scholarly journals Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2260-2262 ◽  
Author(s):  
Upendra P. Hegde ◽  
Wyndham H. Wilson ◽  
Therese White ◽  
Bruce D. Cheson
Keyword(s):  
Platelet Count ◽  
Chronic Lymphocytic Leukemia ◽  
Intravenous Immunoglobulin ◽  
Immune Thrombocytopenia ◽  
Lymphocytic Leukemia ◽  
Platelet Response ◽  
Idiopathic Thrombocytopenia ◽  
Platelet Counts

Fludarabine can exacerbate idiopathic thrombocytopenia (ITP) in chronic lymphocytic leukemia (CLL). We report 3 CLL patients with refractory fludarabine-associated ITP who responded to rituximab. The patients had Rai stages III, III, and IV disease. Before fludarabine treatment, the platelet counts were 141 000/μL, 118 000/μL, and 70 000/μL. ITP developed within week 1 of cycle 3 in 2 patients and within week 2 of cycle 1 in 1 patient. Platelet count nadirs were 4000/μL, 1000/μL, and 2000/μL, respectively, and did not respond to treatment with steroids or intravenous immunoglobulin. Rituximab therapy (375 mg/m2 per week for 4 weeks) was begun on days 18, 23, and 20 of ITP. Patient 1 achieved a platelet count of more than 50 000/μL at day 21 and more than 133 000/μL at day 28, patient 2 achieved a platelet count of more than 50 000/μL at day 4 and more than 150 000/μL at day 10, and patient 3 achieved a platelet count of more than 50 000/μL at day 5 and 72 000/μL at day 28 of rituximab therapy, with platelet response durations of 17+, 6+, and 6 months. These results suggest rituximab can rapidly reverse refractory fludarabine-associated ITP.

scholarly journals Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2260-2262 ◽  
Author(s):  
Upendra P. Hegde ◽  
Wyndham H. Wilson ◽  
Therese White ◽  
Bruce D. Cheson
Keyword(s):  
Platelet Count ◽  
Chronic Lymphocytic Leukemia ◽  
Intravenous Immunoglobulin ◽  
Immune Thrombocytopenia ◽  
Lymphocytic Leukemia ◽  
Platelet Response ◽  
Idiopathic Thrombocytopenia ◽  
Platelet Counts

Abstract Fludarabine can exacerbate idiopathic thrombocytopenia (ITP) in chronic lymphocytic leukemia (CLL). We report 3 CLL patients with refractory fludarabine-associated ITP who responded to rituximab. The patients had Rai stages III, III, and IV disease. Before fludarabine treatment, the platelet counts were 141 000/μL, 118 000/μL, and 70 000/μL. ITP developed within week 1 of cycle 3 in 2 patients and within week 2 of cycle 1 in 1 patient. Platelet count nadirs were 4000/μL, 1000/μL, and 2000/μL, respectively, and did not respond to treatment with steroids or intravenous immunoglobulin. Rituximab therapy (375 mg/m2 per week for 4 weeks) was begun on days 18, 23, and 20 of ITP. Patient 1 achieved a platelet count of more than 50 000/μL at day 21 and more than 133 000/μL at day 28, patient 2 achieved a platelet count of more than 50 000/μL at day 4 and more than 150 000/μL at day 10, and patient 3 achieved a platelet count of more than 50 000/μL at day 5 and 72 000/μL at day 28 of rituximab therapy, with platelet response durations of 17+, 6+, and 6 months. These results suggest rituximab can rapidly reverse refractory fludarabine-associated ITP.

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

Blood ◽  
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.

Immune Thrombocytopenia Associated to Low-Dose Alemtuzumab Therapy in Chronic Lymphocytic Leukemia: A Single Retrospective Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4598-4598
Author(s):  
Gianluigi Reda ◽  
Francesco Maura ◽  
Giuseppe Gritti ◽  
Daniele Vincenti ◽  
Mariarita Sciumé ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Cumulative Dose ◽  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Autoimmune Disorder ◽  
Intravenous Immunoglobulins ◽  
Lymphocytic Leukemia ◽  
Platelet Counts

Abstract Abstract 4598 Immune thrombocytopenia (ITP) is a common autoimmune complication in chronic lymphocytic leukemia (CLL), occurring in up to 5% of patients. The occurrence of alemtuzumab-associated ITP have been rarely reported in CLL and it has never been reported so far as a significant event complicating alemtuzumab treatment in clinical trials. Recently, a new distinctive form of secondary ITP occurring in 6 out of 215 patients with relapsing-remitting multiple sclerosis treated with alemtuzumab in a randomized, controlled phase II trial has been reported (Cuker et al, Blood 2011). We investigated the incidence of ITP in a cohort of 64 consecutive patients treated with low-dose alemtuzumab for relapsed/refractory CLL from 2003 to 2010. Subcutaneous alemtuzumab was administered at the dose of 10 mg three times a week, up to 18 weeks. ITP was documented in 12/64 patients: in 3 patients (4.7%) ITP developed before alemtuzumab treatment and no relapses of the autoimmune disorder were observed during the treatment; in 9 patients (14.8%, with an incidence of 5.7 events/100 patient-year) ITP developed after alemtuzumab treatment. Median time to ITP from initial alemtuzumab exposure was 12 months (range 1–42 months). Concomitant hemolytic anemia (Evans syndrome) was observed in one patient. At ITP onset, median platelet counts were 11×109/L (range 3–70) and anti-platelet antibodies (Capture P® Method, ImmucorGamma, Norcross GA, USA) were found in 7 of the 8 patients tested. No patients showed severe or life-threatening bleeding. Three of nine patients who developed ITP after alemtuzumab therapy, experienced CLL progression requiring chemo-immunotherapy after 3, 4 and 13 months from ITP onset, respectively. One patient achieved a partial remission of CLL with ITP resolution, while the other two died of disease progression. In the remaining six cases, ITP was not associated with disease progression and was treated with corticosteroids and/or intravenous immunoglobulins. Five patients achieved normal platelet counts, while one patient did not respond. Low-dose alemtuzumab (theoretical cumulative dose 540 mg, equal to half of the classic cumulative dose and one-third of the individual dose) is an effective, safe and well tolerated treatment for CLL, as reported by several recent studies (Cortelezzi et al, Leukemia 2009; Brit J Haematol 2011). In our cohort of CLL patients treated with alemtuzumab, the incidence of ITP was 14.8% that is almost three times higher than previously reported in CLL. These data may indicate a role of T-lymphocyte dysregulation induced by alemtuzumab in the pathogenesis of ITP. Our data also suggested the importance of monitoring platelet counts during follow-up in patients treated with low-dose alemtuzumab for both haematological and non-haematological diseases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immune thrombocytopenia in lymphoproliferative diseases

Blood ◽  
1979 ◽  
Vol 53 (4) ◽  
pp. 545-551 ◽  
Author(s):  
BR Kaden ◽  
WF Rosse ◽  
TW Hauch
Keyword(s):  
Platelet Count ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Thrombocytopenia ◽  
Alkylating Agent ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Lymphoproliferative Diseases ◽  
Non Hodgkins Lymphoma ◽  
Membrane Bound ◽  
Positive Direct

We have studied the thrombocytopenia of lymphoproliferative disorders using a measurement of membrane-bound IgG by an antiglobulin consumption assay. Nine patients with chronic lymphocytic leukemia (CLL) and thrombocytopenia had increased membrane-bound IgG. Two patients with non-Hodgkins lymphoma and 1 patient with Hodgkins disease also had thrombocytopenia and increased membrane-bound IgG. Five of the patients with CLL had positive direct antiglobulin (Coombs) tests on red cells; of these, 3 patients had hemolytic anemia. In eight of the 9 patients with CLL, thrombocytopenia, and increased platelet-bound-IgG, the platelet count increased with the administration of prednisone or an alkylating agent, with splenectomy, or with a combination of these.

scholarly journals Immune thrombocytopenia in lymphoproliferative diseases

Blood ◽  
1979 ◽  
Vol 53 (4) ◽  
pp. 545-551 ◽  
Author(s):  
BR Kaden ◽  
WF Rosse ◽  
TW Hauch
Keyword(s):  
Platelet Count ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Thrombocytopenia ◽  
Alkylating Agent ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Lymphoproliferative Diseases ◽  
Non Hodgkins Lymphoma ◽  
Membrane Bound ◽  
Positive Direct

Abstract We have studied the thrombocytopenia of lymphoproliferative disorders using a measurement of membrane-bound IgG by an antiglobulin consumption assay. Nine patients with chronic lymphocytic leukemia (CLL) and thrombocytopenia had increased membrane-bound IgG. Two patients with non-Hodgkins lymphoma and 1 patient with Hodgkins disease also had thrombocytopenia and increased membrane-bound IgG. Five of the patients with CLL had positive direct antiglobulin (Coombs) tests on red cells; of these, 3 patients had hemolytic anemia. In eight of the 9 patients with CLL, thrombocytopenia, and increased platelet-bound-IgG, the platelet count increased with the administration of prednisone or an alkylating agent, with splenectomy, or with a combination of these.

scholarly journals A Case of Immune Thrombocytopenia After COVID-19 Vaccination: Coincidental or Causal Effect? Running Title: ITP After COVID-19 Vaccination

2021 ◽  
Author(s):  
Ernesto Vigna ◽  
Daniele Caracciolo ◽  
Enrica Martino ◽  
Francesco Mendicino ◽  
Eugenio Lucia ◽  
...  
Keyword(s):  
Platelet Count ◽  
Side Effects ◽  
Intravenous Immunoglobulin ◽  
Vaccine Efficacy ◽  
Immune Thrombocytopenia ◽  
Causal Effect ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Platelet Response ◽  
Normal Range

Abstract The discovery and the introduction of different vaccines in the therapeutic armamentarium against SARS-CoV-2 represents a big hope in the fight against the pandemic. However, safety of SARS-CoV-2 vaccination is continuously monitored for the emergence of potential new side effects, such as recently reported thrombotic events, after the use of certain types of vaccines. In this context, we report a case of 31-year-old woman who developed immune thrombocytopenia (ITP) after 3 weeks from receiving SARS-CoV-2 vaccine. She developed significant widespread petechiae and gum bleeding, with severe thrombocytopenia documented at her hemogram. Over a 10-day period, thrombocytopenia was treated first with high dose corticosteroids, intravenous immunoglobulin and platelet transfusions, without a platelet response. Two days later, she received the TPO-mimetic and after three days, his platelet count began to rise reaching the normal range 18 days from her admission to our Hematology department. These findings cannot actually elucidate if vaccination was causal or coincidental effect of ITP, but further highlights the need of additional pharmacovigilance studies to empower SARS-CoV2 vaccine efficacy.

scholarly journals Durability of Platelet Response When Switching from Eltrombopag or Romiplostim to Avatrombopag in Immune Thrombocytopenia (ITP): A Multicenter Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1015-1015
Author(s):  
Hanny Al-Samkari ◽  
Debbie Jiang ◽  
Terry B. Gernsheimer ◽  
Howard A. Liebman ◽  
Susie Lee ◽  
...  
Keyword(s):  
Adverse Event ◽  
Platelet Count ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Rescue Therapy ◽  
Initial Response ◽  
Boxed Warning ◽  
Platelet Response ◽  
Platelet Counts ◽  
Loss Of Response

Abstract BACKGROUND : Thrombopoietin receptor agonists (TPO-RAs) are widely utilized second-line treatments for immune thrombocytopenia (ITP). The TPO-RAs eltrombopag and romiplostim have been FDA approved for over a decade with established efficacy and safety profiles. Avatrombopag is a newer oral TPO-RA approved in 2019 for ITP. Avatrombopag was efficacious in raising platelet counts in clinical trials, and it has an exposure-adjusted safety profile generally comparable to placebo with no boxed warning for hepatotoxicity as does eltrombopag. Also unlike eltrombopag, avatrombopag does not chelate polyvalent cations; therefore, it is administered with food and without restrictions regarding meal composition. A high proportion of patients (~90%) respond to avatrombopag; however, data describing the durability of platelet response on avatrombopag following treatment with other TPO-RAs is limited. AIMS : Understand the time until patients treated with avatrombopag experienced their first loss of response, if any, and their percent of time with a response following switch from eltrombopag or romiplostim. METHODS : We retrospectively evaluated all adults with ITP who switched from eltrombopag or romiplostim to avatrombopag at four U.S. tertiary ITP referral centers from July 2019 through December 2020. Reason for switching from eltrombopag or romiplostim (ineffectiveness, adverse event, convenience) was collected. Patients were treated with avatrombopag for at least two months to evaluate effectiveness. Response was defined as a platelet count ≥30,000/uL. Loss of response was defined as two consecutive platelet counts at least 7 days apart &lt;30,000/uL. In these analyses, platelet counts were disqualified if &lt;8 weeks from receipt of rescue corticosteroids or &lt;4 weeks from intravenous immunoglobulin. RESULTS: 44 patients were included, with a median (range) age of 60 (21-87) years; 55% were female. At avatrombopag initiation, patients had an ITP diagnosis for a mean of 8.1 years with a mean of 4.8 unique prior ITP therapies. 42/44 (95%) of patients responded to avatrombopag at least once and 36/44 (81.8%) responded without the need for rescue therapy. 6/44 (13.6%) responded to avatrombopag and required at least one rescue therapy during exposure. 31/42 (73.8%) of patients never experienced a loss of response. All patients who responded to avatrombopag maintained response for 88.7% of their time on treatment. Patients who responded without the need for rescue therapy maintained their response for 93.6% of their time on avatrombopag. Patients who switched for convenience maintained a response for 96.5% of the time on avatrombopag. Patients who switched for adverse events maintained a response for 90.2% of the time. Patients who switched for efficacy maintained a response for 68.2% of the time. Overall, the median platelet count for all avatrombopag exposure was 107×10 9/L. The median platelet count for convenience switchers was 129×10 9/L, efficacy switchers was 60×10 9/L, and adverse event switchers was 93×10 9/L. CONCLUSION: In a heavily pretreated chronic ITP population who switched from another TPO-RA to avatrombopag, the initial response to avatrombopag was both durable (with up to 74% of patients never experiencing a loss of response) and stable (with patients maintaining a response on average for up to 89% of the time). Figure 1 Figure 1. Disclosures Al-Samkari: Argenx: Consultancy; Dova/Sobi: Consultancy, Research Funding; Novartis: Consultancy; Amgen: Research Funding; Rigel: Consultancy; Agios: Consultancy, Research Funding; Moderna: Consultancy. Gernsheimer: Principia: Research Funding; Rigel: Research Funding; Amgen: Honoraria; Novartis: Honoraria; Cellphire: Consultancy; Dova: Consultancy; Sanofi: Consultancy. Liebman: Pfizer: Consultancy; Dova: Consultancy, Honoraria; Argenx: Research Funding; Amgen: Consultancy; Sanofi/Genzyme: Research Funding; Novartis: Consultancy, Research Funding. Lee: Dova: Honoraria. Bernheisel: Sobi, Inc.: Current Employment. Kolodny: Sobi, Inc.: Current Employment. Wojdyla: Sobi, Inc.: Current Employment. Vredenburg: Sobi, Inc.: Current Employment. Jamieson: Sobi, Inc.: Current Employment. Cuker: Takeda: Research Funding; Sanofi: Research Funding; Spark Therapeutics: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Novartis: Research Funding; Bayer: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Synergy: Consultancy.

Rituximab Is Effective in Refractory Adult Immune Thrombocytopenic Purpura Associated with Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3952-3952
Author(s):  
Thein H. Oo ◽  
Neela Natarajan
Keyword(s):  
Platelet Count ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Immune Thrombocytopenic Purpura ◽  
Peripheral Blood ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Refractory Itp

Abstract Chronic lymphocytic leukemia ( CLL ) is the commonest leukemia in the western world. 2% of CLL patients present with immune thrombocytopenic purpura ( ITP ). Corticosteroids, intravenous immune globulins ( IVIG ) and splenectomy have been the mainstay of treatment of ITP. Rituximab is the monoclonal antibody against CD-20 antigen expressed on the B-lymphocytes. It has established its role in the treatment of many B-cell malignancies in the last one decade. Due to its B-cell depletion capability, interests in employing rituximab in the treatment of many autoimmune diseases have grown in the last few years. Recently, many small case reports/series and a few small trials have reported the efficacy of rituximab in the treatment of refractory ITP. However, not much is known about its efficacy in the ITP associated with CLL. Here, a patient with CLL initially presenting with ITP is described. A 67-year-old white female with a past history of hysterectomy for fibroids and hypertension presented with rectal bleeding and multiple ecchymoses. Physical examination was unremarkable except for skin eccymoses on the extremities and abdomen. Colonscopy revealed hemorrhoids only. Computerized tomograms showed no lymphadenopathy or other abnormalities. Here laboratory data were as follows; hemoglobin 5.8g/dl, WBC 29,400/mm3, platelet 13,000/mm3, lymphocyte 52%, neutrophil 45%, monocyte 2.5%. Chemistry profile was unremarkable. Her blood group was O, Rh-negative. She was initially treated at another institution with packed Red Blood Cells, prednisone 1.5mg/kg qd and daily IVIG 0.4g/kg for 5 days for presumed ITP. Platelet transfusions did not raise the platelet counts. She remained profoundly thrombocytopenic and was subsequently transferred to our hospital. Review of the blood smear revealed anisopoikilocytosis, few tear-drop RBCs, many small-to-medium sized mature lymphocytes, occasional smudge cells, large platelets, few Pseudo-Pelgar-Huet cells but no blasts. Given moderate absolute lymphocytosis ( 15,200/mm3 ), blood film findings and profound thrombocytopenia, a working diagnosis of CLL-associated ITP was entertained. Peripheral blood flow cytometry showed lymphocytes positive for CD5, CD19, CD20 (dim ) and CD23, kappa/lambda ratio of 248:1. Bone marrow biopsy showed moderate lymphocytosis with the same immunophenotype as peripheral blood. Megakaryocytes were abundant. The diagnosis was confirmed. She was treated with a course of high dose methylprednisone, 2 courses of IVIG 1g/kg x 2days with very transient response. Due to this, she underwent splenectomy but her platelet counts remained low. She required another 5 courses of IVIG resulting in brief responses over the next 3 weeks. She was subsequently put on po danazol 200mg bid with short-lived responses. Eventually, she received iv rituximab 375mg/m2 weekly for 4 weeks. She achieved complete remission within 1 month. Two months later, she transferred her care to another facility. Review of the literature showed 1 case report of CLL-associated refractory ITP successfully treated with rituximab and the response duration was 6 months. Three CLL patients with refractory fludarabine-associated ITP also responded to rituximab. Of them, two achieved a platelet count over 100,000/mm3 and 1 achieved a platelet count of 72,000/mm3 within 4 weeks. Duration of responses ranged from 6 to 17 months. Those results together with our case suggest rituximab is an alternative agent for the treatment of CLL-associated ITP. Its potential in ITP associated with B-cell lymphoid malignancies should be explored further.

Efficacy and Safety of a New Intravenous Immunoglobulin Product in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1307-1307
Author(s):  
Tadeusz Robak ◽  
Abdulgabar Salama ◽  
Lidia Kovaleva ◽  
Yaroslava I. Vyhovska ◽  
Simon Davies ◽  
...  
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Intravenous Immunoglobulin ◽  
Primary Endpoint ◽  
Immune Thrombocytopenic Purpura ◽  
Efficacy And Safety ◽  
Platelet Response ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Chronic Itp

Abstract Background Intravenous immunoglobulin (IVIG) is an accepted treatment for immune thrombocytopenic purpura (ITP). A new liquid 10% human IgG preparation stabilized with proline at a pH of 4.8 (trade name: Privigen) was recently developed. It can be stored at room temperature and is therefore always ready to use. Here we report its efficacy and safety in patients with chronic ITP. Patients and Methods Fifty-seven patients with chronic ITP and a platelet count below 20 x 109/L were included in this open-label, single arm, multi-center Phase III trial. IVIG was given at a dose of 1 g/kg on 2 consecutive days at a maximum infusion rate of 4 mg/kg/min. A subset (56.1%) of the patients received premedication (acetaminophen or diphenhydramine) to avoid adverse events. The primary endpoint was the platelet response rate, defined as the percentage of patients showing an increase in platelet count to ≥50 x 109/L within 7 days of the first infusion. Secondary endpoints included platelet counts at specified time points, time to platelet response, duration of platelet response, and regression of hemorrhages at different bleeding sites. Safety was evaluated by the frequency and severity of adverse events. Results The primary endpoint, an increase in platelet counts to ≥50 x 109/L, was achieved by 81% of the subjects (95% CI: 69–89%). The highest median platelet count (149 x 109/L) was observed on day 8. Median time to response was 2.5 days, with 43% of subjects responding within 1 day. Median duration of platelet response (days with platelet count ≥ 50 x 109/L) was 15.4 days. Regression rates for various bleeding sites ranged from 78% to 100%. Regression of bleeding correlated with increases in platelet counts. Adverse events were reported in 52 (91%) subjects. The most common adverse event was headache (67%), the incidence and severity of which was attenuated by premedication with acetaminophen/diphenhydramine. There were 3 serious adverse events, one of which (aseptic meningitis) was considered related to the study medication. Conclusions The present study has shown the safety and significant efficacy of a novel, 10% liquid, ready for use IVIG preparation, in patients with chronic ITP. A rapid increase in platelet counts to a level where severe bleeding episodes become more unlikely was seen in the majority of patients, as expected with IVIG given at 1 g/kg on 2 consecutive days. The increase in platelet counts was associated with a regression of bleeding. Adverse events were generally mild to moderate in severity, corresponded to those expected with IVIG, and could be prevented with premedication.

Association between Platelet Autoantibody Specificity and Response to Intravenous Immunoglobulin G in the Treatment of Patients with Immune Thrombocytopenia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3987-3987
Author(s):  
Kaye L. Johnston ◽  
Ronald S. Go
Keyword(s):  
Platelet Count ◽  
Intravenous Immunoglobulin ◽  
Hodgkin Lymphoma ◽  
Murine Model ◽  
Immunoglobulin G ◽  
Immune Thrombocytopenia ◽  
Lymphocytic Leukemia ◽  
Ivig Treatment ◽  
Number Of Patients ◽  
Intravenous Immunoglobulin G

Abstract Background: Recent studies in murine model of immune thrombocytopenia (ITP) suggest that autoantibodies against GPIba may cause thrombocytopenia through Fc-independent pathway and ITP mediated by anti-GPIb may be less responsive to intravenous immunoglobulin G (IVIG) treatment (Nieswandt B, et al. Blood 2000; Webster ML, et al. Blood 2006). The objective of this study was to investigate the potential association between platelet autoantibody specificity and response to intravenous immunoglobulin G (IVIG) treatment in patients with ITP. Methods: We retrospectively reviewed the clinical history of ITP patients who had platelet autoantibody test and received IVIG for treatment of thrombocytopenia. ITP was diagnosed by usual clinical criteria. All platelet autoantibody tests were performed by the Blood Center of Wisconsin (Milwaukee, WI) using ELISA, which detects antibodies reactive with platelet GPIIb/IIIa, GPIb/IX, and GPIa/IIa. A response was defined as a platelet count of &gt; 50 x 109/L with a minimum increment of 30 x 109/L. Results: We found 17 patients who received IVIG and had platelet autoantibody test performed. The median age was 58 years (range, 20–83) and 10 (59%) were males. ITP was considered idiopathic in 12 patients. In the remaining 5 patients, the following hematologic conditions were present: chronic lymphocytic leukemia (2), Hodgkin lymphoma (1), myelodysplastic syndrome (1), and non-Hodgkin lymphoma (1). Antibodies reactive with GPIIb/IIIa, GPIb/IX, and GPIa/IIa were detected in 13, 10, and 8 patients, respectively. In 3 patients, none of these antibodies were detected. Among the 14 patients with antibodies, 9 (64%) had antibodies against more than 1 glycoprotein. The median pre-treatment platelet count was 9 x 109/L (range, 1–68). Overall, 10 (59%) patients responded to IVIG. A response occurred in 7 of 7 patients without anti-GPIb/IX but in only 3 of 10 patients with anti-GPIb/IX. The difference in the response rates between the 2 groups was statistically significant (P= .0098). Conclusions: Our clinical results support the murine model findings that ITP mediated by anti-GPIb may be less responsive to IVIG treatment. However, because of the small number of patients investigated and the retrospective nature of the study, our findings must be confirmed by other groups in a larger patient population.

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