Rituximab Plus GM-CSF for Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 721-721 ◽  
Author(s):  
Alessandra Ferrajoli ◽  
Susan M. O’Brien ◽  
Stefan H. Faderl ◽  
William G. Wierda ◽  
Farhad Ravandi-Kashani ◽  
...  
Keyword(s):  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Gm Csf ◽  
Cd20 Expression ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Group 3 ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

Abstract Treatment with single agent rituximab is associated with overall response (OR) rate of 15–35% in previously treated patients and up to 44% in untreated patients with CLL. The majority of the responses are partial (PR). GM-CSF was found to increase surface CD20 expression in vitro and potentiate ADCC and therefore improve the efficacy of rituximab. The combination of rituximab and GM-CSF has been investigated in follicular lymphomas and found to be associated with significant responses (McLaughlin et al. Ann. Oncol16:v68, 2005). Therefore, we designed a phase II study of rituximab plus GM-CSF in CLL. Patients were eligible for this study if they belonged to one of the following: Group 1: previously untreated patients, Rai stage 0-II and b2M >3 mg/mL, B symptoms or significant fatigue. Group 2: previously untreated patients ≥ 70 years with indication for treatment (NCI-WG criteria). Group 3: previously treated patients with evidence of active disease (NCI-WG criteria). All patients received 4 weekly infusions of rituximab 375 mg/m2 plus GM-CSF 250 mcg sc three times a week for 8 weeks. Prior to study entry patients were evaluated for genomic aberration (FISH), IgVH mutation status, ZAP70 expression, and number of CD20 antigen sites. Changes in self-reported fatigue were measured using the FACT-An fatigue scale. Eighty-two patients have been enrolled at this time and 55 are evaluable for response and toxicity. Responses (NCI-WG): Pts CR (%) NPR (%)* PR (%) OR (%) *Nodular PR:residual lymphoid nodules present Group 1 9 7 7 (78) Group 2 20 3 2 12 17 (85) Group 3 26 2 3 9 14 (54) OVERALL 55 5 (9) 5 (9) 28 (51) 38 (69) Toxicities attributable to the administration of GM-CSF consisted in Grade 1 injection site reactions in 25% and Grade 1–2 bone pain in 13%. Grade 3 thromobocytopenia was observed in 2% of the patients and Grade 3–4 neutropenia in 4%. Grade 3 infections were observed in 9% of the patients. The following characteristics were correlated with responses. Characteristic Patients CR% OR% FISH 11q-/17p-11 1 (9) 4 (36) 13q-/+12/normal 38 4 (11) 32 (84) p<.001 IgVH Unmutated 23 1 (4) 11 (48) Mutated 28 4 (14) 23 (82) p=.01 ZAP70 Positive 30 1 (3) 17 (57) Negative 23 4 (17) 17 (74) p=NS CD20 sites/cell ≤10,000 20 10 (50) >10,000 16 3 (19) 13 (81) p=.05 Treatment with rituximab plus GM-CSF was associated with a reduction of self-reported fatigue (median score reduction 7 points) in two thirds of the patients. In conclusion, the combination of rituximab plus GM-CSF is well tolerated and associated with an encouragingly high response rate. Favorable genomic profile, mutated IgVH status and high level of CD20 expression predicted for response to this combination. Ongoing correlative studies aim to clarify the mechanism of action of this combination. Accrual to this study is ongoing.

Pentostatin and Cyclophosphamide: An Effective New Regimen in Previously Treated Patients With Chronic Lymphocytic Leukemia

2003 ◽  
Vol 21 (7) ◽  
pp. 1278-1284 ◽  
Author(s):  
Mark A. Weiss ◽  
Peter G. Maslak ◽  
Joseph G. Jurcic ◽  
David A. Scheinberg ◽  
Timothy B. Aliff ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Response Rate ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Severe Nausea ◽  
Treatment Regimens ◽  
Purine Analogs ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

Purpose: Purine analogs and alkylators are important agents in the treatment of chronic lymphocytic leukemia (CLL). Previously, combinations of fludarabine and chlorambucil were abandoned because of increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin may be least myelosuppressive. We hypothesized that combining pentostatin with cyclophosphamide would have less myelotoxicity than combinations using other purine analogs. Patients and Methods: We studied 23 patients with previously treated CLL. All patients received pentostatin 4 mg/m2. Seventeen patients received cyclophosphamide 600 mg/m2, and six patients received cyclophosphamide 900 mg/m2. Both drugs were administered on day 1 of each cycle, and cycles were repeated every 3 weeks for six treatments. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. The median number of prior treatment regimens was three (range, one to five) with 13 patients (57%) refractory to prior fludarabine therapy. Results: The cyclophosphamide 900 mg/m2 dose level was associated with moderate to severe nausea, and we chose cyclophosphamide 600 mg/m2 as the dose for further study. There were 17 responses (74%; 95% confidence interval, 63% to 85%), including four complete responses. The response rate was 77% in fludarabine-refractory patients. Myelosuppression was acceptable with grade 3/4 neutropenia and thrombocytopenia, seen in 35% and 30% of patients, respectively. The relative sparing of thrombopoiesis can be seen in that only one patient (5%) with an initial platelet count of more than 20,000 required platelet transfusions while receiving therapy. Conclusion: Pentostatin 4 mg/m2 with cyclophosphamide 600 mg/m2 is safe and effective in previously treated patients with CLL. On the basis of these results, we are currently studying pentostatin, cyclophosphamide, and rituximab (PCR) therapy in patients with CLL.

A Pilot Study of Genasense® (Oblimersen Sodium, Bcl-2 Antisense Oligonucleotide), Fludarabine and Rituximab in Previously Treated and Untreated Subjects with Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4827-4827 ◽  
Author(s):  
Asher Alban Chanan-Khan ◽  
Blanche Mavromatis ◽  
Kanti R. Rai ◽  
Philomena Casey ◽  
Steven Novick ◽  
...  
Keyword(s):  
Adverse Events ◽  
Lymphocyte Count ◽  
Alkylating Agents ◽  
Single Agent ◽  
Tumor Lysis Syndrome ◽  
Lymphocytic Leukemia ◽  
Serious Adverse Events ◽  
Reduced Dose ◽  
Previously Treated ◽  
Grade 3

Abstract Bcl-2 is an anti-apoptotic protein closely linked to chemotherapy resistance and inferior survival in patients (pts) with CLL. Genasense(GNS) enhances apoptosis induced by fludarabine (F), dexamethasone, and rituximab (R) in vitro, and has limited single-agent activity in heavily pre-treated CLL pts. Down-regulation of Bcl-2 may further sensitize CLL cells to apoptosis induced by F and R without exposing subjects to the toxicity of alkylating agents. CLL and NHL pts occasionally exhibit a “cytokine release syndrome” (spiking fever, back pain, and occasional hypotension) with GNS treatment. We hypothesized that a “step dosing” approach with GNS, similar to that sometimes used for R, could ameliorate these effects and allow safe and effective combination of this agent with F and R. We are currently evaluating this combination in pts with either previously untreated (UT) or relapsed, previously treated (PT) CLL who require systemic treatment. Eligibility includes: plts ≥ 50,000/mm3; serum Cr ≤ 1.5 mg/dL; adequate organ function; negative Coombs; no history of autoimmune hemolytic anemia. In cycle 1, GNS is given by continuous intravenous infusion at 1.5 mg/kg/d days 1 to 7. R is given on a dose-escalating schema (day 4, 125 mg/m2; day 6, 250 mg/m2). F (25 mg/m2/d) is given on days 6 to 8. In subsequent 28-day cycles (up to 6), the dose of GNS is escalated to 3 mg/kg/d days 1 to7 days, with R 375 mg/m2 on day 5 and F days 5 to7. To date, 20 pts have been enrolled (17 PT and 3 UT). Characteristics included: median age, 62 yrs (range 39 to 82 yrs); Rai stage III (2 pts) and IV (6 pts). Prior to administration of either F or R, single-agent GNS treatment at the initial reduced dose in Cycle 1 resulted in a median decrease in lymphocytes of 15% (among all patients regardless of decline in lymphocyte count) (Baseline: 48.3 cells x 103/ml; day 4: 40.1 cells x 103/ml). For the 13 pts who experienced a decline in lymphocyte count in cycle 1 prior to F and R, the median percentage change was 17%, with 4 pts having a > 25% decrease. Three PT pts discontinued from study treatment prior to completing 6 cycles, 2 due to disease progression, and 1 with Grade 3 thrombocytopenia that was unresolved after 4 weeks. Among the 20 pts treated to date (9 ongoing), the most common grade 3 or higher adverse events have been neutropenia, pyrexia and thrombocytopenia. Serious adverse events have been noted in only 6 of 20 pts (all PT pts) and have included 2 pts with fever (1 neutropenic), 2 R infusion reactions, 1 lymph node abscess and 1 tumor lysis syndrome (with sepsis). Conclusions: 20 pts have been treated with combination GNS, F and R. Single-agent activity with GNS has been observed at a reduced dose of 1.5 mg/kg/d in cycle 1. The “step dosing” approach appears to be a well-tolerated, alternative approach to the administration of GNS. Further details of safety and efficacy will be presented.

13q14 Chromosome Deletion Size and Number of Deleted Cells Influence Prognosis In Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3578-3578
Author(s):  
Francesca Maria Rossi ◽  
Davide Rossi ◽  
Clara Deambrogi ◽  
Francesco Bertoni ◽  
Michele Dal Bo ◽  
...  
Keyword(s):  
Clinical Course ◽  
Lymphocytic Leukemia ◽  
Single Institution ◽  
Group 4 ◽  
Median Size ◽  
Mutational Status ◽  
Genome Wide ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Abstract 3578 Introduction: Chronic lymphocytic leukemia (CLL) patients bearing 13q14 deletion are known to experience a more favorable clinical course. Recent studies, focusing on patients with loss of 13q as the sole cytogenetic aberration at diagnosis (del13q-only cases), showed that the number of malignant cells carrying this genetic lesion correlates with a more aggressive clinical behavior. However, whether the size of the 13q deletion may also influence the clinical outcome remains to be elucidated. Patients and Methods: Probes for chromosome 13q (LSI-RB1, LSI-D13S319), 11q (LSI-ATM), 17p (LSI-p53) and chromosome 12 (CEP12) were utilized on nuclei collected at diagnosis from: i) a multi-institutional CLL cohort (342 del13q-only cases) and ii) a consecutive unselected single-institution cohort of 265 cases. RB1 deleted cases (delRB1) were defined as having at least 5% of deleted nuclei. Time to treatment (TTT) intervals, as well as Rai staging, IGHV mutational status, CD38 and ZAP70 expression, B2-microglobulin levels, all evaluated at diagnosis, were also available for all cases that entered the study. Genome wide DNA profile was performed in a pilot series of 90 CLL samples using Affymetrix GeneChip Human SNP6 arrays. Results: According to genome wide DNA analysis, delRB1 occurred in a proportion of del13q-only cases (36/90; 40%), always comprising the deleted region detected with the LSI-D13S319 probe (that covers the miR-15a/16-1 cluster and the DLEU2 gene) and characterized by a larger chromosome loss (median size 2.07 Mb vs. a median size of 0.86 Mb for the canonical del13S319). Maximally selected log-rank statistics identified the 70% of nuclei bearing del13S319 as the most appropriate cut-off value capable of separating del13q-only cases into two subgroups with different TTT distributions. Consistently, del13q-only cases with at least 70% of nuclei bearing del13S319 showed a significantly shorter TTT than del13q-only cases with less than 70% deleted nuclei (p=0.0001). Del13q-only cases were then divided in four subsets according to the percentage of nuclei bearing del13S319 with or without a concomitant delRB1: del13S319 <70% (group 1), 144 cases; del13S319 <70% + delRB1 (group 2), 95 cases; del13S319 >70% (group 3), 64 cases; del13S319 >70% + delRB1 (group 4), 39 cases. The median TTT of group 1 (not reached) was significantly longer than the median TTT of group 2 (92 months, p=0.012), group 3 (68 months, p<0.0001), and group 4 (82 months, p=0.0025; see Fig. 1A). Multivariate Cox proportional hazard analyses selected the presence of delRB1 (p=0.029), along with the IGHV mutational status (p<0.0001), as an independent negative prognosticator in the context of del13q-only cases with low/intermediate Rai risk (Rai stage of 0/I at diagnosis) and <70% of del13S319. Cases belonging to the consecutive unselected single-institution CLL cohort were divided into subsets according to the classification proposed by Döhner et al (NEJM, 2000). Notably, the presence of del13S319 in <70% of cells in the absence of delRB1 identified a patient subset with particularly stable and benign clinical course (group A in Fig. 1B, 48 cases; median TTT not reached). Conversely, patients characterized by del13S319 in <70% of cells but with a larger deletion, as determined by concomitant delRB1 (group B, 24 cases), or del13S319 in >70% of cells (with or without delRB1, group C, 25 cases) or a normal karyotype (group D, 75 cases) had shorter median TTT intervals (ranging from 105 to 129 months, p<0.01 in all the comparisons). Finally, patients affected by CLL bearing trisomy 12 (group E, 48 cases) and del11q or del17p (group F, 45 cases) experienced the worst clinical courses (p<0.0001). Conclusion: In the context of del13q-only cases, different clinical outcomes were associated to the percentage of 13q14 deleted cells, as well as to the size of the 13q14 deletion, as detected by the LSI-RB1 probe. Moreover, the presence of delRB1 emerged as a feature capable of refining the prognostic assessment in the context of CLL cases with <70% del13S319. The underlying genetic mechanisms correlated with the different clinical outcomes and associated with the size of the 13q deletion are presently under investigation. Disclosures: No relevant conflicts of interest to declare.

The Combination of the EBMT Score and the HCT-CI Is Not Better Than the HCT-CI Alone in the Prediction of NRM and OS in Patients Undergoing Allogeneic Hematopoietic Transplantation with Reduced-Toxicity Conditioning

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1925-1925
Author(s):  
Pere Barba ◽  
David Valcarcel ◽  
Lucía López-Corral ◽  
Francesc fernandez-Aviles ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Lymphocytic Leukemia ◽  
Score Distribution ◽  
Predictive Capacity ◽  
Group 3 ◽  
Group 2 ◽  
Reduced Toxicity ◽  
The Impact ◽  
Group 1

Abstract Abstract 1925 In recent years, several pre-transplant models have been developed to predict the outcome after hematopoietic cell transplantation (HCT) through the selection of the best candidates and conditioning regimens. Two models are the most popular one each side of the Atlantic: the HCT Comorbidity Index (HCT-CI) and the European Blood and Marrow Transplantation (EBMT) score. Their predictive capacity has been demonstrated in several studies. Since these models are focused on different pre-HCT characteristics (HCT-CI on comorbidities and the EBMT score on more classical risk factors) we hypothesized that the combination of the two could improve their individual predictive capacity. To that end, we retrospectively analyzed pre-HCT characteristics of all consecutive patients receiving a reduced-toxicity allogeneic HCT (allo-HCT) in 4 Spanish centers from 1999–2008. The HCT-CI and the EBMT scores were calculated as originally defined. Patients were then classified according to the HCT-CI in the original categoriesas originally defined and regardingto the EBMT score in two groups according to the median score of the whole cohort. Multivariate analyseis including pre-HCT characteristics were performed using Cox proportional Hazard models and taking into account the competitive risk structure. The predictive capacity of each model was calculated using the c-statistics. Patients were included in the same protocol of reduced-toxicity allo-HCT with fludarabine-based conditioning in combination with melphalan (70–140 mg/m2) or busulfan (8–10 mg/kg). The median follow-up for survivors was 51 months (range 3–123). A total of 442 recipients (80% transplanted from HLA identical siblings) were included. Most frequent diseases were acute leukemia/MDS (n=156, 35%) and non-Hodgkin lymphoma/chronic lymphocytic leukemia (n=125, 28%). The HCT-CI score distribution was: score 0 (n=87, 20%), score 1–2 (n=130, 29%) and score ≥3 (n=225, 51%) while for the EBMT score was 0–2 (n=62, 14%), 3–4 (n=194, 44%) and >4 (n=187, 42%). The probability of 100-day Non-Relapse Mortality (NRM), 4y-NRM and 4y-overall survival (OS) for the whole cohort were 12% (95%CI 11–14), 35% (95%CI 33–38) and 45% (95%CI 48–50), respectively. In the multivariate analysis, the HCT-CI had and impact on 4y-NRM (score 0: HR 1.0; scores 1–2: HR 1.6 [95%CI 0.9–3], p=0.09; scores ≥ 3: HR 2.3 [95%CI 1.3–3.8], p=0.003) and 4y-OS (score 0:HR of death 1.0; scores 1–2: HR 1.3 [95%CI 0.8–2], p=0.2; scores >2: HR 1.9 [95%CI 1.3–2.8], p=0.002) while the EBMT score did not (p=0.4 and p=0.5, respectively). Using the two models we classified the patients were classified into 3 groups: patients with low HCT-CI (0–2) and low EBMT score (<4) (Group 1), patients with high HCT-CI or high EBMT score (Group 2) and patients with both high HCT-CI and EBMT score (Group 3). The HR for 4y-NRM were: group 1 (HR 1.0), group 2 (HR 1.1 [95%CI 0.6–2], p=0.7), group 3 (HR 1.8 [95%CI 1–3], p=0.04) and for 4y-OS was: group 1 (HR 1.0), group 2 (HR 1 [95%CI 0.6–1.5], p=0.8), group 3 (HR 1.6 [95%CI 1–2.3], p=0.04). Regarding the predictive capacity of each model, the HCT-CI alone captured 58% (c- 95%CI: 53–62), the EBMT score 54% (c- 95%CI: 51–58) while the combination of the two models captured 57% (c- 95%CI: 53–61) of the patients. Finally, the impact of EBMT score was explored in each HCT-CI group. In patients with HCT-CI scores of 0 and 1–2, the EBMT score did not have an impact on NRM and OS. In the cohort of high HCT-CI score (>2), patients with low EBMT score showed a trend to lower risk of NRM (HR 0.6 [95%CI 0.3–1], p=0.08) with a similar risk as for patients with HCT-CI of 1–2 (Figure 1). In conclusion, high HCT-CI scores but not high EBMT scores are associated with worse outcome in patients undergoing reduced toxicity allo-HCT. The addition of the EBMT score contributes little to the HCT-CI, except maybe for patients with more and severe comorbidities. Figure 1. Probability of NRM according to the HCT-CI for all patients and according to the EBMT score in the 225 patients with HCT-CI >2 (MVA) Figure 1. Probability of NRM according to the HCT-CI for all patients and according to the EBMT score in the 225 patients with HCT-CI >2 (MVA) Disclosures: No relevant conflicts of interest to declare.

Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7718-7718
Author(s):  
M. Nishio ◽  
F. Ohyanagi ◽  
A. Horikike ◽  
Y. Okano ◽  
Y. Satoh ◽  
...  
Keyword(s):  
Survival Time ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Single Agent ◽  
Refractory Disease ◽  
Platinum Based Chemotherapy ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

7718 Background: Gemcitabine and irinotecan has been shown to have an antitumor activity as a single agent against previously treated SCLC. The objective of this study was to assess the efficacy and safety of gemcitabine combined with irinotecan in patients with refractory or relapsed SCLC. Methods: Patients with histologically or cytologically confirmed SCLC, 20 to 74 years in age, performance status 0–2, with a history of receiving one platinum-based chemotherapy were eligible for the study. Treatment consisted of gemcitabine (1,000 mg/m2) and irinotecan (150 mg/m2) on days 1 and 15 of a 28-day cycle.The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 30 patients (Simon's two-stage minimax design). Results: Thirty-one patients were enrolled and 30 patients (24 males/6 females, 10 refractory/20 sensitive, median age, 65 years) receive protocol treatment in this phase II trial. The median treatment cycles were 3 (1–10). The overall response rates was obtained in 39.3% (95% CI: 18.1% to 60.5%) of the patients, including two patients with refractory disease and 9 patients with sensitive disease. The median overall survival time was 14.4 months, and the 1-year survival rate was 51%. The median survival time of the patients with refractory disease was 7.4 months, compared with 14.4 months for patients with sensitive disease. The chief grade 3/4 toxicities included neutropenia (42%), thrombocytopenia (3%), diarrhea (9%), and liver dysfunction (3%). The only grade 4 toxicities were one case of grade 4 neutropenia (3.3%) and one case of grade 4 thrombocytopenia (3.3%). Conclusion: Gemcitabine plus irinotecan is an active regimen that seems to be well- tolerated by patients with previously treated SCLC. No significant financial relationships to disclose.

scholarly journals The Frequency of Occurrence of Minimal Residual Disease into Different Prognostic Groups of Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5275-5275
Author(s):  
Aleksei Kuvshinov ◽  
Sergei Voloshin ◽  
Irina Martynkevich ◽  
Ludmila Martynenko ◽  
Andrei Garifullin ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
Prognostic Groups ◽  
Prognosis Group ◽  
Group 3 ◽  
Group 2 ◽  
Minimal Residual ◽  
Group 1

Abstract Background. It is known, that genetic factors and the absence of minimal residual disease (MRD) are strongly affecting prognosis of chronic lymphocytic leukemia (CLL). Aim. To determine the influence of genetic abnormalities (GA) on achieving MRD-negative remissions in patients with CLL. Methods. Twenty-four adult pts (median age 57 years, range 35-67; male 14, female 10) with newly diagnosed CLL were included. The CLL was diagnosed according to the standard basic examination (complete blood count with differential, multicolor flow cytometry (MFC) of blood and bone marrow (BM), lymph node and BM immunohistochemistry (IHC), computered tomography). Cytogenetic studies were performed on blood samples using standard GTG-method. Interphase FISH analyses were performed according to the manufacturer's protocol using DNA probes: LSI 13(RB1)13q14, LSI ATM (11q22), CEP12, LSI TP53 (17p13.1) (Abbott). Immunophenotype (IFT) of CLL cells assessed with combinations: CD3/CD19, CD19/CD5, CD19/CD11c, CD19/CD20, CD19/CD22, CD19/CD23, CD19/CD25, CD19/CD38, CD19/CD43, CD19/CD81, CD19/HLA-DR, and CD19/CD5/CD23. We have used NCI revised guidelines (Hallek M, et al., 2008) for treatment initiation and assessment of response after completion of primary therapy with rituximab-based regimens (FCR or RB). All patients treated subsequently with rituximab maintenance. MRD was detected by MFC. Results. The frequency of GA in CLL was 50.0% (12/24): 15.0% (3/20) - by conventional karyotyping, 47.8% (11/23) - by FISH analyses and 9.5% (2/21) - using both methods. Stratification of patients into prognostic groups based on identified GA. Favorable prognosis (Group 1) - patients with del(13q) (n = 5); neutral prognosis (Group 2) - normal karyotype (n = 12) or trisomy of chromosome 12 (n = 3); unfavorable prognosis (Group 3) - del(11q) (n = 3) or the complex karyotype (n = 1). Statistically significant differences in the frequency of achieving MRD-negative remissions between FCR (5/11) vs. RB (5/13) were not detected (p<0.05). Complete remissions (CR) were reached in 37.5% (9/24) pts, partial remissions (PR) - 62.5% (15/24). The MRD-negative remissions were reached in 10 patients: in Group 1 - 2/5 (40%; CR - 1), in Group 2 - 5/15 (33.3%, CR - 6), in Group 3 - 75.0% (3/4; CR - 2). Statistically significant differences in PFS were detected between MRD-negative vs. MRD-positive groups (p=0.03). Median PFS in MRD-negative has not been reached. Median PFS MRD-positive was 33.1 month. Conclusions. Further researches aimed at examining the relationship between the presence or absence of MRD and genetic prognostic groups, will help to understand the most important factors affecting the overall and progression-free survival. Disclosures No relevant conflicts of interest to declare.

Clinical Significance of Homozygous D13S319 Deletion in B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2799-2799 ◽  
Author(s):  
Stephanie Fink ◽  
Susan Geyer ◽  
Tait Shanafelt ◽  
Stephanie Smoley ◽  
Sarah Paternoster ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Median Percentage ◽  
Time To Treatment ◽  
Treatment Status ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background: In B-CLL, the observation of interphase cells with hemizygous D13S319 deletion at 13q14 (13q-x1) as a sole anomaly in blood is widely considered a favorable prognosis. The observation of cells with 11q-, +12 or 17p- has been associated with a relatively poor prognosis. Over the past 1.5 yrs, 16.2% (174/1,076) of patients (pts) referred for fluorescence in situ hybridization (FISH) testing for B-CLL in our clinical practice had a clone with homozygous D13S319 deletion (13q-x2), but the prognostic significance of this observation is poorly understood. Moreover, 39.3% (142/361) of pts with unfavorable FISH anomalies have 13q-x1 and/or 13q-x2 and the clinical significance of this observation is also unknown. Thus, we investigated pts with 13q- (with or without other chromosome anomalies) to establish the relative clinical significance of 13q- in B-CLL. Methods: We studied 333 pts with B-CLL sampled between 9/1999 and 6/2004 who had FISH performed on interphase nuclei from blood. The FISH probe set was designed to detect 6q-, 11q-, +12, 13q-, 17p-, and translocations involving IgH at 14q32. We classified pts into four groups: 13q-x1 only (group 1), 13q-x1 and 13q-x2 only (group 2), 13q-x2 only (group 3) and 13q-x1 and/or 13q-x2 plus other FISH anomalies (group 4). FISH groups were compared with gender, age, Rai stage, treatment status, time to treatment, CD38 and IgVH mutation. Results: Of the 333 pts, 171 (51.3%) had a 13q-: 71 were in group 1, 25 in group 2, 26 in group 3 and 49 in group 4. %CD38+ differed significantly across FISH groups; in pairwise analyses, the proportion of pts with >30% CD38+ was significantly greater for pts in group 4 vs. group 3 (p=0.0015) although no significant differences were observed for group 3 vs. group 1 or vs. group 2. Pts in group 3 were not significantly different from other FISH groups for Rai stage, IgVH mutation or gender. The median percentage of abnormal nuclei for pts with group 1 was 54.5% vs. 79.5% for pts in group 4 (p<0.0001). The median percent abnormal nuclei for pts in groups 3 and 2 was 72.5% and 68.5%, respectively. Median % abnormal nuclei for group 3 was not significantly different than the other FISH groups. Treatment status was available on 147 pts, where the proportion of pts who had treatment in each group was as follows: group 1, 15/66; group 2, 2/22; group 3, 4/21; and group 4, 9/38. Due to limited sample size and heavy censoring, any analysis on time to treatment is preliminary; however, these early analyses suggest group 4 pts have a lower median time to treatment (9 yrs) compared to groups 3 and 1 (12.3 and 13 yrs, respectively). Conclusions: This study has generated new information about the 13q- anomaly in B-CLL. First, known prognostic markers for B-CLL pts with 13q-x2 are not significantly different than for pts with 13q-x1 or 13q-x1/13q-x2. Second, 13q-x1 and/or 13q-x2 occurring with other unfavorable FISH anomalies have an unfavorable prognosis; i.e. potential benefits of 13q- are trumped when it is observed with unfavorable FISH anomalies. Thus, patients with any form of 13q- alone may have indolent disease while patients with 13q- and unfavorable FISH anomalies should be considered to be in a more aggressive phase.

scholarly journals Does the Conjunctivochalasis Accompanied by Pseudoexfoliation Syndrome Affect the Ocular Surface and Anterior Segment Structures?

2022 ◽  
Author(s):  
Bediz Özen ◽  
Hakan Öztürk
Keyword(s):  
Anterior Chamber ◽  
Ocular Surface ◽  
Anterior Segment ◽  
Tear Film ◽  
Disease Index ◽  
Pseudoexfoliation Syndrome ◽  
Group 3 ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

Abstract Purpose: Probability of coexistence of conjunctivochalasis and pseudoexfoliation syndrome (PES) in same individual may increase with aging. We investigated effects of conjunctivochalasis accompanied by PES on ocular surface (OS) and anterior segment (AS) structures.Methods: Cases with only conjunctivochalasis were determined as group-1 (n=62), cases with conjunctivochalasis accompanied by PES as group-2 (n=45), and healthy cases as group-3 (n=56). OS and AS parameters of groups were compared.Results: Compared to group-1, group-2 had higher grade-3 conjunctivochalasis (17.7% vs 46.7%, p=0.039), greater mean grade of conjunctivochalasis (MGC) (1.72±0.24 vs 2.29±0.32, p=0.036), higher total conjunctivochalasis score (TCS) (4.27±1.13 vs 6.12±1.35, p=0.025), shorter tear-film break-up time (TBUT) (9.17±2.53 vs 5.41±1.32, p=0.010), greater OS disease index (OSDI)-score (16.28±3.15 vs 27.36±4.12, p=0.037). Compared to group-3, both group-1 and group-2 had shorter TBUT (group 3-1: p=0.004; group 3-2: p<0.001) and greater OSDI score (group 3-1: p=0.042; group 3-2: p=0.019). Schirmer tests, central corneal thicknesses, keratometries, axial lengths, anterior chamber depths and lens thicknesses of groups were similar (p>0.05). In group-1 and group-2, as age increased, both MGC (r=0.349, p=0.043; r=0.403, p=0.022, respectively) and TCS (r=0.322, p=0.046; r=0.372, p=0.031) increased. In group-2, as both MGC and TCS increased, TBUT (r=-0.370, p=0.034; r=-0.401, p=0.025) decreased and OSDI score (r=0.338, p=0.045; r=0.362, p=0.040) increased.Conclusions: To our knowledge, this was the first study comprehensively investigating effects of conjunctivochalasis accompanied by PES on OS and AS structures together. We found that conjunctivochalasis might cause OS disease, while presence of PES in conjunctivochalasis cases might worsen OS disease and conjunctivochalasis findings.

scholarly journals Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2497-2506 ◽  
Author(s):  
John C. Byrd ◽  
Richard R. Furman ◽  
Steven E. Coutre ◽  
Jan A. Burger ◽  
Kristie A. Blum ◽  
...  
Keyword(s):  
Adverse Events ◽  
Single Agent ◽  
Extended Treatment ◽  
Key Points ◽  
Treatment Naïve ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3 ◽  
Over Time

Key Points Three-year follow-up of ibrutinib in CLL demonstrated continued activity with durable responses that improve in quality with extended treatment. Toxicity diminished over time with respect to grade ≥3 cytopenias, fatigue, infections, and adverse events leading to discontinuation.

Efficacy and Safety of the Combination of Genasense™ (Oblimersen Sodium, Bcl-2 Antisense Oligonucleotide), Fludarabine and Rituximab in Previously Treated and Untreated Subjects with Chronic Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2129-2129 ◽  
Author(s):  
Blanche Mavromatis ◽  
Kanti R. Rai ◽  
Paul K. Wallace ◽  
Claudia Soho ◽  
Beverly Landrigan ◽  
...  
Keyword(s):  
Single Agent ◽  
Chemotherapy Resistance ◽  
Infusion Reaction ◽  
Lymphocytic Leukemia ◽  
Good Tolerability ◽  
Acute Renal Insufficiency ◽  
Previously Treated ◽  
Grade 3 ◽  
The Impact

Abstract Bcl-2 is an anti-apoptotic protein closely linked to chemotherapy resistance and inferior survival in patients (pts) with CLL. Genasense (G) enhances apoptosis induced by fludarabine (F), dexamethasone, and rituximab (R) in vitro. Despite limited single-agent activity in heavily pre-treated CLL pts, G significantly increased the rate of durable complete responses (CR) in combination with fludarabine (F) and cyclophosphamide in relapsed or refractory CLL (Rai, ASH 2004). Down-regulation of Bcl-2 sensitizes CLL cells to apoptosis induced by F and R. In order to examine the impact of G on the FR combination, we initiated a phase II study of the combination of FRG in pts with either previously untreated (UT) or relapsed, previously treated (PT) CLL who require systemic treatment. Eligibility includes: plts ≥ 50,000/mm3; serum Cr ≤ 1.5 mg/dL; adequate organ function; negative Coombs; no history of autoimmune hemolytic anemia. In cycle 1, G is given by continuous intravenous infusion at 1.5 mg/kg/d days 1 to 7. R is given in a dose-escalating schema: 125 mg/m2 on day 4 and 250mg/m2 on day 6, with F (25 mg/m2/d) on days 6 to 8. In subsequent 28-day cycles (up to 6), the dose of G is escalated to 3 mg/kg/d days 1 to 7, with R 375 mg/m2 on day 5 and F days 5 to 7. Results: To date, 24 pts have been enrolled (19 PT and 5 UT). Characteristics included: median age, 56.5 yrs (range 25–82 yrs); Rai stage III, 6 pts (4 PT and 2 UT) and IV, 6 pts (6 PT and 0 UT). Median prior regimens (PT pts), 2; 13/19 (68%) had received F and R previously. Median # cycles administered: 6 (both UT and PT). Four PT pts discontinued treatment before completing 6 cycles, 2 due to disease progression, and 2 with prolonged (&gt; 4 week) Grade 3 thrombocytopenia/neutropenia. One PT pt completed only 3 cycles of R due to an R-related infusion reaction, but completed 6 cycles of G and F. Among the 5 UT pts, there was 1 case of grade 4 neutropenia. Among the 19 PT pts, there were 2 cases each of grade 4 thrombocytopenia and neutropenia. One of 5 UT pts had an SAE of reversible acute renal insufficiency. Seven of 19 PT pts (8 events total) experienced an SAE. These included R-related infusion reactions (2 pts), bacteremia (2 pts) and 1 pt each with fever, lymph node abscess, pneumonia, and thrombocytopenia/neutropenia. Responses have been observed in 5/5 UT pts (1 molecular CR (mCR), 1 nPR and 3 PR) and 10/19 PT pts (1 mCR, 2 nPR and 7 PR). Conclusions: 24 pts have been treated with the combination of FRG. Employing a three-day regimen of F, good tolerability and efficacy have been noted in relapsed/refractory patients. Based on these results, an additional cohort receiving a full 5-day regimen of F is ongoing with measurement of Genasense PK and bcl-2 intracellular levels (mRNA and protein).

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