EFFICACY OF H.PYLORI ERADICATION TREATMENT WITH LEVOFLOXACIN – BASED TRIPLE THERAPY IN GASTRODUODENITISS PATIENTS

2011 ◽  
pp. 35-41
Author(s):  
Quang Di Bui ◽  
Trong Thang Hoang
Keyword(s):  
Adverse Effects ◽  
Triple Therapy ◽  
Cross Sectional Study ◽  
First Line ◽  
Second Line Therapy ◽  
Cross Sectional ◽  
Intention To Treat ◽  
Line Therapy ◽  
Standard Triple Therapy

Objective: This study is to evaluate the efficacy, tolerability and adverse effects of a triple second line therapy including of Rabeprazole, Amoxicilin và Levofloxacin in patients who have failed first-line Helicobacter pylory (H.Pylori) therapy. Methods: By descriptive cross-sectional study, the authors have examined 101 gastro-duodenitis patients, who had failed first treatment with standard triple therapy, received 10-days therapy including Rabeprazole (20mg b.d), Levofloxacin (500mg b.d) and Amoxycillin (1g b.d). Eradication is confirmed with by the C13-urea breat h test after 4 weeks from completing of treatment. Results: 100% of patients are initially included and noboby is lost for follow-up. Mean age was 44 yr, 38% were male, 68,3% had duodenitis, 20,7% gastritis, 11% gastro-duodenitis. All patients took medications correctly. Per-protocol and intention to treat eradication rates were both 83,3% (95% CI=75,4-91,3). Mild adverse effects were reported overall in 8% of the patients, mainly including rash 2%, myalgias 2% and diarrhea 5%, none of them were severe. Conclusion: This ten-days levofloxacin-base therapy represents an alternative to standard quadruple therapy in patents with previous PPI-Clarithromycin-Amoxicillin failure, being effective, safe and simple.

EFFICACY OF TREATMENT OF H.PYLORI EARDICATION WITH STANDARD TRIPLE THERAPY IN PEPTIC ULCER PATIENTS

2011 ◽  
pp. 122-129
Author(s):  
Quang Di Bui ◽  
Phuoc Lam Nguyen
Keyword(s):  
Peptic Ulcer ◽  
Adverse Effects ◽  
Triple Therapy ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Duodenal Ulcers ◽  
Ulcer Disease ◽  
Intention To Treat ◽  
Standard Triple Therapy

Objectives: The aim of study is to evaluate the efficacy, tolerability and adverse effects of a standard triple therapy including Rabeprazole, Clarithromycin and Amoxicilline at Sai gon Hoan My hospital in order to consider treatment H.pylori for patients who have not yet eradicated before or need to be undertaked by alternative regimens. Methods: By descriptive cross-sectional study, the authors have examined 116 patients sufferring from peptic ulcer received 10-day therapy including Rabe (20mg b.d) plus Clari(500mg b.d) plus Amoxi(1g b.d). Eradication is confirmed with endoscopy after 4 weeks from completing of treatment. Results and Discussion: 100% of patients were initially included and noboby was dropped out of the follow-up satges. The mean age was 49 in which 62% was male, 73(62,9%) presented duodenal ulcer, 28(24,1%) gastric ulcer and 15(13%) simultaneous gastric and duodenal ulcers. All patients took medications correctly. Per-protocol and intention to treat eradication rates were both 75%(95% CI=73,4-78,3). Additionally, 62(53,4%) patients had at least one risky factor for peptic ulcer disease, smoking being the most common one 44(37,9%).The adverse effects were reported overall in 67% of the patients, mainly including changed taste, very bitter, tired 49%, trouble sleeping 12% and diarrhea 5%. Conclusion: this ten-day standard triple therapy used in this study is ineffective with high adverse effects.The first line eradication with new regimens should be alternative.

Erwinia Asparaginase Safety and Feasibility during Therapy for Acute Lymphoblastic Leukemia in Adult Patients with Pegaspargase Hypersensitivity or Severe Toxicity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4915-4915
Author(s):  
Troy Z Horvat ◽  
Joshua J Pecoraro ◽  
Ryan J Daley ◽  
Larry W Buie ◽  
Dan Douer
Keyword(s):  
Adverse Effects ◽  
Lymphoblastic Leukemia ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Remission ◽  
Erwinia Asparaginase ◽  
Grade 3

Abstract Introduction: Severe pegaspargase hypersensitivity during first-line therapy for acute lymphoblastic leukemia (ALL) occurs in 1.8-5.9% of patients (Oncaspar [package insert]; Douer D, et al. J Clin Oncol 2014;32:905-911). Erwinia asparaginase is the preferred therapeutic alternative as it retains excellent activity in patients with Escherichia coli asparaginase or pegaspargase antibodies (Willer A, et al. Blood 2011;118:5774-82; Plourde PV, et al. Pediatr Blood Cancer 2014;61:1232-38; Salzer WL, et al. Blood 2013;122:507-14; Zalewska-Szewczyk B, et al. Clin Exp Med 2009;9:113-16). Furthermore, pegaspargase desensitization may not prevent recurrence of severe allergy (Sahiner UM, et al. Pediatr Int 2013;55:531-33). The risk for allergy and other common asparaginase-related adverse effects exists with Erwinia asparaginase, however most data is from pediatric reports. The aim of this study was to assess the safety and feasibility of using Erwinia asparaginase in adult ALL patients with previous pegaspargase hypersensitivity or intolerance. Methods: This is a single-center retrospective analysis of eight adult ALL patients who received Erwinia asparaginase after intolerance to pegaspargase between November 2011 and July 2015. Toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0. The Memorial Sloan Kettering Investigational Review Board granted an exemption from IRB review. Results: The eight patients received a total of 29 cycles (median 3 cycles each, range 1-6) as part of various pediatric-inspired chemotherapy regimens. Each cycle consisted of Erwinia asparaginase 25,000 units/m2 intramuscularly every 48 hours (either including or excluding weekends). Corticosteroid premedication was given with 52 of 170 total Erwinia asparaginase doses. The median age was 33 years (range 23-72), 7 (87.5%) were males, 75% had B-cell ALL, and 25% had T-cell ALL. Seven patients received Erwinia asparaginase while in first complete remission (CR1) and only one as part of second-line therapy. Patients received a median of 2 prior doses of pegaspargase (range 1-4) before switching to Erwinia asparaginase for either grade 3/4 anaphylaxis (n=6), urticaria/pruritus (n=1), or grade 4 hyperbilirubinemia (n=1). Six patients received all intended cycles, 1 patient was lost to follow up after 1 cycle, and 1 patient was still receiving treatment at the time of analysis. No hypersensitivity reactions occurred and no patient developed arterial or venous thrombosis. Laboratory adverse effects are reported in table 1. One patient died from disease (the 1 patient that received Erwinia asparaginase as part of second-line therapy), 1 patient died in a motor vehicle accident while in first remission, and six patients are still alive and in first remission at 7.5-29.6 months from diagnosis. No morphologic relapses have occurred in patients in first remission (n=7) at a follow up of 4.9-26.4 months after switching to Erwinia asparaginase. Conclusions: Replacing pegaspargase with Erwinia asparaginase after hypersensitivity allowed all patients to continue asparaginase therapy without hypersensitivity. Adverse effects with Erwinia asparaginase were limited to laboratory abnormalities of minimal clinical consequence. In contrast to the known high rate of hepatoxicity in adults treated with pegaspargase, no high grade liver toxicity was seen. In light of the critical role of asparaginase in ALL therapy, our preliminary observations suggest that asparagine depletion with Erwinia asparaginase can proceed as scheduled despite pegaspargase intolerance. Within our small cohort undergoing first-line therapy, relapse did not occur after transitioning to this therapeutic alternative. Table 1. Laboratory abnormalities by grade Grade 1 Grade 2 Grade 3 Grade 4 AST 7 0 0 0 ALT 7 2 0 0 TBILI 1 0 0 0 Amylase 2 0 0 0 Lipase 1 1 0 0 Triglycerides 3 4 3 1 Fibrinogen 2 6 1 0 Total 23 13 4 1 *Laboratory abnormalities were counted per event, not per patient Disclosures Douer: Gilead: Consultancy.

Helicobacter pylori eradication rates in Slovenia in the period from 2017 to 2019 – data from the European Registry on Helicobacter pylori Management (Hp-EuReg)

2020 ◽  
Author(s):  
Bojan Tepes ◽  
Natasa Brglez Jurecic ◽  
Katja Tepes ◽  
Marta Espada Sanchez ◽  
Olga Perez Nyssen ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Intention To Treat ◽  
Line Therapy ◽  
Medical Institutions ◽  
H Pylori ◽  
European Registry

Abstract Background. Helicobacter pylori (H pylori) is the most common chronic bacterial infection in the world, affecting over 50% of the world’s population. H pylori is a grade I carcinogen, responsible for the development of 89% of non-cardia gastric cancers. In the present study, we analyzed the data for H pylori eradication treatments in Slovenia after the 3rd National recommendations were implemented. Patients and methods. Slovenia is part of the European Registry on H pylori Management (Hp-EuReg) since the study was launched in 2013. Data were collected at AEG-REDCap e-CRF from September 2017 to December 2019. H pylori eradication treatment was assessed by modified intention-to-treat (mITT) and per-protocol (PP) analyses. Results. Overall, 823 patients from 3 medical institutions were included. Effectiveness with first line 14-day triple therapy with a proton-pomp-inhibitor (PPI), clarithromycin 500 mg, amoxicillin 1000 mg, all BID, was 93% by mITT (714 patients). In patients allergic to penicillin, first line 14-day triple therapy with PPI-clarithromycin-metronidazole achieved 83% effectiveness by mITT (35 patients). Second-line 14-day triple therapy with a PPI-amoxicillin-levofloxacin achieved 89% mITT eradication rate (51 patients). Second-line therapy with the 10-day three-in-one single capsule containing bismuth-tetracycline- metronidazole achieved optimal effectiveness (100% mITT) in 10 patients ( p=0.02). Conclusions. Slovenia is a country with < 15% H pylori resistance to clarithromycin. Triple therapy with a PPI plus two antibiotics during 14 days reported optimal effectiveness (over 90%). Ten-day quadruple bismuth second-line therapy had better results than 14-day triple therapy with levofloxacin).

Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 51-51
Author(s):  
Xiaoyun Pan ◽  
Lincy S. Lal ◽  
John White ◽  
Seyed Hamidreza Mahmoudpour ◽  
Christian Valencia
Keyword(s):  
Cervical Cancer ◽  
Economic Burden ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Second Line Therapy ◽  
Treatment Regimens ◽  
Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

Efficacy of Cyclosporine Treatment in Patients with MDS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4608-4608
Author(s):  
Alina Kokhno ◽  
Elena Parovitchnikova ◽  
Elena Mikhailova ◽  
Yulia Olshanskaya ◽  
Irina Kaplanskaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stable Disease ◽  
Response Rate ◽  
Bone Marrow Failure ◽  
Normal Karyotype ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Myelodysplastic syndrome (MDS) represents a heterogenous group of myeloid neoplasms characterized by abnormal differentiation and maturation of myeloid cells, bone marrow failure and genetic instability. The recent clinical and laboratory investigations suggest that MDS is closely related to diseases in which the bone marrow failure is mediated at least in part by the immune system. The are few studies concerning the of efficacy of treatment of MDS pts with cyclosporine A (CSA) but they are limited to the group of pts with bone marrow hypoplasia. The aim of our study was to evaluate the efficacy of CSA treatment in MDS pts as first line or second line therapy. 48 pts with different forms of MDS were included in study. The group of first line CSA treatment included 30 pts, male-18/female-12, RA-3, RARS-1, RCMD-18, RAEB-7, RAEBt-1, 20-normal karyotype, 10-different abberations including: 5q−, 16q+, −7, 12q+, −Y, [11p+,7q−] and complex abb. Hypoplastic bone marrow was revealed in 15 pts, hyperplastic-8 pts, hypo/hyper-7 pts. Second line therapy group included 18 pts, male-9/female-9, RCMD-11, RARS-1, RAEB-5, RAEBt-1, normal karyotype-3, cytogenetic anomalies-13 (+8, 5q−,−7, +8 and complex abb.). Hypoplastic bone marrow was revealed in 12 pts, hyperplastic-4 pts, hypo/hyper-4 pts. The first line therapy consited of splenectomy in 8 pts, low doses of Ara-C-3, interferon-α-3, chemotherapy-2 and ATG-2 pts. CSA was applied at 5–10 mg/kg/day initially and then adjusted according to blood levels and toxicity. The maintenance dose was 1–3 mg/kg/day. Minimum time to response evaluation was one month. Complete response (CR) was defined as normal PB counts, BM aspirate; partial response-improvement of PB counts to 50% of normal and freedom from transfusions; stabilization-decrease of transfusion requirements and stabilization of PB counts for more then 1 month. Total response rate in first group was 60% (18 pts) with median follow up of 10 months (2–134). CR was estimated in 20% (6pts), median follow-up 72 months (44–134). 2 pts with CR are in clonal remission. 2 pts from response group developed acute leukemia (AL). 40% of pts showed no response.58% of pts without response developed RAEB or AL. 42% of pts were in stable disease and were treated with another modalities. The response rate in second group was 61% (11 pts) with median follow-up of 7 months (1–78). 22% (4 pts) achieved CR, median follow-up 60 months (43–78). 39% of pts showed no response. 71% from these pts (5) transformed to RAEB or AL. 2 pts remained in stable disease. In both groups response was registrated from 1 to 4 months from treatment initiation (median 3 months). CR was achieved in the majority of pts after 1 year of treatment. Response was achieved in 77% of pts with hypo/hyper and hypoplastic bone marrow and in 12% of pts with hyperplastic bone marrow. Overall survival was decreased in pts with more the 5% blasts in bone marrow (p=0,02 for 1st line group, p=0,075 for 2nd line group), and increased for pts with hypo and hypo/hyper bone marrow cellularity (p=0,002 for 1st line group). There was no impact of cytogenetics. We may conclude, that CSA demonstrates good efficacy in therapy of MDS pts, especially for pts with RA, RARS and RCMD with hypo and hypo/hypercellular bone marrow and reactive lymphoid nodules in bone marrow. It can be initiated as 1st or 2nd line therapy and should be continued at least for 3 months before evaluating of response.

Outcomes in patients (pts) with advanced renal cell carcinoma (aRCC) who discontinued (DC) first-line nivolumab + ipilimumab (N+I) or sunitinib (S) due to treatment-related adverse events (TRAEs) in CheckMate 214.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 581-581 ◽  
Author(s):  
Nizar M. Tannir ◽  
Robert J. Motzer ◽  
Elizabeth R. Plimack ◽  
David F. McDermott ◽  
Philippe Barthelemy ◽  
...  
Keyword(s):  
Risk Groups ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Post Hoc ◽  
Study Dose ◽  
Clinical Trial Information

581 Background: The phase 3 CheckMate 214 trial demonstrated superior efficacy for N+I vs S in aRCC, although more patients discontinued N+I compared with S due to TRAEs. This is a post hoc analysis of outcomes in pts who DC N+I or S due to TRAEs. Methods: Untreated pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3Wx4 (induction) and then N 3 mg/kg Q3W (maintenance), or S 50 mg daily for 4 wk on, 2 wk off (6-wk cycles). This analysis includes all pts who DC due to TRAEs reported during extended follow-up (≤100 d after last study dose). Results: Of 550 N+I randomized pts, 135 (25%) DC due to TRAEs, most commonly increased ALT, diarrhea, and increased AST (all 3%); 64 (12%) of 535 S randomized pts DC due to TRAEs, most commonly increased ALT, diarrhea, and pancreatitis (all 1%). In N+I pts who DC due to TRAEs, 47% DC during N+I induction, 7% completed induction but no N maintenance, and 46% completed induction and received N maintenance (median [range] 8 [1–47] doses). At 30-mo minimum follow-up, ORR per investigator, CR rate, and 24-mo OS rate were higher in pts who DC N+I vs S due to TRAEs. Outcomes in pts who DC S due to TRAEs were similar to those in all S ITT pts and worse than in N+I pts who DC due to TRAEs (Table). At 24 mo, 42% of pts who DC N+I due to TRAEs were alive and free from second-line therapy. Consistent outcomes were seen in pts who DC N+I due to TRAEs across IMDC risk groups (data to be presented). Pts who DC N+I due to TRAEs experienced more immune-related select TRAEs and received more high-dose steroids (≥40 mg prednisone daily or equiv.), but times to onset and resolution and resolution rates of select TRAEs were similar vs all treated N+I pts. Conclusions: Discontinuation of first-line N+I due to TRAEs did not result in impaired outcomes, and a high proportion of pts remain alive and free from second-line therapy. Clinical trial information: NCT02231749. [Table: see text]

scholarly journals Adding Bismuth to Rabeprazole-Based First-Line Triple Therapy Does Not Improve the Eradication of Helicobacter pylori

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Meng-Chieh Wu ◽  
Yao-Kuang Wang ◽  
Chung-Jung Liu ◽  
Fang-Jung Yu ◽  
Fu-Chen Kuo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Eradication Rate ◽  
Therapy Group ◽  
Resistance Rate ◽  
Controlled Study ◽  
First Line ◽  
Intention To Treat ◽  
Bismuth Subcitrate

This randomized controlled study aimed to evaluate whether adding bismuth to the standard first-line triple therapy could improve the eradication rate of Helicobacter pylori. A total of 162 patients with Helicobacter pylori infection were randomly assigned to either the 7-day triple therapy group (RAK regimen: rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg bid; n=81) or the bismuth plus triple therapy group (n=81). In the RBAK group, bismuth subcitrate 360 mg twice daily was added to the RAK regimen. A follow-up endoscopy or urea breath test was performed at least 4 weeks after eradication to confirm the treatment efficacy. Comparable compliance and Helicobacter pylori eradication rates were observed in both groups in either intention-to-treat [RAK 72.8% (59/81) versus RBAK 77.8% (63/81); p=0.47] or per protocol analysis [RAK 74.7% (59/79) versus RBAK 81.8% (63/77); p=0.26]. Adverse effects were commonly reported (50.6% for both groups) although most of these did not cause cessation of treatment. The resistance rate was 27.2% for metronidazole and 12.3% for clarithromycin. Adding bismuth to the standard 7-day triple therapy did not substantially increase the eradication rate. Further study is needed clarifying whether extending the duration of RBAK regimen to 10–14 days can lead to a better result.

scholarly journals Autoimmune Cytopenias Following Alemtuzumab-Induced Renal Transplant: Clinical Features and Treatment Outcomes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2434-2434
Author(s):  
Elisa Lucchini ◽  
Asad Luqmani ◽  
Maria Atta ◽  
Simona Deplano ◽  
Mark Layton ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Relapse Rate ◽  
Rapid Onset ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Duration Of Response ◽  
Autoimmune Cytopenias

Abstract Background: The anti-CD52 monoclonal antibody alemtuzumab (Alem) induces a rapid-onset, profound and long-lasting depletion of lymphocytes: B cells recover within 12 months, while T cell recovery is still incomplete after 30 months. Alem is used as induction therapy for solid organ transplantations, including renal. Autoimmune complications following Alem include thyroid disorders (20-30%), immune thrombocytopenia (ITP) (2-3%), and autoimmune hemolytic anemia (AIHA) and autoimmune nephropathies (< 1%). Methods: we retrospectively analyzed 41 patients (pts) attending the Haematology Clinic at Hammersmith Hospital (HH), who developed autoimmune cytopenias (ITP or AIHA) after an Alem-induced renal transplant. The autoimmune cytopenia was defined as a rapid onset of isolated thrombocytopenia and/or anemia without other explanation. For ITP, complete response (CR) and response (R) were defined according to IWG standard criteria (Rodeghiero,Blood,2009). For AIHA, CR was defined as a stable Hb level >120 g/L, no transfusion requirement and no signs of hemolysis; partial response (PR) as a rise in Hb levels >20 g/L, without transfusion requirement. The study aim is to report clinical features and treatment outcomes of these 41 pts. Results: Between 1/11/05 and 14/12/16, 1431 pts received an Alem-induced renal transplant at HH. 34 (2.3%) developed ITP and 7 (0.48%) AIHA; 28 (68%) pts were males. Median age at renal transplant was 48 (range 20-69) years. The cytopenia developed a median of 35 months (range 6-161) after Alem administration. Median lowest platelet count was 5.5x109/L (range 0-41) and median nadir of hemoglobin (Hb) was 58 g/L (range 35-65). ITP pts: 2 pts achieved spontaneous CR. Of the remaining 32, 91% received steroids, IVIG or both as first line therapy, with an overall response rate (ORR) of 62%. 10 pts (31%) maintained the response without any further treatment. 22 pts required second line therapy, 11 required ≥ 3 lines of treatment. Treatments included: thrombopoietin receptor agonists (TPO-RA), rituximab (RTX), MMF and/or a combination. TPO-RA were used 15 times, with an ORR of 80%, a relapse rate of 33% and a median duration of response (DOR) of 22 months (range 3-48); 10/12 pts (83%) who responded to TPO-RA, discontinued treatment after a median of 64 days (range 7 - 528): 6 maintained the response after discontinuation. RTX was used 10 times, with an ORR of 90%, a relapse rate of 22% and a median DOR of 27 months (range 3 - 83). A combination of RTX and TPO-RA was used 7 times, with an ORR of 71%, a relapse rate of 40% and a median duration of response (DOR) of 5 months (range 2-44); the 5 responders discontinued treatment after a median of 49 days (range 14-462): 3/5 maintained their response. After a median follow-up of 38 months (range 3-96), all ITP pts maintained a response (91% CR and 9% R); 4 were still on treatment (2 TPO-RA and 2 MMF). AIHA pts: 6 of 7 (86%) pts with AIHA received first line steroids +/- IVIG with an ORR of 67%. 4 pts needed second line therapy: all received RTX with an ORR of 50%. 2 pts needed ≥ 3 lines of therapy. After a median follow-up of 68 months (range 27-102) all AIHA pts maintained a response (57% CR and 43% PR), without any ongoing treatment. Adverse events: 33 pts (80%) experienced 1 or more adverse events (AEs): 25 cardiovascular (including 14 thrombosis), 21 infections (16 grade ≥3), 5 steroid-induced diabetes, 3 graft failures, 10 malignancies (6 solid tumors and 4 PTLD). 6 of the ITP pts also developed AIHA (Evans syndrome). 3 ITP pts died. Conclusions: ITP and AIHA represent important complications of Alem-induced renal transplant. Response rates after first-line therapy for ITP were comparable to primary ITP (30%). However, long-term response rate, sustained response to RTX and the proportion of pts able to continue in remission after discontinuing TPO-RA are higher than seen with primary ITP. Recovery from cytopenias may occur in conjunction with T cell reconstitution post Alem (this is under investigation). The large majority of AEs were related to multifactorial heavy immunosuppression and increased thrombotic risk distinguishing this group of pts. Hence for ITP and AIHA, steroids should be limited, as they are curative in only a few pts and burdened by many side effects. Both RTX and a short course of TPO-RA appear valid options, but the choice should be driven by the individual balance between thrombotic and infectious risks versus persistence of cytopenias. Disclosures Cooper: Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Fludarabine, Cyclophosphamide and Rituximab (FCR) Related Prolonged Cytopenia Is Frequent and Adverse Factor Affecting Survival of Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1790-1790
Author(s):  
Petra Obrtlikova ◽  
Anna Jonasova ◽  
Magda Siskova ◽  
Eduard Cmunt ◽  
Adela Berkova ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

Abstract Abstract 1790 Background: The immunochemotherapy regimen composed of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as highly effective frontline or second line therapy for chronic lymphocytic leukemia (CLL). This regimen may be however associated with prolonged cytopenia and the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aims and methods: In our retrospective single center analysis, we evaluated the efficacy and the toxicity of FC or FCR regimen in unselected population of CLL patients with treatment indication. The overall survival (OS) and progression free survival (PFS) was calculated for all patients as intent to treat analysis. The prolonged cytopenia was defined as cytopenia (grade 2–4 according to CTCAE v.4 ) developing during of after the last cycle of FC/FCR and persisting two or more months. Cytopenia was evaluated in patients with follow-up at least 6 months after this treatment. Patients were excluded from analysis of cytopenia if they underwent immediate other treatment (antibody maintenance, high dose therapy with autologous stem cell transplantation (ASCT) consolidation, or they received other therapy due to unsatisfactory response to FCR). Patients with missing laboratory data after FC(R) were also excluded. Kaplan Maier curves for PFS and OS were calculated and log rank test was used for survival comparison. Results: Altogether, 252 patients started the treatment with FC or FCR in the years 2000–2012 at our institution. There were 86 (34%) women and 166 (66%) men with a median age of 62 years (31–87) at the time of FC(R) therapy. 52 (21%) pts received FC regimen, including 40 pts treated in first line therapy and 12 pts in second line therapy. FCR therapy was administered in 200 pts (79%): 153 pts received FCR as first line therapy, 38 pts as second line therapy and 8 pts as third or fouth line therapy. The median number of FC cycles was 5 (1–8) with or without R. The estimated OS for the first line therapy was 87,5% in FCR group vs 80% at 3y in FC group (p ns) (Hallek,CLL8: 87% vs 83%) and PFS was 70% in FCR group vs 50% in FC group (p=0,004) with the median of follow-up 45 months. Altogether 184 pts fulfill the criteria for cytopenia analysis. The most frequent immediate subsequent therapy considered as exclusion for this analysis was ASCT consolidation (n 20). Out of 184 pts, 146 recieved FC(R) as 1st line treatment and 38 subsequent therapy. The prolonged cytopenia was observed in 54 pts (29%), 42 (29%) in 1st line group and 12 (32%) in subsequent line group. Median duration of cytopenia was 8 m (2–65), 29 out of 54 patients have had persistent cytopenia at the time of last follow up. The cumulative probability to develop cytopenia was 30.3% at 2y among all pts and 29.7% among first line FCR treated pts. There was no significant difference between FC and FCR treated pts. Eleven pts developed MDS/AML, 7 cases were observed in the followed group of 184 pts (with probability 6.1% at 6y), in all cases the cytopenia preceded the MDS onset, 6y probability to develop MDS was 25.2% for patients who develop prolonged cytopenia after FC(R). Moreover 2 MDS and 1 AML were observed among 20 pts treated with ASCT (6y probability 5.6%, 8y probability 22.5%). The OS probability from 1stcycle of FC(R) was significantly better for pts without cytopenia (75.5% vs 57.5% at 5y, p<0.005), nonsigificant trend was observed if only first line FCR pts were analyzed (88% vs 85%). The median survival for the MDS pts from the time of MDS dg was 6 months only. Conclusions: Although the FCR is the best available standard treatment option for CLL pts, it is associated with prolonged cytopenia in 30% of cases. These patients with prolonged cytopenia afte FC(R) have considerably high probability (25.2%) to develop MDS and they have worse OS compared to pts without cytopenia. Disclosures: No relevant conflicts of interest to declare.

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