Neunert

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Newly Diagnosed ◽

First Line ◽

Current Standard ◽

First Line Therapy ◽

Line Therapy ◽

Remission Rates ◽

Treatment Naïve ◽

Treatment Paradigm

Abstract Immune thrombocytopenia resulting from antibody-mediated platelet destruction combined with impaired platelet production is a common cause of thrombocytopenia. The decision to treat newly diagnosed patients is based on several factors including ceasing hemorrhagic manifestations, increasing the platelet count, prevention of bleeding, and inducing remission. Current standard first-line therapy is a course of corticosteroids. Although this treatment paradigm increases the platelet count in the majority of patients, a high percentage relapse after discontinuation of corticosteroid therapy. For this reason, intensification of first-line therapy that results in superior long-term remission rates would be desirable. This manuscript focuses primarily on adults with idiopathic thrombocytopenic purpura (ITP), highlighting pediatric data and practice when applicable. The primary aim is to outline upfront strategies for treatment-naive patients with ITP to enhance remission rates, taking into account assessment of the risks and benefits of these approaches.

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