Ruxolitinib – better prognostic impact in low-intermediate 1 risk score: evaluation of the ‘rete ematologica pugliese’ (REP) in primary and secondary myelofibrosis

Abstract In order to reduce toxicity in elderly patients with newly diagnosed APL, since 3/1997 the Italian cooperative group GIMEMA evaluated an amended AIDA protocol for patients aged > 60 years, consisting of the same induction with ATRA and Idarubicin but only 1st consolidation course (Idarubicin + Cytarabine), followed by 2 years maintenance with ATRA alone. Up to now, 56 patients (25 males and 31 females, median age 66.2 years, 46 with PS 0-1 and 10 with PS 2) are fully evaluable. At onset, according to GIMEMA-PETHEMA risk score, 18 were low-risk(32.5%), 31 intermediate risk (55%) and 7 high risk (12.5%). After induction treatment, 54 patients (96.4%) achieved CR and 2 (3.6%) died from haemorrhage (1) and infection (1). ATRA syndrome was documented in 5 patients (9.3%): 13/56 patients (23.2%) showed during induction other toxicities (WHO 3 – 4) not related to ATRA. After CR achievement, 2 patients died in CR from haemorrhage (1) and infection (1) and 52 received the consolidation course: on the whole, during consolidation 4 patients (7.6%) had a toxicity WHO 3 – 4 and 2 of them (3.8%) died from haemorrhage (1) and infection (1). The remaining 50 patients started maintenance treatment: up to now, 12 patients (22.2%) relapsed, after a median time from morphological CR of 19 months (range 7 – 86). Overall survival (OS) was 76.1% and 73.3% at 3 and 5 years, respectively. Disease free survival (DFS) was 64.5% and 61.3% at 3 and 5 years, respectively. At the univariate analysis, PS =2 (p=0.0019), WBC count > 3 x 109 /l (p=0.018) and male gender (p=0.03) had a bad prognostic impact on DFS, while only PS=2 (p=0.05) did it on OS. Age, PLTS count, WBC count > 10 x 109 /l, and risk score did not affect both OS and DFS. At the multivariate analysis on DFS, only PS =2 retained prognostic significance (HR = 3.8). In conclusion, the amended GIMEMA protocol has shown to be effective and safe in elderly APL patients, as the rate of death in CR was reduced when compared with previous results in not amended GIMEMA LAP AIDA 0493: however, to face with a relapse rate > 20%, future strategies might be designed which exploit the use of more targeted approaches including combinations of ATRA, arsenic trioxide, and anti-CD33 monoclonal antibodies.

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Pre-Transplant Risk-Assessment for Patients with Acute Myeloid Leukemia (AML) Receiving Allogeneic Hematopoietic Stem Cell Transplants.

Blood ◽

10.1182/blood.v114.22.2302.2302 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2302-2302

Author(s):

Philipp G. Hemmati ◽

Theis H. Terwey ◽

Philipp le Coutre ◽

Gero Massenkeil ◽

Lam G Vuong ◽

...

Keyword(s):

Stem Cell ◽

Risk Score ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Disease Stage ◽

Unrelated Donor ◽

Prognostic Impact ◽

Hematopoietic Stem ◽

Substantial Impact ◽

Female Donor

Abstract Abstract 2302 Poster Board II-279 Purpose: The presence of comorbidities was shown to have a substantial impact of the outcome of patients undergoing cancer treatment. In chronic myeloid leukemia (CML) the EBMT risk score proofed to be highly valuable in predicting the outcome of patients following allogeneic stem cell transplantation (alloSCT). We therefore investigated, whether a slightly modified EBMT risk score may be used to predict the outcome of patients with AML following alloSCT. Patients and Methods: We retrospectively analyzed 233 patients with AML (median age: 47 years, range: 17 – 68 years) who underwent alloSCT at our institution between 1994 and 2007. 180 patients (77%) had de novo AML and 53 patients (23%) had secondary or therapy-related AML. A favorable karyotype was present in 11 patients (5%) whereas 101 (43%) or 82 patients (35%) had an intermediate risk or a poor risk karyotype. 131 patients (56%) received myeloablative conditioning (MAC) whereas 102 patients (44%) were conditioned using reduced intensity conditioning (RIC). The EBMT risk score was calculated analogous to the original score established by Gratwohl et al. (Lancet 352, 1998) and included the following variables: age (<20, 20-40 or >40 years), interval from diagnosis to alloSCT (<1 year or ≥1 year), disease stage (CR1, >CR1 or no CR), donor/recipient gender match (female donor/male recipient or other), and donor type (HLA-identical sibling or other). Altogether, 6 patients (3%) were younger than 20 years, 82 patients (35%) were between 20-40 years, and 145 patients (62%) were older than 40 years. The interval from diagnosis to alloSCT was <1 year in 180 patients (77%) and ≥1 year in 53 patients (23%). 121 patients (52%) were transplanted in CR1, 41 patients (18%) underwent alloSCT >CR1, and 71 patients (30%) had active (relapsed/refractory) disease at the time of alloSCT. A female donor/male recipient transplantation was performed in 59 patients (25%). Transplants were from a matched-related donor (MRD) in 103 patients (44%). A matched-unrelated or a mismatched-unrelated donor was chosen in 101 (44%) or in 28 patients (12%). Only 1 patient was transplanted from a haplo-identical donor. Results: After a median follow-up of 48 months (range: 6 – 170 months) for the surviving patients, 108 patients (46%) are alive, 101 (43%) of which are in continuous CR. Causes of death (total 125 patients (54%)) were relapse in 70 patients (30%), infections/graft versus host-disease in 54 patients (23%), or other (1 patient (0.5%)). At 10 years after alloSCT, projected overall survival (OS) or disease-free survival (DFS) were 41% or 39%. Non-relapse mortality (NRM) or incidence of relapse were 32% or 43%. Of the 233 patients, 30 (13%) had an EBMT risk score of 0-1, 48 (21%) had a score of 2, 50 (21%) had a score of 3, 40 (17%) had a score of 4, 51 (22%) had a score of 5, and 14 (6%) had a score of 6-7. OS in the different score groups were 67% (score 0-1), 50% (score 2), 48% (score 3), 33% (score 4), 23% (score 5), or 21% (score 6-7) and differed significantly between the groups (p=0.0005). NRM in patients with an EBMT risk score >4 as an abritary cut-off was significantly higher as compared to patients with a score ≤4 (53% versus 25%; p=0.009). Likewise, the incidence of relapse was significantly lower in patients with an EBMT risk score ≤3 as an abritary cut-off when compared those with a score >3 (31% versus 57%; p<0.0001). In univariate analysis, disease stage had a negative prognostic impact on OS (CR1: 54%, >CR1: 32%, no CR: 25%; p<0.0001). Likewise, OS in patients with a MRD was significantly higher as compared to patients with other donor types (MRD: 50%, other: 34%; p= 0.003). In contrast, age, interval from transplantation to alloSCT, and donor/recipient gender match did not influence OS in our analysis. Conclusions: These data indicate that a modified EBMT risk score may be used to predict the outcome of patients with AML following alloSCT. Disclosures: No relevant conflicts of interest to declare.

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Circulating Mir-16 and Mir-25 As New Prognosticators For Multiple Myeloma

Blood ◽

10.1182/blood.v122.21.1853.1853 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1853-1853 ◽

Cited By ~ 1

Author(s):

Flavia Pichiorri ◽

Alberto Rocci ◽

Craig C Hofmeister ◽

Susan Geyer ◽

Tiffany Talabere ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Prognostic Significance ◽

Cox Proportional Hazards ◽

Response To Therapy ◽

Differentially Expressed ◽

Prognostic Impact ◽

Continuous Variables ◽

Circulating Micrornas ◽

Non Invasive

Abstract Purpose While international stage (ISS) and the presence of absence of cytogenetic abnormalities on FISH somewhat define the clinical risk of MM patients, additional biomarkers are necessary for more precise risk-based classification. Emerging studies have shown that circulating microRNAs (miRNAs) can be detected in patients with a variety of malignancies, including MM, and they could be non-invasive biomarkers. We measured serum miRNA levels of a large cohort of well-characterized previously untreated MM patients and correlated results with clinical outcome to test their prognostic impact. Methods and Patients To profile the expression of circulating microRNAs in the serum of MM patients, we performed NanoString-nCounter microRNA assays on samples obtained from a discovery cohort of 54 newly diagnosed MM patients enrolled on a randomized GIMEMA phase 3 study comparing Velcade-Melphalan-Prednisone-Thalidomide versus Velcade-Melphalan-Prednisone followed by maintenance with Velcade-Thalidomide. To further analyze the expression of the differentially expressed microRNAs, stem-loop-RT-PCR was performed on a validation cohort of 234 MM patients enrolled in the same trial. The prognostic significance of differentially expressed microRNAs were evaluated in relation to progression-free (PFS) and overall survival (OS) using univariate and multivariate Cox proportional hazards models. The utility of incorporating microRNA expression into a risk score with known risk factors – specifically ISS stage and the presence of del17, t(4;14) or t(14;16) by FISH – was also explored. Results Out of the 800 miRNAs evaluated, only 25 were detectable (≥100 counts) in at least 20% of the patients. The expression of these miRNAs were then measured in a validation set, but only 10 (miRs-92a, 21, 30a, 720, 451, 223, 126, 19b, 25 and miR-16) were validated to be differentially expressed. We found that levels of miR-16 and miR-25, used as continuous variables, had significant impact on OS duration: miR-16 (HR 0.87; p=0.019) and miR-25 (HR 0.81; p=0.0012) where low expression corresponded with worse survival. Based on these observations we generated a microRNA-based risk score which was significantly associated with OS duration (p=0.008). We then integrated this score with ISS stage and presence of high risk features by FISH, generating an integrated-microRNA risk score that was significantly associated with OS (p<0.0001), and was better than a risk score that combined ISS and FISH (p=0.014), see figure. Conclusions Circulating miR-16 and miR-25 can risk stratify elderly, previously untreated, MM patients beyond ISS-stage and high risk genetic features. The opportunity to isolate circulating miRNAs allows us to sequentially sample cancer patients in a relatively non-invasive manner, opening new avenues of investigation for disease stratification and response to therapy. Disclosures: Bringhen: Onyx: Consultancy.

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Development of a dedicated TAVR risk score based on aorta calcification; 4 cities for assessing calcification prognostic impact: the C4CAPRI trial

Archives of Cardiovascular Diseases Supplements ◽

10.1016/j.acvdsp.2018.10.152 ◽

2019 ◽

Vol 11 (1) ◽

pp. 70

Author(s):

B. Harbaoui ◽

Hélène Eltchaninoff ◽

M. Rabilloud ◽

G. Souteyrand ◽

E. Durand ◽

...

Keyword(s):

Risk Score ◽

Prognostic Impact

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Impact of Comorbidities In Patients with Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Treated with Azacitidine (AZA)

Blood ◽

10.1182/blood.v116.21.4973.4973 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4973-4973

Author(s):

Patricia Font ◽

Valle Gomez Garcia De Soria ◽

Javier Loscertales ◽

Julio Garcia Suarez ◽

Marta Callejas ◽

...

Keyword(s):

High Risk ◽

Respiratory Tract ◽

Cell Transplantation ◽

Risk Score ◽

Respiratory Tract Infections ◽

Response Rate ◽

Low Risk ◽

Prognostic Impact ◽

Tract Infections ◽

The Impact

Abstract Abstract 4973 Background: Comorbidity in older patients with AML or high risk MDS is frequent, and usually affects the therapeutic decision making. The hematopoietic cell transplantation specific comorbidity index (HCTCI) developed by Sorror et al, is widely used in predicting post-transplantation outcome in patients with AML and MDS. Recently, the HCTCI showed prognostic impact in a cohort of patients with high risk MDS treated only with supportive care. AZA have shown clinical efficacy in elderly patients with high risk MDS. However, it is not clear if AZA is safe and effective in patients with comorbidities. Purpose: To study the impact of comorbidity, determined by the HCTCI, in a retrospective cohort of patients with MDS or AML treated with AZA Patients: Between October 2007 and July 2010, 30 patients diagnosed with MDS or AML received AZA 75 mg/m2 /d × 7d/4 weeks, or less intensive schedules (7d/4w n=2, 5d/4 weeks n= 12, 5-2-2 n= 16). Median age was 71 years (range 44–88), 16M/14F. Regarding HCTCI, 17 patients were classified in low-intermediate risk, score 0–2, and 13 patients in high risk (score ≥ 3). Patients with HCTCI of 0–2 were classified as: 8 patients with MDS (High/ Int2 MDS n= 4, Intermediate-1 MDS n= 4), 8 patients with AML in first relapse after intensive chemotherapy (IC) or stem cell transplantation (SCT) and <20% of marrow blasts, and 1 patient with AML with MDS related changes. The group of patients with HCTCI ≥3 included: 7 MDS (high/int2 MDS n=5, secondary MDS n=1, Int-1 MDS n =1), 6 AML (AML with MDS related changes n= 3, AML in relapse after IC or SCT and <20% blasts n=3). Response to treatment was estimated according to the International Working Group. Results: The median number of cycles of AZA was 7 (1-26); 5 cycles in the HCTCI of score 0–2 and 7 cycles in the HCTCI>= 3. There were three patients who received only 1 cycle due to progression (n=1) and early death, caused by infection (n=2). Both patients showed neutropenia before starting AZA, one showed HCTCI of low risk. Responses were evaluated when 3 or more cycles were administered. Overall response rate (ORR) was 48% (14/27), with 13% complete response (CR). In the group of patients with HCTCI of 0–2, ORR was 40% (6/15) including 2 CR, 1 marrow CR, 2 partial response (PR), and 1 patient with haematological improvement (HI). Median overall survival (OS) for responders with low risk by HCTCI was 18 months (4-28). Transformation to AML was seen in two responding patients, after 16 and 18 months. Allo SCT was performed in one patient. Regarding patients with HCTCI ≥3, ORR was 66% (8/12), including 2 CR, 2 PR, 4 HI, 3 of them with transfusion independence. Median OS for responders was 11 months (range 5–33 months). Transformation to AML was seen in a patient after 23 months of treatment, and relapse with 10% of blasts was observed in a patient with CR after six months of AZA. Grade 3–4 toxicity according to WHO was observed in 5 patients, 3 of them with HCTCI low (1 bleeding event, 4 respiratory tract infections). One patient with HCTCI ≥3 died after 8 months of HI, because no treatment-related event. One patient with HI and HCTCI≥3 did not continued AZA after 5 cycles because frequent respiratory tract infections. Conclusions In this preliminary cohort, AZA was well tolerated and active in patients with HCTCI≥3. The response rate was in accordance with results observed with a similar cohort of patients without significant comorbidities. These results might be confirmed with larger number of patients in further studies. Disclosures: Font: Celgene: Membership on an entity's Board of Directors or advisory committees.

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Association Analysis and Polygenic Risk Score Evaluation of 38 GWAS-identified Loci in a Chinese population with Parkinson’s Disease

Neuroscience Letters ◽

10.1016/j.neulet.2021.136150 ◽

2021 ◽

pp. 136150

Author(s):

Ran Zheng ◽

Song Qiao ◽

Ying Chen ◽

Chongyao Jin ◽

Yi Fang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Association Analysis ◽

Risk Score ◽

Chinese Population ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Score Evaluation

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Presence of Unfavorable Cytogenetic Abnormalities Is the Strongest Predictor of Poor Survival in Secondary Myelofibrosis.

Blood ◽

10.1182/blood.v106.11.2585.2585 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2585-2585

Author(s):

David Dingli ◽

Schwager M. Schwager ◽

Mesa A. Ruben ◽

Chin Yang Li ◽

Ayalew Tefferi

Keyword(s):

De Novo ◽

Prognostic Score ◽

Young Patients ◽

Prognostic Impact ◽

Poor Survival ◽

Myeloid Metaplasia ◽

Cytogenetic Abnormalities ◽

Laboratory Variables ◽

The One ◽

Secondary Myelofibrosis

Abstract Post-polycythemic (PPMM) and post-thrombocythemic (PTMM) myeloid metaplasia are consensually referred to as secondary myelofibrosis (sMF). Prognostic variables in sMF are not as well defined as they are for agnogenic myeloid metaplasia (AMM). Such information is particularly crucial for management decisions in transplant-eligible patients. Accordingly, we examined the prognostic impact of several clinical and laboratory variables in 66 young patients (age < 60 years) with sMF including 37 with PPMM and 29 with PTMM. Multivariate analysis of parameters other than cytogenetics identified older age (p=0.02), anemia (hemoglobin level < 10 g/dL; p=0.007), and PPMM (p=0.009) as independent risk factors for shortened survival. However, when such analysis was restricted to patients in whom cytogenetic studies were performed (n=31), the presence of unfavorable cytogenetic abnormalities (i.e. clones other than 20q- and 13q-) became the one and only adverse prognostic factor for survival (p=0.001). Figure Figure The prognostic value of cytogenetics was independent of the Dupriez prognostic score (p=0.003). Figure Figure A similar analysis in a temporal cohort of 50 age-matched patients with AMM also identified unfavorable cytogenetics as an independent predictor of poor survival along with thrombocytopenia and anemia. The current study suggests an important prognostic role for cytogenetics in both de novo and secondary myelofibrosis.

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