Is the International Prognostic INDEX for CLL (CLL-IPI) Useful to Predict Time to First Treatment of Patients with EARLY Disease? Results of a Prospective Multicenter Analysis

Abstract BACKGROUND: The CLL-IPI score is a large cooperative effort in which clinical data collected from 8 randomized trials were used to develop an internationally applicable prognostic index for CLL patients. The model includes 5 independent parameters that predict for overall survival such as age, clinical stage, del(17p) and/or TP53 mutation, IGHV mutation status and β2-microglobulin (B2M) level. A potential limitation for an extensive use of CLL-IPI is represented, however, by the fact that only 20% of patients included in the full analysis set had early disease. PATIENTS: The present analysis based on an observational multicenter CLL database including 337 Binet stage A patients (O-CLL1 protocol, clinicaltrial.gov identifier NCT00917540) was designed to assess the utility of the CLL-IPI score to predict time to first treatment (TTFT) in patients with early disease. RESULTS: Patients were followed up for a total of 2038 person-years (median, 42 months; range, 1-82 months), during which 91 (26.9%) experienced disease-progression requiring therapy according to 1996 IWCLL guidelines. The CLL-IPI score enabled Binet stage A patients to be divided into three subgroups [i.e., score 0-1, low-risk (n=229); score 2-3, intermediate-risk(n=99); score 4 or higher, high-risk (n=9)] that differed with respect to TTFT (P<0.0001). A comparative performance analysis between CLL-IPI and 2007 MD Anderson Cancer Center (MDACC) score, barely based on traditional clinical parameters (i.e., age, gender, Rai substage, absolute lymphocyte count, number of involved nodal groups and B2M), revealed that prediction of the TTFT was more accurate with the former. The c-statistic of the MDACC model was 0.62 (95% CI: 0.49-0.75) a level below than that of the CLL-IPI (c=0.70; 95% CI:0.58-0.81) and below the accepted 0.7 threshold necessary to have value at the individual patient level. These results are in keeping with the change in area under the receiver operating characteristic (ROC) curve (AUC) which increased from 0.646 (95% CI: 0.578-0.714) to 0.720 (95%CI:0.658-0.783) when moving from MDACC model to CLL-IPI score. Since the CLL-IPI score was originally derived from patients with active CLL enrolled in phase 3 trials we sought for different cut-off scores that better predict for TTFT in our patient cohort of early CLL. According to the recursive partitioning (RPART) analysis, a classification tree was built that identified three subsets of patients who scored 0 (low- risk,n=139), 1(intermediate-risk, n=90) and >1 (high-risk, n=108), respectively. The probability of remaining free from therapy at 5 years was 85% in the low-risk group, 68% in the intermediate-risk group and 47% in the high-risk group (P<0.0001)(Fig 1). Our revised IPI score remained a predictor of TTFT also when analysis was limited to 262 Rai stage 0 (P<0.0001) and 99 clinical monoclonal B-cell lymphocytosis (cMBL) cases (P=0.006). CONCLUSIONS: The results of this study confirm the utility of CLL-IPI score for predicting TTFT in a prospective cohort of community-based patients with early CLL at presentation. Our effort to adapt CLL-IPI score to patients with early disease meets the need to separate Binet stage A patients into different prognostic groups suitable for individualized follow-up programmes and possibly for early therapeutic interventions. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

The Follicular Lymphoma International Prognostic Index (FLIPI) Predicts Treatment Outcome in Patients with Advanced Stage Follicular Lymphoma Treated Front-Line with Rituximab and the Combination of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP).

Blood ◽

10.1182/blood.v106.11.925.925 ◽

2005 ◽

Vol 106 (11) ◽

pp. 925-925 ◽

Cited By ~ 1

Author(s):

Christian Buske ◽

Eva Hoster ◽

Martin Dreyling ◽

Joerg Hasford ◽

Michael Unterhalt ◽

...

Keyword(s):

Treatment Outcome ◽

Relative Risk ◽

High Risk ◽

Follicular Lymphoma ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Intermediate Risk ◽

Advanced Stage ◽

Front Line

Abstract Background: The Follicular Lymphoma International Prognostic Index (FLIPI) has been developed to predict prognosis and to allow risk adapted treatment decisions in patients with follicular lymphoma (FL) before the widely use of Rituximab. However, the addition of Rituximab to standard induction chemotherapy with its long-term beneficial effects has profoundly changed the treatment outcome in patients with advanced stage FL and has become the new standard in the first line therapy of this disease. Therefore, we addressed the question, whether the prognostic value of the FLIPI could be reconfirmed in patients with advanced stage FL treated initially with a rituximab/chemotherapy combination. Methods: The FLIPI index was tested in patients treated with Rituximab and CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone, R-CHOP) in a prospective multicenter phase 3 trial of the GLSG using the time to treatment failure (TTF) as target parameter. Results: 362 Patients treated with R-CHOP were evaluable for TTF. Of the 338 patients evaluable for all FLIPI risk factors, 14% of patients were classified as low, 41% as intermediate and 45% as high risk. After a median follow-up time of 20 months, patients with low risk and intermediate risk FLIPI had almost identical TTF (2-years TTF 92% vs 90%, 95% C.I., 83% to 100% and 84% to 96%, respectively). In contrast, the TTF was significantly shorter in the high risk FLIPI group (2-years TTF 67%, 95% C.I., 58% to 76%) as compared to the combined low/intermediate risk FLIPI group (relative risk 3.0, 95% C.I., 1.7 to 5.1; p < 0.0001). In addition, responding patients with high risk FLIPI had a significantly shorter progression free survival as compared to the low/intermediate risk group (relative risk 3.3, 95% C.I., 1.8 to 6.0; p < 0.0001). When postremission treatment was taken into account, the FLIPI separated the high risk group from the low/intermediate risk group in 65 patients treated with autologous stem cell transplantation (relative risk 6.0, 95% C.I., 1.4 to 25.2) as well as in 242 patients who had received IFN-α maintenance or no postremission therapy (relative risk 3.2, 95% C.I., 1.8 to 5.8). As the FLIPI was able to separate the high from the low/intermediate risk group in patients with advanced follicular lymphoma treated initially with Rituximab and CHOP we next performed a multivariate analysis to determine the impact of the individual parameters incorporated in the FLIPI on the TTF. The serum LDH level greater than the upper normal limit (relative risk 2.6, 95% C.I., 1.5 to 4.5) and the hemoglobin level below 12 g/dl (relative risk 2.5, 95% C.I., 1.4 to 4.3) were independently associated with a shorter TTF in these patients, whereas the age and the number of nodal areas were not discriminant. Conclusion: Taken together, these data indicate that the FLIPI is a valid prognostic index for identifying high-risk patients in FL, also after front-line combined immuno-chemotherapy. The index will remain an important tool to adjust treatment decisions in individual patients according their risk profile and to design clinical trials for the different risk groups in the era of antibody-based therapy.

Download Full-text

A Critical Analysis of Prognostic Factors in Patients with HTLV-1 Adult T-Cell Leukemia/Lymphoma: A Multicenter Clinicopathologic Experience and New Prognostic Score.

Blood ◽

10.1182/blood.v112.11.1784.1784 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1784-1784

Author(s):

Adrienne A. Phillips ◽

Iuliana Shapira ◽

Robert D. Willum ◽

Jasotha Sanmugarajah ◽

William B. Solomon ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

Median Survival ◽

Risk Group ◽

Performance Status ◽

Recursive Partitioning ◽

Prognostic Index ◽

Low Risk ◽

Intermediate Risk ◽

A Performance

Abstract Purpose: Adult T-Cell Leukemia/Lymphoma (ATLL) is a rare aggressive Human T-cell Lymphotropic Virus Type-I (HTLV-I) associated peripheral T-cell neoplasm with 4 recognized clinicopathologic subtypes: acute, lymphomatous, chronic, and smoldering. Since the initial description of these variants, several studies have sought to identify additional prognostic factors. We assessed prognostic models already in use for aggressive non-Hodgkin lymphomas to develop a novel risk stratification scheme. Methods: Data regarding patients with ATLL were collected from 3 medical centers between 8/92 and 5/07. Descriptive statistics were used to assess categorical and continuous variables. Overall survival (OS) was defined as time from diagnosis to death. Survival curves for OS were estimated using the Kaplan-Meier method. Univariate associations between individual clinical factors and OS were evaluated using the log-rank test for categorical variables and the Cox model for continuous variables. Maximum logrank analysis was used to select the optimal cut-off for calcium. In order to develop a simple risk model and allow for interactions of factors independently associated with OS, we used recursive partitioning analysis. Results: 89 patients with ATLL were identified; 37 males (41.6%) and 52 females (58.4%) and median age 50 years (range 22 to 82). The acute subtype of ATLL predominated (68.5%), followed by lymphomatous (20.2%), chronic (6.8%) and smoldering (4.5%). Median OS for all sub-types was 24 weeks (range 0.9 to 315). According to the International Prognostic Index (IPI), 8 patients (9.1%) were classified as low risk, 11 patients (12.5 %) as low intermediate risk, 13 patients (14.8 %) as high intermediate risk, and 56 patients (63.6 %) as high risk, 1 patient could not be evaluated due to missing data. Median OS by IPI risk group was 271, 65, 31 and 16 weeks, respectively (p<0.01). The Prognostic Index for PTCL-U (PIT) could be determined in 68 patients; 10 patients (14.7 %) had a score of 0–1 (group 1), 19 patients (27.9 %) had a score of 2 (group 2), 31 patients (45.6 %) had a score of 3 (group 3), and 8 patients (11.8 %) had a score of 4 (group 4). Median OS by PIT risk group was 61.1, 28, 24, and 11.3 weeks respectively (p<0.01). A new risk model was developed using the variables of the IPI and PIT. In addition, calcium level at diagnosis was also included as it had independent prognostic value. Recursive partitioning of OS based on these variables gave a tree with 5 nodes, which fell into three risk categories: low risk patients with Stage I–II disease and a performance status <2; the medium risk group composed of two sets of patients: those with Stage III–IV disease with an ECOG performance status < 2 or those with an ECOG performance status ≥ 2 with calcium ≤ 11 mg/dL and age ≤ 60; and the high risk group (also comprising 2 sets of patients): those with a performance status ≥ 2 with calcium ≤ 11 mg/dL and age > 60 or those with a performance status ≥ 2 and calcium > 11 mg/dL. There were 10 patients (11.2%) in the low risk (median survival= 156.6 weeks), 31 (34.8%) in the intermediate risk (median survival = 45.4 weeks), and 48 (53.9%) in the high risk (median survival= 13 weeks) categories (p<0.01). Conclusion: This retrospective series confirms a poor outcome for North American patients with HTLV-1 related ATLL. Although the IPI and PIT identified subsets of patients, these models had liabilities. We propose a new prognostic model based on recursive partitioning analysis that successfully identifies three prognostic categories based on performance status, stage, age and calcium level at diagnosis in a more robust and distinct fashion. Table 1. Comparison of Prognostic Scores and Kaplan Meier Survival Estimates (%) of patients with ATLL International Prognostic Index (IPI) (n = 88) Prognostic Index for PTCL-U (PIT) (n = 68) ATLL Prognostic Score (APS) (n= 89) Time (wks) Low n= 8 Low-Intermed n= 11 High-Intermed n= 13 High n= 56 Group 1 n= 10 Group 2 n= 19 Group 3 N= 31 Group 4 n= 8 Low n= 10 Intermed n= 31 High n= 48 13 8 (100%) 10 (100%) 9 (75.5%) 31 (53.1%) 10 (100%) 13 (68.4%) 19 (66.3%) 3 (25.0%) 9 (100%) 27 (87.1%) 23 (46.4%) 26 8 (100%) 9 (90.0%) 6 (56.6%) 17 (31.1%) 10 (100%) 9 (51.3%) 13 (45.4%) 0 (0%) 9 (100%) 23 (77.0%) 9 (19.9%) 52 6 (75.0%) 6 (60.0%) 3 (28.3%) 9 (17.6%) 5 (50%) 5 (28.5%) 8 (30.7%) 0 (0%) 8 (88.9%) 13 (46.0%) 4 (8.8%) 78 5 (75.0%) 4 (40.0%) 2 (18.9%) 2 (4.0%) 4 (40%) 3 (17.1%) 2 (7.7%) 0 (0%) 7 (88.9%) 7 (24.8%) 0 (0%) 104 3 (56.2%) 3 (30.0%) 2 (18.9%) 2 (2.0%) 2 (30%) 3 (17.1%) 2 (3.8%) 0 (0%) 4 (61.0%) 6 (17.7%) 0 (0%) Median OS (wks) 271 65 31 16 61.1 28 24 11.3 156.6 45.4 13

Download Full-text

Serbian lymphoma study group: Demografic characteristics of 257 patients with follicular lymphoma

Vojnosanitetski pregled ◽

10.2298/vsp140115014s ◽

2015 ◽

Vol 72 (6) ◽

pp. 483-488

Author(s):

Olivera Simonovic ◽

Lana Macukanovic-Golubovic ◽

Bosko Andjelic ◽

Darko Antic ◽

Biljana Mihaljevic

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Treatment Decision ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Prognostic Groups

Background/Aim. Follicular lymphoma (FL) is a B-cell tumor usually with indolent clinical course, yet in some cases the course of the disease can be very aggressive. The aim of the re-search was to determine distribution of patients into prognostic groups based on the International Prognostic Index (IPI) and Folicular Lymphoma International Prognostic Index (FLIPI) criteria, as well as to determine the importance of classifying patients into the prognostic groups, since this could potentially have the influence on selection of the treatment modality. Methods. The retrospective study was performed on 257 patients with follicular lymphoma diagnosed between January 2000 and April 2011. Results. Based on the IPI score, 153 (59.53%) patients had low risk, 57 (22.18%) low intermediate risk, 15 (5.84%) high intermediate risk, 9 (3.50%) high risk, whereas the classification of 23 patients diagnosed with FL remained with unknown risk according to the IPI. Based on the FLIPI prognostic index, 113 (43.97%) patients had low risk, 70 (27.24%) intermediate risk and 51 (19.84%) high risk, whereas the classification of 23 (8.95%) patients remained unknown. On the basis of the FLIPI 2 prognostic index, 48 (18.68%) patients had low risk, 145 (56.42%) intermediate risk and 41 (15.95%) high risk. The classification into prognostic groups for 23 (8.95%) patients remained unknown. According to the IPI, FLIPI and FLIPI 2 there were the patients that required treatment in all the risk groups. Conclusion. The FLIPI and FLIPI 2 effectively identify patients at high risk, thus helping in treatment decision for each single patient.

Download Full-text

A risk model for relapsed/refractory aggressive NHL integrating clinical risk factors and pretransplant Deauville score

Blood Advances ◽

10.1182/bloodadvances.2020002814 ◽

2020 ◽

Vol 4 (22) ◽

pp. 5762-5771

Author(s):

Ho-Young Yhim ◽

Yael Eshet ◽

Ur Metser ◽

Chae-Hong Lim ◽

Katherine Lajkosz ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

International Prognostic Index ◽

Prognostic Index ◽

Salvage Chemotherapy ◽

Low Risk ◽

Clinical Risk Factors ◽

Intermediate Risk ◽

Clinical Risk ◽

Deauville Score

Abstract There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P < .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P < .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P < .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

Download Full-text

Cause of death in patients with newly diagnosed chronic lymphocytic leukemia (CLL) stratified by the CLL-International Prognostic Index (CLL-IPI).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.8026 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 8026-8026

Author(s):

Yucai Wang ◽

Sara J Achenbach ◽

Kari G. Rabe ◽

Tait D. Shanafelt ◽

Timothy Call ◽

...

Keyword(s):

High Risk ◽

Cause Of Death ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Lymphocytic Leukemia ◽

Intermediate Risk ◽

Newly Diagnosed ◽

Second Malignancies ◽

Very High

8026 Background: CLL progression and CLL-related complications (infections and second malignancies) were the leading cause of death (COD) in a prospective cohort of CLL patients (Strati, BJH 2017). The CLL-IPI integrates major clinical and molecular prognostic factors and stratifies patients into 4 risk groups with distinct prognosis. It is unknown if COD differs according to CLL-IPI risk group in patients with newly diagnosed CLL. Methods: Patients diagnosed with CLL between 1/2000-12/2019 and seen within 1 year of diagnosis were identified from the Mayo Clinic CLL database. Cumulative incidences of cause-specific death were analyzed using Gray’s test, with deaths from different causes treated as competing events and deaths from unknown causes excluded. Results: 1276 patients were included in this study. The median age at diagnosis was 63 years (range 24-92), and 880 (69%) were male. Based on CLL-IPI score, 449 (35%) had low risk disease, 443 (35%) had intermediate risk disease, and 384 (30%) had high/very high risk disease. Median follow-up time for the study was 6 years; 286 deaths occurred. The COD was CLL progression in 99 (35%), infection in 16 (6%), second malignancy in 47 (16%), CLL-unrelated in 59 (21%), and unknown in 65 (23%) patients. The rates of death due to CLL progression were higher (17.3% at 5 years; 30.3% at 10 years) than the rates due to CLL-related complications (5.7% at 5 years; 12.9% at 10 years) or due to CLL-unrelated causes (8.6% at 5 years; 16.9% at 10 years) in the CLL-IPI high/very high risk group, but not the CLL-IPI low or intermediate risk group (Table). A higher CLL-IPI risk group was associated with a higher rate of death due to CLL progression ( P < 0.001), as well as a higher rate of death due to CLL-related complications ( P = 0.013), and CLL-unrelated causes ( P < 0.001). Conclusions: Causes of death in newly diagnosed CLL patients differ according to their CLL-IPI risk group. In patients with high/very high risk CLL, improving CLL disease control with novel agents seems justified. In patients with low/intermediate risk CLL, there should be increased efforts to reverse immune dysfunction to reduce infections and second malignancies. [Table: see text]

Download Full-text

Validation of Mantle Cell International Prognostic Index (MIPI) in Mantle Cell Lymphoma (MCL) in a Retrospective Single Institution Series

Blood ◽

10.1182/blood.v112.11.2828.2828 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2828-2828

Author(s):

Annalisa Chiappella ◽

Barbara Botto ◽

Filippo Marmont ◽

Ernesta Audisio ◽

Ileana Baldi ◽

...

Keyword(s):

High Risk ◽

Clinical Course ◽

Prognostic Score ◽

International Prognostic Index ◽

Prognostic Index ◽

Low Risk ◽

Intermediate Risk ◽

Single Institution ◽

Mantle Cell

Abstract Introduction: The clinical course of MCL is characterized by a continuous pattern of relapse and a poor long term outcome with a median Overall Survival (OS) of four years and a 15% of long term survivors. Recently a new clinical prognostic score (MIPI), including performance status, age, LDH level and leukocyte count has been reported. This score allows a more reliable estimation of individual clinical course. We retrospectively applied the MIPI score to patients with MCL. Patients and methods: Between 1999 and 2007, 40 patients with MCL diagnosed and treated in a single institution entered into the study. Clinical characteristics were as follows: median age 56 years (range 37–81), 80% male; 82% stage IV; 78% bone marrow involvement and 15% MCL with blastoid variant. First line treatments were: high dose chemoimmunotherapy including Rituximab (R) with autologous stem cell transplantation (R-HDC) in 26 patients and Rituximab-CHOP like chemotherapy (R-CHOP) in 14. Crude Kaplan-Meier OS and progression-free survival (PFS) curves were estimated both overall and stratified by MIPI and International Prognostic Index (IPI) score. Differences between curves were tested using the 2-tailed log-rank test. In order to quantify the predictive discrimination of MIPI and IPI scores, univariate logistic models (with death and progression event as binary outcomes) were fitted and the area under the receiver operating characteristic (ROC) curves (c index) was estimated. Results: According to MIPI score 17 patients (43%) were at low risk (LR, score 0–3), 13 patients (32%) at intermediate risk (IR, score 4–5) and 10 patients (25%) at high risk (HR, score >5). According to IPI score 14 patients (35%) were at low risk (LR), 16 patients (40%) at low-intermediate risk (LIR) and 10 patients (25%) at intermediate-high and high risk (IH-HR). At the end of the treatment, 30 patients achieved a CR, five a PR and five did not respond. Relapses occurred in 17 patients and seven of them died of lymphoma. With a median follow-up (FU) of 29 months, OS was 85% (95% CI: 66%–93%); with a median FU of 21 months, PFS was 70% (95% CI: 51%–83%). Twenty-nine months OS rates for MIPI score were: LR 100%, IR 81%, HR 66% respectively (p=.07) and for IPI score were: LR 92%, LIR 94%, IH-HR 65% respectively (p=.09). Twenty-one months PFS rates for MIPI score were: LR 92%, IR 59%, HR 45% respectively (p=.006) and for IPI score were: LR 73%, LIR 87%, IH-HR 44% respectively (p=.09). MIPI score was more predictive than IPI score for the death event and for the progression event: the c index was 74% and 73% for MIPI compared to 72% and 69% for IPI respectively. In a subgroup analysis performed on 26 R-HDC patients, OS and PFS rates stratified for MIPI were: for OS, LR 100% vs IR 80% vs HR 69% (p=.4) and for PFS, LR 91% vs IR 80% vs HR 57% (p=.04) respectively. Discussion: in our retrospective series of patients, MIPI prognostic score discriminates among patients with different PFS. Relapses remain the most important issue for all patients affected by MCL, namely in HR group according to MIPI. New therapeutic strategies are warranted to improve the prognosis of MCL.

Download Full-text

Treatment Outcome and a Practical 10-Point Prognostic Index in Adult Patients with Non-M3 Acute Myeloid Leukemia: A Retrospective, Multicenter Study in Malaysia

Blood ◽

10.1182/blood-2019-126656 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2606-2606

Author(s):

Tze Shin Leong ◽

Sen Mui Tan ◽

Lee Ping Chew ◽

Tee Chuan Ong ◽

Siew Lian Chong ◽

...

Keyword(s):

Overall Survival ◽

Treatment Outcome ◽

High Risk ◽

Relapse Rate ◽

Survival Benefit ◽

Risk Group ◽

Prognostic Index ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk

Background: Literature on Acute Myeloid Leukemia (AML) survival and prognostic factors were often derived from strict trial studies from developed country. A simple yet practical prognosis index has not been developed and tested in resource limited setting such as Malaysia. We described the treatment outcome and designed a 10 point prognostic index to predict survival of adult AML (non-M3) in real clinical practice in Malaysia. Methods: Data were retrospectively collected and analyzed from all adults with AML diagnosed and treated from 2007 to 2017 in three main hematology centers in Malaysia, Ampang Hospital, Sarawak General Hospital and Miri General Hospital. Treatment pattern and survival outcome were described. Multivariable analysis using Cox regression statistics were performed to identify significant prognostic variables affecting overall survival. Each variable were assigned points based on hazard ratios. A sum of the points led to a maximum score of 10. Patients were then categorized into low (0 point), intermediate (1 to 3 points) or high-risk group (4 points or above). Results: Demographics and treatment outcome of patients are shown in Table 1 & 2. There were 1277 adult patients, diagnosed with AML where 86.5% (n= 1106) of them were non M3 AML. Out of these, 908 patients (82.2%) received intensive chemotherapy treatment. Median age of diagnosis was 45 years. The remission post induction rate was 64.3% with induction death, refractory and relapse rate of 8.8%, 20.0% and 27.7% respectively. Median overall survival (OS) and Event Free Survival (EFS) time was 15 months and 12 months. The 3-year OS and EFS was 32.9% and 28.5% respectively. At the time of analysis, 66.1% of patients were dead (n=600) with disease progression being the main cause of death (n=416, 45.8%). Three year overall OS for patients who underwent allogeneic stem cell transplant (n=301, 33.1%) versus patients without transplantation were 53.7 % versus 22.0 % (HR 2.597, p <0.001). Cumulative incidence of relapsed and non-relapse mortality for transplant patients, shown in Figure 1 were 27.5% and 22.1%. Multivariate analysis in Table 3 showed that age 60 years old and above, male gender, white cell count more than 100 x 109 /L ,relapsed less than 12 months of treatment, refractory state after induction and high risk genetic group (based on EuropeanLeukemiaNet/Medical Research Council risk stratification by genetics) are prognostic factors associated with worse OS and EFS. The information was used to develop a 10 point prognostic index based on calculation described in Table 3. Overall survival decreased with each additional index point. When stratified according to risk group, the 3 year OS for low risk, intermediate risk and high risk group was 53.3%, 34.3% and 4.9% respectively. This is shown in Table 4 & Figure 2. Relapse rate was also lower in the low-risk group (8.8%), compared to intermediate-risk group (19.2%) and high-risk group (35.2%). Comparing transplant and non transplant cohort shown in Figure 3, there was no survival benefit in the low-risk group (58.6% vs 49.2%, p=0.122) but significant survival benefit in both intermediate-risk group (56.6% vs 23%, p<0.001) and adverse-risk group (13% vs 7%, p=0.002). Discussion/Conclusion: This is one of few survival studies that involved patients of different ethic groups in Asia (Malay, Chinese, Indian and native Borneo Sarawakians). Our results are comparable to data from large population based database such as US SEER and EURO CARE. This is the first prognostic index incorporating genetics, baseline characteristics and dynamic response, eg. refractory and/or relapsed post induction in non M3 AML. The results reaffirmed the importance of these factors in determining the clinical outcome and prognosis of patients with AML. When stratified using our 10 point prognostic index, our cohort of patients who is in low risk group has lower relapse rate and did not have significant survival benefit from allogeneic transplant compare to stratification using only the ELN/MRC genetic classification.(Table 5 & 6). In resource limited setting, measurable residual disease (MRD) monitoring and advanced genetic testing are difficult financially. This prognostic scoring index is an economical and practical alternative to guide physicians on treatment after induction therapy. However, it still needs to be validated by a larger cohort of patients in a prospective study. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Neither the FLIPI Nor the FLIPI2 Accurately Segregates Low- Risk From Intermediate- Risk Follicular Lymphoma Patients in Terms of Progression-Free Survival

Blood ◽

10.1182/blood.v118.21.2663.2663 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2663-2663

Author(s):

Inas El-Najjar ◽

Janet Matthews ◽

John Gribben ◽

Silvia Montoto

Keyword(s):

Follicular Lymphoma ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Free Survival ◽

Study Population

Abstract Abstract 2663 Background: Follicular Lymphoma International Prognostic Index (FLIPI) is the most frequently used prognostic index for risk stratification in follicular lymphoma (FL) patients. The FLIPI was designed retrospectively in the pre-rituximab era, with overall survival (OS) as the end-point. Follicular Lymphoma International Prognostic Index 2 (FLIPI2) is a more recent index designed prospectively in the rituximab era to overcome these drawbacks. Aim: To compare the efficacy of the FLIPI and FLIPI2 prognostic indexes in discriminating patients with FL with a distinct outcome in terms of OS and progression-free survival (PFS). Patients: From 1985 to 2007, 302 patients were newly diagnosed with grade 1–3a FL in our institution. The FLIPI could be retrospectively assigned in 220 patients and the FLIPI2 in 149 patients. The 122 patients (47 male/75 female; median age: 56 years –range: 25–87) in whom both the FLIPI and FLIPI2 indexes were assessable constitute the study population. Seventy-five patients (61%) received treatment immediately after diagnosis (of which, 25 patients received rituximab containing regimens), whereas the remainder were managed expectantly. Main characteristics at diagnosis are as follows: age>60 years, 41%; stage III-IV, 70%; Hb<12 g/L, 17%; bone marrow involvement, 45%; largest lymph node diameter>6cm, 26%; B2M>ULN, 20% and LDH>ULN, 17%. The median follow-up for alive patients was 86 months (range: 12– 270). Results: Five-year OS and PFS were 74% (95%CI: 69–79) and 38% (95%CI: 32–44), respectively, for the 302 patients. There were no significant differences in the outcome of these patients in comparison with the 122 patients comprising the study population. The distribution of the 122 patients according to the FLIPI and FLIPI2 as well as the 5-year OS and 5-year PFS are shown in the table. The FLIPI and the FLIPI2 indexes predicted OS (p<0.0001 both for the FLIPI and the FLIPI2), but the FLIPI2 did not accurately separate patients with low-risk from those with intermediate risk in terms of OS (p=0.3). The FLIPI score predicted PFS (p=0.001) but was not able to discriminate patients with low-risk from those with intermediate-risk (p=0.6). There was a trend for the FLIPI2 to predict PFS (p=0.06) but it did not segregate the low-risk group from the intermediate-risk group (p=0.3) Conclusions: The FLIPI separates patients into 3 risk groups, well-balanced in terms of the proportion of patients in each group with a distinct OS. In contrast the, majority of the patients fall into the intermediate risk group according to the FLIPI2, and overlaps with the low risk group in terms of OS. With regards to PFS, both indexes are poor at separating low and intermediate risk groups. In summary, both indexes are good at defining a relatively small high-risk population but do not accurately segregate the rest. FLIPI2 does not appear to be superior to FLIPI for risk stratification. This supports that the future lies in uncovering biological factors that might help in the guidance of treatment, in addition to segregating patients more accurately into specific risk groups. Disclosures: Gribben: Roche: Honoraria; Genentech: Honoraria; GSK: Honoraria; Muundipharma: Honoraria. Montoto:Genentech: Research Funding; Roche: Honoraria.

Download Full-text

CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP

Journal of Clinical Oncology ◽

10.1200/jco.2015.65.6520 ◽

2016 ◽

Vol 34 (26) ◽

pp. 3150-3156 ◽

Cited By ~ 115

Author(s):

Norbert Schmitz ◽

Samira Zeynalova ◽

Maike Nickelsen ◽

Roopesh Kansara ◽

Diego Villa ◽

...

Keyword(s):

High Risk ◽

B Cell ◽

Risk Model ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Intermediate Risk ◽

Data Set ◽

Cns Relapse

Purpose To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods A total of 2,164 patients (18 to 80 years old) with aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database. Results The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups. Conclusion The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions.

Download Full-text

55例血管免疫母细胞性T细胞淋巴瘤的临床特征和预后模型

Blood ◽

10.1182/blood-2020-141699 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 37-38

Author(s):

Xiaohong Tan ◽

Jie Sun ◽

Sha He ◽

Chao Rong ◽

Hong Cen

Keyword(s):

High Risk ◽

Prognostic Model ◽

Risk Group ◽

Prognostic Index ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Ecog Ps ◽

Medical University

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct subtype of peripheral T-cell lymphoma with unique clinical and pathological features. This study aim to analyze the characteristics of AITL and to design a prognostic model specifically for AITL, providing risk stratification in affected patients. We retrospectively analyzed 55 newly diagnosed AITL patients at the Affiliated Tumor Hospital of Guangxi Medical University from January 2007 to June 2016 and was permitted by the Ethics Committee of the Affiliated Tumor Hospital of Guangxi Medical University. Among these patients, the median age at diagnosis was 61 (27-85) and 54.55% (30/55) of the patients were older than 60 years. 43 patients were male, accounting for 78.18% of the whole. Among these, 92.73% (51/55) of the diagnoses were estimated at advanced stage. A total of 20 (36.36%) patients were scored >1 by the ECOG performance status. Systemic B symptoms were described in 16 (29.09%) patients. In nearly half of the patients (27/55; 49.09%) had extranodal involved sites. The most common extranodal site involved was BM (11/55; 20.00%). 38.18% (21/55) and 27.27% (15/55) patients had fever with body temperature ≥37.4℃ and pneumonia, respectively. 40% (22/55) patients had cavity effusion or edema. Laboratory investigations showed the presence of anemia (hemoglobin <120 g/L) in 60% (33/55), thrombocytopenia (platelet counts <150×109/L) in 29.09% (16/55), and elevated serum LDH level in 85.45% (47/55) of patients. Serum C-reactive protein and β2-microglobulin levels were found to be elevated in 60.98% (25/41) and 75.00% (36/48)of the patients, respectively. All patients had complete information for stratification into 4 risk subgroups by IPI score, in which scores of 0-1 point were low risk (9/55;16.36%), two points were low-intermediate risk (17/55; 30.92%), three points were high-intermediate risk (20/55; 36.36%), and four to five points were high risk (9/55; 16.36%). 55 patients were stratified by PIT score with 7.27% (4/55) of patients classified as low risk, 32.73% (18/55) as low-intermediate risk, 34.55% (19/55) as high-intermediate risk, and 25.45% (14/55) as high risk depending on the numbers of adverse prognostic factors.The estimated two-year and five-year overall survival (OS) rate for all patients were 50.50% and 21.70%. Univariate analysis suggested that ECOG PS (p= 0.000), Systemic B symptoms (p= 0.006), fever with body temperature ≥ 37.4℃ (p= 0.000), pneumonia (p= 0.001), cavity effusion or edema (p= 0.000), anemia (p= 0.013), and serum LDH (p= 0.007) might be prognostic factors (p< 0.05) for OS. Multivariate analysis found prognostic factors for OS were ECOG PS (p= 0.026), pneumonia (p= 0.045), and cavity effusion or edema(p= 0.003). We categorized three risk groups: low-risk group, no adverse factor; intermediate-risk group, one factor; and high-risk group, two or three factors. Five-year OS was 41.8% for low-risk group, 15.2% for intermediate-risk group, and 0.0% for high-risk group (p< 0.000). Patients with AITL had a poor outcome. This novel prognostic model balanced the distribution of patients into different risk groups with better predictive discrimination as compared to the International Prognostic Index and Prognostic Index for PTCL. Disclosures No relevant conflicts of interest to declare.

Download Full-text