Agent Orange Exposure Does Not Predict for Shorter Overall Survival in Patients with Chronic Lymphocytic Leukemia: A National Veteran Affairs Tumor Registry Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5568-5568
Author(s):  
Craig Mescher ◽  
Nicole Randall ◽  
Gobind Tarchand ◽  
Lisa M. Baumann Kreuziger ◽  
Dave Gilbertson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Agent Orange ◽  
Second Line ◽  
First Line ◽  
Tumor Registry ◽  
Risk Of Death ◽  
Veteran Affairs ◽  
To Receive

Abstract BACKGROUND: Agent Orange (AO), a 1:1 mixture of herbicides + TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), was used during the Vietnam War to destroy dense jungle and enemy crops. In 2002 the Department of Veteran Affairs (VA) determined that chronic lymphocytic leukemia (CLL) was associated with AO exposure. Case-control studies suggest an increased risk of death from CLL in areas where herbicide use was highest. There is also an increased incidence of other cancers (prostate, melanoma) in AO-exposed veterans. Limited data exists as to the specific impact of AO exposure on CLL disease presentation and outcome. METHODS: Patients (pts) diagnosed with CLL from 2009-2013 were identified in the National VAMC Tumor Registry. Baseline demographic and laboratory parameters were obtained, including Rai stage, marrow cytogenetics (when available), and lymphocyte doubling time (LDT). AO exposure was identified according to the medical record. The VA Benefits and Compensation officers determine AO exposure based on whether a person served on land and in the brown waters in Vietnam during the appropriate timeframe. Timing and types of CLL therapies were identified to determine if AO exposure influenced CLL treatment. RESULTS: 2052 CLL pts were identified, of which 418 had AO exposure. AO-exposed pts presented at a younger age (63.2 versus [vs] 70.5 years (yrs), p <0.0001), had a higher hemoglobin (14.3 vs 13.8 g/dl, p<0.001) and lower lactate dehydrogenase (LDH) (203 vs 227 IU/L, p = 0.01) compared to those without AO exposure. There were no differences in white cell, platelet, or absolute lymphocyte counts, Rai stage or LDT among the groups. Cytogenetic data was available for 1167 pts. There was no difference in the incidence of 17p-, 11q-, or 13q- between the two groups. Median overall survival (OS) was significantly better in patients with AO exposure, even when adjusted for age and Rai stage (median not reached vs 91.2 months, p <0.0001. OS benefit was primarily seen in pts age 60-69 yrs (p = 0.002), and those with 11q- (p = 0.001). No OS differences were found in pts with 17p- or 13q-. Among all pts, regardless of AO exposure status, OS decreased with higher Rai stage. There was a trend towards AO-exposed pts to be more likely to receive CLL-directed therapies (37% vs 32%, p = 0.07). AO exposed pts were more likely, than unexposed pts, to receive therapies as follows: fludarabine, chlorambucil, rituximab (FCR) first-line (38% vs 21%) and second-line (11.6 vs 5%); bendamustine + rituximab (BR) first-line (25% vs 18%), second-line (35 vs 26%), and third-line (31 vs 23%). Pts with no AO exposure were more likely to receive single agent chlorambucil or cyclophosphamide as first-line therapy (17 vs 10%). CONCLUSION: Pts with AO exposure, compared to unexposed pts, had an OS benefit independent of age and Rai stage, with this benefit seen primarily in younger pts (age 60-69 yrs) and in those with 11q-. AO-exposed pts were also more likely to receive disease-specific therapy. This unexpected OS finding will require further analyses for confounding variables, but could potentially be related to earlier treatment with regimens as FCR or BR. Disclosures Morrison: Celgene: Speakers Bureau; Genentech: Speakers Bureau; Gilead: Speakers Bureau; Pharmacyclics: Speakers Bureau; Celgene: Other: Data Monitoring Committee; Merck: Other: Adjudication Committee.

The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study

2017 ◽  
Vol 59 (6) ◽  
pp. 1348-1355 ◽  
Author(s):  
Craig Mescher ◽  
David Gilbertson ◽  
Nicole M. Randall ◽  
Gobind Tarchand ◽  
Julie Tomaska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Agent Orange ◽  
Registry Study ◽  
Tumor Registry ◽  
Veteran Affairs ◽  
The Impact

Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2319-2325 ◽  
Author(s):  
Michel Leporrier ◽  
Sylvie Chevret ◽  
Bruno Cazin ◽  
Najda Boudjerra ◽  
Pierre Feugier ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Clinical Remission ◽  
Remission Rate ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Clinical Remission Rate ◽  
Remission Rates ◽  
Advanced Stages ◽  
To Receive

Abstract To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P &lt; .0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%;P = .003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (&lt; 5%) and autoimmune hemolytic anemia (&lt; 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P = .003) and less frequent nausea-vomiting (P = .003) and hair loss (P &lt; .0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.

Fludarabine Monophosphate as First Line Therapy for Chronic Lymphocytic Leukemia (CLL) - 11 Years Clinical Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4970-4970
Author(s):  
J.E. Novoa ◽  
A.L. Rojo ◽  
B. Beñaran ◽  
R. Draper ◽  
H. Calvo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Response Rate ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Intravenous Formulation

Abstract Background: fludarabine (F) has become the standard first line therapy for chronic lymphocytic leukemia (CLL) in younger patients. Treatment of early stage patients with chlorambucil without risk stratification has not been shown to prolong survival. In recent years effective and potentially curative approaches such as nucleosides analogues, stem cell transplantation or monoclonal antibodies have been developed. The attraction of monoclonal antibodies is based on selective targeting of tumor - relevant surface markers and a distinct mechanism of action (antibody-dependent cellular cytotoxicity). Aims: to assess the efficacy, safety and quality of life of F in previously untreated B-cell CLL patients in a group of medical institutions in Uruguay during 11 years (1995–2006). Methods: 168 patients between the period 1995 – 2006 were evaluated.120 of them received F intravenous formulation (1995–2006) and 48 the oral one (2002–2006). Age: 48 – 85 years old, media 67 years old. Gender: male 90, female 78. Inclusion criteria for B-cell CLL was Binet stages B, C and A progressive (Ap), 18 to 85 years old, non multiorganic failure, performance status 0 – 2 (WHO), written informed consent. First condition was non previous treatment. Staging: Binet A 12/168, B 116/168 & C 40/168. Treatment: as first line therapy all the patients received (minimum): 6 cycles of i.v. Fludarabine (Fludara®, Schering) 25 mg/m2/daily (5 days) e/30 days or Oral Fludarabine, 40 mg/m2/daily (5 days), 6 cycles. Results: on this B-cell CLL cohort the overall response rate (ORR) was 78% (CR+PR), 80% of them have immunophenotypic response. Safety: on the 1100 cycles in 168 patients, the toxicity was: 1 AIHA, 2 pancytopenia, 3 plaquetopenia. Grade 3–4 infection rate was 1,3%. No alopecia was observed in any patient. Kaposi sarcoma (0,7%). Mortality rate: 1,7% (3/168 patients). Other adverse factors to overall survival were, age over 65 (p=0,0001) and hepatic impairment (p=0,0001). Toxicity: (WHO>2): granulocytopenia 28%, thrombocytopenia 8%, infection 2%. Although fludarabine-treated patients experienced more significant myelosuppression, no difference in the treatment group was demonstrated. Causes of death: Richter 12%, sepsis 5%, associated disease 34%, second malignancy 17% and others 30%. Comparing oral with intravenous formulation in overall survival the results were: CLL 34% vs 36% (p= NS). Conclusions: fludarabine monofosfate (Fludara®) looks like an effective and safe treatment for B-cell CLL. The oral and intravenous formulations have a similar response rate in elderly and young patients. The challenge remains to integrate new information to apply novel therapies in a disease-specific and risk-adapted maner. A longer follow up and a larger trial, might be needed to confirm these results.

Resminostat in advanced hepatocellular carcinoma (HCC): Overall survival subgroup analysis of prognostic factors in the SHELTER trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15088-e15088 ◽  
Author(s):  
Michael Bitzer ◽  
Tom M. Ganten ◽  
Marcus A. Woerns ◽  
Jens T. Siveke ◽  
Matthias M. Dollinger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lower Risk ◽  
Vascular Invasion ◽  
Line Treatment ◽  
Second Line ◽  
Monotherapy Group ◽  
First Line ◽  
Treatment Groups ◽  
Risk Of Death ◽  
Baseline Characteristics

e15088 Background: Previously published results of the phase I/II SHELTER study demonstrated efficacy and safety of the novel pan-HDAC inhibitor resminostat in second-line treatment of HCC patients (pts) who had progressed under first-line sorafenib. As patient baseline characteristics might influence treatment outcome, an analysis of their potential influence on overall survival (OS) was performed. Methods: 45 pts with advanced-stage HCC and centrally confirmed radiologic progression under first-line sorafenib were included in a multi-center, two-arm trial. Resminostat was administered either alone or in combination with sorafenib. A Cox proportional-hazards model was used to evaluate the interaction between baseline characteristics and the effect of the two treatment groups on overall survival. Results: In the combination group, pts with Child-Pugh-A, ECOG 0 or absence of vascular invasion had a statistically significant lower risk of death compared to pts with Child-Pugh-B (HR 0.19, 95% CI 0.06-0.55), ECOG 1 (HR 0.15, 95% CI 0.05-0.44), or vascular invasion (HR 0.37, 95% CI 0.15-0.93), respectively. For pts with BCLC-B there was a strong trend, although not statistically significant, of a lower risk of death when compared to pts with BCLC-C (HR 0.43, 95% CI 0.13-1.49). Etiology, prior TACE therapy, extrahepatic spread and interval between first- and second-line treatment had no impact on overall survival in this study. Similar findings were observed in the monotherapy group. Comparing the impact of these baseline characteristics in the combination and monotherapy group, no statistically significant different influence on OS between both treatment groups was observed. Conclusions: Resminostat in combination with sorafenib provides a substantial OS benefit (median OS of 8.1 months) for advanced HCC patients who had developed progressive tumor disease under first-line sorafenib therapy. Subgroup analysis of patient baseline characteristics revealed a significant influence of Child-Pugh index, ECOG classification, and vascular invasion on overall survival, whereas e.g. the interval between first- and second-line treatment had no impact on overall survival. Clinical trial information: NCT00943449.

How to Treat Chronic Lymphocytic Leukemia? Data From a Clinical Registry by Office-Based Hematologists in Germany (TLN Registry)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4606-4606
Author(s):  
Wolfgang Knauf ◽  
Wolfgang Abenhardt ◽  
Ali Aldaoud ◽  
Christian Lerchenmüller ◽  
Michaela Koska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Median Treatment ◽  
First Line Therapy ◽  
Free Interval ◽  
Line Therapy ◽  
Appropriate Treatment

Abstract Abstract 4606 Introduction: The treatment of patients with Chronic Lymphocytic Leukemia (CLL) has changed significantly over the last years. To select an appropriate treatment, multiple factors have to be considered. In particular, the stage of disease, patient’s age, comorbidities and personal preferences, respectively, influence decision making. The clinical tumor registry on lymphoid neoplasms (TLN Registry) conducted by the iOMEDICO AG in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML) was established to collect data on the daily practice treatment of 3000 non-selected patients with lymphoid neoplasms. Here, we present data regarding treatment and sequences of regimes in patients (pts) with CLL treated by office-based hematologists in Germany. Methods: While targeting 500 CLL pts, the registry prospectively collects data on pts characteristics, tumor history, treatment, response rates and sequences of regimes. In addition data on adverse drug reactions and concomitant diseases are documented. CLL pts older than 18 years receiving a first- or second line therapy which has started no longer than 4 weeks before patient enrolment can be recruited into the registry if informed written consent is present. All pts are followed for 5 years. Currently, 116 sites across Germany are participating. Results: The TLN Registry started in May 2009. Currently, 492 pts with CLL have been recruited. The mean age at the start of first line therapy is 69 years. The majority of pts (63%) are male. About 20% of the pts in first line therapy are treated within clinical trials. Median time between diagnosis and start of first line therapy is 22 months (range 0 – 285 months). Most of the pts receive Bendamustine/Rituximab (BR, 34%) or Fludarabin/Cyclophosphamide/Rituximab (FCR, 21%) in first line therapy. Overall, 97% of the first line therapies were successful (91% CR/PR, 6% SD). In particular, 99% of BR (98% CR/PR, 1% SD) and 100% of FCR (98% CR/PR, 2% SD) therapies were successful. Over time, a change in treatment selection becomes apparent. 50% of the pts started first line therapy before October 2009. They mainly received BR (19%), Bendamustine (16%), FCR (16%) or Chlorambucil (15%), respectively. Pts starting first line therapy after October 2009 mainly received BR (43%) or FCR (24%). Bendamustine-containing regimens are more often used as first line therapy in pts older than 75 years as compared to younger ones (62% vs. 42%). Fludarabine-containing regimens are more often used in pts younger than 75 years (37% vs. 6%). Similar to the first line therapy, BR is the most often used second line therapy (52%). About 41% of the pts have completed first line therapy and have not yet started second line therapy. The median treatment-free interval since the end of the first line therapy is 10 months. Data on second line therapy are available in 24% of the pts. The majority of these pts (73%) were recruited at the start of second line therapy. Most of them receive BR as second line therapy after first line therapy either with Chlorambucil (17%) or Bendamustine (13%). The median treatment-free interval between the end of first line therapy and the start of second line therapy is 16 months (range 1 – 49 months). Conclusion: The registry provides an overview on particularities and changes in routine treatment of pts with CLL treated by office-based hematologists in Germany. Implementation of new standards affecting treatment preferences are currently under evaluation. BR and FCR are widely accepted and very effective as first line therapies. Our data indicate that age is an important factor for selecting the appropriate treatment. Further analyses will investigate additional variables influencing the choice of treatment. With more data becoming available the sequences of regimes and their effectiveness can be analyzed. Disclosures: No relevant conflicts of interest to declare.

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.

Epidemiology and Risk Factors of Invasive Fungal Infections Among 795 Patients with Chronic Lymphocytic Leukemia from the Padua University

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2527-2527 ◽  
Author(s):  
Andrea Visentin ◽  
Carmela Gurrieri ◽  
Silvia Imbergamo ◽  
Federica Lessi ◽  
Speranza Antonia Di Maggio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Stem ◽  
Anova Test ◽  
Risk Of Death

Abstract Background Invasive fungal infections (IFI) are serious and life-threatening complications of hematological malignancies particularly in patients affected by acute myeloid leukemia and following hematopoietic stem cell transplantation. However, only few epidemiological data concerning fungal infections in chroniclymphoproliferativedisorders are available. In this work we aimed to identify the clinical and biological features of patients with chronic lymphocytic leukemia (CLL) affected by IFI. Methods We performed a single-center retrospective study based on the CLL patients referred to the Hematology Unit of University of Padua from 1983 to 2015. IFI were defined as infective events caused by yeasts ormouldsthat required inpatient management and/or intravenous antifungal therapies. We included only proven and probable IFI. Time to IFI (TIFI) and overall survival (OS) were calculated from the date of CLL diagnosis to IFI development or death (event), respectively, or last available follow-up (censored). Diagnostic work-up of fungal infection included blood cultures, serumgalactomannanantigen test for 3 consecutive days (cut-off 0.5), β-1,3-(D)-glucanand high resolution chest computed tomography andbronchoalveolarlavages when clinically indicated. We also collected the closest immunoglobulin (IG) levels data before the onset of each IFI or serious bacterial infective events. IGs measured during infections were not included in the analysis, because they could have been influenced by the infectious event. The last available serum IG levels were considered for patients who did not suffer from any IFI. Results 795 patients with CLL were recruited in this study. 60% were male and the median age at diagnosis and at IFI onset were 65 and 68 years, respectively. The median follow-up was 8.5 years and 316 patients required treatment during the follow-up. 11 out of 795 (1.4%) patients developed IFI during the follow-up. Among them, 7 patients (64%) had probable Aspergillosisand 4 had proven IFI (3 Aspergillusspp and 1 Candida kruseii) based on histological confirmation and/or microbiological isolation of the specific fungal agent. 9 patients wereBinet stage A, 2Binet B and noneBinet C at CLL diagnosis. The median lines of treatment were 5 ranging from 2 to 9. Six out of 11 (55%) patients showed high-risk cytogenetic by FISH analysis (11q or 17p deletion), 2 harbored complex karyotypes, 62% (5/8) hadunmutated IGVH gene. By Kaplan-Meyer analysis we showed that IFI occurred in 2.1% and 7.0% of the cohort after 10 and 20 years of follow-up, respectively (Figure 1A). However, considering the number of chemotherapy regimens, the estimated cumulative incidence of IFI was higher in patients who were treated with at least 4 lines of chemo-immunotherapy (10-year TIFI were 9.0% and 0.3%, p<0.0001, Figure 1B). IFI occurrence was associated with a very poor prognosis. In fact, the median overall survival of patients who developed IFI was 125 months as compared to 250 months of the remaining cohort (Log-rank test, p=0.0001, Figure 1C). Since IFI was itself the main cause of death of these subjects. In multivariable analysis, patients with IFI had almost 10 times higher-risk of death (HR 10, p=0.0012) that other patients. We demonstrated that, at the time of IFI events, patients had lower levels of IG as compared to a group of 72 patients who had serious bacterial infections or to 712 subjects who did not have any infections. The medianIgGlevels were 4.11, 6.38 and 8.38 g/L for patients with IFI, bacterial infections and without history of infections, respectively (ANOVA test, p<0.0001, Figure 1D). The median IgA levels were 0.35, 0.78 and 1.39 g/L for patients with IFI, bacterial and none infections, respectively (ANOVA test, p<0.0001, Figure 1E). The medianIgMlevels were 0.28, 0.59 and 0.65 g/L for patients with IFI, bacterial and none infections, respectively (ANOVA test, p=0.0038, Figure 1F). Conclusions Herein, we described the epidemiology of invasive fungal infections among a large cohort of CLL patients from a single institution over 32 years. We demonstrated that IFI significantly impacts on the survival of CLL patients and we provided evidence of the importance of previous chemo-immunotherapy and IG levels on the risk of developing IFI. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Survival and Treatment of Black Patients with Chronic Lymphocytic Leukemia in the Veterans Health Affairs

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4847-4847
Author(s):  
Martin W. Schoen ◽  
Suhong Luo ◽  
Kenneth R. Carson ◽  
Kristen M. Sanfilippo
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Access To Care ◽  
Median Survival ◽  
Care Delivery ◽  
Lymphocytic Leukemia ◽  
Veterans Health ◽  
Black Race ◽  
Black Patients ◽  
To Receive

Abstract Background: Chronic Lymphocytic Leukemia (CLL) is the most prevalent adult leukemia in western countries and disparities in outcomes based on race have been identified. In national registry data and institutional studies, black patients were found to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. However, racial disparities commonly correlate with access to care, comorbidities, and differences in treatment. In order to limit these potential confounders not available in other data, we studied patients in the Veterans Health Administration (VHA) network to understand differences in treatment and outcomes of black vs. non-black patients with CLL in a single care delivery system. Methods: We used the Veterans Administration Central Cancer Registry to identify patients diagnosed with CLL between September 1999 and October 2015 who were identified by race. Pharmacy records were used identify patients who received fludarabine, cyclophosphamide, rituximab, bendamustine, or chlorambucil as initial treatment of CLL. Comparisons between groups were performed with t-test or chi-square as appropriate. Comorbidity was assessed with Charlson (Romano) index and median survival by the Kaplan-Meier method. Cox proportional hazards regression modeling was used to assess associations between race and while adjusting for age, comorbidity, type of treatment, time to treatment and BMI. The study was approved the Saint Louis VA Medical Center institutional review board. Results: An initial cohort of 7155 patients with CLL was identified, of whom 2597 received chemotherapy within the VHA. Of those receiving chemotherapy, 14.8% were black (345/2597). The median year of treatment was 2006. Black patients were younger (64.0 years vs. 67.1, p<0.001) with similar mean comorbidity scores (2.3 vs. 2.2 p=0.24) compared to non-black patients. The mean time from CLL diagnosis to treatment was shorter for black patients (24.2 months vs. 28.3 p=0.02). Black patients were more likely to receive fludarabine based regimens (43.6% vs. 30.2%, p<0.001) and less likely to receive chlorambucil (25.5% vs. 32.5%, p=0.01). There were no differences based on race in treatment with bendamustine (10.4% vs. 11.4%, p=0.57), cyclophosphamide (8.6% vs. 11.0%, p=0.15) or rituximab alone (11.9% vs 14.9%, p=0.13). Second line treatment was administered to 197 black patients, which was more frequent than non-black (51.2% vs. 43.9%, p=0.01). Mean overall survival from diagnosis was 68.2 months in black patients compared to 72.5 months in non-black (p=0.07) and median overall survival was 76 vs. 83 months (p=0.051) respectively. Mean survival from start of chemotherapy (43.7 months vs. 43.6, p=0.95) in black and non-black patients and median survival was 47 vs. 50 months (p=0.34) respectively. In unadjusted analyses, black race was not associated with differences in survival after chemotherapy (hazard ratio (HR) 1.07, 95% CI:0.93-1.22, p=0.34) nor in overall survival (1.14, 95% CI:0.99-1.30, p=0.051). After adjusting for age, comorbidity index, BMI, duration of observation and treatment characteristics, black race was associated with poorer overall survival (adjusted HR 1.25, 95% CI:1.08-1.44, p=0.002) and survival after chemotherapy (adjusted HR 1.22, 95% CI:1.05-1.41, p=0.008). Conclusions: In this retrospective analysis of patients treated for CLL at the VHA, black patients had worse survival compared to non-black patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine. Future studies should be performed to understand potential differences in CLL disease biology in different racial groups as a potential cause of adverse outcomes in this patient population. Disclosures Carson: Washington University in St. Louis: Employment; Roche: Consultancy; Flatiron Health: Employment. Sanfilippo:BMS/Pfizer: Speakers Bureau.

Bendamustine and Rituximab for the Treatment of Chronic Lymphocytic Leukemia: The Moffitt Cancer Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4620-4620
Author(s):  
Heather Barnes Pound ◽  
Viet Q. Ho ◽  
Celeste M. Bello ◽  
Jennifer L. Cultrera ◽  
Martine Extermann ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Response Rates ◽  
Primary Objective ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line

Abstract Abstract 4620 Introduction: Although bendamustine is approved for the treatment of chronic lymphocytic leukemia (CLL), the combination of bendamustine and rituximab (BR) is currently under active investigation in the relapsed/refractory setting as well as for front-line use. Emerging data now suggests BR is acceptable for first-line use and indeed is listed in the NCCN Compendia as a first-line option. Herein, we report the results of a single-center retrospective review of BR use in first-, second- and third-line and beyond and its effects on response rate. Methods: We retrospectively reviewed 21 consecutive patients with CLL that received BR at the Moffitt Cancer Center (MCC) between July 2008 and November 2010. Bendamustine was dosed at 70 mg/m2 IV on Days 1 and 2 every 3–4 weeks; rituximab was dosed at 375 mg/m2 IV once with each cycle along with anti-microbial prophylaxis. Data collected included, but was not limited to age, gender, cytogenetic profile, number of previous therapies, Rai stage at time of treatment and response (based on 1996 NCI-WG definition). The primary objective was to assess response rates. The major secondary objective was to assess the effect of cytogenetics on response rates. All analyses were performed using descriptive statistics. Results: Twenty-one patients received treatment with BR; 7 patients received BR as first-line therapy, 7 received BR as second line therapy and the remaining 7 received BR as third-line therapy or beyond. The median age at time of treatment was 66; 12 of 21 patients were male (57%); All Rai Stages were represented, Stage 0 (n=1), Stage 1 (n=4), Stage 2 (n= 3), Stage 3 (n=5), Stage 4 (n=6). 38% of patients were positive for Del11q, 33% for Del13q, 9.5% for Del17p, and 9.5% for mutated IgVH. In previously untreated patients, 6/7 had a documented complete remission (CR) (71.4%) or partial (PR) (14.3%) response; one patient progressed (PD) on therapy. In second-line therapy, all patients had a documented CR (28.6%) or PR (71.4%). In patients treated with BR as 3rd or 4th line therapy, 3 patients had a CR, 2 patients had stable disease (SD), and 2 had PD. Of the 8 patients with Del11q, 37.5% achieved a CR, 4 had PR and 1 had PD. Of the 7 patients with Del13q, 4 achieved CR and 3 had a PR. Both patients with Del17p had PD. Of the 2 patients with mutated IgVH, one patient achieved a PR while the other had PD. Conclusion: Based on these results, the combination of bendamustine and rituximab in patients with CLL is efficacious and well tolerated in patients with both newly diagnosed and relapsed/refractory disease. Disclosures: Off Label Use: Bendamustine and rituximab for CLL. Ho:Genentech: Honoraria; Cephalon: Consultancy. Cultrera:Genentech: Speakers Bureau. Sotomayor:Genentech: Membership on an entity’s Board of Directors or advisory committees. Pinilla-Ibarz:Genentech: Speakers Bureau; Cephalon: Speakers Bureau.

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