Soluble Interleukin-2 Receptor and C-Reactive Protein Levels Are Associated with the Efficacy of Bendamustine As a Salvage Treatment for Indolent Lymphoma

Abstract Background: Bendamustine has demonstrated a favorable efficacy and toxicity profile in relapsed or refractory indolent lymphoma. Limited information is available regarding the prognostic factors (particularly laboratory parameters) of bendamustine treatment, although studies have shown a relationship between the hampered effect of bendamustine and an increase in lactate dehydrogenase (LDH) levels. Therefore, we retrospectively evaluated clinical and laboratory factors immediately prior to initiating bendamustine treatment and analyzed its correlation with the clinical outcome among patients with relapsed or refractory indolent lymphoma. Patients and methods: We analyzed 55 relapsed or refractory indolent lymphoma patients who had been treated with bendamustine alone (n = 19) or rituximab plus bendamustine (n = 36) at our hospital from 2000 to 2015. The median age at diagnosis was 65 years and the median follow-up period was 552.5 days. Histological analysis revealed follicular lymphoma (n = 21), mantle cell lymphoma (n = 10), MALT lymphoma (n = 7), lymphoplasmacytoid lymphoma (n = 5), and other low-grade B cell lymphomas (n = 4). We further analyzed the relationships between the clinical outcome [overall response rate (ORR), complete response (CR), progression-free survival (PFS), and overall survival (OS)] and clinical data, including sex, patient age (≥65 years), performance status (≥2), IPI (≥HI), FLIPI (≥HI), no. of previous therapies (≥2), prior purine analogue treatment, response to last treatment, and laboratory parameters [white blood cell count (≥5000/µl), lymphocyte count (≥1000/µl), platelet count (≥10000/µl), LDH (elevated or normal), sIL-2R (elevated or normal), and CRP (elevated or normal)], before starting bendamustine treatment. Results: The median number of cycles of bendamustine was 4 (range: 1-8). The ORR was 80.3% with a CR of 39.2%. Moreover, the CR rate was significantly worse in patients who had elevated sIL-2R and CRP, high or high-intermediate IPI scores, and a high WBC count (P = 0.002, P < 0.001, P = 0.072, and P < 0.046, respectively). Among follicular lymphoma patients, elevated CRP was only associated with a low CR rate (P = 0.028). In multivariate analysis, sIL-2R, CRP, and a high WBC count were all significantly associated with a worse CR rate (P = 0.044, P = 0.002, and P = 0.032, respectively). The 1- and 2- year OS rates were 80.3% and 76.1%, respectively. The OS was significantly higher in a group of the patients who obtained CR after bendamustine, were treated with rituximab plus bendamustine, and did not receive prior purine analogue treatment (P = 0.007, P = 0.008, and P < 0.001, respectively). An elevated CRP was associated with worse OS (P = 0.055). In multivariate analysis, only CR after bendamustine was significantly associated with improved OS (P = 0.023). The 1- and 2-year PFS rates were 69.2% and 60.5%, respectively. PFS was significantly better in patients who obtained CR after bendamustine treatment, had a normal CRP, had not received more than 2 previous therapies, and had a good performance status (P < 0.001, P = 0.007, P = 0.031, and P = 0.033, respectively). In multivariate analysis, any prognosis factors were significantly associated with PFS. Conclusion: This is the first study to demonstrate a correlation between laboratory parameters (i.e., CRP and sIL-2R) and the clinical outcome in patients with relapsed or refractory indolent lymphoma who were treated with bendamustine. In this study, CRP and sIL-2R levels as well as the WBC count were associated with the CR rate. In addition, the CRP levels were associated with OS and PFS, but LDH levels were not associated with any clinical outcomes. Previous studies have reported that the elevation of serum CRP and sIL-2R levels were associated with poor OS or PFS in patients who were treated with rituximab combined with CHOP in diffuse large B-cell lymphoma or follicular lymphoma. Our study indicates that serum CRP and sIL-2R levels are also important laboratory parameters for patients with indolent lymphoma who underwent bendamustine treatment. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Significance of cytogenetic findings for the clinical outcome in patients with T-cell lymphoma of angioimmunoblastic lymphadenopathy type.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.2.593 ◽

1996 ◽

Vol 14 (2) ◽

pp. 593-599 ◽

Cited By ~ 43

Author(s):

B Schlegelberger ◽

T Zwingers ◽

K Hohenadel ◽

D Henne-Bruns ◽

N Schmitz ◽

...

Keyword(s):

Multivariate Analysis ◽

T Cell ◽

Clinical Outcome ◽

Cell Lymphoma ◽

Prognostic Significance ◽

T Cell Lymphoma ◽

Chromosome 1 ◽

Survival Duration ◽

Angioimmunoblastic Lymphadenopathy ◽

Structural Aberrations

PURPOSE The aim of this study was to evaluate the significance of cytogenetic findings for the clinical outcome of patients with Angioimmunoblastic Lymphadenopathy (AILD)-Type T-cell lymphoma. MATERIALS AND METHODS In a retrospective analysis, the cytogenetic findings of 50 patients with AILD-type T-cell lymphoma were correlated with the frequency of spontaneous and therapy-induced remissions and with survival using the statistical methods of Kaplan and Meier and the model of Cox for multivariate analysis. Treatment was not uniform because the patients were treated in different hospitals during a period of 8 years and because a standard therapy has not yet been established. RESULTS The following cytogenetic findings were associated with a significantly lower incidence of therapy-induced remissions and a significantly shorter survival duration: presence of aberrant metaphases in unstimulated cultures (P = .04 for both parameters); clones with an additional X chromosome (P = .0001 and P = .03, respectively); structural aberrations of the short arm of chromosome 1, preferentially involving 1p31-32 (P < .001 and P = .04, respectively); and complex aberrant clones with more than four aberrations (P = .0003 and P = .005, respectively). Multivariate analysis showed that these cytogenetic findings had a significant influence on survival, but therapy modalities did not. Only the presence of complex aberrant clones was an independent prognostic factor. Trisomy 3 had no effect on survival, but patients without trisomy 5 (P = .08) tended to live longer. CONCLUSION This is the first study that seems to indicate that cytogenetic findings have prognostic significance in AILD-type T-cell lymphoma. These results must be proven in prospective studies of homogeneously treated patients.

Download Full-text

The Mantle Cell Lymphoma International Prognostic Index (MIPI) at Diagnosis Is Associated with Survival of Mantle Cell Lymphoma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v112.11.1143.1143 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1143-1143 ◽

Cited By ~ 3

Author(s):

Lihua Pan ◽

Katherine A Guthrie ◽

Brian G. Till ◽

Oliver W. Press ◽

John M. Pagel ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Performance Status ◽

International Prognostic Index ◽

Prognostic Index ◽

High Dose ◽

Hematopoietic Stem ◽

Risk Of Death ◽

Mantle Cell ◽

Wbc Count

Abstract Mantle Cell Lymphoma (MCL) exhibits short remission durations and a poor prognosis. To improve on these outcomes, many have advocated the use of high-dose therapy (HDT) and ASCT. The MIPI predicts overall survival (OS) from diagnosis, yet it remains unknown if the MIPI assessed at diagnosis (MIPI-Dx) or prior to transplant (MIPI-Tx) can be used to predict OS from ASCT. To address this question we retrospectively evaluated the association of the MIPI-Dx and MIPI-Tx, and other characteristics with OS following HDT and ASCT in 87 consecutive MCL patients transplanted at our center. Baseline characteristics included: median age at diagnosis=56 years (range, 35–70), median age at transplant=57 years (range, 35 – 70), stage III-IV=97%, median LDH/upper limit of normal (ULN) at diagnosis=0.91 (range, 0.46–5.65), median LDH/ULN at transplant= 0.88 (range, 0.39–3.00), median white blood cell (WBC) count at diagnosis=7.50 x 109 / liter (range, 1.40 – 54.70), mean WBC count at transplant=4.66 x 109 /liter (range, 0.07 – 17.60), median number of prior chemotherapy regimens=2 (range, 1–5). The estimated 5-year OS and PFS for the entire cohort were 56% (95% CI, 39–73%) and 45% (95% CI, 30 – 60%), respectively with a median follow up among surviving patients of 2.0 years (range 0.1 – 10.1 years). The MIPI-Dx was a better predictor of OS (p<0.001) than MIPI-Tx (p=0.09), when evaluated as a continuous variable. Similarly, when stratified as a categorical variable, the MIPI-Dx (p=0.09) was superior to the MIPI-Tx (p=0.34) in estimating survival. When compared to patients with a MIPI-Dx of 0–2, those with a score of 3, 4, and 5–8 at diagnosis had a 3.3 (95% CI 0.3–32, p=0.3), 6.1 (95% CI 0.7–54.8, p=0.11), and 11.1 (95% CI 1.3–92.9, p=0.03) fold higher risk of mortality after transplant, respectively (Figure). We next determined if any pre-transplant factors could improve our ability to predict outcome after ASCT. Multivariable modeling identified pretransplant factors of ECOG PS >0 (hazard ratio (HR) of 3.0, p=0.03), number of prior regimens >2 (HR 5.2, p=0.01), lack of complete remission (CR) (HR 3.4, p=0.04), and elevated LDH (HR 4.4, p=0.01) as associated with higher risk of death after transplant. These results indicate that the MIPI-Dx is a robust prognostic tool that can even be used to predict outcomes after a later transplant, suggesting that it may continue to reflect the biology of an individual patient’s disease over time. Further assessment of survival predictions after ASCT can be made independently by examining pre-transplant factors including performance status, number of prior regimens, attainment of CR, and LDH. Though these data require prospective validation, our results can be used to counsel patients about outcomes and account for potential differences in results from clinical trials of HDT and ASCT for MCL. Figure Figure

Download Full-text

Delaying therapy in Pts age ≥ 65 with untreated AML

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.6560 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 6560-6560

Author(s):

E. Estey ◽

F. Giles ◽

G. Garcia-Manero ◽

H. Kantarjian

Keyword(s):

Multivariate Analysis ◽

Supportive Care ◽

Death Rate ◽

Performance Status ◽

Normal Karyotype ◽

Potential Influence ◽

Death Rates ◽

And Performance ◽

Wbc Count ◽

Referring Physicians

6560 186 pts age ≥ 65 with untreated normal karyotype AML given ara-C-containing Rx at MDA from 1996–2005 had course 1(C1) CR and death rates of 57% and 13%, while in 133 pts with abnormalities of chromosomes 5 and/or 7 (−5/−7) the C1 CR rate was essentially identical to the C1 death rate (30% and 27%). Knowledge of cytogenetics, while thus valuable in planning Rx, may not be available for ≥ 1 week after presentation, raising questions as to the advisability of waiting this long to begin Rx. We previously reported a multivariate analysis in 197 pts, median age 64 and with presenting WBC < 50,000, given idarubicin + ara-C for untreated AML at M.D. Anderson between 2001- and 2004, finding that the independent predictors of CR were age and cytogenetics but not the number of days from MDA presentation to MDA Rx (Estey et al. 2004 ASH meeting,abstract #879). Because Rx was delayed for > 1 week in only small numbers of older pts we now extend these observations to 684 pts age ≥ 65 with untreated AML and presenting WBC < 50,000 given induction Rx (± ara-C) at MDA since 1996. Time from MDA presentation to Rx was < 1 week in 423, 1–2 weeks in 126, 2 weeks-1 month in 80, and > 1 month in 55. This time was not affected by age, bilirubin, creatinine, or by whether induction Rx contained ara-C. However, 7% of pts Rxed within 2 weeks of diagnosis had performance status 3–4 vs. only 1% of pts Rxed after a delay of > 14 days (p = 0.008), leading us to limit analysis to pts with performance status 0–2. Results were as follows: Although CR rates were higher, results were qualitatively similar considering only pts given ara-C-containing Rx. Recognizing the potential influence of unrecorded covariates, the data suggest that delay of Rx in pts age ≥ 64 with untreated AML, WBC count < 50,000, and performance status < 3 does not affect outcome of induction therapy, a possibility given more credence by the several days that elapse between diagnosis of AML by referring physicians and MDA presentation. Delaying Rx allows knowledge of cytogenetic status, thus permitting investigational Rx, or supportive care only, to be directed to pts with -5/-7. [Table: see text] No significant financial relationships to disclose.

Download Full-text

Majority of Transformed Lymphomas Have High SUVs on PET Scanning Similar to Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽

10.1182/blood.v110.11.2614.2614 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2614-2614

Author(s):

Ariela Noy ◽

Matthew Weissler ◽

Heiko Schoder ◽

Mithat Gonen ◽

Henry Yeung

Keyword(s):

Follicular Lymphoma ◽

Fdg Pet ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Pet Scan ◽

Aggressive Lymphoma ◽

Indolent Lymphoma ◽

Biopsy Site ◽

Pet Scans

Abstract Background: In our previous work, we correlated non-Hodgkins (NHL) histology with intensity of FDG uptake (SUVmax) on positron emission tomography in untreated patients: an SUVmax greater than 10 predicted an aggressive lymphoma with >80% certainty and an SUVmax greater than 13 predicted an aggressive lymphoma with >90% certainty. We sought to evaluate SUVmax in a series of patients with transformed lymphoma. Methods: All PET scans for lymphoma indications at our institution 1999-5/2007 were evaluated. Patients were included if they had biopsy proven transformation. FDG-PET scans were included if they were no more than sixty days prior to or 90 days after biopsy proven transformation. Patients had no therapy for sixty days prior to PET scan unless there was documented progression of disease after the last treatment. Results: Among the indolent diagnoses (n= 44), the following specific histologies were identified: 9 follicular lymphoma grade 1 (FL I), 9 FL grade 2 (FL 2), 7 small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL), 11 marginal zone lymphoma (MZL) including one of mucosa associated lymphoid tumor (MALT) type, one mycoses fungoides, and one indolent lymphoma otherwise not specified. 5 FL 3 (FL 3), including one specified as grade 3a (FL 3a) were considered indolent if they preceded a diagnosis of DLBCL. Among the aggressive diagnoses (n= 28), the following specific histologies were identified: 37 DLBCL, one follicular lymphoma grade IIIa included as it was preceded by FLI, one large peripheral T-cell lymphoma, and 5 Large cell lymphoma(LCL), not otherwise characterized on account of biopsy size. Standard uptake values (SUV) were measured at the biopsy site when possible (n=38). In 6 patients the biopsy site was completely excised before the PET scan. The SUV of biopsy site ranged from 3-38, with a median of 10 and mean of 15. Among evaluable patients, 17/36 (47%) biopsies had an SUV above 10; and 12/36 (33%), above 13. The SUVmax for a transformed aggressive lymphoma ranged from 3.2–40, with a median of 12 and mean of 15. 27/44 (61%) patients had an SUVmax above 10; and 21/44 (48%), above 13. Conclusions: Similar to patients with de-novo aggressive lymphoma, the majority of patients with transformed lymphomas have high SUVmax for a given pre-treatment staging study. Therefore, transformation to aggressive lymphoma should be suspected in patients with indolent lymphoma found to have high SUVs on FDG PET, and biopsies should be directed to the site of greatest PET avidity whenever feasible.

Download Full-text

Diffuse Large B-Cell Lymphoma (DLBCL) Patients with Composite Histology Have Improved Early Outcome Compared to De Novo DLBCL When Treated with R-CHOP

Blood ◽

10.1182/blood.v112.11.2819.2819 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2819-2819

Author(s):

Matthew J. Maurer ◽

Thomas E. Witzig ◽

William R. Macon ◽

Sergei I. Syrbu ◽

James R. Cerhan ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

B Cell ◽

De Novo ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Indolent Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background: A significant percentage of DLBCL patients present with a composite histology, often seen as a node containing both follicular lymphoma and DLBCL or DLBCL in the node and discordant indolent lymphoma in the bone marrow. Literature from the pre-rituximab era suggests DLBCL patients with transformed lymphoma or composite histology have worse outcome than de novo DLBCL. Here we report on early events in a cohort of R-CHOP treated patients. Goal: To determine whether patients with composite lymphoma have an inferior event free survival (EFS) and overall survival (OS) compared to de novo diffuse large B-cell lymphoma when treated with R-CHOP. Methods: Newly diagnosed patients treated with an R-CHOP containing regimen were prospectively enrolled in our Lymphoma SPORE registry from 9/2002 through 6/2007. Pathology was centrally reviewed. All patients were followed for retreatment, disease progression, and death. Results: 401 DLBCL patients were enrolled; 14% (57/401) had a composite histology. 33 patients had DLBCL and another histology, predominantly follicular lymphoma (n=29), in the same node. 20 patients had a non-DLBCL histology in a distinct location from the DLBCL; this was primarily indolent lymphoma in the bone marrow (n=15). 4 patients had both. 19% (75/401) of patients died during follow-up and 30% (121/401) had an event (death due to any cause, progression, or retreatment). Median follow-up for living patients was 34 months (range, 5–73). Composite DLBCL patients had higher event-free (3 year EFS = 79%) and overall (3 year OS = 93%) survival then de novo DLBCL (3 year OS = 66%, 3 year EFS 79%), p=0.05 and p=0.005 respectively. These differences remained statistically significant after adjusting for the International Prognostic Index (IPI): EFS HR = 0.53, 95% CI: 0.29–0.97, p=0.02; OS HR=0.28, 95% CI: 0.10–0.76, p=0.002. OS and EFS for composite DLBCL more closely resembled R-CHOP treated grade III follicular lymphoma (A,B) from the same cohort (3 year EFS = 81%, 3 year OS = 93%). Improved outcome for composite DLBCL was consistent whether the additional histology was in the same node or distinct from the DLBCL. Conclusions: R-CHOP treated DLBCL patients with indolent discordant bone marrow involvement or other composite histology have improved early OS and EFS compared to de novo DLBCL. Further follow-up is needed to assess the long-term prognosis of composite DLBCL in the rituximab era. Histology N Age > 60 Stage III/IV LDH > ULN PS > 1 >2 EN Sites 3 YR EFS 3 YR OS * Denotes statistically significant difference at p=0.05 de novo DLBCL 344 58% 56% 56% 17% 22% 66% 78% Composite DLBCL 57 65% 77%* 34%* 18% 32% 79%* 93%* Figure Figure

Download Full-text

Prognostic Factors of Elderly Diffuse Large B-Cell Lymphoma Treated with R-CHOP: Performance Status and Age Over Eighty, but Neither Lactate Dehydrogenase Level, Stage, Nor Relative Dose Intensity Delivered, Associated with Clinical Outcome

Blood ◽

10.1182/blood.v118.21.1610.1610 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1610-1610

Author(s):

Kazunari Aoki ◽

June Takeda ◽

Yuki Hunayama ◽

Nobuhiko Yamauchi ◽

Aiko Kato ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Cox Regression ◽

Cell Lymphoma ◽

Performance Status ◽

Dose Intensity ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Grade 3 ◽

Large B Cell

Abstract Abstract 1610 Introduction: As for the prognostic factors of elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP, limited reports have been available. Although the maintenance of relative dose intensity (RDI) has been considered to improve the outcome, recent reports show that dose-reduced R-CHOP also has successful results on elderly DLBCL (Lancet Oncology. 2011; 12: 460). As rigid adherence to R-CHOP protocol is difficult in the treatment of elderly DLBCL, we investigated the relationship between RDI delivered and clinical outcomes in elderly patients with DLBCL. Method: We retrospectively analyzed a total of 109 consecutive DLBCL patients over 70 years who were diagnosed and received R-CHOP in our institution between January 2004 and January 2011. Among them, 56 % were male, and 38 % were over 80 years. 49 % of patients had an Ann Arbor stage III or IV, and ECOG performance status (PS) were >= 2 in 37 %. Lactate dehydrogenase (LDH) levels were higher than normal in 60 %. Age-adjusted IPI was 2–3 in 45 %. Charlson comorbidity index (CCI) was >= 2 in 23 %. Most patients with localized disease received 3 cycles of R-CHOP (delivered with 21-day interval) followed by radiation, and patients with advanced disease received 6 or 8 cycles of R-CHOP. In the first cycles of R-CHOP therapy, patients aged 70–79 years received 70 % dose of cyclophosphamide, adriamycin and vincristine. Patients over 80 years received 50 % dose of them. Predonisolone was also reduced to 40–60 mg on day 1–5 according to patients' condition. Thereafter, the doses were individually adjusted according to attending physicians' judgment. 78 % of the patients experienced grade 3–4 neutropenia and 21 % grade 3 febrile neutropenia. Two patients died of neutropenia and infection. 65 % of patients received prophylactic G-SCF. By using clinical records of these patients, we estimated the prognostic factors using the Cox regression model. Estimates of prognostic factors were expressed as hazard ratios (HR) and 95 % confidence interval (CI) based on the Cox regression. We did two-sided statistical tests, with a 5 % level of significance. This study was approved by our institutional review board. Result: After median follow up for living patients of 25.5 months, 41 deaths has occurred (including 22 due to lymphoma), and 2-year overall survival (OS) and progression-free survival (PFS) were 71.3 % [95 % CI 60.8 %–79.5 %] and 53.5 % [95 % CI 42.7 –63.1 %], respectively. Univariate and multivariate analysis revealed that LDH and staging at diagnosis were not associated with prognosis. PS >= 2 (HR 2.94, 95 % CI 1.48–5.84, P=0.002) and age >= 80 years (HR 2.05, 95 % CI 1.04–4.04, P=0.039) retained independent adverse prognostic values for 2-year OS in multivariate analysis. Dividing entire population into 3 groups using these 2 prognostic factors, 2-year OS were 82.7 % (70 <= age < 80 and PS < 2), 67.3 % (70 <= age < 80 and PS>=2 or age>=80 and PS < 2), and 52.5 % (age >= 80 and PS >= 2), respectively (log-rank, P=0.0004). Among the all 109 patients, 91 patients received >=3 cycles of R-CHOP and RDI could be calculated. RDI was strongly associated with age (R-squared 0.42, RDI (%) = 201-1.90x age (years)). When high age-adjusted RDI group (H-aaRDI) was defined as the group of patients who satisfied □eRDI > 201 - 1.90x age', and low age-adjusted RDI group (L-aaRDI) as □eRDI< 201 - 1.90x age', 2-year OS were equivalent between H-aaRDI and L-aaRDI groups (79.8 % vs 78.7 %, log-rank, P=0.36). When multivariate analysis was performed against those 91 patients, 2-year OS was also independently associated with PS >=2 (HR 3.12, 95 % CI 1.35–7.20, P=0.008) and age >=80 (HR 2.41, 95 % CI 1.04–5.59, P=0.041). Lower age-adjusted RDI did not have prognostic value (HR 1.28, 95 % CI 0.55 – 2.94, P=0.57). Conclusion: Our retrospective analysis confirmed the efficacy of reduced-dose R-CHOP against elderly DLBCL, as was reported previously. Their prognosis was not associated with LDH level, staging, nor RDI delivered, but with ECOG PS and age over 80. Our findings indicated that strict adherence to keep RDI may not be necessary in the treatment of elderly DLBCL. The simple method to define optimal dose of R-CHOP for elderly should be explored. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Expression of the Follicular Lymphoma Variant Translocation 1 Gene in Diffuse Large B-Cell Lymphoma Correlates With Subtype and Clinical Outcome

American Journal of Clinical Pathology ◽

10.1309/ajcp12hirwsrqlan ◽

2008 ◽

Vol 130 (6) ◽

pp. 957-962 ◽

Cited By ~ 2

Author(s):

David R. Czuchlewski ◽

Balazs Csernus ◽

Darya Bubman ◽

Elizabeth Hyjek ◽

Peter Martin ◽

...

Keyword(s):

Clinical Outcome ◽

Follicular Lymphoma ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Variant Translocation ◽

Large B Cell

Download Full-text

Majority of Transformed Lymphomas Have High SUVs on PET Scanning Similar To Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽

10.1182/blood.v108.11.2402.2402 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2402-2402

Author(s):

Matthew Weissler ◽

Ariela Noy ◽

Heiko Schöder ◽

Mithat Gönen ◽

Henry Yeung

Keyword(s):

Follicular Lymphoma ◽

Fdg Pet ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Pet Scan ◽

Aggressive Lymphoma ◽

Indolent Lymphoma ◽

Biopsy Site ◽

Pet Scans

Abstract Background: In our previous work, we correlated non-Hodgkin’s (NHL) histology with intensity of FDG uptake (SUVmax) on positron emission tomography in untreated patients: an SUVmax greater than 10 predicted an aggressive lymphoma with >80% certainty and an SUVmax greater than 13 predicted an aggressive lymphoma with >90% certainty. We sought to evaluate SUVmax in a series of patients with transformed lymphoma. Methods: All PET scans for lymphoma indications at our institution 1999–2005 were evaluated. Patients were included if they had biopsy proven transformation. FDG-PET scans were included if they were no more than sixty days prior to or 90 days after biopsy proven transformation. Patients had no therapy for sixty days prior to PET scan unless there was documented progression of disease after the last treatment. Results: Among the indolent diagnoses (n= 28), the following specific histologies were identified: 7 follicular lymphoma grade I (FL I), 5 follicular lymphoma grade II (FL II), 5 small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), 6 marginal zone lymphoma (MZL) including one of mucosa associated lymphoid tumor (MALT) type, one mycoses fungoides, and one indolent lymphoma otherwise not specified. Three follicular lymphomas grade III (FL III), including one specified as grade IIIa (FL IIIa) were considered indolent if they preceded a diagnosis of DLBCL. Among the aggressive diagnoses (n= 28), the following specific histologies were identified: 22 DLBCL, one follicular lymphoma grade IIIa included as it was preceded by FLI, one large peripheral T-cell lymphoma, and 4 “Large cell lymphoma” (LCL), not otherwise characterized on account of biopsy size. Standard uptake values (SUV) were measured at the biopsy site when possible (n=25). In 3 patients the biopsy site was completely excised before the PET scan. The SUV of biopsy site ranged from 2.9–26.7, with a median of 9 and mean of 11. Excluding the three patients who had an excisional biopsy, 10/25 (40%) biopsies had an SUV above 10; and 8/25 (32%), above 13. The SUVmax for a transformed aggressive lymphoma ranged from 3.2–30.2, with a median of 10.8 and mean of 14. 16/28 (57%) patients had an SUVmax above 10; and 12/28 (43%), above 13. Conclusions: Similar to patients with de-novo aggressive lymphoma, the majority of patients with transformed lymphomas have high SUVmax for a given pre-treatment staging study. Therefore, transformation to aggressive lymphoma should be suspected in patients with indolent lymphoma found to have high SUVs on FDG PET, and biopsies should be directed to the site of greatest PET avidity whenever feasible.

Download Full-text

High Expression of the Endoplasmic Reticulum Protein MZB1 predicts Inferior Prognosis in Chronic Lymphocytic Leukemia, Follicular Lymphoma and Diffuse Large B-Cell Lymphoma and Is Associated with a Unique Gene Expression Profile,

Blood ◽

10.1182/blood.v118.21.3657.3657 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3657-3657

Author(s):

Tobias Herold ◽

Medhanie A Mulaw ◽

Vindi Jurinovic ◽

Till M Seiler ◽

Klaus H. Metzeler ◽

...

Keyword(s):

Gene Expression ◽

Multivariate Analysis ◽

Follicular Lymphoma ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Data Sets ◽

Expression Levels ◽

Large B Cell Lymphoma

Abstract Abstract 3657 Introduction: The marginal zone B and B1 cell-specific protein (MZB1) was recently described as a key regulator of the secretion of IgM molecules, the control of calcium homeostasis and integrin-mediated adhesion in B-lymphocytes. We recently identified MZB1 gene expression as a novel prognostic factor being part of a highly significant 8 gene expression signature in chronic lymphocytic leukemia (CLL). Since several neoplasm's derive from mature B-lymphocytes and differ in clinical behavior and prognosis, but share unique functions like immunoglobulin production and secretion we asked whether these different diseases share common molecular mechanisms and prognostic factors. Here, we show that MZB1 expression is a novel, strong prognostic factor in a variety of B-cell neoplasm's. Methods: We analyzed 106 previously untreated and 33 relapsed CLL patients by quantitative PCR and correlated the MZB1 gene expression with overall survival (OS), time to treatment (TTT) and known risk factors of CLL. To expand the study on other hematological malignancies we additionally analyzed the public available gene expression data sets of follicular lymphoma (FL; GSE16131; n=184), diffuse large B-cell lymphoma (DLBCL; GSE10846; n=414), multiple myeloma (MM; GSE2658, n=559), and acute myeloid leukemia (AML; GSE12417; n=306). To adjust for clinical variables, multivariate Cox model were fitted to the respective data sets. To identify genes strongly correlated with MZB1 expression levels, we compared the CLL, DLBCL, FL and AML datasets and performed a multistep correlation analysis. Results: High MZB1 expression was a significant parameter of inferior prognosis in previously untreated (OS: HR: 1.63 (CI: 1.14–2.33), p=0.007; TTT: HR: 1.43 (CI: 1.13–1.81), p=0.003) and relapsed CLL patients (OS: not significant; TTT: HR: 1.48 (CI: 1.12–1.95), p=0.005) and was associated with known clinical and molecular parameters including unmutated IGVH status (p<0.001) and advanced Binet stage (Binet A vs. C p=0.001). Thus, due to the high correlation with IGVH status, MZB1 expression remained not an independent factor in multivariate models including both factors. In addition, MZB1 expression was also a predictor of OS in FL (221286_s_at HR: 1.16 (CI: 0.98–1.37) p=0.086; 223565_at: HR: 1.3 (CI: 1.1–1.61) p=0.015) and DLBCL (221286_s_at: HR: 1.17 (CI: 1.06–1.3) p=0.003; 223565_at: HR: 1.21 (CI: 1.08–1.35) p=0.001) but not in other hematologic malignancies like MM or AML. Again, high MZB1 expression levels correlated with prognostic markers in both, FL and DLBCL. However, a multivariate analysis in DLBCL including the International Prognostic Index (IPI), the gene expression subtype of DLBCL and MZB1 expression (continuous) confirmed MZB1 as an independent predictor of OS. Similar results were obtained from a multivariate analysis in follicular lymphoma including MZB1 expression (continuous) and IPI. We also identified genes that closely correlated with MZB1 expression in CLL, FL, DLBCL and AML based on the multistep correlation analysis. We compared the four datasets using these genes and observed that FL, DLBCL, and CLL show stronger similarity to each other than to the AML group. Interestingly, the ratio of probesets positively correlated to MZB1 expression levels to negatively correlated probesets was the highest in the AML group (CLL=3.69; FL=3.4; DLBCL=0.60; AML=78.7). The similarity of the lymphoma subsets was further strengthened by the analysis of the deregulated pathways based on these genes. Among the top seven pathways deregulated only in CLL, FL, and DLBCL were protein processing in endoplasmic reticulum, endocytosis, MAPK signaling pathway and Fc gamma R-mediated phagocytosis. Discussion: In conclusion we discovered a novel prognostic marker that predicted OS in all analyzed malignancies of mature B-cell origin and showed additional prognostic value in multivariate analysis in both, FL and DLBCL. The differential analysis of genes co-expressed with MZB1 further strengthened the prognostic relevance of MZB1 across different mature B-cell diseases. Due to its biological function in neoplasm's of mature B-cell origin and the potential involvement in known oncogenic pathways MZB1 may represent a target for future therapeutic interventions. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Association between early PSA increase and clinical outcome in patients treated with enzalutamide for metastatic castration resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.231 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 231-231

Author(s):

Vincenza Conteduca ◽

Simon J. Crabb ◽

Emanuela Scarpi ◽

Catherine Hanna ◽

Francesca Maines ◽

...

Keyword(s):

Prostate Cancer ◽

Multivariate Analysis ◽

Clinical Outcome ◽

Performance Status ◽

Specific Antigen ◽

Response To Treatment ◽

Rank Test ◽

Castration Resistant Prostate Cancer ◽

Primary Resistance ◽

Castration Resistant

231 Background: Prostate specific antigen (PSA) decline by 50% from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration resistant prostate cancer (mCRPC). However, in clinical practice, PSA changes are monitored monthly in several centers. We evaluated the association between PSA changes at 4 weeks and clinical outcome. Methods: We retrospectively evaluated mCRPC patients treated with enzalutamide after docetaxel. Early PSA increase was defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥ 30% (PSA30w4) and ≥ 50% (PSA50w4) from baseline.Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Interval (95% CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed including the following variables: PSA+20w4, PSA30w4, PSA50w4 and PSA50w12, baseline PSA, performance status, LDH values, sites of metastases, age. Results: We assessed 193 patients with median age of 73.1 years (range, 42.8 to 90.7). The median follow-up was 11.7 months. PSA+20w4 was associated with shorter PFS (median PFS 2.0 vs. 6.1 months; HR 4.03; 95% CI 2.62-6.19; p < 0.0001) and shorter OS (median OS 5.9 vs. 15.6 months; HR 3.48; 95% CI 2.12-5.69; p < 0.0001). At multivariate analysis, PSA+20w4 remained predictive of both PFS and OS [HR 4.03 (95% CI 0.2.62-6.19; p < 0.0001) and HR 3.48 (95% CI 2.12-5.69; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95% CI 0.21-0.67; p = 0.0009) and HR 0.34 (95% CI 0.19-0.60; p = 0.0003), respectively]. No cases of PSA flare were reported. Conclusions: An early PSA increase, defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4), could be useful to identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA+20W4 as an early and cheap biomarker of primary resistance to enzalutamide.

Download Full-text