Serum Free Light Chain Ratio (FLCr) Is a Powerful Prognostic Factor For Survival In Newly Diagnosed Multiple Myeloma (MM) In The Era Of New Agents Namely On ISS Stage II Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3150-3150 ◽  
Author(s):  
Graça V Esteves ◽  
Manuel L Neves ◽  
Helena F Martins ◽  
Maria Joao Costa ◽  
Sara Valle ◽  
...  
Keyword(s):  
Risk Factors ◽  
Prognostic Factor ◽  
Light Chain ◽  
Mayo Clinic ◽  
Prognostic Value ◽  
Myeloproliferative Neoplasms ◽  
Stage Ii ◽  
Newly Diagnosed ◽  
Baseline Serum

Abstract Introduction MM is characterized by the presence of a monoclonal immunoglobulin in the serum and/or urine, produced by malignant plasma cells. MM has a highly uncertain evolution and prognostic depending on age, stage and cytogenetic abnormalities. FLC is a readily available laboratory test and has independent prognostic significance in all the plasma cell disease entities helping to clarify International Staging System (ISS). Its value in the era of new therapeutic drugs is to be proved. Purpose To determine the prognostic value of baseline serum FLCr in patients with newly diagnosed MM, consecutively treated with thalidomide or bortezomib based regimens. Methods This is a retrospective study, from July 2004 to December 2012. We studied the relationship of baseline FLCr with outcome and its contribution to clarify the prognostic value of ISS. Serum FLC levels were measured in frozen sera at initial diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Beckman Coulter nephelometric analyzer. FLCr was calculated as k/λ (reference range: 0,26-1,65). Abnormal FLCr was defined of < 0,03 or > 32,00 and standard FLCr of 0,03-32. Patients have been staged by ISS and Mayo Clinic stratification. All patients received at least two cycles of a thalidomide based regimen, 91 patients (38,9%): thalidomide, doxorubicin, dexamethasone (TAD), 37 patients (15,8%) and melphalan/cyclophosphamide, thalidomide, prednisone (M/CTP), 54 patients (23,0%) or bortezomib based regimens, 143 patients (61,1%): bortezomib, doxorubicin and dexamethasone (PAD), 53 patients (22,6%), bortezomib, cyclophosphamide and dexamethasone (Cy-Bor-D), 7 patients (2,9%) and melphalan/cyclophosphamide, bortezomib, prednisone (M/CVP), 83 patients (35,6%). Median follow-up from diagnosis was 25 months. Follow-up was through the review of each patient’s complete medical records at our center. Statistical analysis was performed with SPSS 20 ®. Results We reviewed 234 patients consecutively treated. Male gender was 46,6% and median age was 67 years (22-84y). The Ig type was IgG in 59,4%, IgA in 22,2%, IgD in 1,7%, light chains MM in 15,4% and non-secretory MM in 1,3%. The median Hb level was 10,7g/dL (4,9-16,7g/dL) and serum albumin was 27,4 g/L (9,0-50-0g/L). Twenty five percent of patients had a creatinine clearance <30ml/mn, 30,1% elevated LDH and median β2-microglobulin was 4,08 mg/L (0,97-100,8mg/L). According to ISS, 35,0% of patients were on stage I, 28,2% on stage II and 36,8% on stage III. Mayo Clinic stratification revealed 21,4% with 0, 31,2% with 1, 28,2% with 2 and 19,2% 3 risk-factors. Sixty percent of patients had k light chain clonality: 50,9% had abnormal FLCr (< 0,03 or > 32,00) and 49,1% had standard FLCr 0,03-32,00. FISH was performed in 74,4% patients: 26,0% presented high-risk features. Overall survival (OS) and progression free survival (PFS) were significantly different according the patients presented 0, 1, 2 or 3 Mayo Clinic risk factors, with median survival times of 83, not reached (NR), 39 and 36 months, for OS, p=0,000, and 41, 41, 17 and 17 months for PFS, p=0,000. Patients with abnormal FLCr had similar outcome of standard FLCr. Patients in ISS II had significant different OS according the FLCr: 77 and 39 months for standard and abnormal FLCr, respectively, P=0,015. There was no such correlation on stages I and III. Conclusions Baseline serum FLCr associated to others risk-factors like serum β2-microglobuline and albumin is a powerful prognostic factor for survival in newly diagnosed MM treated with thalidomide or bortezomib-based therapies. FLCr helps to clarify the outcome of ISS stage II patients identifying a subgroup with clearly inferior outcome. Disclosures: Esteves: Yassen: Consultancy; Celgene: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.

Serum Free Light Chain Ratio (FLCr) Is a Powerful Prognostic Factor For Survival In Newly Diagnosed Multiple Myeloma (MM) Eligible For High Dose Melphalan (HDM)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1873-1873
Author(s):  
Graça Esteves ◽  
Manuel L Neves ◽  
Helena Martins ◽  
Carlos M. Martins ◽  
Maria Joao Costa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Light Chain ◽  
Prognostic Value ◽  
Stage Ii ◽  
Newly Diagnosed ◽  
Baseline Serum ◽  
Significant Difference

Abstract Introduction MM is a B cell malignancy characterized by the presence of a monoclonal immunoglobulin (Ig) in the serum and/or urine produced by clonal plasma cells. MM has a variable outcome depending on age, stage and cytogenetic abnormalities. FLCr is a readily available laboratory test and has independent prognostic significance in all the plasma cell disease entities, helping to clarify International Staging System (ISS), namely the heterogeneous stage II. In the era of new therapeutic agents trending to personalized therapy, its prognostic value needs to be proved. Purpose To evaluate the prognostic value of baseline serum FLCr on outcome of patients with newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib based regimens. Methods This is a retrospective study, from January 2005 to December 2012. We analyzed the relationship of baseline FLCr with outcome and its contribution to clarify the prognostic value of ISS. Serum FLC levels were measured in frozen sera drew at diagnosis before treatment, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Beckman Coulter nephelometric analyzer. FLCr was calculated as k/λ (reference range: 0,26-1,65). Abnormal FLCr was defined of <0,03 or >32,00 and standard FLCr of 0,03-32. Patients have been staged by ISS and Mayo Clinic stratification. All patients received at least two cycles of a bortezomib based regimen (64,7%), with doxorubicin and dexamethasone (PAD) in 55 patients (53,9%), with cyclophosphamide and dexamethasone (Cy-Bor-D) in 11 patients (10,8%) or thalidomide, doxorubicin and dexamethasone (TAD) in 36 patients (35,3%). Median follow-up from diagnosis was 30 months. Follow-up was through the review of each patient’s complete medical records at our center. Statistical analysis was performed with SPSS 20 ®. Results We reviewed 102 patients treated with thalidomide or bortezomib based-regimens eligible for HDM. Fifty one percent of patients were male and median age was 52 years (22-70y). The Ig type was IgG in 62,7%, IgA in 14,7%, IgD in 3,9%, light chains MM in 17,7% and non-secretory MM in 1,0% of patients. The median Hb level was 9,8 g/dL (5,3-16,7mg/L) and median serum albumin was 31,5 g/L (22,3-48,3g/L). Creatinine clearance <30ml/mn occurred in 18,6% of patients, 34,3% had elevated LDH and median β2-microglobulin was 6,61 mg/L (1,06-45,77mg/L). According to ISS, 39,2%% of patients were on stage I, 25,5%% on stage II and 35,3% on stage III. Clonal k light chain present in 58,8% of patients: 64,7% had abnormal FLCr (<0,03 or >32,00). Cytogenetic FISH analysis was performed in 86,3% of patients: 32,4% presented high-risk features. We observed a significant difference on overall survival (OS) and progression free survival (PFS) according to Mayo Clinic risk-factors: 0, not reached (NR), 1, NR, 2, 49 months and 3, 71 months for OS (P=0,000) and 0, 68 months, 1, 55 months, 2, 16 months and 3, 24 months for PFS (P=0,000). According the FLCr there was a significant advantage on OS for standard FLCr: NR vs 71 months (P=0,035). A trend to a better OS (P=0,061) was observed in stage II patients with standard FLCr but no significant difference at any stage. Conclusions Baseline serum FLCr associated to others risk-factors like serum β2-microglobuline and albumin is a powerful prognostic factor for survival in newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib-based therapies. We fail to fully demonstrate FLCr prognostic value on ISS stage II patients, only a trend for better outcome with standard FLCr. Disclosures: Esteves: Janssen-Cylag and Celgene. Consultancy on the area of multiple myeloma and acute myeloid leukaemia: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.

Transfusion-Dependency Is the Most Important Prognostic Factor for Survival in 1000 Newly Diagnosed MDS Patients with Low- and Intermediate-1 Risk MDS in the European LeukemiaNet MDS Registry

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2775-2775 ◽  
Author(s):  
Louise de Swart ◽  
Alex Smith ◽  
Pierre Fenaux ◽  
David Bowen ◽  
Guillermo Sanz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Mortality Rate ◽  
Serum Ferritin ◽  
Research Funding ◽  
Prognostic Value ◽  
Newly Diagnosed ◽  
Important Prognostic Factor ◽  
Transfusion Dependency

Abstract Abstract 2775 Background: The ELN EUMDS registry collects information about demographics and disease-management of newly diagnosed low- and intermediate-1 risk MDS patients. Objective: To define the prognostic impact of transfusion-dependency and serum ferritin levels. Results: From April 2008 until December 2010, 1000 patients have been registered in fourteen European countries. The median age is 74 years (range 18–95), 60% are male. The WHO subgroups are RCMD (35.8%), RARS (18.2%), RA (17.6%), RAEB-1 (11.6%), del5q (6.2%), MDS-U (3.1%) and RAEB-2 (0.4%). IPSS score (n=935) is 0 in 48.8%, 0.5 in 31.2% and 1 in 13.5%. At time of registration 19% of the patients had started MDS specific treatment, increasing to 46% at 18 months of follow-up, usually consisting of erythroid-stimulating agents (ESA). At registration 29% of the patients were transfusion-dependent, which remained stable during follow-up. The number of transfusion-dependent patients with ESA treatment decreased from 58% to 27% at 18 months of follow-up. Overall survival at 18 months of follow-up was 89%. The mortality rate in transfusion-independent and transfusion-dependent patients at 18 months of follow-up was 5% and 21%, respectively (P<0.0001). Prognostic value of the IPSS score was confirmed with Cox regression analysis: the hazard ratio (HR) with IPSS score 0.5 was 2.20 (95% Confidence Intervals (CI); 1.40–3.48) and with IPSS score 1.0 was 3.08 (95% CI; 1.78–5.31) respectively, adjusted for age, sex, country and WHO category. For overall survival based on ferritin status, patients were divided in three groups according to their ferritin levels, based on expected clinical significance; group 1. ≤300 μg/L, group 2. >300 <1000 μg/L and group 3. ≥1000 μg/L. The mortality rate according to serum ferritin at registration in these groups was 6%, 14% and 23%, respectively, with HRs 1.80 (95%CI 1.06–3.03) and 3.21 (95% CI 1.66–6.20), including adjustment for transfusion status and number of transfusions. To define the relationship between serum ferritin and transfusion-dependency, the serum ferritin levels in the three groups were compared in transfusion-independent and transfusion-dependent patients. The mortality rate according to serum ferritin at registration in transfusion-independent patients was 3%, 6% and 3%, respectively (HR 2.17 and 0.95 respectively). The mortality rate according to serum ferritin at registration in transfusion-dependent patients was 14%, 21% and 35%, respectively (HR 1.69 and 3.93 respectively) (Table 1; Graph 1). To define the prognostic value of transfusion burden, patients were divided in groups based on transfusion status: 1. No transfusions, 2. Transfusions <20 units, 3. Transfusion >20 units. The mortality rate in these groups was 5%, 18% and 30%, respectively. The adjusted HRs were 3.67 (95% CI; 2.28–5.91) and 5.50 (95% CI; 3.18–9.52), respectively (Table 1). Conclusion: After 18 months of follow-up serum ferritin levels appear to be an important prognostic factor for transfusion-dependent patients only. However, transfusion burden is the most important prognostic factor for survival in patients with more than 20 units transfused compared to non-transfused patients. An increased risk was also apparent for moderately transfused patients (<20 units) so direct toxicity of transfusions (toxic iron radicals?), even at a relatively low iron load, might have an important adverse impact on survival. Disclosures: Fenaux: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding. Germing:Celgene: Consultancy, Research Funding.

Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7605-7605
Author(s):  
H. Ege ◽  
M. Gertz ◽  
S. N. Markovic ◽  
M. Q. Lacy ◽  
A. Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Mayo Clinic ◽  
Lymphocyte Count ◽  
Staging System ◽  
Absolute Lymphocyte Count ◽  
Independent Prognostic Factor ◽  
Newly Diagnosed

7605 Background: In the setting of autologous stem cell transplantation (ASCT) in multiple myeloma (MM), it has been shown that peripheral blood absolute lymphocyte count (ALC) on day 15 is an independent prognostic factor for clinical outcomes. Recently the International Staging System (ISS) for MM has been developed as a simple staging system to assess survival in newly diagnosed MM patients. The role of ALC on survival in newly diagnosed MM patients is unknown. Methods: Between 1994 and 2002, 1,835 consecutive MM patients were evaluated at the Mayo Clinic, Rochester. Of these patients, we retrospectively analyzed 584 MM patients that were originally diagnosed and followed at the Mayo Clinic. The primary end point was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). OS was measured from the date of diagnosis to time of death or last follow-up. ALC was analyzed as a continuous variable and dichotomized based on finding the optimal cut point based on the log-rank statistic. ALC was then compared to the ISS. Results: The median age of the cohort was 67 years (range: 29–94 years), including 234 females and 350 males. The median follow-up was 32 months (range: 1–136 months). The median ALC at diagnosis was 1.2 x 109/L (range: 0.12–5.44 x 109/L). ALC, as a continuos variables was identified as a prognostic factor for OS (HR= 0.466, 95%CI= 0.396–0.547, p < 0.0001). MM patients with an ALC ≥ 1.3 x 109/L experienced a superior OS compared with MM patients with an ALC < 1.3 x 109/L (55.5 months versus 22.6 months, p< 0.0001). In the multivariate analysis, ALC was independent prognostic factor when compared to the ISS (HR = 0.580, 95%CI=0.518–0.647, p< 0.0001). Conclusions: Our study shows that ALC at diagnosis for MM is an independent prognostic factor for OS, suggesting how the host immune status plays a critical role in the survival of patients with MM. No significant financial relationships to disclose.

scholarly journals Prognostic Value of D-dimer in patients with acute coronary syndrome treated by percutaneous coronary intervention: a retrospective cohort study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Runzhen Chen ◽  
Chen Liu ◽  
Peng Zhou ◽  
Yu Tan ◽  
Zhaoxue Sheng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Percutaneous Coronary Intervention ◽  
Prognostic Value ◽  
Coronary Intervention ◽  
Risk Scores ◽  
Risk Of Death ◽  
Clinical Risk ◽  
Percutaneous Coronary ◽  
D Dimer

Abstract Background Associations between D-dimer and outcomes of patients with acute coronary syndromes (ACS) remain controversial. This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI). Methods In this observational study, 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The X-tile program was used to determine the optimal D-dimer thresholds for risk stratifications. Cox regression with multiple adjustments was used for outcome analysis. Restricted cubic spline (RCS) analysis was performed to assess the dose-response association between D-dimer and outcomes. The C-index was calculated to evaluate the additional prognostic value of D-dimer when added to clinical risk factors and commonly used clinical risk scores, with internal validations using bootstrapping methods. The primary outcome was all-cause death. Results During a median follow-up of 720 days, 225 deaths occurred. Based on the thresholds generated by X-tile, ACS-PCI patients with median (420–1150 ng/mL, hazard ratio [HR]: 1.58, 95 % confidence interval [CI]: 1.14–2.20, P = 0.007) and high (≥ 1150 ng/mL, HR: 1.98, 95 % CI: 1.36–2.89, P < 0.001) levels of D-dimer showed substantially higher risk of death compared to those with low D-dimer (< 420 ng/mL). RCS analysis depicted a constant relation between D-dimer and various outcomes. The addition of D-dimer levels significantly improved risk predictions for all-cause death when combined with the fully adjusted models (C-index: 0.853 vs. 0.845, P difference = 0.021), the GRACE score (C-index: 0.826 vs. 0.814, P difference = 0.027), and the TIMI score (C-index: 0.804 vs. 0.776, P difference < 0.001). The predicted mortality at the median follow-up (two years) was 1.7 %, 5.2 %, and 10.9 % for patients with low, median, and high D-dimer, respectively, which was well matched with the observed mortality (low D-dimer group: 1.2 %, median D-dimer group: 5.2 %, and high D-dimer group: 12.6 %). Conclusions For ACS patients treated by PCI, D-dimer level was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and risk scores. Risk stratifications based on D-dimer was plausible to differentiate ACS-PCI patients with higher risk of death.

scholarly journals Uptake and detection rate of a stepwise cardiometabolic disease detection program in primary care—a cohort study

2019 ◽  
Vol 30 (3) ◽  
pp. 402-407
Author(s):  
Daphne M Stol ◽  
Monika Hollander ◽  
Ilse F Badenbroek ◽  
Mark M J Nielen ◽  
François G Schellevis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Care ◽  
Cohort Study ◽  
High Risk ◽  
Newly Diagnosed ◽  
Additional Risk ◽  
High Risk Patients ◽  
Detection Program ◽  
Risk Patients

Abstract Background Early detection and treatment of cardiometabolic diseases (CMD) in high-risk patients is a promising preventive strategy to anticipate the increasing burden of CMD. The Dutch guideline ‘the prevention consultation’ provides a framework for stepwise CMD risk assessment and detection in primary care. The aim of this study was to assess the outcome of this program in terms of newly diagnosed CMD. Methods A cohort study among 30 934 patients, aged 45–70 years without known CMD or CMD risk factors, who were invited for the CMD detection program within 37 general practices. Patients filled out a CMD risk score (step 1), were referred for additional risk profiling in case of high risk (step 2) and received lifestyle advice and (pharmacological) treatment if indicated (step 3). During 1-year follow-up newly diagnosed CMD, prescriptions and abnormal diagnostic tests were assessed. Results Twelve thousand seven hundred and thirty-eight patients filled out the risk score of which 865, 6665 and 5208 had a low, intermediate and high CMD risk, respectively. One thousand seven hundred and fifty-five high-risk patients consulted the general practitioner, in 346 of whom a new CMD was diagnosed. In an additional 422 patients a new prescription and/or abnormal diagnostic test were found. Conclusions Implementation of the CMD detection program resulted in a new CMD diagnosis in one-fifth of high-risk patients who attended the practice for completion of their risk profile. However, the potential yield of the program could be higher given the considerable number of additional risk factors—such as elevated glucose, blood pressure and cholesterol levels—found, requiring active follow-up and presumably treatment in the future.

scholarly journals Discriminating uninfected surgical bed cysts from bacterial brain abscesses after Carmustine wafer implantation in newly diagnosed IDH-wildtype glioblastomas

2021 ◽  
Author(s):  
Alexandre Roux ◽  
Hichem Ammar ◽  
Alessandro Moiraghi ◽  
Sophie Peeters ◽  
Marwan Baroud ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mass Effect ◽  
Cyst Formation ◽  
Individual Risk ◽  
Newly Diagnosed ◽  
Postoperative Mri ◽  
Carmustine Wafer ◽  
Brain Abscesses ◽  
Individual Risk Factors

Abstract PurposeCarmustine wafers can be implanted in the surgical bed of high-grade gliomas, which can induce surgical bed cyst formation, leading to clinically relevant mass effect.MethodsAn observational retrospective monocentric study was conducted including 122 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent a surgical resection with Carmustine wafer implantation as first line treatment (2005–2018).FindingsTwenty-two patients (18.0%) developed a postoperative contrast-enhancing cyst within the surgical bed: 16 uninfected cysts and six bacterial abscesses. All patients with an uninfected surgical bed cyst were managed conservatively, all resolved on imaging follow-up, and no patient stopped the radiochemotherapy. Independent risk factors of formation of a postoperative uninfected surgical bed cyst were age ≥ 60 years (p = 0.019), number of Carmustine wafers implanted ≥ 8 (p = 0.040), and partial resection (p = 0.025). Compared to uninfected surgical bed cysts, the occurrence of a postoperative bacterial abscess requiring surgical management was associated more frequently with a shorter time to diagnosis from surgery (p = 0.009), new neurological deficit (p < 0.001), fever (p < 0.001), residual air in the cyst (p = 0.018), a cyst diameter greater than that of the initial tumor (p = 0.027), and increased mass effect and brain edema compared to early postoperative MRI (p = 0.024). Contrast enhancement (p = 0.473) and diffusion signal abnormalities (p = 0.471) did not differ between postoperative bacterial abscesses and uninfected surgical bed cysts.ConclusionsClinical and imaging findings help discriminate between uninfected surgical bed cysts and bacterial abscesses following Carmustine wafer implantation. Surgical bed cysts can be managed conservatively. Individual risk factors will help tailor their steroid therapy and imaging follow-up.

Histology as a Prognostic Factor in Early Gastric Cancer

1992 ◽  
Vol 78 (3) ◽  
pp. 181-184
Author(s):  
Massimo Ferrari ◽  
Enrico Ghislandi ◽  
Giuseppe Landonio ◽  
Margherita Majno ◽  
Tiziano Porretta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Lymph Node ◽  
Prognostic Factor ◽  
Early Gastric Cancer ◽  
Lymph Node Involvement ◽  
Depth Of Invasion ◽  
Undifferentiated Histology ◽  
Node Involvement

Of 431 patients with gastric cancer observed in our Istitution, 23 (5.3 %) had early gastric cancer (EGC). Macroscopic presentation, histology, depth of invasion, and lymph node involvement were evaluated in all the cases. All patients underwent surgery and an intensive follow-up was performed. Five of the 23 patients progressed, and the risk factors were examined. Histology seemed to be the main prognostic factor in our study, since intestinal type of EGC was associated to a significantly better prognosis. Total gastrectomy is indicated in the proximal localization of EGC, and should perhaps be performed also in cases presenting undifferentiated histology.

The Addition of sFLCR Improves ISS Prognostication in Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1490-1490 ◽  
Author(s):  
Marie-Christine Kyrtsonis ◽  
Theodoros P. Vassilakopoulos ◽  
Nikolitsa Kafasi ◽  
Dimitris Maltezas ◽  
Athanasios Anagnostopoulos ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Light Chain ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Prognostic Information ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Poor Outcomes ◽  
Chain Type

Abstract We have recently shown that serum free light chain ratio (sFLCR) provides independent prognostic information in patients with newly diagnosed MM (Kyrtsonis et al, Br J Haematol, 137: 240–243, 2007). The aim of the present study was to extend our previous observations in a multicenter setting and to investigate the potential additive effect of sFLCR to the ISS system, in determining the prognosis of patients with MM. We analyzed 214 newly diagnosed MM patients (125 kappa-, 89 lambda-). Serum free light chain levels were measured in sera drawn at diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK). Then, the sFLCR was calculated, accordingly as kappa/lambda or lambda/kappa, depending on the monoclonal light chain type of the patient. Based on our previous study “high” sFLCR was defined as ratios ≥3.57 and ≥45.09 for kappa- and lambda- MM respectively. The median age of the patients was 68 years (33–92), 51% were males, 28%, 30%, and 42% had Durie-Salmon stages I, II, and III, 14% creatinine &gt;2 mg/dl, and 13% had Bence-Jones MM. ISS stage was 1, 2, or 3 in 33%, 33%, and 34% of the patients, 48% had CRP ≥4 mg/l, 18% elevated LDH, 31% hemoglobin &lt;10 g/dl, 32% albumin &lt;3.5 g/dl, and 51% bone marrow infiltration ≥50%. The median sFLCR was 6.00 in the 125 kappa-MM, and 46.43 in the 89 lambda-MM patients. With a median follow-up of 16 months (1–105), 88 MM patients with “low” sFLCR had a 3-year disease specific survival (DSS) of 93±4% vs. 63±6% for 126 patients with “high” sFLCR. The corresponding 5-year DSS rates were 83±7% vs. 43±10% (p=0.0001). In multivariate analysis, “high” sFLCR provided prognostic information independent of the value of ISS, as further reflected by the data presented in the table. LDH levels further contributed in the discrimination of prognosis in multivariate analysis: A subgroup of 19 patients (9% of total) with “high” sFLCR plus ISS=3 plus elevated LDH had a 0% projected DSS at 19 months. sFLCR and the previously described models remained predictive of the outcome, if only patients requiring treatment at diagnosis were analyzed. In conclusion, baseline sFLCR appears to be an easily determined, powerful, independent and very promising novel prognostic factor for survival in patients with newly diagnosed MM. Establishment of the optimal cutoff and prospective validation is needed. Its addition to ISS and LDH can identify subgroups of patients with excellent or very poor outcomes. DSS According to the Combined sFLCR and ISS System Patient Subgroup Pts (#,%) 3-yr DSS (%) 5-yr DSS (%) p “Low” sFLCR and ISS &lt;3 61 (29) 95 90 Either “High” sFLCR or ISS=3 96 (46) 82 56 &lt;0.0001 “High” sFLCR and ISS=3 50 (24) 37 24

Rates and Outcomes of Follicular Lymphoma Transformation in the Rituximab Era: A Report From the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1546-1546
Author(s):  
Brian K Link ◽  
Matthew J Maurer ◽  
Grzegorz S. Nowakowski ◽  
Stephen M Ansell ◽  
William R Macon ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Mayo Clinic ◽  
Cell Lymphoma ◽  
Management Strategies ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
University Of Iowa ◽  
The University

Abstract Abstract 1546 Background: Follicular lymphoma (FL) is an incurable disease with an undefined optimal management strategy. Global priorities in goals of care are avoidance of death and transformation to aggressive subtypes. Retrospective series, – most including patients diagnosed before ubiquitous rituximab use, - describe diverse rates of transformation with a common consensus of 3% per year, and with a median survival post transformation of less than 2 years. This study sought to characterize transformation events in a prospective observational series begun after diffusion of early rituximab use in FL. Methods: Newly diagnosed FL patients were prospectively enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) from 2002–2009. Clinical data were abstracted from medical records using a standard protocol. Patients were actively followed for retreatment, transformation, and death. Inclusion criteria for this analysis were initial diagnosis of grade I-IIIa FL. Exclusion criteria for this cohort include composite diffuse large B-cell lymphoma (DLBCL), FL grade IIIb, or evidence of clinical or pathological transformation at the time of FL diagnosis. Transformation was defined as refractory/recurrent disease with either a) biopsy confirmed subtype of FLIIIb, DLBCL or higher grade B-cell lymphoma; or b) clinical indication of transformation (sudden rise in LDH, rapid discordant localized nodal growth, new involvement of unusual extranodal sites, new B symptoms or hypercalcemia). Risk of transformation was analyzed via time to transformation using a death as a competing risk. Time to transformation was defined as the date of initial FL diagnosis to date of transformation. Overall survival was defined as the date of initial diagnosis to date of death or last known follow-up for patients still alive. Results: There were 631 newly diagnosed grade I-IIIa FL patients with a median age at enrollment of 60 years (range 23–93). 54% were male. The most common types of initial therapy were observation (33%), rituximab (R) monotherapy (12%), alkylator based chemotherapy +/− R (22%), and anthracycline based chemotherapy +/− R (20%). At a median follow-up of 60 months (range 11–110), 79 patients had died, 311 patients had an event (death, progression, or retreatment), and 60 patients (9.5%) had transformed. Transformation was biopsy proven in 48 of the 60 patients (80%). The overall transformation rate at 5 years (TX5) was 10.7% (95% CI: 8.3%–13.8%) (Figure 1). Time to transformation was associated with a FLIPI score of 3–5 (HR=2.37, 95% CI 1.28–4.39, p=0.006), but was not significantly associated with other standard clinical characteristics. Risk of transformation was different in the common initial treatment groups with the highest rate in patients who were initially observed (TX5=14.4%) and lowest rate in patients who initially received R monotherapy (TX5=3.2%)(p=0.058). Outcome after transformation was inferior to MER subjects with de-novo diagnosed DLBCL (p<0.0001). The median overall survival from date of transformation was 44 months (95% CI: 22-NA). Survival after transformation was superior in patients who transformed greater than 18 months after FL diagnosis compared to patients who transformed earlier (5 yr OS =70% vs 20%) (p=7 ×10−5), and for those initially observed (median unreached) versus those patients who were initially treated with alkylator or anthracycline based chemotherapy (median survival of 11 months)( p=0.016). Conclusions: Follicular transformation rates in this modern large prospective observational study are similar to risk of death without transformation and slightly lower at 5 years than most previous reports. Post-transformation prognosis is substantially better than described in older series. These observed differences may be a function of the prospective nature of the study design, modern management strategies, or patient selection factors. Initial management strategies may influence the risk of transformation. Marked survival differences following early vs. late transformation suggest that these may be different biologic events. Disclosures: Link: Genentech: Consultancy, Research Funding; Celgene: Consultancy; Millenium: Consultancy. Johnston:Novartis: Consultancy.

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