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.

scholarly journals The Psychosocial Transplant Evaluation Rating Scale (TERS) Prospectively Predicts Inferior Overall Survival Outcome for High Risk Scoring Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 207-207 ◽  
Author(s):  
Dawn Speckhart ◽  
Scott R. Solomon ◽  
Xu Zhang ◽  
Lawrence E. Morris ◽  
Asad Bashey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Cell Transplantation ◽  
Rating Scale ◽  
Disease Risk ◽  
Psychosocial Risk ◽  
Hematopoietic Stem ◽  
Transplant Evaluation ◽  
The Relationship

Abstract Several studies have begun to examine the relationship between psychosocial variables and outcome in hematopoietic stem cell transplantation (HSCT). Previous studies have also looked at the relationship between the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and disease risk on overall survival in HSCT. Research has shown that disease risk and HCT-CI may have a negative relationship with outcome in HSCT. In this study, psychosocial data was collected prospectively on 437 patients undergoing related and unrelated allogeneic HSCT. All patients were assessed using the Transplant Evaluation Rating Scale (TERS). Based on the patient’s TERS score, each patient was stratified into one of two groups (low/moderate risk (n=371) vs. high risk (n=66)) based on their predicted psychosocial risk for problems during transplant. The 1-year overall survival (OS) for the low/mod risk TERS group versus the high TERS risk group was 78% and 61%, respectively (p=.005). Stratification by CIBMTR disease risk identified 261 patients with low and intermediate risk disease of which 228 had low/mod risk TERS score and 33 had high risk TERS score. The is a significant survival advantage for Low/Mod Risk TERS patients vs. High Risk TERS patients at 100 day, 1 year and overall survival being 97% vs 79% (P=.01), 85% vs 58% (P=.002) and 68% vs 42% (P=.002) with a median follow up of 48 months (graph attached). An adjusted logistic regression analysis showed that psychosocial factors have a significant impact on overall survival despite all patients being required to have 24 hour caregiver support, a pre-transplant psychosocial evaluation and post-transplant psychosocial intervention. The analysis controlled for other variables such as age, gender, performance status, disease risk and transplant type. These results highlight the impact of psychosocial factors on HSCT outcome, as those patients who are expected to do well based on their low/intermediate disease risk may not perform as expected due to psychosocial risk factors. These results suggest the need to perform careful psychosocial assessments on all HSCT patients in order to predict mortality risks for the individual patient and to help the transplant team strategize how to better manage the high risk psychosocial patient. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Utilization of Resources and Overall Outcome in Patients Undergoing Hematopoietic Stem Cell Transplantation Related to Psychosocial Factors as Measured by the Transplant Evaluation Rating Scale (TERS).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3332-3332
Author(s):  
Dawn S. Speckhart ◽  
H.K. Holland ◽  
Scott R. Solomon ◽  
Lawrence E. Morris ◽  
Asad Bashey
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Rating Scale ◽  
Risk Group ◽  
Psychosocial Risk ◽  
Moderate Risk ◽  
Hematopoietic Stem ◽  
Risk Patients ◽  
Transplant Evaluation ◽  
Length Of Hospitalization

Abstract Several studies have begun to examine the relationship between psychosocial variables and outcome in hematopoietic stem cell transplantation (HSCT). Data presented at the 2006 ASH Convention, demonstrated a significant relationship between psychosocial variables, such as those assessed on the Transplant Evaluation Rating Scale (TERS), and objective outcomes, such as length of hospitalization and survival. The 2006 data included 200 consecutive patients (136 autologous, 65 allogeneic) undergoing HSCT. Based on the patient’s TERS score, each patient was stratified into one of two groups (low/moderate risk (n=173) vs. high risk (n=28)) based on their predicted psychosocial risk for problems during transplant. With the addition of 166 patients (Current N=366: 239 autologous, 127 allogeneic) the difference in length of hospitalization between low/moderate risk (10 days) versus high risk (19 days) patients remains significant (p<.02). For allogeneic patients (N=127), there continues to be an improved overall survival in low/moderate risk patients in the first 12 to 18 months following HSCT compared to high risk patients (p = .246). To determine whether similar factors impact utilization of resources in patients undergoing HSCT, we prospectively conducted psychosocial assessments on 112 consecutive allogeneic HSCT patients. An analysis of cost was completed for all patients in both the low/moderate risk group and high risk group. The mean cost differential for high risk patients is noted to be 27% higher than those patients in the low/moderate risk group (p = .122). This trend reinforces earlier data presented and suggests a correlation between pre-transplant psychosocial risk factors and resource utilization in HSCT. Overall Survival Overall Survival

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 &lt;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 (&gt;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.,&lt;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&lt;0.001), and survival (OS; relative risk: 2.8, 95% CI:1.6-5, p&lt;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

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

Psychosocial Factors as Measured by the Transplant Evaluation Rating Scale (TERS) Predict Length of Hospitalization and Transplant Outcomes Following Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 75-75 ◽  
Author(s):  
Dawn S. Speckhart ◽  
Scott R. Solomon
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Rating Scale ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Transplant Patients ◽  
Transplant Evaluation ◽  
Length Of Hospitalization

Abstract Although psychological and social factors are recognized as being important in the evaluation of patients for hematopoietic stem cell transplantation (HSCT), no standard approach to psychosocial assessment currently exists. In solid organ transplantation, psychosocial assessments have been integrated into the selection of appropriate candidates, and certain psychosocial variables, such as active substance abuse, have been shown to negatively impact outcomes in solid organ transplant patients. To determine whether similar factors impact outcomes in patients undergoing HSCT, we prospectively conducted psychosocial assessments on 221 consecutive patients (155 autologous, 66 allogeneic) undergoing HSCT. The relationship between psychosocial variables, such as those assessed on the Transplant Evaluation Rating Scale (TERS), and objective outcomes, such as length of hospitalization and survival was evaluated. Based on the patient’s TERS score, each patient was stratified into one of two groups (low/moderate risk (n=187) vs. high risk (n=34)) based on their predicted psychosocial risk for problems during transplant. Although the two groups were similar in regards to known pre-transplant prognostic factors such as age, performance status, disease risk, and transplant type, there was a significant difference in the median length of hospitalization between patients who score low/moderate (10 days) and those who scored high (21.5 days) on the TERS. This difference was significant both for patients receiving autologous (9 vs. 15 days, p&lt;.02) and allogeneic transplants (16 vs. 45 days, p&lt;.001). Furthermore, 2-year overall survival was significantly improved in allogeneic transplant patients who score low/moderate vs. those that scored high on the TERS (72% vs. 46%; p&lt;=.02). These findings suggest a strong correlation between pre-transplant psychosocial risk factors, resource utilization and patient outcome in HSCT. Figure 1. Overall survival following allogeneic stem cell transplantation according to TERS score Figure 1. Overall survival following allogeneic stem cell transplantation according to TERS score

MDM2 SNP309 and TP53 SNPArg72Pro Polymorphisms in Myelodysplastic Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1745-1745
Author(s):  
João Agostinho Machado Neto ◽  
Fabiola Traina ◽  
Paula Melo Campos ◽  
Marilisia Andreoli ◽  
Irene Lorand Metze ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Disease Progression ◽  
Low Risk ◽  
Healthy Controls ◽  
Mdm2 Snp309 ◽  
P53 Pathway ◽  
Hematopoietic Stem ◽  
High Risk Disease

Abstract Abstract 1745 Poster Board I-771 Introduction Myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, refractory cytopenia and a tendency to progress towards acute myeloid leukemia (AML). The progression of the disease may be associated with genetic or epigenetic alterations and a possible change in protein function. MDM2/P53 pathway plays an important role in the control of apoptotic and proliferation mechanisms. Single nucleotide polymorphisms (SNPs) were identified in the TP53 and MDM2 genes. MDM2 SNP309 results in higher levels of MDM2 and attenuates p53 pathway. The SNP in codon 72 of the TP53 gene results in either a C or G nucleotide and leads to either Proline (Pro) or Arginine (Arg), respectively. The Arg variant has been shown to be more potent in apoptosis induction and the Pro variant has been shown to be better in inducing cell-cycle arrest and to have a greater ability to repair damaged-DNA. The aim of the present study was to investigate the incidence of MDM2 and TP53 polymorphisms in MDS patients and to correlate the frequency of these SNPs with age, neutrophis and platelets at diagnosis, low risk versus high risk disease according to FAB (RA and RARS versus AREB and AREBt) and IPSS (Low and Int-1 versus Int-2 and high), cytogenetic risk (low versus intermediate and high risk), disease progression and overall survival. Patients and Methods We studied 103 healthy controls and 63 patients with MDS. According to FAB, patients were distributed as follows: 43 RA, 10 RARS, 7 RAEB, 1 RAEBt and 2 CMML. The median follow-up time was 40 months (range 2 – 159 months). Samples were obtained from peripheral blood or bone marrow and were screened for the presence of polymorphisms MDM2 SNP309 and TP53 SNPArg72Pro, by PCR analysis with specific primers and appropriate restriction enzyme. Appropriate statistical analyses were used for each test. Results The frequencies of genotypes for MDM2 SNP309 and TP53Pro7Arg were similar between MDS and healthy controls; MDM2 SNP309: 51% vs 53%, for TT, 38% vs 32% for TG, and 11% vs 15% for GG, TP53Pro7Arg: 47.5% vs 44%, for Arg/Arg, 47,5% vs 42% for Pro/Arg, and 5% vs 14% for Pro/Pro. No differences were observed between MDS patients with presence or absence of the polymorphisms in relation to age, neutrophis and platelets at diagnosis, low risk versus high risk disease according to FAB, IPSS and cytogenetic risk, disease progression and overall survival. Conclusions MDM2 and TP53 polymorphisms have been described to affect the risk for cancer, onset age and overall survival in solid tumors and leukemias. This was the first study to report these SNPs in MDS and leads to believe that these polymorphisms are not associated with risk for the disease and with clinical data. Keywords: MDM2, p53, myelodysplasia, polymorphisms Disclosures No relevant conflicts of interest to declare.

A Prognostic Score For Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3389-3389
Author(s):  
Bernd Gruhn ◽  
Ilona Wolff ◽  
James F. Beck ◽  
Clemens Arndt
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Myeloid Leukemia ◽  
Disease Risk ◽  
Univariate Analysis ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Blood Stem Cells

Abstract Background The effects of certain risk factors on the survival of adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT) have been the subject of research for many years. The impact of graft source and donor type, for instance, has already been examined closely. Lately iron parameters like ferritin became point of interest. Several prognostic scores utilizing those risk factors have been proposed. However, observations of pediatric populations considering those factors remain rare and no score in this regard for children with HSCT is available yet. Methods We retrospectively analyzed the effects of patient sex, recipient-donor sex match status, patient age, donor age, disease risk, graft source, donor HLA match as well as ferritin, albumin, total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), cholinesterase (CHE), gamma glutamyl transpeptidase (GGT), C-reactive protein (CRP) and lactate dehydrogenase (LDH) taken at the time of transplantation on the 5-year-overall survival of 132 children with malignant or non-malignant diseases undergoing allogeneic HSCT between 2001 and 2011 in a single center. The graft source was either bone marrow (n=82) or peripheral blood stem cells (n=50). The patients had the following underlying diseases: acute lymphoblastic leukemia (n=44), acute myeloid leukemia (n=29), chronic myeloid leukemia (n=5), myelodysplastic syndrome (n=16), non-Hodgkin lymphoma (n=7), solid tumor (n=4), severe aplastic anemia (n=7), myelofibrosis (n=2) and genetic disease (n=18). Conditioning regimen was myeloablative in all cases. The disease risk was formed by dividing the patients into two groups according to their clinical risk. Patients with genetic diseases, severe aplastic anemia, refractory cytopenia, myelofibrosis, leukemia and lymphoma in first or second remission as well as chronic myeloid leukemia in chronic phase were low risk, while patients with solid tumors, leukemia and lymphoma in relapse or in more than second remission and refractory anemia with excess blast in or not in transformation were high risk. For statistics we used Kaplan-Meier-method for univariate analysis and Cox regression for multivariate analysis. Results On univariate analysis 5-year-overall survival decreased significantly in patients with ferritin >1500 µg/L (40.8% versus 78.8%, p<0.001), GGT >1 µmol/L∙s (43.2% versus 67.9%, p=0.032), CRP >10 mg/L (54.6% versus 69.4%, p=0.017), LDH >6 µmol/L∙s (22.2% versus 66.8%, p=0.001), CHE <60 µmol/L∙s (35.7% versus 70%, p=0.002) as well as in patients with high disease risk (38.3% versus 74.7%, p<0.001), peripheral blood stem cells as graft source (47.1% versus 72.2% for bone marrow, p=0.001). For HLA donor match there was a 5-year-overall survival of 82.0% for matched related, 58.4% for matched unrelated, 56.3% for mismatched unrelated and 50.0% for haploidentical related donors (p=0.020). Other factors did not show a significant correlation. We subsequently developed a score of those parameters that were significant in multivariate analysis, i.e. disease risk (HR=3.744, p=0.035), ferritin (HR=6.860, p=0.002) and cholinesterase (HR=4.556, p=0.043), dividing the patient population into three groups: low with no risk factor, intermediate with one risk factor and high with two or three risk factors. For this score we found a 5-year-overall survival of 92.3% for low risk group, 66.2% for intermediate risk and 17.4% for high risk (p<0.001). Conclusion Our data show that ferritin, cholinesterase and disease risk are factors that decisively influence the prognosis after allogeneic HSCT in children. They should be evaluated in further trials as well as our proposed score. The characteristics that showed up significant in univariate but not in multivariate analysis appear to have an influence as well and might show a stronger correlation in larger trials. Disclosures: No relevant conflicts of interest to declare.

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.

Early Mortality in Acute Promyelocytic Leukemia May Be Higher Than Previously Reported.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1015-1015 ◽  
Author(s):  
Ash A Alizadeh ◽  
James S. McClellan ◽  
Jason R. Gotlib ◽  
Steven Coutre ◽  
Ravindra Majeti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
High Risk ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Low Risk ◽  
Intermediate Risk ◽  
Risk Patients

Abstract Abstract 1015 Poster Board I-37 Background: Early mortality, mostly from hemorrhagic complications, occurs in less than 10% of patients currently treated in clinical trials for acute promyelocytic leukemia (APL). However, data about the proportion of patients developing such complications prior to clinical trial enrollment are scarce in the literature (Sanz M, et al Blood 2009). Approximately 5% of newly diagnosed patients with APL have been reported not to be eligible for participation in clinical trials due to very poor clinical condition, and their outcome has never been reported. However, enrollment on clinical trials may be difficult in specific clinical situations, such as after hours/weekend admissions and/or emergent requirement for therapy. This study reports the incidence, time of occurrence and clinical features of APL patients with a focus on early mortality. Methods: 150 consecutive APL patients treated at Stanford University between 8/1986 and 7/2009 were identified. Thirteen patients were excluded for lack of appropriate clinical information. Clinical features of patients with APL were analyzed for factors that might be relate to prognosis, including age, gender, white blood cell count, platelet count, fibrinogen, PTT, and INR. Continuous variables were compared with the t-test and categorical variables by Fisher's exact test or X-square statistic. The Kaplan–Meier method was applied to assess overall survival time. Results: Of the 137 patients included in this analysis, the median age at diagnosis was 45 (1-93) years and 78 (57%) were females. Using the PETHEMA criteria, there were 37, 46 and 20 patients with high-, intermediate- and low-risk disease (34 patients could not be classified based on partial/missing data). With a median follow-up time of 748 (0-6,235) days for the entire cohort, 52 (38%) have died. 19 (14%) and 11 (8%) of these patients died within 7 and 3 days of presentation, respectively. Patients with high-risk features had a 13% and 24% chance of dying with 3 and 7 days of presentation, respectively, with significantly inferior outcomes (p=0.045) when compared to those with intermediate-risk patients (6% and 13%) and low-risk disease (5% and 5%). Patients with unknown risk category faired similarly to low-risk patients. The most common cause of early mortality in these 19 patients was intracranial hemorrhage (n=11). Patients with early death (ED) (either <=3 or <=7 days) tended to be older than APL patients with non-early deaths (>7d), or APL patients alive as of their last follow-up (median age 54 years vs. 50 years vs. 39 years), and were more likely to have higher risk disease, though coagulopathy appeared not significantly different amongst the groups. Median fibrinogen, PTT and INR for each individual group are presented on Table 1. The 3-year overall survival (% +/- SE) of the low, intermediate, and high risk patients was 90+/-7, 74+/-7, and 64+/-8, respectively, though early mortality (death within 7 days) was a major determinant of this stratification (p=0.045). Conclusions: Risk of early death in APL patients appears to be higher than previously reported in clinical trials, where trial registration may exclude patients requiring urgent therapeutic interventions. In this cohort, 25% and 13% patients with high- and intermediate-risk APL died within 7 days of presentation, respectively. Risk group stratification was very predictive of risk of early death. Disclosures: No relevant conflicts of interest to declare.

Association of CD33 Expression Level with Disease Risk-Group Classification and Induction Response In Pediatric AML: A Report From the Children's Oncology Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2732-2732
Author(s):  
Jessica A. Pollard ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Phoenix A. Ho ◽  
Rhonda Ries ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Risk ◽  
Risk Group ◽  
Group Classification ◽  
Low Risk ◽  
Intermediate Risk ◽  
Oncology Group ◽  
High Risk Disease ◽  
Pediatric Aml ◽  
Cebpa Mutations

Abstract Abstract 2732 Our previous analysis of diagnostic AML bone marrow (BM) samples from a subset of patients enrolled on Children's Oncology Group (COG) AAML03P1, a pilot study in which conventional chemotherapy was used in combination with the CD33 targeted therapeutic gemtuzumab ozogamicin (GO), demonstrated that CD33 expression is highly variable in pediatric AML and that low or absent CD33 expression was not associated with inferior clinical response. Moreover, patients with the highest CD33 expression did not have superior outcomes. Low CD33 expression was associated with low risk disease [core binding factor (CBF) AML e.g. t(8;21), inv(16) or t(16;16), CEBPA mutated AML, NPM1 mutated AML] whereas the highest CD33 expression levels were seen in patients with high-risk disease [FLT3/ITD+ disease with allelic ratio >0.4, high risk cytogenetics e.g. -7, -5, -5q]. These findings refute previous adult AML data in which CD33 expression is directly correlated with response to single agent GO and suggest, within AAML03P1, that clinical response is linked to underlying disease biology. In this larger analysis, we prospectively evaluated CD33 expression levels of AML blasts isolated from 676 pediatric diagnostic BM samples (238/340 and 438/968 patients enrolled on COG AAML03P1 and COG AAML0531 respectively) to determine whether this association persists in a larger cohort. CD33 expression, as defined by mean fluorescent intensity (MFI) of the blast population, varied over 2-log fold, and a median MFI of 128 was observed (range 3–1550.07). The study population was divided into quartiles (Q) based on CD33 expression (n= 169 patients per quartile). Median MFI was 37.49 (range 3–62) for Q1, 90 (range 62.21–128) for Q2, 171 (range 128–245) for Q3 and 349 (range 245.52–1550.07) for Q4. Samples were also screened for disease-relevant molecular mutations: 89/650 (14%) were FLT3/ITD positive; 69/587 (12%) were positive for NPM1 mutations; and 35/585 (6%) positive for CEBPA mutations. FLT3/ITD prevalence significantly increased with increasing CD33 quartile (Q1 7%, Q2 10%, Q3 17%, Q4 20%; p<0.001), whereas no definitive trend in prevalence was observed for NPM1 (Q1 7%, Q2 14%, Q3 15%, Q4 12%; p=0.158) or CEBPA mutations (Q1 6%, Q2 8%, Q3 6%, Q4 4%; p=0.307). Cytogenetic data was available for 613 (91%) samples; 177 (29%) CBF AML samples were identified and their prevalence declined with increasing quartile (Q1 51%, Q2 40%, Q3 20%, Q4 6%; p<0.001). There was no apparent association between CD33 expression and high-risk cytogenetics; however, analysis was limited by the small number of patients (9/613, 1.4%) with such mutations. For risk-group classification, complete cytogenetic and molecular data were available for 535 (79%) samples: 204/535 (38%) were classified as low-risk and 64/535 (12%) were defined as high-risk. There was an inverse association between CD33 expression and prevalence of low-risk AML (Q1 59%, Q2 50%, Q3 27%, Q4 17%; p<0.001). In contrast, the prevalence of high-risk disease increased with each quartile (Q1 5%, Q2 8%, Q3 17%, Q4 18%; p<0.001). We observed a higher median CD33 MFI with high-risk disease (median MFI 195.315; range 12–720) than with low-risk (median MFI 80.5; range 5–1550.07) or intermediate-risk (i.e., neither low- nor high-risk) disease (median MFI 163.06; range 7–1351) (p<0.001). Response from end of induction I (CR) was also determined for our patient cohort. Rates of CR were similar across CD33-expression quartiles (Q1 78%, Q2 75%, Q3 75%, Q4 72%; p=0.581). Moreover, CR rates for each risk group did not vary across quartiles (low-risk: Q1 84%, Q2 85%, Q3 88%, Q4 82%; p=0.917; intermediate-risk: Q1 77%, Q2 65%, Q3 72%, Q4 71%; p=0.594; high-risk: Q1 57%, Q2 67%, Q3 60%, Q4 72%; p=0.801). This large scale analysis supports our earlier finding that CD33 expression in pediatric AML is heterogeneous and associated with conventional risk-group criteria. As outcome data matures from COG AAML0531, the phase III counterpart of AAML03P1 in which patients are randomized to GO treatment, we will determine whether the addition of GO improves survival of patients with low versus high CD33 expression and whether this finding translates into enhanced outcomes for associated disease-risk groups. Disclosures: Franklin: Amgen : Employment, Equity Ownership.

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