Association between Platelet-Associated Immunoglobulin G Levels and Response to Corticosteroid Therapy in Patients with Newly Diagnosed Immune Thrombocytopenia

2020 ◽  
pp. 1-6
Author(s):  
Masuho Saburi ◽  
Masao Ogata ◽  
Yasuhiro Soga ◽  
Takako Satou ◽  
Kazuhito Itani ◽  
...  
Keyword(s):  
Corticosteroid Therapy ◽  
Immunoglobulin G ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
First Line ◽  
Laboratory Findings ◽  
Platelet Production ◽  
First Line Therapy ◽  
Line Therapy ◽  
Immature Platelet Fraction

<b><i>Objective:</i></b> Platelet-associated immunoglobulin G (PA-IgG) refers to IgG attached to the surface of platelets, while the immature platelet fraction (IPF) reflects the state of platelet production in bone marrow. Since PA-IgG and IPF are increased in patients with immune thrombocytopenia (ITP), reflecting amounts of platelet antibodies and compensatory platelet production, respectively, we hypothesized that these laboratory findings may provide useful markers for predicting treatment response in patients with ITP. We therefore retrospectively investigated associations between levels of these markers at diagnosis and response to first-line therapy in patients with ITP. <b><i>Methods:</i></b> Forty-three patients diagnosed with ITP at Oita Kouseiren Tsurumi Hospital between May 2010 and November 2018 were included. Patients were divided into 2 groups based on response to corticosteroid as first-line therapy. Laboratory findings were compared between responders and nonresponders. <b><i>Results:</i></b> Median PA-IgG was 285 ng/10<sup>7</sup> cells (range, 45.5–18,200 ng/10<sup>7</sup> cells), and median IPF was 15.5% (range, 5.4–62.1%). Median levels were higher than the respective upper limits of normal range (PA-IgG, 0–46 ng/10<sup>7</sup> cells; IPF, 1.1–9.5%). First-line therapy was performed using standard-dose prednisolone (0.5–1.0 mg/kg/day) in 32 patients and high-dose dexamethasone (40 mg/day, 4 days) or methylprednisolone (125–1,000 mg/day, 3–4 days) in 11 patients. Twenty-four patients (55.8%) responded to first-line therapy. In univariate analysis, type of corticosteroid (<i>p</i> = 0.17) tended to differ between groups but did not differ significantly, and no difference in IPF level was apparent between responders (15.35%; range, 5.4–41.5%) and nonresponders (16.7%; range, 6.3–62.1%; <i>p</i> = 0.15). PA-IgG was significantly higher among nonresponders (430 ng/10<sup>7</sup> cells; range, 101–18,200 ng/10<sup>7</sup> cells) than among responders (254.5 ng/10<sup>7</sup> cells; range, 45.5–470 ng/10<sup>7</sup> cells; <i>p</i> = 0.004). Multivariate analysis revealed PA-IgG was independently associated with response to first-line therapy (odds ratio, 1.000; 95% confidence interval, 1.000–1.010; <i>p</i> = 0.029). <b><i>Conclusion:</i></b> Our data suggested that PA-IgG at diagnosis could offer a useful predictor of response to first-line corticosteroid therapy for ITP.

scholarly journals First-Line Therapy for Immune Thrombocytopenia

2019 ◽  
Vol 39 (03) ◽  
pp. 259-265 ◽  
Author(s):  
Siraj Mithoowani ◽  
Donald M. Arnold
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Bleeding Complications ◽  
High Dose ◽  
First Line ◽  
Risk Of Bleeding ◽  
First Line Therapy ◽  
Line Therapy ◽  
Increased Risk ◽  
Count Response

AbstractImmune thrombocytopenia (ITP) is an autoimmune disease affecting blood platelets that causes thrombocytopenia and an increased risk of bleeding. First-line therapy is indicated for patients with bleeding complications or who are at increased risk of bleeding, and the decision to initiate therapy depends not only on the platelet count, but also on other endpoints including quality of life. The choice of first-line therapy depends primarily on how quickly a platelet count response is required, with intravenous immune globulin providing the more rapid response, followed by high-dose dexamethasone and prednisone. In this narrative review, we discuss key issues with first-line therapy in ITP including when to initiate therapy, treatment options and special considerations for children. Evidence-based guidelines are lacking for the emergency management of patients with ITP who present with significant bleeding; we provide our approach to this critical situation.

scholarly journals Inhibition of platelet phagocytosis as an in vitro predictor for therapeutic potential of RBC antibodies in murine ITP

Blood ◽  
2020 ◽  
Vol 135 (26) ◽  
pp. 2420-2424 ◽  
Author(s):  
Ramsha Khan ◽  
Melissa Menard ◽  
Chao-Ching Jen ◽  
Xi Chen ◽  
Peter A. A. Norris ◽  
...  
Keyword(s):  
Blood Cells ◽  
Immune Thrombocytopenia ◽  
Therapeutic Potential ◽  
Sufficient Condition ◽  
First Line ◽  
Phagocytosis Assay ◽  
First Line Therapy ◽  
Line Therapy

Abstract Polyclonal anti-D is a first-line therapy for immune thrombocytopenia (ITP). Monoclonal antibodies are desirable alternatives, but none have yet proven successful despite their ability to opsonize erythrocytes (or red blood cells, RBCs) and cause anemia. Here, we examined 12 murine erythrocyte–specific antibodies of different specificity and subtypes and found that 8 of these antibodies could induce anemia in antigen-positive mice. Of these 8 antibodies, only 5 ameliorated ITP. All antibodies were examined for their in vitro ability to support macrophage-mediated phagocytosis of erythrocytes. Antibodies which supported erythrocyte phagocytosis in vitro successfully ameliorated ITP in vivo. To examine the ability of each antibody to inhibit phagocytosis of platelets, the antibodies were used to sensitize erythrocytes in vitro and these were added to a platelet phagocytosis assay. Antibodies that inhibited platelet phagocytosis in vitro also all ameliorated ITP in vivo. We conclude that inducing anemia is not a sufficient condition for amelioration of ITP but that the antibody’s ability to prevent platelet phagocytosis in vitro predicted its ability to ameliorate ITP. We suggest that inhibition of in vitro platelet phagocytosis may prove to be a valuable tool for determining which erythrocyte antibodies would likely be candidates for clinical use in ITP.

High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer

2002 ◽  
Vol 50 (5) ◽  
pp. 383-391 ◽  
Author(s):  
Ychou M. ◽  
Raoul J. ◽  
Desseigne F. ◽  
Borel C. ◽  
Caroli-Bosc F. ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Single Agent ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Blood ◽  
2020 ◽  
Author(s):  
Norbert Schmitz ◽  
Lorenz H Truemper ◽  
Krimo Bouabdallah ◽  
Marita Ziepert ◽  
Mathieu Leclerc ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Allogeneic Transplantation ◽  
T Cell Lymphoma ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Peripheral T Cell Lymphoma ◽  
First Line Therapy ◽  
Line Therapy

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

Reassessment of treatment modalities for paediatric patients with chronic immune thrombocytopenia

2009 ◽  
Vol 29 (02) ◽  
pp. 171-176 ◽  
Author(s):  
G. Janssen ◽  
A. Borkhardt ◽  
H. J. Laws
Keyword(s):  
Lupus Erythematosus ◽  
Immune Thrombocytopenia ◽  
Spontaneous Recovery ◽  
Treatment Modalities ◽  
First Line ◽  
Second Line Therapy ◽  
Chronic Itp ◽  
First Line Therapy ◽  
Line Therapy ◽  
Acute Form

SummaryApproximately 70% of children have the acute form of immune thrombocytopenia (ITP), which is defined by recovery within six months of presentation with or without treatment. Chronic ITP is to be reserved for patients with platelets < 100 000/μl for more than twelve months and exclusion of other diagnosis like systemic lupus erythematosus or bone marrow failures. In children, the chance of spontaneous recovery is 52% after diagnosis of chronic ITP. The Intercontinental Childhood ITP Study group recommends that children without bleeding may not require therapy regardless of their platelet count. Whereas in patients with bleeding symptoms first line therapy is defined and includes steroids or immunoglobuline, second line therapy in refractory patients with significant hemorrhagic problems is unclear. Guidelines recommend splenectomy, but for more than 50 years patients and physicians look for pharmacological alternatives. It may be that rituximab is a promising option which has been proven to be effective with few adverse effects. Till now the treatment has focused on immunomodulation. Research has now focused on stimulating platelet production. In this review we discuss old and new therapy modalities for children with cITP.

High-Dose Bi-Weekly THP-COP Induction Treatment Followed by High-Dose Therapy with Autologous Peripheral Blood Stem Cell Transplantation for Advanced-Stage Follicular Lymphoma as First-Line Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5207-5207
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Masutaka Higashimura ◽  
Akihito Momoi ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Most patients with advanced-stage follicular lymphoma(FL) cannot be cured by conventional chemotherapy and have median survival of 7 to 10 years. High-dose chemotherapy (HDT) supported by autologous stem cell transplantation(ASCT) gives a survival benefit for patients with aggressive lymphoma. Recent several multicenter studies have shown that clinical and molecular remissions can be attained in patients with FL receiving intensified high-dose sequential chemotherapy and autografting. We have reported the efficacy and safety of high-dose bi-weekly THP-COP with G-CSF support (HDBW-TCOPG) for non-Hodgkin’s lymphoma. Therefore, we performed a pilot clinical trial to evaluate the efficacy and toxicity of HDBW-TCOPG followed by HDT with ASCT as first-line therapy in patients with advanced-stage FL. Patients and methods: Between August 1998 and December 2003, 10 Japanese patients with previously untreated FL from whom informed consent was obtained were included in this single-center pilot study. Median age was 48 years. All patients had stage 3 or 4 disease, aaIPI LI 8 and HI 2. Histological subtypes of FL included grade 1 4; grade 2 4; grade 3a 2. HDBW-TCOPG consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 from day 1 to 5; lenograstim 2.0 mg/kg/day from day 3. Five patients who enrolled after rituximab was approved for indolent B-cell lymphoma in Japan received induction therapy combined HDBW-TCOPG with rituximab 375mg/m2 on day -2 (R-HDBW-TCOPG). Six cycles were administered at intervals of two weeks. PBSC were collected during the later cycles of HDBW-TCOPG or on the recovery of high-dose etoposide regimen (500mg/m2 for 3 days) administered after the completion of HDBW-TCOPG. Leukaphereses were performed until a minimum of 2.0x106/kg CD34+ cells had been collected. The conditioning regimen consisted of ranimustine 200mg/m2 on day-7 and -2; paraplatin 300mg/m2 on day -6, -5, -4, -3; etoposide 500mg/m2 on day −5, −4, −3; cytarabine 2.5 g/m2 every 12 hours on day −2, −1 (MCE-CA regimen) in 2 patients or cyclophosphamide 50mg/kg on day −2, −1 (MCEC regimen) in 8 patients. Results: Sufficient numbers of PBSC were collected in 5 of 7 patients mobilized with HDBW-TCOPG and in all 5 patients with high-dose etoposide. The median time to reach total number of leukocytes of 1.0 x109/l was nine days (range 8–11). All 10 patients who were in PR at the end of HDBW-TCOP(G) achieved CR post APBSCT. After a median follow up of 36.6 months (range 7–66 months) PFS and OS are 90% and 90%, respectively, for all patients. One patient developed secondary myeloid leukemia with t(3;21) and died at 35 months after APBSCT without signs of recurrence of lymphoma. Another patient who relapsed at 35 months after transplantation. IgH or BCL2 rearrangement was detected by PCR analysis prior to therapy in three patients and one of them still showed detectable disease after HDBW-TCOPG induction. However, all three patients demonstrated MRD negativity after HDT with ASCT. Conclusion: HDBW-TCOPG as induction therapy followed by HDT with ASCT is feasible for advanced-stage FL with acceptable toxicity, and this short term highly intensified therapy may induce cure of the disease by minimizing MRD, but longer follow up is needed to evaluate the impact on survival.

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