Prognostic Value of Molecular Markers for Guiding Post-Remission Therapy in Patients with De Novo Acute Myeloid Leukemia (AML) and Intermediate-Risk Cytogenetics

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2522-2522
Author(s):  
Marta Pratcorona ◽  
Mireia Camós ◽  
Montserrat Torrebadell ◽  
Maria Rozman ◽  
Ana Carrió ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Value ◽  
De Novo ◽  
Low Risk ◽  
High Dose ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Molecular Features ◽  
Mutational Status

Abstract The heterogeneous prognosis of patients with intermediate-risk cytogenetics AML (AML-IR) can be partially clarified by screening of NPM1 mutations (NPMmut) and internal tandem duplication of FLT3 (FLT3-ITD). Nonetheless, additional factors might influence the prognostic effect of these molecular lesions, such as the FLT3-ITD mutant level. Moreover, the optimal post-remission strategy might differ depending on the underlying molecular lesion. In this regard, we analyzed the outcome, according to NPM1 and FLT3 mutations and post-remission therapy given, of a series of patients diagnosed with de novo AML-IR in a single institution who received intensive chemotherapy. Patients were treated following 4 sequential protocols of CETLAM group during the period 1994–2006, consisting of 1 or 2 cycles of standard induction chemotherapy and 1 course of high-dose cytarabine-based consolidation therapy. Thereafter, patients underwent hematopoietic stem cell transplantation (HSCT) according to donor availability and presumed risk (protocols LAM 99 & 2003). NPM1 mutations and FLT3-ITD were screened in diagnostic DNA by PCR amplification followed by Genescan analysis. The ratio between FLT3-ITD and wildtype FLT3 alleles (ITD/wt ratio) was calculated using the area under the peak of corresponding alleles. Overall, 134 patients (51% male; median age, 53; range: 17–70) with AML-IR (normal karyotype, 66%) were studied. NPM1mut and FLT3-ITD were found in 45% and 37% of patients, respectively, with a median ITD/wt ratio of 0.59 (0.045–5.5). After induction regimen, 109 patients (81%) achieved complete response (CR). The only variables predictive of a favorable response were NPMmut (90% vs. 75%; p=0.01) and age <60 (85% vs. 72.5%; p=0.05). After a median follow-up of 69 months, relapse risk (RR) at 5 years was 54% (±5%). RR was higher in patients presenting with hyperleukocytosis (>50 × 109/L), NPMwt, and FLT3-ITD. Interestingly, the prognostic value of FLT3-ITD depended on the relative mutant level, and detection of FLT3-ITD with a low ITD/wt ratio (i.e.,<0.3) did not increase the risk conferred by underlying NPM1 mutational status. In accordance, a composite variable based on NPMmut and quantitative FLT3-ITD was created defining 2 prognostic categories: a low-risk group (LOWmol), constituted by patients with NPMmut and either absence of FLT3-ITD or low ITD/wt ratio, and a high-risk subset (HIGHmol), defined by the absence of NPMmut and/or high ITD/wt ratio. This molecular stratification showed independent prognostic value for RR (5-year RR: 24%±10% vs. 81%±7 in LOWmol vs. HIGHmol patients, respectively; p<0.001), and survival (OS; relative risk: 2.8, 95% CI:1.6-5, p<0.001; figure Moreover, the effect of post-remission therapy varied in both molecular-defined subgroups. Thus, among patients with an age ≤60, 5-year survival in LOWmol patients with a planned autologous HSCT (autoHSCT) was 83%±9%, not differing significantly from that of patients undergoing allogeneic HSCT (intention-to-treat analysis; figure On the other hand, 5-year OS of HIGHmol patients who underwent allogeneic HSCT in first CR was 73%±13, which compared favorably with other post-remission strategies (5-yr OS: 27%±7%; p=0.019). In conclusion, in patients with intermediate-risk AML, the combined assessment of NPM1 mutations and quantitative estimation of FLT3-ITD allows the distinction of 2 categories of patients with different prognosis. Thus, whereas autoHSCT arises as an effective postremission therapy in patients harboring low-risk molecular features, allogeneic HSCT in first CR seems to overcome adverse prognosis of patients with high-risk disease. Nonetheless, the validity of this molecularly-based therapeutic algorithm warrants confirmation in other studies. Figure Figure

scholarly journals The Transplant Evaluation Rating Scale predicts overall survival after allogeneic hematopoietic stem cell transplantation

2020 ◽  
Vol 4 (19) ◽  
pp. 4812-4821
Author(s):  
Melhem M. Solh ◽  
Dawn Speckhart ◽  
Scott R. Solomon ◽  
Asad Bashey ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Rating Scale ◽  
Disease Risk ◽  
Multivariable Analysis ◽  
Low Risk ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Transplant Evaluation

Abstract To evaluate the impact of psychosocial risks on post–hematopoietic stem cell transplantation (HSCT) outcomes, we prospectively conducted psychosocial assessment of 556 consecutive allogeneic HSCT patients who received their first allogeneic transplant at our center between 2003 and 2017. The Transplant Evaluation Rating Scale (TERS) score was prospectively assessed by a psychologist before transplantation, and patients were categorized as low, intermediate, or high risk based on their TERS score. Patients in the high-risk TERS group had significantly longer hospital stays during the first 180 days and 1 year post–allogeneic HSCT compared with the low-risk group (16 vs 13 and 21 vs 16 days; P = .05 and .02, respectively). The survival estimates for low-, intermediate-, and high-risk TERS groups at 3 year were as follows: overall survival (OS), 73%, 60%, and 65%; disease-free survival (DFS), 63%, 55%, and 60%; nonrelapse mortality (NRM), 11%, 20%, and 17%; and relapse, 26%, 25%, and 23%, respectively. In a multivariable analysis, intermediate- and high-risk TERS scores predicted for inferior OS, similar DFS, and higher NRM compared with low-risk TERS score. In a subset analysis of patients with low/intermediate risk per Disease Risk Index, multivariable analysis showed that high- and intermediate-risk TERS scores predicted for significantly worse OS, worse DFS, higher NRM, and similar relapse rates compared with low-risk TERS score. Our findings show that psychosocial factors as measured by TERS score are strong predictors of morbidity and mortality after HSCT among patients with low/intermediate disease risk.

Efficacy of Reduced Intensity Conditioning (RIC) with FLU-BU-ATG and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Pediatric ALL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2314-2314 ◽  
Author(s):  
Reggie Duerst ◽  
David Jacobsohn ◽  
William T. Tse ◽  
Morris Kletzel
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Pediatric All ◽  
Very High ◽  
Reduced Intensity

Abstract Reduced Intensity Conditioning (RIC) regimens prior to allogeneic HSCT have gained acceptance in the treatment of adults with myelodysplasia, leukemia and multiple myeloma. RIC reduces the risk for regimen related morbidity and mortality enabling patients with pre-existing medical conditions that would have been precluded from allogeneic HSCT to attempt a curative approach. The resilience of pediatric patients (pts) following high-dose conditioning regimens and the concern that ALL cells are inherently more resistant to a graft-vs-leukemia effect have limited accrual of pediatric ALL pts to RIC protocols despite the potential benefit for reduced long-term morbidity. We report the experience of 10 pediatric ALL pts (6 M, 4 F, median age 9.5 years) treated for recurrent ALL with RIC and allogeneic HSCT. A uniform RIC regimen comprised of fludarabine, 30 mg/m2 for 6 consecutive days (days −10 through −5), followed by intravenous busulfan, 0.8 – 1 mg/kg for 8 doses or targeted AUC 4000 μMol*min for 2 doses (days −5 and −4) and equine ATG, 40 mg/kg or rabbit ATG, 2 mg/kg for 4 days (days −4 through −1) was administered. Pts with prior CNS involvement received whole brain (2400 cGy) and spinal (1800 cGy) irradiation immediately prior to the RIC. Stem cell sources included 7 unrelated donors and 3 matched sibs. 9 of 10 stem cell donations were peripheral blood stem cells (PBSC). The median cell doses infused were 6.5 x 108 MNC/kg and 4.2 x 106 CD34+ cells/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) alone in 5 patients, CsA and mycophenolate mofetil in 5 pts. Growth factor support was not used. Each of the pts had at least two very high-risk features--prior HSCT (n = 6), CR > 3/refractory disease (8), prior CNS disease (6), Ph+ (2), pre-exisiting neurologic (1) or cardiac (1) dysfunction or aspergillous infection (1). Full donor chimerism was achieved in 9 of 10 with a median time to reach an ANC >500/μl of 16 days (range 11–62) and an unsupported platelet count > 20,000/μl was achieved in 8 of 10 at a median of 25 days (15–67). 2 pts developed Gr IV acute GVHD, 2 of 5 pts surviving more than 100 days developed chronic GVHD. Only 3 patients have relapsed: 1 refractory T-ALL pt recurred day +27 and 2 Ph+ pts had a molecular relapse day +61 and +196. The latter pt is in subsequent continuous molecular remission for over 1 year on imatinib therapy. 6 pts have died, 5 in the first 100 days of HSCT from complications of GVHD (2), relapse (1), pulmonary failure (in 1 pt S/p 3 prior allogeneic HSCT) and PTLD (1). 1 pt succumbed from complications of chronic GVHD day +756. The RIC regimen and supportive care are primarily an outpatient experience. During the first 30 days post HSCT, pts spent an average of only 9 days in hospital (23 of the first 100 days). Despite very high-risk features, 4 of 10 pts survive (3 CCR) at a median of 500 days post HSCT. Thus, RIC and allogeneic HSCT also offers promise for efficacy in pediatric ALL.

Are men with favorable intermediate-risk prostate cancer candidates for active surveillance?

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 82-82
Author(s):  
Ann Caroline Raldow ◽  
Danjie Zhang ◽  
Ming-Hui Chen ◽  
Michelle H. Braccioforte ◽  
Brian Joseph Moran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Active Surveillance ◽  
Locally Advanced ◽  
Low Risk ◽  
P Value ◽  
High Dose ◽  
Intermediate Risk ◽  
Increased Risk ◽  
Risk Prostate Cancer

82 Background: Active surveillance (AS) is considered appropriate for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, with grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may also be an initial option for men with favorable intermediate-risk PC. We estimated and compared the risk of PC-specific mortality (PCSM) following high dose radiation therapy and androgen deprivation therapy as appropriate amongst men with low, favorable intermediate, unfavorable intermediate, and high-risk PC. Methods: The study consisted of 6,595 consecutively treated men (median age: 68 years) with localized or locally advanced PC at the Chicago PC Center between 1997 and 2013. Fine and Gray competing risks regression analyses (table) were used to assess the risk of PCSM in men with favorable intermediate, unfavorable intermediate or high-risk compared to low-risk PC, adjusting for age at and year of treatment. Results: After median follow-up of 7.76 years, 820 men died: 72 of PC. While men with favorable intermediate-risk did not have significantly increased risk of PCSM as compared to low-risk PC (adjusted hazard ratio (HR) 1.28, 0.63-2.62 95% confidence interval (CI), p-value 0.49), men with high (adjusted HR 9.91, 5.48-17.94 95% CI, p-value <0.0001) or unfavorable intermediate-risk PC (adjusted HR 3.17, 1.60-6.30, p-value 0.001) did. Eight-year point estimates of PCSM were low: 0.68% [0.32-1.31% 95% CI] and 0.44% [0.25-0.75% 95% CI] for men with favorable intermediate and low-risk PC, respectively. Conclusions: Men with low and favorable intermediate-risk PC have similar and low estimates of PCSM during the first decade following standard management. These results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC. [Table: see text]

Impact of allogeneic hematopoietic stem cell transplantation on pediatric acute myeloid leukemia of FAB subtypes M4 and M5

2020 ◽  
Author(s):  
Yu-juan Xue ◽  
Pan Suo ◽  
Yi-fei Cheng ◽  
Ai-dong Lu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Pediatric Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Background: FAB-M4 and M5 are unique subgroups of pediatric acute myeloid leukemia. However, for these patients, few studies have demonstrated the clinical and biological characteristics and efficacy of hematopoietic stem cell transplantation (HSCT), and especially haplo-HSCT. Procedure: We retrospectively evaluated the outcomes of 70 children with FAB-M4/M5 enrolled in our center from January 2013 to December 2017. Results: Of the patients, 32, 23, and 15 were in low-risk, intermediate-risk, and high-risk groups, respectively. T(16;16), inv16/CBFB-MYH11 was the most frequent cytogenetic abnormality. Among detected genetic alterations, WT1 was mutated at the highest frequency, followed by FLT3-ITD, NPM1, and CEBPA. Thirty-three patients received HSCT (haplo-HSCT = 30), of which four, 18, and 11 were in low-risk, intermediate-risk, and high-risk groups, respectively. For all patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 85.3 ± 4.3%, 69.0 ± 5.7%, and 27.9 ± 5.2%, respectively. By multivariate analysis, low-risk stratification predicted superior OS, EFS, and PLT ≤ 50 × 109/L at diagnosis, with FLT3-ITD mutations predicting higher CIR and poorer EFS. In intermediate- and high-risk groups, HSCT was independently associated with higher EFS and lower CIR. With a median post-transplant observation time of 30.0 months, the 3-year OS, EFS, CIR, and non-relapse mortality in the haplo-HSCT group were 74.2 ± 8.6%, 68.3 ± 8.9, 24.6 ± 7.6%, and 6.6 ± 4.1%, respectively. Conclusions: Risk-oriented treatment is important for pediatric FAB-M4/M5. For intermediate- and high-risk groups, HSCT significantly improved survival and haplo-HSCT might be a viable alternative approach.

High-risk Neuroblastoma: Poor Outcomes Despite Aggressive Multimodal Therapy

2021 ◽  
Vol 17 ◽  
Author(s):  
Adil Abdelhamed Abbas ◽  
Alaa Mohammed Noor Samkari
Keyword(s):  
High Risk ◽  
Multimodal Therapy ◽  
Treatment Strategies ◽  
Low Risk ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Clinical Behavior ◽  
Frequent Relapses ◽  
Recent Developments ◽  
Poor Outcomes

: Neuroblastoma (NBL) is a highly malignant embryonal tumor that originates from the primordial neural crest cells. NBL is the most common tumor in infants and the most common extracranial solid tumor in children. The tumor is more commonly diagnosed in children of 1-4 years of age. NBL is characterized by enigmatic clinical behavior that ranges from spontaneous regression to an aggressive clinical course leading to frequent relapses and death. Based on the likelihood of progression and relapse, the International Neuroblastoma Risk Group classification system categorized NBL into very low risk, low risk, intermediate risk, and high risk (HR) groups. HR NBL is defined based on the patient's age (> 18 months), disease metastasis, tumor histology, and MYCN gene amplification. HR NBL is diagnosed in nearly 40% of patients, mainly those > 18 months of age, and is associated with aggressive clinical behavior. Treatment strategies involve the use of intensive chemotherapy (CTR), surgical resection, high dose CTR with hematopoietic stem cell support, radiotherapy, biotherapy, and immunotherapy with Anti-ganglioside 2 monoclonal antibodies. Although HR NBL is now better characterized and aggressive multimodal therapy is applied, the outcomes of treatment are still poor, with overall survival and event-free survival of approximately 40% and 30% at 3-years, respectively. The short and long-term side effects of therapy are tremendous. HR NBL carries a high mortality rate accounting for nearly 15% of pediatric cancer deaths. However, most mortalities are attributed to the high frequency of disease relapse (50%) and disease reactiveness to therapy (20%). Newer treatment strategies are therefore urgently needed. Recent discoveries in the field of biology and molecular genetics of NBL have led to the identification of several targets that can improve the treatment results. In this review, we discuss the different aspects of the epidemiology, biology, clinical presentations, diagnosis, and treatment of HR NBL, in addition to the recent developments in the management of the disease.

Prognostic Impact of Genetic Characterization in the GIMEMA LAM99P Study for Newly Diagnosed Adult AML. Relevance of Combined Analysis of Conventional Karyotyping, FLT3 and NPM Mutational Status.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 226-226
Author(s):  
G. Saglio ◽  
Francesco Lo Coco ◽  
A. Cuneo ◽  
F. Pane ◽  
G. Rege Cambrin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Genetic Characterization ◽  
High Risk Group ◽  
Low Risk ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Mutational Status ◽  
Molecular Studies ◽  
The Impact

Abstract Between 1998 and 2002, 509 patients with AML (median age 46 yrs, range 15–60) were enrolled in the multicenter LAM99P study of the Italian GIMEMA group. To better evaluate the clinical impact of genetic characterization, all patients received a uniform protocol and diagnostic samples were centralised for cytogenetic and molecular studies. Therapy consisted of HU pre-treatment (2g/m2 for 5 days) followed by induction with DNR (50 mg/m2 d 1, 3, 5), cytarabine (100 mg/m2 d 1–10) and etoposide (100 mg/m2 d 1–5) and consolidation with cytarabine (500 mg/m2/q12 hrs d 1–6) and DNR (50 mg/m2 d 4–6). After consolidation, eligible patients with an identical HLA donor were to receive allogeneic SCT and the remaining peripheral blood autologous SCT. Cytogenetic and molecular genetic characterization (including analysis of major fusion genes, FLT3 and NPM status) was available in 397 (78%) patients. Compared to previous GIMEMA studies, the possibility to collect samples during the 5d of HU pretreatment considerably improved genetic characterization and in particular centralised karyotyping by overcoming the problem of sampling and shipment over the w-end. After induction, 269/397 (68%) patients achieved CR. For induction response, conventional K identified 3 distinct risk groups as follows: low risk (inv. 16 and t8;21), intermediate (normal K and other anomalies not comprised in the high risk group) and high risk (t3;3, inv.3, t9;22, 11q23, 5/7 abnormalities complex K,) with CR rates of 92%, 67% and 39%, respectively (P<.0001). NPM mutations were significantly associated with older age, higher WBC, normal K and FLT3-ITD. CR rates in NPM+ (mutated) vs. NPM- (wildtype) groups were 76% vs. 60% for the whole population and 81% vs, 61% for patients in the normal K group (P<.001 for both comparisons). Multivariate analysis for CR indicated that low risk K and NPM+ were independent factors favorably affecting CR achievement while FLT3 status had no significant impact on CR. The analysis of prognostic factors for DFS and OS was carried out in 269 patients in CR (median follow-up of 39 mos.) and multivariate analysis performed after adjusting for unfavorable factors (WBC count). Multivariate analysis of variables influencing OS showed the following: low vs intermediate K, P=.0005; high vs intermediate K, P<.0001; FLT3+ vs. FLT3−, P=.06. Multivariate analysis for DFS showed: low risk vs. intermediate risk K, p=.01; high risk vs. intermediate risk K, p= .03; FLT3+ vs. FLT3-, p=.0002. NPM status did not significantly influence DFS in either the whole population or in the normal K group. In particular, there was no difference in the DFS rates among patients NPM+ and NPM- in the normal K/FLT3- group while in the normal K/FLT3+ group there was a trend (p=.06) for lower relapse rate for NPM+ patients as compared to NPM- ones. These results highlight the relevance of combining cytogenetic and molecular studies in the diagnostic work up of AML and confirm the impact of karyotype on all outcome estimates as well as of FLT3 status on DFS. As to NPM mutations, these appear a favorable predictor of CR achievement. Further investigations in large clinical trials are needed to assess the prognostic value of NPM mutations on outcome in AML with normal karyotype.

Validation of the International Prognostic Scoring System (IPSS) for Waldenstrom's Macroglobulinemia (WM) and the Importance of Serum Lactate Dehydrogenase (LDH).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2845-2845
Author(s):  
Meletios A. Dimopoulos ◽  
Marie-Christine Kyrtsonis ◽  
Evdoxia Hadjiharissi ◽  
Argiris Symeonidis ◽  
Eurydiki Michalis ◽  
...  
Keyword(s):  
Platelet Count ◽  
High Risk ◽  
Protein Concentration ◽  
Elevated Serum ◽  
Staging System ◽  
Low Risk ◽  
Serum Lactate Dehydrogenase ◽  
High Dose ◽  
Intermediate Risk ◽  
Monoclonal Protein

Abstract Abstract 2845 Poster Board II-821 Recently, the IPSS has been proposed as a staging system for patients with WM who require treatment. This system is based on five adverse covariates: age >65 years, hemoglobin '11.5 g/dL, platelet count '100×109/L, beta2-microglobulin >3 mg/L and serum monoclonal protein concentration >7 g/dL. Low risk is defined by the presence of ' 1 adverse characteristic and age '65 years, intermediate risk by the presence of 2 adverse characteristics or only age >65 years and high risk by the presence of >2 adverse characteristics. The aim of our analysis was to independently validate the significance of IPSS not only for overall survival (OS) but also for cause-specific survival (CSS) (i.e deaths unrelated to WM or to complications of treatment are censored). Furthermore, we wanted to assess whether elevated serum LDH may add to the strength of IPSS. From the data base of the Greek Myeloma Study Group, we identified 335 patients with clearly defined criteria for diagnosis and for initiation of treatment who were treated over the last 20 years. Main primary therapies included alkylating agents (43%), CHOP (3%), nucleoside analogues (3%) and rituximab either alone (3%) or in combination with conventional chemotherapy (44%). Before the initiation of treatment the median age of patients was 68 years (range 28 to 89 years). Fifty-nine percent of patients were >65 years, while 75% of patients had hemoglobin levels of <11.5 g/dL, 57% had beta2-microglobulin of >3 mg/L, 33% had lymphadenopathy, 32% splenomegaly, 23% presence of B-symptoms, 12% platelet count of <100×109/L and 6% had serum monoclonal protein concentration of >7 g/dL. Among 152 patients who had died by the time of this analysis, 33 patients (22%) had died due to causes not related to WM, to disease transformation, to myelodysplasia or to complications of treatment. Most frequent causes were second primary solid tumors, celebrovascular accidents, coronary artery disease and congestive heart failure. For the whole group of patients median OS was 105 months and median CSS was 116 months. Patients were divided into low risk (23%), intermediate risk (38%) and high risk (39%), according to IPSS. Median OS was 161 months, 105 months and 64 months respectively (p<0.01) and median CSS was 172 months, 116 months and 94 months, respectively (p<0.01). Elevated serum LDH >250 IU/L (normal upper limit 225 IU/L) was found in 18% of patients. Serum LDH was elevated in 16%, 12% and 24% of patients with low, intermediate and high risk, respectively. Median OS according to low or elevated LDH was 109 versus 63 months (p<0.01) and median CSS was 116 versus 64 months, respectively (p<0.01). Serum LDH was able to divide high risk patients into two subgroups with different outcome. The median OS was 94 and 35 months, for normal and high LDH group, respectively (p<0.01) and the median CSS was 104 and 36 months, for normal and high LDH group, respectively (p<0.01). We conclude that the recently proposed IPSS for WM is a robust staging system and it is also applicable to patients who received primary treatment with rituximab-based regimens. Elevated serum LDH is an adverse prognostic factor in WM. The combination of high risk according to IPSS and elevated serum LDH identified a subset of patients with very poor outcome. Such patients should be included in trials that evaluate novel agents and new treatment strategies including upfront high dose therapy. Disclosures: No relevant conflicts of interest to declare.

Myeloproliferative neoplasms and thrombosis

Blood ◽  
2013 ◽  
Vol 122 (13) ◽  
pp. 2176-2184 ◽  
Author(s):  
Tiziano Barbui ◽  
Guido Finazzi ◽  
Anna Falanga
Keyword(s):  
High Risk ◽  
Myeloproliferative Neoplasms ◽  
Low Risk ◽  
Related Factors ◽  
Hematopoietic Stem ◽  
Clonal Proliferation ◽  
Mutational Status ◽  
Novel Drugs ◽  
Risk Patients ◽  
Quantitative Changes

Abstract Major causes of morbidity and mortality in myeloproliferative neoplasms are represented by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. The pathogenesis of thrombosis results from a complex interplay of clinical and disease-related factors. Abnormalities of blood cells arising from the clonal proliferation of hematopoietic stem cells involve not only quantitative changes but also qualitative modifications that characterize the switch of these cells from a resting to a procoagulant phenotype. According to age and previous thrombosis, patients are classified in a “high risk” or “low risk”. Novel disease-related determinants such as leukocytosis and JAK2V617F mutational status and/or mutational burden are now under active investigation. In low-risk polycythemia vera patients, only phlebotomy and primary antithrombotic prophylaxis with aspirin is recommended, while in high-risk patients cytotoxic therapy is considered. Whether novel drugs targeting the constitutively active JAK2/STAT pathway will improve the management of thrombosis is a challenge for future studies.

The prognostic value of multilineage dysplasia in de novo acute myeloid leukemia patients with intermediate-risk cytogenetics is dependent on NPM1 mutational status

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 6147-6148 ◽  
Author(s):  
Marina Díaz-Beyá ◽  
María Rozman ◽  
Marta Pratcorona ◽  
Montserrat Torrebadell ◽  
Mireia Camós ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
De Novo ◽  
Intermediate Risk ◽  
Multilineage Dysplasia ◽  
Mutational Status ◽  
Acute Myeloid

scholarly journals Efficacy and Safety of FLAG-Ida As Frontline Therapy in a Pediatric AML Population: A Single Institution Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2342-2342
Author(s):  
Andrew Doan ◽  
Holly K.T. Huang ◽  
Ari J. Hadar ◽  
Jemily Malvar ◽  
Teresa Rushing ◽  
...  
Keyword(s):  
High Risk ◽  
De Novo ◽  
Low Risk ◽  
Molecular Testing ◽  
Hematopoietic Stem ◽  
Disease Response ◽  
Frontline Therapy ◽  
De Novo Aml ◽  
Pediatric Aml

Abstract Children with acute myeloid leukemia (AML) are commonly treated using a daunorubicin-cytarabine ±etoposide (DA/ADE) backbone as developed by the Medical Research Council (MRC) AML 12 trial and since adopted by the Children's Oncology Group (COG). This regimen is an anthracycline-intensive regimen, incorporating mitoxantrone in the consolidation phase, with a stated cumulative cardiotoxic exposure of ~444 mg/m 2 doxorubicin equivalents, though recent data suggests mitoxantrone is more cardiotoxic than previously considered (~10x more cardiotoxic than doxorubicin instead of 3x). The MRC AML15 trial randomized DA/ADE versus fludarabine-cytarabine-idarubicin (FLAG-Ida) and found superior event-free survival (EFS) from FLAG-Ida, with fewer cycles of intensive chemotherapy (4 vs 5), and less than half the cardiotoxic exposure, potentially reducing acute and long-term morbidity. Experience with FLAG-Ida as frontline therapy in children with de novo AML is limited. Following MRC 15, minimal residual disease (MRD) monitoring has become standard of care for risk stratification in AML, but MRD data for the FLAG-Ida regimen in children has not yet been reported. We collected data from 30 pediatric patients (age 0.3-20.0 years) with newly diagnosed de novo AML (no preceding myelodysplastic syndrome, secondary AML, or prior malignancy) and no underlying genetic disease (e.g., Trisomy 21, Fanconi Anemia, Kostmann Syndrome, Shwachman-Diamond Syndrome) treated at our institution with MRC 15-style FLAG-Ida between 2014 and 2021 (Table 1). Each case was characterized by cytogenetics, chromosomal microarray analysis (since 2015, in 29/30), and a proprietary molecular testing panel (since 2017, in 21/30); AML risk category was assigned at diagnosis using the contemporary COG classification (AAML1831). Following Induction I and II, MRD was measured in each patient by multiparameter flow cytometry using a 'difference from normal' approach (MRD+ defined by contemporary COG threshold, MRD≥0.05%). Patients with poor disease response (MRD+) or high-risk cytogenetics proceeded to hematopoietic stem cell transplantation (HSCT) in first remission. Patients routinely received antimicrobial prophylaxis with sulfamethoxazole-trimethoprim, an azole or echinocandin, and levofloxacin. The study was approved by the Institutional Review Board. Following Induction I, 28/30 (93%) patients were MRD negative, and 30/30 (100%) patients following Induction II. Only 1/20 (5%) patients without high-risk AML required HSCT for slow-responding disease; 1/30 (3%) patients were unable to proceed to consolidation (prolonged myelosuppression). No patient developed treatment-related mortality (TRM) during pre-HSCT chemotherapy (2 subsequent to HSCT). Cardiac evaluation in surviving patients was normal (LVSF&gt;28%) post-therapy in 23/24 (96%). Median survival for patients alive at last follow-up was 2.3 years with overall 3-year EFS and overall survival (OS) of 73±9% and 80±8%, respectively (Figure 1A). Survival for patients in the low-risk subset is depicted (Figure 1B, 1C); all low-risk patients were alive at last follow-up. FLAG-Ida was well tolerated and effective in our pediatric AML population with no TRM, excellent early disease response by MRD, and encouraging albeit early EFS and OS. This compares favorably with the adult MRC AML 15 experience as well as with the COG DA/ADE regimen, particularly for MRD response (in AAML0531, ~30% patients were MRD+ following Induction I [Brodersen et al 2020]). These data support our continued use of FLAG-Ida in pediatric AML alone or in combination with targeted and/or molecular therapies. Further study of FLAG-Ida as frontline therapy in children with AML is warranted. Figure 1 Figure 1. Disclosures Gaynon: Takeda pharmaceuticals: Other: member of DSMC committee. Orgel: Jazz Pharmaceuticals: Consultancy.

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