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

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.

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

Blood ◽

10.1182/blood-2018-99-115258 ◽

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.

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

Blood ◽

10.1182/blood.v120.21.1790.1790 ◽

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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Real-World Treatment Patterns and Outcomes Among Patients with Hairy Cell Leukemia

Blood ◽

10.1182/blood.v126.23.2125.2125 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2125-2125

Author(s):

Sudeep Karve ◽

Victoria Divino ◽

Andrew Gaughan ◽

Mitch DeKoven ◽

Guozhi Gao ◽

...

Keyword(s):

Health Plan ◽

Real World ◽

Index Date ◽

Treatment Patterns ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Abstract Background and Objective : Hairy cell leukemia (HCL) is a rare condition and accounts for ~2% of all leukemia cases in the US. NCCN guidelines recommend first-line agents including pentostatin and cladribine among patients with HCL. However, a paucity of data exists with regard to real-world treatment patterns among patients with HCL. Current study evaluates treatment patterns and associated clinical outcomes among patients with HCL using a large US administrative claims database. Methods : This retrospective observational study was conducted using the IMS Health PharMetrics Plus Health Plan Claims Database (2006-2014), which includes over 150 million unique health plan members across the US and is nationally representative of the commercially-insured US population. Data includes date stamped medical and pharmacy records along with information on health plan enrollment. Individuals with at least 2 medical claims with a diagnosis for HCL (identified using ICD-9-CM cod: 202.4x) were selected and the first observed claim defined the "index date." Patients <18 years of age at index date or with other malignancies during 6 months (the "pre-index period") prior to index date were excluded. Patients were required at least 90 days of continuous enrollment (the variable "follow-up period") in the health plan post index date with exception of patients who died within 3 months of diagnosis. Patients were followed until death (recorded on inpatient discharge disposition), end of enrollment or end of database, whichever occurred earlier. Study measures including patient demographic and baseline clinical characteristics, line of therapy (LOT), treatment patterns, relapse (receipt of same or new regimen in subsequent LOT following a gap of 365 days) and refractory disease (receipt of same or new regimen where the gap of two adjacent LOTs was <365 days) and post-treatment complications were assessed during the follow-up period. All analyses were descriptive in nature. Results : The study cohort included 749 patients after applying the selection criteria (mean follow-up from diagnosis 32 months). At diagnosis, the mean age (standard deviation) of the study cohort was 56 (10) years and majority of patients were male (77%). Mean baseline comorbidity burden (assessed using Charlson Comorbidity Index score) was 0.8 (1.1) with hypertension (24%) and aplastic anemia (22%) being the two most common co-morbidities. Only 38% (n=282) of patients received first-line chemotherapy post diagnosis. Majority initiated first-line cladribine (76%) as a single agent, while 9% had evidence of single agent pentostatin. Mean time to initiation of first-line therapy from diagnosis was 132 (294) days and average time on first-line therapy was 34 (104) days. Among patients with first-line therapy 14% received second-line therapy and rituximab (53%) and cladribine (21%) were frequently observed second-line agents. Post first-line therapy, mean time to initiation of second-line therapy was 303 (406) days. Among second-line initiators, 76% had refractory disease and 24% had relapsed following first-line. Neutropenia and fever were frequently reported complications while on chemotherapy. Conclusion : The real-world chemotherapy utilization patterns observed in this study are consistent with the NCCN guidelines with cladribine and pentostatin being the agents of choice for first-line therapy. Following diagnosis, more than one-third of patients initiated chemotherapy and only a small proportion of these received second-line chemotherapy suggesting durable response with first-line therapy. Limited follow-up post first-line therapy may have impacted the proportion of patients initiating second-line therapy as well as categorization of refractory and relapse disease. Disclosures Karve: AstraZeneca: Employment. Divino:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gaughan:AstraZeneca: Employment. DeKoven:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gao:MedImmune: Employment. Lanasa:MedImmune: Employment.

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Phase II study of mFOLFOX-4 followed by mFOLFIRI in advanced gastric cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15546 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15546-e15546

Author(s):

H. Kwon ◽

S. Lee ◽

S. Oh ◽

S. Kim ◽

H. Kim

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Second Line ◽

Time To Progression ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Grade 3 ◽

Gastric Cancer Patients

e15546 Background: FOLFOX followed by FOLFIRI regimen has been commonly used in colorectal cancer. This combination has also been evaluated in a number of phase II studies in the first- and second-line treatment setting of advanced gastric cancer. We have evaluated the efficacy and toxicity of modified FOLFOX-4 followed by modified FOLFIRI regimens in advanced gastric cancer patients. Methods: Previously untreated patients with advanced or recurrent gastric cancer were enrolled. As first-line therapy, patients received modified FOLFOX-4, bolus ldLV 50mg followed by a 5-FU bolus 400mg/m2 and 22-hour infusion 600mg/m2 on day 1 and 2, with oxaliplatin 85mg/m2 on day 1 every 14 days. At progression, patients received modified FOLFIRI, bolus ldLV 50mg followed by a 5-FU bolus 400mg/m2 and 22-hour infusion 600mg/m2 on day 1 and 2, with irinotecan 150mg/m2 on day 1 every 14 days as second-line therapy. Results: Fifty-six patients were enrolled in first-line mFOLFOX-4. Of these, 32 (57.1%) patients received sequential mFOLFIRI as second-line chemotherapy. In first- line therapy, mFOLFOX-4 achieved 41.4% (95% CI, 28–54%) partial response and 32.1% (95% CI, 20–45%) stable disease. The median time to progression was 4.2 months (95% CI, 2.8–5.5 months). In second-line therapy, mFOLFIRI achieved 18.8% (95% CI, 4–33%) partial response and 31.3% (95% CI, 14–48%) stable disease. The median time to progression was 3.1 months (95% CI, 1.4–4.7 months). Median survival was 12.8 months (95% CI, 9.5–16.0 months) in overall 56 patients, and median survival of sequential chemotherapy was 13.2 months (95% CI, 9.4–16.9 months) in 32 patients. In first-line mFOLFOX-4, NCI-CTC grade 3/4 hematological toxicities were neutropenia and thrombocytopenia in 28 (7.6%), 1 (0.3%) of the cycles, respectively and neutropenic fever was observed in 7 cycles (1.9%). Grade 1/2 sensory neuropathy was observed in three patients (5.6%). In second-line mFOLFIRI, NCI-CTC grade 3/4 hematological toxicity was neutropenia in 20 (19.8%) of the cycles, and neutropenic fever was observed in 5 cycles (4.6%). Grade 3 diarrhea was observed in one patient (3.1%). Conclusions: As sequential chemotherapy, the mFOLFOX-4 followed by mFOLFIRI regimen is both feasible and safe for advanced gastric cancer patients. No significant financial relationships to disclose.

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

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2011.4.5 ◽

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.

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Effective treatment of refractory acquired pure red blood cell aplasia with eltrombopag and sirolimus: a case report

Therapeutic Advances in Hematology ◽

10.1177/2040620720940144 ◽

2020 ◽

Vol 11 ◽

pp. 204062072094014

Author(s):

Yuzhou Huang ◽

Xianyong Jiang ◽

Bing Han

Keyword(s):

Cyclosporin A ◽

Clonal Evolution ◽

Complete Response ◽

Pure Red Cell Aplasia ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Acquired pure red cell aplasia (aPRCA) is a kind of anemia characterized by severe reticulocytopenia and reduced bone marrow erythroblastic cells. For patients who are refractory to the first-line therapy (cyclosporin A with/without glucocorticoids), second-line therapy is considered less effective. We report on a patient with primary aPRCA who was refractory to cyclosporin A, glucocorticoids, and several second-line regimens. The patient was treated with sirolimus for 10 months with no improvement in hemoglobin but complete response was achieved after adding eltrombopag at a dosage of 25 mg/day. Eltrombopag was well tolerated with no evidence of clonal evolution at the end of follow up. This case provided a new attempt at treating patients with refractory/relapse aPRCA with eltrombopag, probably in combination with sirolimus.

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Molecular Response to Tyrosine Kinase Inhibitors (TKIs) for Chronic Myeloid Leukemia (CML). an Update on Experience at Tawam Hospital, Abudhabi, UAE in the Light of ELN Guidelines

Blood ◽

10.1182/blood.v124.21.5526.5526 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5526-5526

Author(s):

Arif Alam ◽

Sabir Hussain ◽

Amar Lal ◽

Donna Lee ◽

Jorgen Kristensen

Keyword(s):

Tyrosine Kinase ◽

Disease Progression ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Front Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Abstract Background Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder characterized by the presence of a balanced reciprocal translocation involving the long arms of chromosomes 9 and 22. The fusion gene that is created by this translocation (BCR-ABL1) encodes for a constitutively active protein tyrosine kinase that is primarily responsible for the leukemic phenotype. Targeted therapy with Tyrosine Kinase Inhibitors (TKIs) has become the recommended first-line treatment for patients with CML. Commercially available TKIs include Imatinib, Nilotinib, Dasatinib, Ponatinib and Bosutinib. The first three drugs are approved for first line therapy while the later 2 are for resistant disease. Monitoring of the response to therapy is done with quantification of the BCR-ABL transcripts by RQ-PCR–based molecular technique. Methods Retrospective review of charts of patients diagnosed with CML between January 2010 and June 2014. Data points were measured at 3, 6, 12, and 24 months post initiation of therapy and results were documented as per ELN guidelines. Results 56 patients were diagnosed with CML. The median age was 33 years (range 19-73 years). Male to female ratio was 4:1. Sokal score was calculated for 53 patients (data for 3 patients was incomplete) 21 were low risk, 24 were intermediate risk and 8 were high risk. 7 patients were lost from follow up after diagnosis and are excluded from analysis. 1 patient has not reached the 3 month mark and is also excluded from analysis. 13 patients were started on initial treatment with Imatinib 400 mg while 35 with second generation TKIs (Dasatinib 100 mg daily or Nilotinib 300 mg BID) daily as upfront therapy. With a median follow up of 27 months (range 3 month to 51 months) 4/13 (30%) patients on Imatinib as first line therapy were able to achieve optimal repsone (one at a dose of 600 mg daily). 8 patients were switched to second line therapy and 7/8 patients have achieved MMR (1 patient remains in full cytogenetic relapse due to non-compliance). 35 patients were treated with 2ndgeneration TKIs as first line therapy. 22 out of 35 (62 %) patients have achieved optimal results within 18 months of front line therapy . Second line therapy was initiated in patients achieving suboptimal results or intolerance in 11 patients. 5 of these patients subsequently achieved MMR while 5 remain with suboptimal results. 1 patient had disease progression while one was lost to follow-up after achieving a partial cytogenetic response at 6 months. Interestingly 12 (25%) patients achieved MMR/CMR within 6 months of starting TKIs. Of these only 1 was on Imatinib while the rest were on 2ndgeneration TKIs. MMR 4.5 or undetectable levels of bcr-abl transcript have been documented in 10 patients (20 %) for the whole cohort. 4 patients had disease progression on TKI (treatment failure rate of 8 %). One patient had disease progression to accelerated and then blast crisis (lymphoid and myeloid) while the other 3 patients are alive with only CHR with one resistant to all TKIs, one with intolerance of all TKIs and one secondary to noncompliance. Conclusion We have previously reported on our experience with CML. We have now updated our report with a larger cohort of patients. The median age remains much lower as compared to Western countries, just reflecting differences in the age distribution of the population in the UAE with 80% being below the age of 65 years. MMR report from Enestnd trial is 67-71% in favor of Nilotinib as compared to Imatinib 44%, while the Dasision trial reported a MMR of 44 % in favor of Dasatinib with faster rate to response. Our results mirror the results of these phase 3 randomized trial with optimal response of 62 % with second generation TKIs% as compared to 30 % with Imatinib as front line therapy. Expatriates accounts for approximately 80% of the population in the UAE and many are temporary employed, having limited health care coverage, limited financial means as well as limited possibilities to attend regular follow-ups. This leads to compliance problems, loss from follow-up and suboptimal management and monitoring of their disease. These factors also complicate any chance of treatment free period for patients who achieve undetectable levels of bcr-abl transcripts. Additionally absence of technology for mutational analysis makes it impossible to determine underlying reasons for suboptimal response with accuracy. Disclosures Alam: BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Hussain:BMS: Honoraria; Novartis: Honoraria. Lal:BMS: Honoraria; novartis: Honoraria.

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The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience

Terapevticheskii arkhiv ◽

10.26442/terarkh201890738-50 ◽

2018 ◽

Vol 90 (7) ◽

pp. 37-50

Author(s):

Y Y DYAKONOVA ◽

O I BYDANOV ◽

A M POPOV ◽

Y V OLSHANSKAYA ◽

E G BOICHENKO ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Therapy Group ◽

Lymphoblastic Leukemia ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Cell Acute Lymphoblastic Leukemia ◽

Therapeutic Element

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials.

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EFFICACY OF MODIFIED BISMUTH QUADRUPLE THERAPY (RBMA) AS FIRST-LINE THERAPY FOR ERADICATION OF HELICOBACTER PYLORI IN PATIENTS WITH CHRONIC GASTRITIS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2019.2.5 ◽

2019 ◽

pp. 28-32

Author(s):

Van Huy Tran

Keyword(s):

Helicobacter Pylori ◽

Adverse Effects ◽

Chronic Gastritis ◽

Eradication Rate ◽

High Rate ◽

First Line ◽

Helicobacter Pylori Eradication ◽

Quadruple Therapy ◽

First Line Therapy ◽

Line Therapy

Background and aims: Efficacy with substitution of tetracycline with amoxicillin, an antibiotics having a very low resistance rate and a high tolerability, in bismuth quadruple therapy (BQT) have not been studied in Vietnam. Our study aimed to evaluate the efficacy and tolerability of modified BQT vs. standard BQT for first-line Helicobacter pylori eradication. Patients and methods: This is a randomized, prospective study. 120 patients with H.pylori positive-chronic gastritis were randomly divided into two groups. The RBMA group containing rabeprazole 20 mg, bismuth subsalicylic 524mg, metronidazole 500mg, amoxicillin 1000mg, all 2 times a day, for 14 days. The RBMT group received rabeprazole, bismuth subsalicylic, metronidazole and tetracycline. Evaluation for compliance and drug-related side effects were evaluated at the end of two weeks. 4-6 weeks after the end of treatment, the H.pylori eradication rate was determined by the C13urease breath test. Results: Eradication rate was not statistically significative different between the RBMA and the RBMT: 91.2%; 95% confidence interval, 78.2% - 96.7%) vs. 90%; 95% CI, 81.6% - 96.3%) by per-protocol analysis (p = 0.42) and 86.7% (95%CI, 75.84% - 93.09%) vs. 75% (95%CI, 62.1% - 85.3%) by intention-to-treat analysis (ITT, p = 0.06). Adverse effects were significant higher in the RBMT group than in the RBMA group (48.3% vs. 26.7%; p = 0.071) and rate of good compliance was significantly higher in RBMA group than in RBMT group (p < 0.05). Conclusion: The modified BQT including rabeprazole, bismuth, metronidazole and amoxicillin achieved a fairly high rate of H.pylori infection eradication with a higher compliance and lower rate of adverse effects compared to the BQT in patients with chronic gastritis. Further studies need to conduct to confirm this new regimens as a first-line therapy in our country. Key words: Modified bismuth quadruple therapy, BQT, Helicobacter pylori eradication

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GCT-28. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE

Neuro-Oncology ◽

10.1093/neuonc/noaa222.248 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii333-iii333

Author(s):

Lei Wen ◽

Zhaoming Zhou ◽

Qingjun Hu ◽

Juan Li ◽

Mingyao Lai ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Late Recurrence ◽

Salvage Chemotherapy ◽

Recurrence Time ◽

First Line ◽

Primary Tumor Site ◽

First Line Therapy ◽

Line Therapy

Abstract PURPOSE Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because relatively higher recurrence usually occurs after first line therapy. METHODS Between January 2003 and December 2018, 111 consecutive patients diagnosed with NGGCTs reviewed. Those who progressed after first line therapy were included in this study. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed. RESULTS Totally, thirty patients (30/111, 27.0%) relapsed in our cohort, including 19 patients with accurate relapse information detail, and 11 patients who died of disease progression during follow up but without exact time and site of relapse. The median OS from diagnosis of the disease was 49.2 months (95% CI: 14.1 to 84.3 months) and 3-year OS was 54.3%. Patients who received both CSI and chemotherapy relapsed less than those who received reduced volume of radiotherapy or only CSI or only chemotherapy (22.5% vs. 45.5%, p=0.034). Of 19 patients who had detail information of recurrence time and site, the median time from diagnosis of disease to relapse was 9.5 months (2.2 to 72.1 months). Regarding to recurrence site, most patients relapsed in primary site (10/19, 52.6%) or distant intracranial (6/19, 31.6%). The recurrence site of other 3 patients were spinal (n=1), ventricular (n=1) and peritoneal (n=1). CONCLUSION Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from both CSI and salvage chemotherapy.

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