scholarly journals Differential Impact of ALK Mutations in Neuroblastoma

2021 ◽  
pp. 492-500
Author(s):  
Tara O'Donohue ◽  
Nitya Gulati ◽  
Audrey Mauguen ◽  
Brian H. Kushner ◽  
Neerav Shukla ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Tyrosine Kinase Receptor ◽  
Differential Impact ◽  
Mutation Site ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
The Impact

PURPOSE The tyrosine kinase receptor anaplastic lymphoma kinase (ALK) can be abnormally activated in neuroblastoma, and somatic ALK mutations occur in 6%-10% of patients. The differential clinical impact of these mutations has not been clearly elucidated. METHODS Data on patients with neuroblastoma harboring ALK mutations were retrospectively analyzed. ALK sequencing was performed by whole-genome sequencing, hybrid-based capture of targeted exomes, or hotspot ALK mutation profiling. The differential impact of ALK mutation site on clinical characteristics, response to treatment, and survival was analyzed. In a subgroup of patients with locoregional neuroblastoma diagnosed after 2014, the impact of all ALK mutations was compared with wild-type ALK. RESULTS Of 641 patients with neuroblastoma with ALK status analyzed on at least one tumor sample, 103 (16%) had tumors harboring ALK mutations. Mutations existed across all ages (birth to 67.8 years), stages (30% locoregional and 70% metastatic), and risk groups (20%, 11%, and 69% with low-, intermediate-, and high-risk disease, respectively). Mutation sites included F1174 (51%), R1275 (29%), R1245 (10%), and others (10%). Mutation site was not prognostic for progression-free survival or overall survival in the entire cohort, high-risk subgroup, or locoregional subgroup. Locoregional tumors with any ALK mutation were generally invasive: L2 by International Neuroblastoma Research Group staging in 30/31 patients with a 2-year progression-free survival (59%, 95% CI, 37.4 to 80.5) that was inferior to historical controls. This observation was corroborated in the post-2014 subgroup in which gross total resection was less likely for ALK-mutated tumors. CONCLUSION Somatic ALK mutations are present across all stages and risk groups of neuroblastoma. No specific mutation carries differential prognostic significance. Locoregional neuroblastoma has an invasive phenotype when harboring somatic ALK mutations in this population.

Prognostic Indices in Older DLBCL Patients Receiving R-CHOP: An Analysis of the U.S. Intergroup Study (E4494, CALGB 9793).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 813-813
Author(s):  
R.H. Advani ◽  
H. Chen ◽  
T.M. Habermann ◽  
V.A. Morrison ◽  
E. Weller ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Risk Category ◽  
Free Survival ◽  
Prognostic Tool ◽  
The Impact ◽  
The U.S

Abstract Background: We reported that addition of rituximab (R) to chemotherapy significantly improves outcome in DLBCL patients (pt) >60 years (JCO24:3121–27, 2006). Although the IPI is a robust clinical prognostic tool in DLBCL, Sehn et al (ASH 2005: abstract 492) reported that a revised (R) IPI more accurately predicted outcome in pt treated with rituximab-chemotherapy. Methods: We evaluated outcomes of the Intergroup study with respect to the standard IPI, R-IPI, age-adjusted (aa) IPI for evaluable pt treated with R-CHOP alone or with maintenance rituximab. We further assessed a modified IPI (mIPI) using age ≥ 70 y as a cutoff rather than age 60 y. Results: The 267 pt in this analysis were followed for a median of 4 y. Pt characteristics were: age > 70 (48%) (median=69), male 52%, stage III/IV 75%, >1 EN site 30%, LDH elevated 60%, PS ≥2 15%. On univariate analysis all of these characteristics were significant for 3 y failure-free survival (FFS) and overall survival (OS). The IPI provided additional discrimination of risk compared to the R-IPI with significant differences in FFS and OS for 3 vs 4–5 factors. The aa-IPI defined relatively few pt as low or high risk. The impact of age was studied using a cut-off of 70 years in a modified IPI, yielding 4 risk groups as shown below. Conclusions: For pt ≥ 60 treated with rituximab-chemotherapy the distinction between 3 vs 4,5 factors in the IPI was significant.The IPI also provided additional discrimination of risk compared to the R-IPI. In this older group of pt, use of an age cutoff ≥70 y placed more patients in the low risk category. It is of interest to apply the mIPI in other datasets with DLBCL pt >60 y. Group # Factors # Pt % 3y FFS* % 3y OS* *All risk groups significantly different; logrank p < 0.001 **95 % CI: FFS (0.46,0.66), OS (0.58,0.78) ***95 % CI: FFS (0.21,0.45), OS (0.31,0.55) L: Low, LI: Low Intermediate, HI: High Intermediate, H; High IPI L 0–1 12 78 83 LI 2 28 70 80 HI 3 33 56** 68** H 4–5 37 33*** 43*** R-IPI Very Good 0 0 - - Good 1–2 40 72 81 Poor 3–5 60 46 57 aa-IPI L 0 12 78 83 LI 1 35 68 78 HI 2 44 47 59 H 3 9 31 35 mIPI (age ≥ 70) L 0–1 27 77 86 LI 2 28 62 74 HI 3 29 47 58 H 4–5 16 28 36

Age-related efficacy and safety of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in subgroups of patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Post hoc analysis of SPARTAN.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5024-5024 ◽  
Author(s):  
Julie Nicole Graff ◽  
Matthew Raymond Smith ◽  
Fred Saad ◽  
Boris A. Hadaschik ◽  
Hiroji Uemura ◽  
...  
Keyword(s):  
High Risk ◽  
Safety Profile ◽  
Age Groups ◽  
Progression Free Survival ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Cox Models ◽  
Free Survival ◽  
Age Related ◽  
The Impact

5024 Background: SPARTAN, a randomized phase 3 placebo (PBO)-controlled study in pts with high-risk nmCRPC and PSA doubling time ≤ 10 mo, showed that, compared with PBO, addition of APA to ongoing ADT treatment (tx) prolonged metastasis-free survival (MFS) by > 2 y, reduced the risk of symptomatic progression by 55%, and increased second progression-free survival (PFS2), which is the time from randomization to disease progression on first subsequent anticancer tx, or death. The impact of APA in terms of benefit and safety profile was evaluated in pts aged < 65, 65-74, and ≥ 75 y. Methods: Pts with nmCRPC were randomized 2:1 to APA (240 mg QD) or PBO; ADT was continuous. APA effect was analyzed by Cox models and Kaplan-Meier methods across age subgroups. Results: Baseline characteristics among age groups were similar, although ECOG PS 1 vs 0 increased with age. MFS benefit with APA was highly significant for all age subgroups (Table). In pts ≥ 75 y, MFS risk with APA vs PBO was reduced by 59%; MFS risk was reduced by 86% and 76% for pts < 65 and 65-74 y, respectively. Risk of PFS2 with APA vs PBO was reduced across all age subgroups. PFS2 in pts < 65, 65-74, and ≥ 75 y: HR, 0.09 (p < 0.0001); HR, 0.56 (p = 0.0343); HR, 0.59 (p = 0.0092), respectively. Risk of symptomatic progression was lessened with APA vs PBO for all age subgroups (Table). There was a similar increase in incidence of tx-emergent adverse events (TEAE) with age in both tx arms that remained higher with APA. Incidence of grade 3/4 TEAE (≥ 75 vs < 65 y): APA, 50% vs 37%; PBO, 37% vs 28%. Conclusions: Pts in all age subgroups with high-risk nmCRPC had significant improvement in MFS with APA + ongoing ADT. The safety profile of APA was similar across age subgroups. Clinical trial information: NCT01946204. [Table: see text]

Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 686-692 ◽  
Author(s):  
Joerg Hasford ◽  
Michele Baccarani ◽  
Verena Hoffmann ◽  
Joelle Guilhot ◽  
Susanne Saussele ◽  
...  
Keyword(s):  
High Risk ◽  
Kinase Inhibitors ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
Risk Groups ◽  
High Risk Group ◽  
Prognostic Scores ◽  
Imatinib Treatment ◽  
Free Survival ◽  
Eutos Score

AbstractThe outcome of chronic myeloid leukemia (CML) has been profoundly changed by the introduction of tyrosine kinase inhibitors into therapy, but the prognosis of patients with CML is still evaluated using prognostic scores developed in the chemotherapy and interferon era. The present work describes a new prognostic score that is superior to the Sokal and Euro scores both in its prognostic ability and in its simplicity. The predictive power of the score was developed and tested on a group of patients selected from a registry of 2060 patients enrolled in studies of first-line treatment with imatinib-based regimes. The EUTOS score using the percentage of basophils and spleen size best discriminated between high-risk and low-risk groups of patients, with a positive predictive value of not reaching a CCgR of 34%. Five-year progression-free survival was significantly better in the low- than in the high-risk group (90% vs 82%, P = .006). These results were confirmed in the validation sample. The score can be used to identify CML patients with significantly lower probabilities of responding to therapy and survival, thus alerting physicians to those patients who require closer observation and early intervention.

scholarly journals Rituximab Maintenance Benefits Less for Follicular Lymphoma Patients with Low Risk of the Follicular Lymphoma International Index

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3544-3544
Author(s):  
Tingyu Wang ◽  
Ru Li ◽  
Rui Lv ◽  
Ying Yu ◽  
Jiawen Chen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Low Risk ◽  
Control Group ◽  
Intermediate Risk ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Risk Patients

Abstract Background Follicular lymphoma (FL) is an incurable indolent disease with a heterogeneous course. The Follicular Lymphoma International Prognostic Index (FLIPI) is the most commonly used prognostic system to predict survival. Rituximab-based immunochemotherapy is now the standard choice for the first-line therapy of FL, followed by rituximab maintenance (RM) in patients with response, which prolongs the progression-free survival (PFS). However, the role of RM in different FLIPI risk groups has never been studied as we know. In this study, we aimed to illustrate the effect of RM in FLIPI risk groups. Methods Newly diagnosed FL patients at our center were enrolled in this analysis. All the patients received the rituximab-based chemoimmunotherapy induction regimens. Response assessments were determined according to Lugano's 2014 criteria. Patients who didn't respond to induction were excluded. Categorical variables were compared using Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results From May 2003 to September 2020, 203 newly diagnosed FL were included. 192 patients (95.0%) achieved remission (complete response, CR/partial response, PR) after immunochemotherapy induction, of whom 96 patients continued rituximab maintenance therapies every 3 months for 1-2 years (RM group) (median 7 times，range 4 to 12). 96 patients received no maintenance or fewer than 4 times (control group) (median 0 times, range 0-3). There were no significant differences in baseline characteristics other than the Ann Arbor stage and pathological grade. The RM group patients were more likely to be at low grade (71.8% vs 54.9%, P = 0.042) and advanced stage (90.6% vs 78.7% , P = 0.027) (Table 1). After a median follow-up of 36.4 months (95% confidence interval [CI], 32.2 to 40.6), median OS and PFS were not reached. The 5-year OS rates and PFS rates were 95.1% (95%CI, 90.2%-100%) and 83.0% (95%CI, 75%-91%)(Fig 1). And RM significantly prolonged the PFS, with 5-year PFS rates 92.2% (95%CI, 85.1%-99.3%) and 70.3%(95%CI, 55%-85.6%) (P = 0.0003) (Fig 2). According to FLIPI risk stratification, patients were classified into low-risk, intermediate-risk, and high-risk groups. The 5-year PFS rates were 97.7% (95%CI, 93.2%-100%), 84.7% (95%CI, 70.4%-99%), and 67.8% (95%CI, 49%-86.6%), respectively (Fig 3). For low-risk patients, there was no significant difference in PFS for the RM group vs the control group. However, for both intermediate risk and high-risk patients, PFS was significantly longer in the RM group compared to the control group (P &lt; 0.0001). The PFS rates at 5 years in intermediate-risk patients were 100% and 77.8% (95%CI, 40.8%-92.6%), for the RM group vs control group, high risk 76.4% (95%CI, 54.3%-98.5%), and 54.9% (95%CI, 21.6%-88.2%), respectively (Fig 4). Conclusion Standard rituximab maintenance significantly prolongs progression-free survival in FLIPI intermediate risk and high-risk patients with FL, but not in the FLIPI low risk group. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

Medulloblastoma

2017 ◽  
Author(s):  
Kevin C De Braganca ◽  
Roger J Packer
Keyword(s):  
High Risk ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Free Survival ◽  
High Risk Disease ◽  
Poor Treatment ◽  
Short And Long Term ◽  
Standard Risk

Medulloblastoma is the most common malignant brain tumor in pediatric patients. Patients are presently stratified to either standard or high-risk groups based on clinical and pathologic criteria. Approximately 80% of patients with standard risk disease are cured of their primary disease. High-risk and recurrent disease groups have a poorer outcome; 5-year progression-free survival is only 65% with high-risk disease. Disease control after recurrence is very poor. Treatment is multimodal and also aims to limit short- and long-term toxicities. Recent identification of four molecular subtypes of medulloblastoma may change risk assignment and therapy. Addressing the medical and psychosocial issues of survivors continues to improve the quality of life for these patients beyond the disease’s treatment.

Minimal residual disease (MRD) status pre- and post- high-dose therapy/autologous stem (HDC/ASCT) cell transplantation for multiple myeloma (MM) in the era of novel agents.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8605-8605
Author(s):  
Adetola Kassim ◽  
Jeremy Scott McDuffie ◽  
Claudio A Mosse ◽  
Bipin N. Savani ◽  
John P. Greer ◽  
...  
Keyword(s):  
Residual Disease ◽  
Prognostic Significance ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Disease Stage ◽  
High Dose ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact

8605 Background: MRD assayed by multi-parameter flow cytometer (MFC), has prognostic significance after HDT/ASCT for MM (Paiva et. al. 2008). The frequency of MRD negativity (-) after induction therapy using novel agents such as immunomodulatory drugs like lenalidomide (IMiDs), and proteasome inhibitors like bortezomib, is unknown. The impact of HDT/ASCT on MRD status in this patient group has not been studied. Methods: We performed a retrospective study of all MM patients undergoing HDT/ASCT (January 2010 - December 2012) in our institution. No restrictions on inclusion were made based on the International Myeloma Working Group response criteria. All patients had novel agents as part of their initial induction regimen. Statistical analysis was by SPSS software (V 12.0). MRD status was determined by MFC on bone marrow samples pre- HDC/ASCT [M1] and post- HDC/ASCT (D100 [M2] and I year [M3]). MFC was done with antibodies against CD45, CD19, CD138, CD38, CD20, CD56, and anti-k and l cytoplasmic antibodies. Results: MRD status was available on 91 patients pre-transplant. Of these patients, 80 had MFC recorded at M2 and 17 patients had MFC recorded at M3. Fifty-eight percent were male and 76% were Caucasian. Forty percent received IMiDs, while 60% got proteasome based therapies. Of the 91 patients with MRD pre-HDC/ASCT, 58% (53/91) were MRD (-), and of these patients 89% (41/46) remained MRD (-) at M2. 48 patients were MRD positive (+) pre-HDC/ASCT, 58% (20/34) became MRD (-) at M2. Age, cytogenetic risk, disease stage, number of chemotherapy cycles or immunofixation status had no impact on MRD status. There were only 6 relapses in the cohort, thus the impact of MRD status on progression-free survival could not be studied. Conclusions: Novel agents improve depth of response pre-transplant. HDC/ASCT increases MRD negativity post-transplant. MRD status could aid better timing of HDC/ASCT or adoption of a risk-adapted strategy for high-risk patients. MRD status validation in a prospective cohort is underway at our center (NCT01215344). With future follow-up, the impact of MRD on progression-free survival in the era of novel agents will be determined.

Carfilzomib-based induction/consolidation with or without autologous transplant (ASCT) followed by lenalidomide (R) or carfilzomib-lenalidomide (KR) maintenance: Efficacy in high-risk patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8002-8002
Author(s):  
Francesca Gay ◽  
Roberto Mina ◽  
Delia Rota-Scalabrini ◽  
Monica Galli ◽  
Angelo Belotti ◽  
...  
Keyword(s):  
High Risk ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Medical Need ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk ◽  
Clinical Trial Information ◽  
1Q Gain

8002 Background: Cytogenetic abnormalities (CA) are one of the most powerful prognostic factors in multiple myeloma (MM). In the FORTE study, carfilzomib-lenalidomide-dexamethasone induction/consolidation with ASCT (KRd_ASCT) significantly improved progression-free survival (PFS) vs KRd without ASCT (KRd12, HR 0.64) or carfilzomib-cyclophosphamide-dexamethasone (KCd) plus ASCT (KCd_ASCT, HR 0.53). KR maintenance significantly improved PFS vs R (HR 0.63). Methods: MM patients (pts) were randomized to KRd_ASCT vs KCd_ASCT vs KRd12 and, thereafter, to KR vs R maintenance. Subgroup analyses according to FISH evaluated the impact of each single high-risk (HiR) CA [del17p, t(4;14), t(14;16), del1p and 1q gain (3 copies) or amp1q (≥4 copies)] and that of combined CA, defining HiR by the presence of ≥1 HiR CA and double-hit (DH) by the presence of ≥2 HiR CA. Pts negative for all the HiR CA were considered at standard risk (SR). The primary objective was the impact of treatment on PFS according to pt risk. Results: 396 out of 474 enrolled pts were included in the analysis with complete FISH data: 243 HiR, 105 DH and 153 SR. Among HiR pts, 60 had del17p, 65 t(4;14), 20 t(14;16), 44 del1p, 126 1q gain and 49 amp1q. SR pts benefited from intensification with KRd_ASCT vs KRd12 (HR 0.47, p = 0.05) and KCd_ASCT (HR 0.38, p = 0.01), with a 4-year PFS of 80%, 67% and 57%, respectively. In HiR pts, KRd_ASCT improved PFS vs KRd12 (HR 0.6, p = 0.04) and KCd_ASCT (HR 0.57, p = 0.01), with a 4-year PFS of 62%, 45% and 45%, respectively. The advantage with KRd_ASCT vs KRd12 (HR 0.53, p = 0.07) and KCd_ASCT (HR 0.49; p = 0.03) was also observed in DH pts (4-year PFS 55%, 31% and 33%, respectively). Analyses by single CA were limited by the small number of pts in each subgroup, but a trend towards a PFS benefit from KRd_ASCT vs KRd12 was seen in pts with del17p (HR 0.61, p = 0.3), t(4;14) (HR 0.59, p = 0.2) and 1q gain (HR 0.45, p = 0.02). In pts with del1p, KRd_ASCT (HR 0.24, p = 0.06) and KRd12 (HR 0.33, p = 0.09) showed superiority over KCd_ASCT, while amp1q pts had the worst outcome regardless of treatment (KRd_ASCT vs KCd_ASCT, HR 1.16, p = 0.73; KRd12 vs KCd_ASCT, HR 1.34, p = 0.45). KR improved PFS vs R in SR (3-year PFS 90% vs 73%, HR 0.42, p = 0.06), HiR (3-year PFS 69% vs 56%, HR 0.6, p = 0.04) and DH pts (3-year PFS 67% vs 42%, HR 0.53, p = 0.1). Despite the small subgroups, a beneficial trend with KR vs R was observed in pts with del17p (HR 0.59, p = 0.37), t(4;14) (HR 0.59, p = 0.3), 1q gain (HR 0.54, p = 0.07) and del1p (HR 0.23, p = 0.08), while amp1q pts showed the worst outcome and no benefit from KR vs R (HR 0.83, p = 0.7). Conclusions: KRd_ASCT and KR maintenance are highly effective in SR and also in HiR and DH pts, with impressive 4-year PFS from diagnosis (KRd_ASCT: HiR 62%, DH 55%) and 3-year PFS from maintenance (KR: HiR 69%, DH 67%), thus supporting their use in HiR pts, who represent an unmet medical need. Clinical trial information: NCT02203643.

Comorbidity as Prognostic Variable in MDS: Comparative Evaluation of the HCT-CI and CCI in a Core Data Set of 582 Patients of the Austrian MDS Platform.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1648-1648
Author(s):  
Wolfgang R Sperr ◽  
Friedrich Wimazal ◽  
Michael Kundi ◽  
Christian Baumgartner ◽  
Thomas Noesslinger ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Data Set ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Prognostic Variable ◽  
Prognostic Parameter ◽  
Comorbidity Index ◽  
The Impact

Abstract Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective erythropoiesis, peripheral cytopenia(s), and an increased risk to transform to secondary acute myeloid leukemia (AML). The prognosis in MDS is variable and depends on the variant of disease, other disease-related features, and patient-related parameters. In the present study, the influence of comorbidity on survival and AML evolution was analyzed retrospectively in 582 patients (270 females and 312 males, f/m ratio: 1:1.2) with de novo MDS (observation period: 1985–2007). The median age was 71 years (range 18–96 years). Of the 582 patients, 275 died so far. The median survival (OS) of all patients was 3.12 years, and the median event-free survival (EFS) was 2.3 years. The median AML-free survival (AFS) was not reached. All in all, 127 patients (22%) developed secondary AML after a median time of 9.7 months (range 0.3–116.6 months). Two different scoring systems for comorbidity, the hematopoietic stem cell transplantation comorbidity index (HCT-CI) and the Charlson comorbidity index (CCI) were applied. As assessed by log rank test, the overall survival (OS) was found to differ among patients in the three different HCT-CI risk groups (p&lt;0.05) and among patients in the four different CCI risk groups. By univariate analysis, the HCT-CI was found to be of prognostic value for OS and EFS in patients meeting WHO- or FAB criteria (p&lt;0.05). The CCI was also found to be of prognostic value for OS in patients diagnosed according to either WHO or FAB criteria (p&lt;0.05). With regard to EFS, the CCI was a prognostically significant variable only for patients meeting WHO criteria (p&lt;0.05), but not in patients diagnosed according to FAB criteria (p&gt;0.05). Calculating AML-free survival (AFS), neither the CCI nor the HCT-CI were of prognostic significance (p&gt;0.05). To evaluate whether comorbity is an independent prognostic parameter in patients with MDS, multivariate analyses were performed. These analyses included the HCT-CT or the CCI together with IPSS, LDH, and the patients’ age. In these analyses, chronic comorbid conditions were found to be independent prognostic risk factors concerning OS and EFS, but not concerning AFS. Specifically, the HCT-CI was an independent prognostic parameter regarding OS (p&lt;0.05) and EFS (p&lt;0.05) for patients diagnosed according to WHO- or FAB-criteria. In contrast, the CCI was of prognostic significance regarding OS for patients meeting WHO- or FAB-criteria, whereas the CCI was not found to be an independent prognostic factor regarding EFS (p&gt;0.05). Regardless of the score applied (HCT-CI or CCI), the highest predictive value of comorbidity was observed in IPSS low risk patients (p&lt;0.05) concerning OS. Of the other variables included in our multivariate analysis, the IPSS was an independent prognostic parameter for OS, EFS, and AFS. Interestingly, age was an independent prognostic variable for OS and EFS, but not concerning AFS, similar to the impact of comorbidity, whereas LDH was an independent predictive factor concerning EFS and AFS. Together, our data show that comorbidity is an independent risk factor for survival in patients with MDS. Therefore, comorbidity should be considered as an important co-variable in the risk assessment in MDS and in the overall treatment plan in these patients.

Prevalence and Clinical Implications of N-RAS Mutations in Childhood AML – A Report From the Children's Oncology Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3115-3115
Author(s):  
Jason N. Berman ◽  
Robert B. Gerbing ◽  
Lillian Sung ◽  
Kristen Miller ◽  
Jessica A. Pollard ◽  
...  
Keyword(s):  
Signal Transduction ◽  
High Risk ◽  
Prognostic Significance ◽  
Low Risk ◽  
Signal Transduction Pathways ◽  
Free Survival ◽  
Ras Mutations ◽  
Significant Difference ◽  
Pediatric Aml ◽  
The Impact

Abstract Abstract 3115 Poster Board III-52 Mutations in the RAS proto-oncogenes are frequent in acute myeloid leukemia (AML) and serve as prototypic Class I lesions, initiating key downstream hyper-proliferative signal transduction pathways. N-RAS mutations (N-RASmut) are common in AML, occurring in 10-20% of adult and pediatric AML patients; however their prognostic significance in both adults and children remains disputed. Due to a frequent association with a normal karyotype, delineating the impact of these mutations on outcome may enable appropriate risk-adapted therapeutic approaches. Here, we report on the incidence and prognostic significance of N-RASmut in a cohort of 825 pediatric AML patients treated on 2 recent co-operative group studies, CCG-2961 and COG AAML03P1. In total, of the 825 children with de novo AML who underwent N-RAS mutational analysis, 86 (10%) were positive. Gender, age, race, presence of hepatosplenomegaly and FAB subtype were comparable between patients with and without N-RASmut. There was no statistically significant difference between those with and without N-RASmut with respect to specific chromosome class. FLT3/Internal tandem duplications (FLT3/ITD) were less common in those with N-RASmut (2% vs. 9%, p=0.03). In contrast, nucleophosmin (NPM) mutations were more common in those with N-RASmut (13% vs. 5%, p=0.02). Overall, N-RASmut showed a significant correlation with low risk AML (CBF, CEBPαa, or NPM, p=0.04) and an inverse relationship with high risk disease (-5/5q- or -7, FLT3/ITD/high allelic ratio, p=0.007). Patients with N-RASmut had similar complete remission (CR) rates following two courses of induction chemotherapy compared with non-mutated patients (79% vs. 79%, p=0.92). Those in CR had a similar relapse rate regardless of the presence of N-RASmut (RR 39% vs. 36%, p=0.97). Five year event free survival (EFS) and overall survival (OS) from study entry were also comparable, however N-RASmut patients demonstrated a marked increase in overall treatment related mortality (TRM) (21% vs. 14%, p=0.03), which was maintained when high and low risk patients were excluded (22% vs. 11%, p=0.05). Evaluation of TRM in CCG-2961 compared with COG AAML03P1 demonstrated that increased TRM in N-RASmut was only seen in patients treated on CCG-2961 and TRM was primarily due to invasive fungal and gram negative infections. Interestingly, for patients treated on CCG-2961, who received interval compressed intensive induction therapy, this increase in TRM correlated with a decrease in both OS and disease free survival from CR. Remission specimens from patients with N-RASmut were negative for the mutation, demonstrating that an increased infectious risk could not be attributed to a host polymorphism. We found N-RASmut did not contribute to increased disease recurrence in pediatric AML. Our findings indicate that N-RAS mutations do not identify a high risk population, however, as such mutations lead to downstream activation of signal transduction pathways, they may identify a target for directed therapy. Disclosures No relevant conflicts of interest to declare.

The FLIPI2 SCORE Predicts PROGRESSION-FREE SURVIVAL (PFS) and OVERALL SURVIVAL (OS) IN AN INDEPENDENT SERIES of Follicular LYMPHOMA: A Single Institution EXPERIENCE

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3128-3128 ◽  
Author(s):  
María José Terol ◽  
Ana Isabel Teruel ◽  
Paula Amat ◽  
Danella Elaluf ◽  
Mar Tormo ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Risk Group ◽  
Progression Free Survival ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Free Survival ◽  
Intermediate Group ◽  
Independent Series

Abstract Abstract 3128 Background: follicular lymphoma is an incurable, long-lasting disease with an heterogeneous outcome. Several prognostic systems have been proposed, and recently a new one, the FLIPI2 score based on five parameters has been published. However, in order to confirm its prognostic utility, further studies at other centers are highly recommendable. Aim: to validate the new FLIPI2 score in independent series of follicular lymphoma patients diagnosed at our institution between February 1990 and July 2010. Patients and methods. We considered 180 patients consecutively diagnosed with follicular diagnosis in the period described and from whom all variables required were available. The variables included were: beta2microglobulin higher than the upper normal value, longest diameter of the largest involved node longer than 6 cm, bone marrow infiltration, hemoglobin level lower than 120 g/L and age older than 60 years (one point if present). Three risk groups were identified: low risk (0 points), intermediate risk (1 -2) and high risk (3 or more) Progression-free survival was measured from date of treatment until date of progression or death from any cause. Continuous variables were summarized as median and range, categorical variables reported as counts, and PFS and OS carried out using the Kaplan-Meier method and curves compared by the log-rank test. Results: median age was 55 years (range, 24 to 77), male sex 92 (51%), Ann Arbor Stage I-II: 32(18%), III-IV: 143 (82%), age > 60 y 70 (39%), Hb < 120 g/L 38 (21%), β2microglobulin > UNV: 45 (25%), LDH > UNV: 34 (19%), bone marrow infiltration 82 (48%), longer diameter of the largest involved node > 6 cm 64 (36%). 47 patients (26%) received rituximab-containing regimens and 124 received conventional chemotherapy regimens (pre-rituximab era). Median follow-up of the series was 66.9 months (range,1.3-221). Using the FLIPI score (n=162) 58 patients (36%) were in the low risk group, 54 (33%) were in the intermediate group and 50 (31%) in the high risk group. Using the FLIPI2 (n=180) 36 patients (20%) were in the low risk group, 103 (57%) in the intermediate group and 41 (23%) in the high risk group. According to FLIPI 5y- PFS rate was 79% for the low risk group, 63% for the intermediate group and 32% for the high risk group, p < 0.001. According to FLIPI2 score, 5y-PFS rate was 82% for the low risk, 54% for the intermediate and 43% for the high risk groups, p=0.017. Concerning OS, applying the FLIPI, 5y-OS rate for the low, intermediate and high risk groups were 94%m 84% and 64%, respectively, p=0.003. Using the FLIPI2, 5y-OS for the low, intermediate and high risk groups were 96%, 80% and 67% respectively, p=0.006. Conclusions: in our experience the FLIPI2 score is a reproducible prognostic index in patients with follicular lymphoma although the FLIPI score seems to discriminate better between groups than the FLIPI2 score. Disclosures: No relevant conflicts of interest to declare.

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