Abstract 1772
Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of ...HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010).
Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD.
Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62).
One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001).
Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up.
No relevant conflicts of interest to declare.
Abstract 1731
Symptom burden in primary, post-ET and post-PV myelofibrosis (MF) is frequently severe and correlates with a poor prognosis. However, symptom manifestations are heterogeneous with ...variable presence of specific symptoms, splenomegaly and cytopenias. We sought to identify the spectrum and features of MF symptomatic phenotypes by cluster analysis of prospectively gathered information on MF symptoms and disease features.
Data was collected among an international cohort of subjects with MF. Data included demographics, disease features and completion of the Brief Fatigue Inventory (BFI) and Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) (Blood 2011; 118:401–408). Surveyed symptoms addressed key disease features on a 0 (absent) to 10 (worst-imaginable) scale. Cluster development was based on consideration of r-squared in hierarchical clustering using Ward’s linkage. Final cluster assignment was based on the nonhierarchical k-means method. Comparisons between symptom clusters were based on ANOVA and chi-squared tests.
Results:
Data from 329 prospectively enrolled persons with MF was collected (Chinese 102, French 54, German 19, Italian 22, Dutch 45, English 51, Spanish 29, Swedish 7) including 223 PMF, 67 post-ET MF and 39 post-PV MF patients. Participants were of typical age (mean 59) and gender (47% F). Among all participants, four natural symptom clusters were identified (Figure 1). Among clusters, disease features including leukopenia, thrombocytopenia, and enlarged spleen varied significantly between clusters (P<0.05).
The “Fatigue Dominant with Few Lab Abnormalities” Profile (n=150 (46%; 69% PMF, 20% post-ET MF, 11% post-PV MF)). Cluster 1, the largest, is characterized by fatigue-dominant complaints in the setting of the lowest overall MPN-SAF TSS and highest proportion of males (59%). Individuals among this group have the lowest prevalence of laboratory abnormalities (65% total; anemia, 67%; thrombocytopenia, 20%) or clinical deficiencies including enlarged spleen (average 6.0 cm below costal margin), prior thrombosis (9%), prior hemorrhage (5%) or prior RBC-transfusions (20.4%). Interestingly, individuals in this group are most likely to have had prior splenectomy (5.8%).
The “Cognitive Complaints with Enlarged Spleen” Cluster (n=105 (32%; 65% PMF, 20% post-ET MF, 15% post-PV MF)). Cluster 2 is the 2nd largest cluster. Subjects have relatively few abnormal lab values (67% vs 65%–77%) but have high severity of fatigue, sexual difficulties, insomnia, inactivity and reduced QOL. These individuals have the largest spleen size (8.7cm below costal margin).
The “Nighttime and Cognitive Complaints” Group (n=53 (16%; 64% PMF, 25% post-ET MF, 11% post-PV MF)). Cluster 3 is the smallest cluster. Subjects have many cognitive and nighttime-related complaints including sexual difficulties, night sweats, insomnia, and concentration problems. Subjects with post-ET MF are predominant. This cluster also has the 2ndsmallest spleen size (7 cm) or history of prior thrombosis (9.6%), hemorrhage (7.8%) or requirement for transfusions (21.2%).
The “Severe Fatigue with Few End-organ Complaints” Cluster (n=21 (6%; 81% PMF, 14% post-ET MF, 5% post-PV MF)). Cluster 4 is the most symptomatic cohort with the highest proportion of subjects with PM. There is a lower frequency of end-organ complaints including abdominal pain, cough, and headaches. Symptoms including sexual difficulties, sad mood and insomnia are predominant. No subjects had prior splenectomy. Subjects also have the highest prevalence of prior thrombosis (29%), hemorrhage (14%), and transfusions (43%). Additionally, this cohort has the largest prevalence of lab abnormalities (77%) with thrombocytopenia (71%), leukopenia (41%) and anemia (41%).
This analysis will allow us to examine a new framework for evaluating persons with MF using symptom profiles and is the 1st cluster evaluation of MF. Lab and physical findings contrast significantly between symptom clusters indicating these phenotypic symptoms likely result from etiological factors present in specific disease phenotypes. Future studies should evaluate whether there is a correlation between cluster profiles, prognosis and genotype. Display omitted
Kiladjian:Celgene: Research Funding; Novartis: Honoraria, Research Funding; Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.
Abstract 1726
We previously reported that symptom burden among persons with ET and PV can be severe and adversely affect QOL. The presence of severe symptoms is linked to poor prognosis. There is ...considerable inter-subject heterogeneity regarding which symptoms are present in which subjects. No studies have empirically evaluated whether disease characteristics can be grouped in related symptom clusters. Using our previously validated 18 item Myeloproliferative Neoplasm Assessment Form (MPN-SAF) (Blood 2011;118:401–408) given in conjunction with the 9 item Brief Fatigue Inventory (BFI) (Cancer 1999;85:1186–1196), we sought to evaluate symptom burden by means of cluster analysis.
Data was collected from an international cohort of subjects with MPNs including demographics, disease features and the completed BFI and MPN-SAF instruments. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual difficulties, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst-imaginable) scale. Development of symptom clusters was based on consideration of r-squared in hierarchical clustering using Ward linkage. Final cluster assignment was based on the nonhierarchical k-means method. Comparisons between symptom clusters were based on ANOVA and chi-squared tests.
Results:
Data from 1,141 subjects with PV (N=519) and ET (N=622) was prospectively collected (Chinese 236, French 305, German 45, Italian 114, Dutch 191, English 56, Spanish 109, Swedish 85. Age (mean 59, range, 26–87) and gender (54% F) were typical. Five clusters were selected (Figure 1). Frequencies of prior bleeding, spleen size, anemia, presence of any lab abnormality, language, gender, and MPN type varied significantly between clusters (P<0.05).
The “Reduced Symptom” Profile (n=421 (37%; 60% ET, 40% PV) The largest cluster, subjects had increased complaints of sexual difficulties and fatigue. There was a slightly higher proportion of subjects with ET (60%) versus PV. There were fewer lab abnormalities (28% prevalence) and less prior bleeding (3%) compared to other clusters. Spleen size was smallest of the cluster (1 cm below costal margin).
The “Fatigue-dominant” Group (n=286 (25%; 56% ET, 44% PV)). Subjects in this cluster were predominantly female and had relatively few laboratory abnormalities (19%) than other cohorts. They are characterized by high severity of fatigue compared to end-organ symptoms. Symptom profiles emphasize fatigue, QOL and insomnia with some end-organ complaints. The cohor 63% of the cohort.
The “End-Organ Complaints” Group (n=210 (18%; 49% ET, 51% PV)). Male predominant (56%), subjects had mainly macro-vascular symptom complaints including sexual difficulties, insomnia, and overall QOL, with few microvascular related symptoms (low itching/night sweats).
“Cognitive Complaints” Cluster (n=110 (10%; 53% ET, 47% PV)). The smallest cluster and female predominant (64%), main complaints include fatigue, insomnia, loss of concentration, numbness, and sad mood.
The “Highly Symptomatic” Cluster (n=114 (10%; 44% ET, 56% PV)). Subjects had many cognitive complaints and symptoms correlated with severe micro-vascular abnormalities (pruritus) and or splenomegaly. This cluster had the largest spleen sizes (mean 3 cm), the highest prevalence of prior thrombosis (29%), and highest frequency of lab abnormalities (43%). Cognitive and end-organ complaints were rated as most severe.
This analysis offers new means of evaluating persons with PV and ET utilizing symptom clusters. Laboratory and physical abnormalities differed significantly between symptom clusters indicating that our groupings likely result from biological alterations present in specific disease phenotypes. Future studies should investigate correlations between clusters and prognosis and genotype. Display omitted
Kiladjian:Celgene: Research Funding; Novartis: Honoraria, Research Funding; Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.
Abstract 2852
The 18-item Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF, Scherber et al Blood 2011) given in conjunction with the 9-item Brief Fatigue Inventory (BFI, Mendoza et al ...Cancer 1999) is a patient-completed questionnaire for assessing symptoms in persons with MPNs. The MPN-SAF has been translated and validated in 9 languages to date. The Total Symptom Score (TSS) is computed from 10 of the most pertinent MPN-SAF items to assess symptom burden in MPN patients and to evaluate response to therapy. Psychometric properties of the TSS have been previously reported (Emanuel et al Blood 2012). The purpose of this analysis is to compare MPN-SAF symptoms and psychometric properties of the TSS across 9 languages in an international sample.
Data were collected in an international cohort of subjects with MPNs. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual problems, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst imaginable) scale. TSS was computed using the published scoring algorithm on a 0 (all symptoms absent) to 100 (all symptoms worst imaginable) scale. Demographic and disease-related data including disease type, gender, and age had to be present to be included in analysis. Demographics were compared across languages groups using ANOVA and chi-squared tests. Symptoms and TSS were compared across language groups using a general linear model adjusting for disease type, age, and gender with post-hoc Tukey pairwise comparisons. Internal consistency and factor structure of the TSS were investigated overall and within language groups using Cronbach's alpha and principal-axis factoring analysis.
Results:
1,851 subjects with polycythemia vera (PV N=655), essential thrombocythemia (ET N=769) and myelofibrosis (MF N=427; 286 primary MF, 61 PV-MF, 80 ET-MF) were prospectively enrolled and administered the MPN-SAF and BFI in 1 of 9 languages: English UK 55, English US 102, Italian 186, Swedish 114, German 112, French 457, Spanish 192, Dutch 236, and Chinese 397. Age (median 61, range, 15–94) and gender (55% F) were typical. Disease type and age varied across language groups (both p <0.001).
Symptom frequencies ranged from 19% (fever) to 88% (fatigue) overall with mean severities ranging from 0.4 (SD=1.3, fever) to 4.3 (SD=2.3, fatigue). Fatigue had the highest mean severity among all symptoms within each language group. Overall, mean TSS was 21.5 (SD=16.7) with the Swedish (mean=18.1, SD=15.2) and Dutch (mean=27.6, SD=17.1) cohorts reporting the lowest and highest unadjusted TSS means, respectively. When comparing symptom items across languages (adjusting for disease type, age, and gender), concentration and sexual problems had the most statistically significant pairwise differences (11 and 10, respectively, out of a possible 36) followed by dizziness and overall quality of life (9 each, out of a possible 36). No statistically significant pairwise differences were observed for abdominal discomfort, headache, extremity tingling, or insomnia. For the TSS, the Dutch cohort appeared to statistically significantly differ (all p <0.05) with all other languages except the English cohorts. All other TSS pairwise comparisons were not statistically significant.
The TSS had excellent internal consistency overall (Cronbach’s alpha 0.83) as well as within language groups (Cronbach’s alpha 0.81–0.86). Overall factor analysis identified a single underlying construct among the 10 TSS items. Factor loadings ranged from 0.41 for fever to 0.73 for inactivity. A single factor solution was appropriate for each language group with factor loadings ranging from 0.18 to 0.85.
This analysis suggests that the available translations of the MPN-SAF are generally acceptable for use in a broad context. The TSS demonstrated acceptable internal consistency and similar factor structure across all language groups. Most symptom and TSS comparisons between languages were not statistically significant, but for the few which differed, further studies are needed to evaluate whether these variances are due to disease-related factors or due to linguistic or cultural influences present in the cohorts.
Kiladjian:Novartis: Honoraria, Research Funding; Celgene: Research Funding; Shire: Honoraria. Griesshammer:Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.
Abstract 3804
Poster Board III-740
Epigenetic therapy with a hypomethylating agent is becoming the standard of care in some intermediate and high-risk Myelodysplastic Syndromes (MDS) and Chronic ...Myelomonocytic Leukemia (CMML).
This multicenter, open label, single-arm study evaluated the efficacy and safety of the 5-day decitabine (DACOGEN, Janssen Cilag Farmaceutica S.A. and Eisai Inc.) dosing regimen in patients with MDS and CMML on a “Real World Program”.
Eligible patients were enrolled at different sites from South Korea and Argentina. A report prepared ad-hoc was completed. WHO classification was taken into account, as well as International Prognostic Scoring System (IPSS), performance status by ECOG, co-morbidities, previous treatments and IWG 2006 criteria. Efficacy was evaluated with at least 2 cycles. Inclusion Criteria: ≥18 years of age; de novo or secondary MDS; all WHO Subtypes and CMML type 1 and type 2. Exclusion Criteria: Acute Myeloid Leukemia (AML) or other progressive malignant disease. All patients received decitabine 20 mg/m2 IV over 1 hour x 5 days, with cycles repeated every 4 weeks.
One hundred sixteen patients enrolled (Intend-To Treat) and 99 were evaluable: median age 64, 73% male, 93% de novo MDS, median time from diagnosis 9 months, and 19% with prior chemotherapy treatment. WHO classification was: RA 1%; RARS 2%; RCMD 25%; RCMDRS 4%, RAEB-1 12%; RAEB-2 28%; MDSu 1%; CMML type-1 17% and type-2 9%. IPSS: High (17%), Int-2 (25%), Int-1 (55%) and Low (3%). Co-morbidities were described in 51%. This report includes data from a 24-month follow-up period. Patients received a median of 5 cycles (range 1-13), with 42% receiving ≥6 cycles. Overall improvement rate in the evaluable population was 35% by IWG 2006 criteria (19% CR + 4% mCR + 4% PR + 8% HI) and the rate of stable disease or better was 50%. Median time to first and best response was 2.2 and 3.9 months respectively. 37% of patients died during study period. Adverse events attributed to the study drug were febrile neutropenia (59%), thrombocytopenia and bleeding (18%), asthenia (30%), fatigue (12%), and eosinophilia (4%). Three patients received an Allo Stem Cell Transplant after achieving CR and did well. Two percent of patients responded after cycle 4. Four patients withdrew decitabine after getting CR, they relapsed and re-treatment was successful. Twenty-one percent of patients developed AML during follow-up.
Decitabine showed a prompt clinical activity and the overall improvement rate was 35%. This drug had a manageable toxicity profile. Previous chemotherapy treatment was an unfavorable risk factor. Although delayed response has been observed (2%), no less than 4 cycles should be given. Relapse was a rule after withdrawing treatment, so keeping dosing and interval is really important. This treatment was very active in CMML and allowed patients to be transplanted in a better condition.
Display omitted
No relevant conflicts of interest to declare.
Abstract 3839▪▪This icon denotes a clinically relevant abstract
We have previously reported on the validation of the 18 item Myeloproliferative Neoplasm Assessment Form (MPN-SAF) (Blood ...2011;118:401–408) given in conjunction with the 9 item Brief Fatigue Inventory (BFI) (Cancer 1999;85:1186–1196) to assess symptomatic burden in an international sample of MPN patients (pts), including validation in English, Italian, Swedish, German, French, Spanish, and Dutch. We desired to assess the utility of an average total symptom score (TSS) from the most pertinent and representative MPN symptoms for purposes of assessing the burden of symptoms in MPN pts, and subsequent tracking in response to therapy.
Data was collected among an international cohort of MPN pts and their physicians, including patient demographics and disease features and completion the BFI, MPN-SAF and the EORTC-QLQ-C30. Among pts who completed at least 5 of 10 specific items on the BFI and MPN-SAF, an average score was calculated as the TSS. TSS items included “worst” fatigue from the BFI and 9 items from the MPN-SAF including concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss and fever. The TSS thus had a possible range of 0–10 with 10 representing the highest level of symptom severity. Data was then analyzed for internal consistency, and divergent, convergent validity, and construct validity.
Patient Demographic and Disease Characteristics:1433 MPN pts were prospectively enrolled (Argentina 22, France 482, Germany 59, Italy 186, Netherlands 236, Puerto Rico 10, United Kingdom 57, United States 102, Spain 157, Sweden 114, Uruguay 8) including 594 ET, 538 PV and 293 MF pts (8 missing; MF: 61% Primary MF, 23% post-ET MF, 15% post-PV MF). 1408 pts completed at least 5 of the 10 items necessary to calculate a TSS. Pts were of characteristic age (mean 62, range 20–94) and gender (54% female) common to disease. TSS Burden of MPN Symptoms: Consistent with prior studies, the majority of pts (>50%) were symptomatic in each TSS item except for items associated with high disease severity, namely bone pain (48.6%), weight loss (30.6%) and fever (18.4%). Fatigue carried the highest symptom intensity (4.4, SD=2.8), followed by problems with concentration (2.5, SD=2.8) and early satiety (2.5, SD=2.7). Overall mean TSS was 2.1 (SD=1.6). Divergent Validity: TSS significantly differed among MPN disease subtypes (p<0.001) with means of 1.9 (SD=1.5), 2.2 (SD=1.6), and 2.5 (SD=1.7) for ET, PV, and MF pts, respectively. Statistically significant differences in TSS were also observed between pts with clinically deficient (>4, n=480) versus non-clinically deficient QOL (<4, n=894; mean 3.3 versus 1.5; p<0.001). When comparing to MD perceptions, TSS was significantly higher when MDs rated >2 of 6 common MPN-related symptoms as clinically significant (2.8, n=400) versus <2 symptoms (1.6, n=726; p<0.001). No significant trends were observed when comparing disease type by the presence of a current medical therapy. Convergent Validity: The TSS was strongly correlated with patient-reported QOL (r=0.59, p<0.001). Overall excellent correlations existed between the TSS and EORTC-QLQ-C30 functional subscales (all p<0.001 and r>0.50 except social functioning r=0.48). Additionally, excellent correlations were observed between the TSS and EORTC-QLQ-C30 fatigue and pain symptom scales (r>0.5, p<0.001). Internal Consistency and Construct Validity: The TSS had excellent internal consistency (Cronbach’s alpha=0.83). Factor analysis identified a single underlying construct among the 10 TSS items (significant eigenvalues being >1). Factor loadings ranged from 0.43 for fever and weight loss to 0.71 for inactivity. The single factor suggests that the arithmetic mean of the 10 items is an appropriate global TSS score.
The TSS demonstrated excellent psychometric properties. Overall, results of validity and internal consistency indicate that the TSS is a concise, valid, and accurate assessment of symptom burden among MPN pts. This new scoring will facilitate ease of implementation of the MPN-SAF into larger clinical trials and reduce ambiguity associated with interpreting response outcomes. Future analyses to investigate the impact of therapies on TSS are ongoing.
No relevant conflicts of interest to declare.
Epigenetic therapy with a hypomethylating agent is becoming the standard of care in some intermediate and high-risk myelodysplastic syndromes (MDS). The DNA-targeted hypomethylating agent, decitabine ...(DACOGEN, Janssen Cilag Farmaceutica S.A. and Eisai Inc.), has been approved for patients (pts) with intermediate-1 (INT-1), intermediate-2 (INT-2), and high-risk MDS in Argentina. An alternative regimen with decitabine 20 mg/m2 IV over 1 hour once daily for 5 consecutive days repeating every 4 weeks, permits its use in the outpatient clinic. Clinical and hematological response and safety were analyzed retrospectively for pts with all FAB subtypes of MDS who had received this dosing regimen at 17 centers in our country between July 2007 and June 2008. Inclusion criteria were: ≥18 years of age; de novo or secondary MDS; and International Prognosis Scoring System (IPSS) score ≥0.5. Exclusion criteria were: diagnosis of acute myeloid leukemia (AML) or other progressive malignant disease. Patients with prior therapy were not excluded. The primary endpoint was overall response, assessed by IWG 2006 criteria. Thirty-eight pts were enrolled: median age 67 years; 71% male and 29% female. The diagnosis was de novo MDS in 34 pts (89%) and secondary MDS in 4 (11%). The median time from diagnosis to first dose of decitabine was 7 months. Eastern Cooperative Oncology Group performance status scores were 0 (21%), 1 (47%), 2 (26%) and 3 (5%). IPSS scores were INT-1 (50%), INT-2 (8%), and high-risk (42%). Cytogenetic abnormalities were found in 37% of pts. FAB classification was: RA (21%), RARS (8%), RAEB (18%), RAEB-T (24%) and CMML (29%). A median of 3.5 cycles (range, 1–8) were given. Dosage had to be reduced in 7 pts (18%) due to comorbidity and cytopenias. Overall improvement rate in the intent-to-treat population was 45% (Table), including: 9% complete response (CR), 5% marrow complete response (mCR), 5% partial response (PR) and 26% hematological improvement (HI). Two pts (5%) had stable disease. Four pts (11%) were non-evaluable for response. Most pts had their first hematological response by cycle 2 and their best response by cycle 4. The mean ± SD time to best response was 2.7±3 months. No differences in clinical and hematological response were observed between pts with INT-2/High compared to INT-1 (8/19 and 9/19, respectively); red cell and platelet transfusion requirements resolved during the first 2 cycles in 13/16 and 7/8 pts, respectively. Overall improvement rates were similar in pts with more and less than 1 year since MDS diagnosis (9/18 and 8/20, respectively). Overall survival was 71% during the observational period (up to 11 months). The most frequent adverse events were neutropenia without fever (47%) and with fever (21%), especially during cycle 2, and thrombocytopenia (23%). This study showed prompt clinical activity for an alternative 5-day dosing schedule of decitabine in the outpatient setting and an overall improvement rate of 45%, with an initial response by cycle 2, the best response by cycle 4, and acceptable tolerability.
<>Table. Response to 5-Day Decitabine Dosing Schedule
IWG 2006 CriteriaITT (N=38)Overall Improvement Rate (CR+mCR+PR+HI)17 (45%)CR (Complete Response)3 (9%)mCR (Marrow Complete Response)2 (5%)PR (Partial Response)2 (5%)HI (Hematological Improvement)10 (26%)SD (Stable Disease)2 (5%)Failure (Progressive Disease or Death)15 (39%)Non-Evaluable4 (11%)
Background: monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 1 to 3%. Although it has an indolent evolution, some patients (pts) will develop a malignant transformation. ...Thus, prognostic factors that may identify pts who will progress are important. We update our experience published before.
Methods: we performed a retrospective analysis of 387 pts with MGUS diagnosed between 1982 and 2008 in our institution to identify simple haematological variables associated with progression. Actuarial progression free survival (PFS) and overall survival (OS) were also calculated. MGUS was diagnosed when monoclonal component (MC) was present at a concentration of 3 gr per decilitre or less, no or only moderate amounts of monoclonal light chains in the urine, absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to monoclonal protein; and if performed a proportion of plasma cells of 10 percent or less. MC was detected by agarose gel and/or cellulose acetate electrophoresis in serum and/or urine. The identification of the MC was performed by immunoelectrophoresis or immunofixation and the quantification of immunoglobulins, by radial immunodifussion. Progression to myeloma was defined by: MC > 3 gr/dl, plasma cell infiltration > 10%, or associated lytic bone lesions. Progression to another B-cell neoplasm was considered when there was histologic evidence of the disease. The identification of prognostic factors was made using Cox models. PFS and OS were calculated using the Kaplan Meier method and the curves were compared with the log-rank test.
Results: The median (md) age at diagnosis was 62 years (range 24–89 years) and 18% of the pts were younger than 50. Anemia not related to the monoclonal protein was present in 18% of the pts. Albumin, beta 2 microglobulin and erythrocyte sedimentation rate (ESR) were normal in 88%, 50% and 41% of the pts, respectively. MC was 0.6 gr/dl (range 0.1–2.9). In 70% of the cases it was IgG, 15% IgA, 13% IgM and 2% biclonal. The light chain was Kappa in 65% of the pts. Bence Jones was detected in only 9%. Uninvolved immunoglobulins (UI) were reduced in 21% of the pts. Bone marrow analysis were performed in 79 pts (20%) and md plasma cell infiltration was 3 (range 0 – 10). The 387 pts were followed for 2340 person-years (md 4.75 years, range 0 – 31) during which 31 pts (8%) evolved to a malignancy (23 multiple myeloma, 7 NHL, and 1 amyloidosis) and 17 (4.6%) died (3 related to progressive disease, 6 related to non hematological malignancy, 2 associated to cardiovascular disorders, 2 secondary to infection and 4 of unknown cause). PFS and OS at 10 years were 89% and 91%, respectively. The overall risk of progression was 1.3% per year. Among all the variables analysed (age, gender, hemoglobin, albumin, beta 2 microglobulin, ESR, type and concentration of MC, Bence Jones and reduction of UI), only MC concentration (HR 4.81, CI 2.2 – 10.32, p = 0.00007) and ESR (HR 3.67, CI 1.7 – 7.88, p = 0.001) had prognostic value for progression.
Conclusions: MC concentration and ESR at diagnosis identified a subgroup of pts with higher risk of transformation in our experience.
Objective: To determine the prevalence of JAK2 V617F mutation and its clinical correlation in patients with chronic myeloproliferative disorders (CMD): polycythemia vera (PV), essential ...thrombocythemia (ET) and idiopathic myelofibrosis (IMF).
Materials and methods: Detection of JAK2 V617F mutation by allele specific-PCR.
Results: One hundred and three patients with CMD were included in the study. JAK2 V617F distribution was PV 40/45 (89%), ET 30/43 (69%), and IMF 7/15 (47%). In PV and ET patients only, 18 had thrombosis at diagnosis and 12 during follow-up (these were microvascular: 11, venous: 7 and arterial: 12); of these 28/70 (40%) were JAK2pos versus 2/18 (11%) JAK2neg; P=0·02. In a median of 4 years, two patients with PV JAK2pos evolved to myelofibrosis and one patient with PV presented in leukemic transformation (JAK2pos before and after transformation); six patients died: four patients with IMF and two patients with PV.
Conclusions: We found an association between JAK2 V617F and thrombotic events in patients with PV and ET.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract 4838
Myelodysplastic Syndromes (MDS) are so heterogeneous, that new prognostic scoring systems are being continuously developed to help choose the best treatment strategy. The International ...Prognostic Scoring System (IPSS) excludes secondary MDS, prior therapy and Chronic Myelomonocytic Leukemia (CMML) with leucocytosis. Recently, a new risk model has been published by Kantarjian et al. (Cancer 2008; 113; 6; 1351) that is applicable to all MDS patients.
To validate this new risk model in our MDS population.
We analyzed 253 patients reported from 15 centers in our country from Jan 2007 through Jun 2009. We took into account age, performance status (PS), hemoglobin, platelets, leucocytes, bone marrow blasts, karyotype, and transfusion requirements. The new model divided patients into 4 prognostic groups: Low Risk (LR): 0-4; Intermediate-1 (I-1): 5-6; Intermediate-2 (I-2): 7-8; and High Risk (HR): ≥9. We assessed the prognostic impact of this New Risk Model and compared results to IPSS. Mortality Rate and AML progression risk were analyzed.
164 patients were evaluable, mean age 69 (R 21-92), primary MDS: 144, and secondary MDS: 20. Risk Group assessment for the new score: LR (34%), I-1 (31%), I-2 (18%), and HR (17%). The mean Follow-up was 22 months;
are shown in table and graphic.
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Even though our sample is not considerably big, and follow-up is short, we confirmed 4 categories with different prognosis and found a close correlation with Mortality Rate. This New Scoring System allowed us to identify Low Risk IPSS patients with different outcomes, highlighted the importance of adding new prognostic factors like age and performance status, refined the cut-offs of thrombocytopenia and anemia, and recognized the adverse impact of prior transfusions needs. Display omitted
No relevant conflicts of interest to declare.
