Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe

2018 ◽  
Vol 100 (4) ◽  
pp. 367-371 ◽  
Author(s):  
Inge G.P. Geelen ◽  
Noortje Thielen ◽  
Jeroen J.W.M. Janssen ◽  
Mels Hoogendoorn ◽  
Tanja J.A. Roosma ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Response Monitoring ◽  
Routine Treatment

Effects of GSTP1 Ile105Val polymorphism on both susceptibility and treatment response of chronic myeloid leukemia

Meta Gene ◽  
2021 ◽  
Vol 28 ◽  
pp. 100865
Author(s):  
Ait Boujmia Oum Kaltoum ◽  
Dehbi Hind ◽  
Qachouh Meryem ◽  
Kassogue Yaya ◽  
Nadifi Sellama ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Gstp1 Ile105val

Scoring Systems For Predicting Outcome Of Chronic Myeloid Leukemia In Adults Are Poorly Informative In Pediatric Patients Treated With Imatinib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2725-2725 ◽  
Author(s):  
Meinolf Suttorp ◽  
Ingmar Glauche ◽  
David Gurrea Salas ◽  
Josephine Tabea Tauer ◽  
Christina Nowasz ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Pediatric Patients ◽  
Scoring Systems ◽  
Prognostic Scores ◽  
Sokal Score ◽  
Eutos Score ◽  
Risk Categorization ◽  
Risk Categories

Abstract Introduction Imatinib (IM) front-line treatment impressively improved survival of children with chronic myeloid leukemia (CML). In contrast to adult CML, specific scoring systems predicting the treatment response in individual pediatric patients (pts) are still lacking. Here we analyzed a cohort of pediatric pts with CML applying the established prognostic scores for adults in a comparative fashion. We question the value of four scoring systems (Sokal-, Sokal young-, Hasford-, Eutos-Score) especially with regard to grouping individual children differently or homogeneously into a defined risk category. In addition, we analyzed which scoring system would classify most specifically the prognosis of pediatric CML with regard to early molecular response (MR) on IM. Methods A total of 90 pts (male/female: 57/33; median age: 11.6 yrs, range: 1-18) with CML-CP enrolled in the prospective trial CML-PAED-II were included in this analysis. Registry data were collected on standardized forms filled in by the treating physicians. On this basis the Eutos-, Sokal- and Hasford-Scores were calculated using internet resources of the ELN (www.leukemia-net.org/content/leukemias/cml/cml_score), whereas the Sokal young Score (Sy) – a score described specifically for adolescents and younger adults (Sokal JE, Blood 1985;66:1352) – was manually calculated. Pts were grouped using the original three risk categories (low=LR, intermediate=IR, high=HR) or two categories, respectively, for the Eutos-Score (LR or HR). Evaluation of therapeutic response was performed by assessing the MR by measurement of the transcript ratio BCR-ABL1/ABL1 in blood specimen sent to the central reference laboratory at month 3 after start of IM treatment. Measurements were expressed according to the International Scale. Results By Sokal-Score 59/90 pts were classified as LR, 20/90 pts as IR and 11/90 pts as HR. By Hasford Score 57/90 pts were classified as LR, 25/90 pts as IR, and 8/90 pts as HR. By Eutos Score 73/90 pts were classified as LR and 17/90 pts as HR. As the hematocrit value was not collected systematically at diagnosis, this necessary parameter for calculating the Sy-Score was applicable only in 46/90 pts and thus 44/46 pts were classified as LR, 2/46 as IR, and 0/46 as HR. Comparing results of individual pts only 25/46 pts (54%) were categorized homogeneously as LR by applying all 4 scoring systems, while 54/90 pts (60%) were classified as LR if Sy-Score was excluded. Thus, the remaining 21/46 pts (46%) were grouped heterogeneously by applying each of the 4 prognostic scores, and correspondingly 33/90 pts (37%) were classified heterogeneously within different risk categories by the Eutos, Hasford and Sokal Score. Only 3 pts were categorized homogenously as HR by each of the Sokal, Hasford, and Eutos Score and by applying all 4 scoring systems no patient was concordantly classified as HR. When comparing only the Sokal-Score to the Sy-Score, discordant results were obtained in 19/46 (41%) pts. BCR-ABL1/ABL1 transcript ratio could be analyzed quantitatively in 72/90 pts at month 3 after treatment initiation. In this cohort we identified 46/72 good responders (ratio BCR-ABL1/ABL1 <10%) and 26/72 poor responders (ratio >10%). Although the Eutos-score performed best in in a logistic regression analysis with an Odds Ratio OR=3.02 to predict an unfavorable course of IM-treated CML in the HR group, the discrimination did not reach statistical significance (p=0.08). However, by reducing the cut-off point for the Eutos Score from 87 to 64 an OR=4.8 with p=0.004 was achieved, thus indicating that a refined risk categorization appears beneficial. Conclusion Comparing risk categorization by all four scores in individual pediatric pts, results may vary considerably. Keeping in mind that the number of pts analyzed is still small, especially applying the Sy-Score seems not to provide benefit in this cohort with a median age of only 11 years. Contrasting results in adults, in this pediatric cohort the Sokal- and Hasford-Scores did not predict a poor IM treatment response at month 3 while the Eutos Score achieved borderline significance. Thus, there is an urgent need for the development of a more specific pediatric risk score. Disclosures: No relevant conflicts of interest to declare.

Flow cytometric analysis as an additional predictive tool of treatment response in children with chronic-phase chronic myeloid leukemia treated with imatinib

2017 ◽  
Vol 64 (9) ◽  
pp. e26478
Author(s):  
Haruko Shima ◽  
Nobutaka Kiyokawa ◽  
Masashi Miharu ◽  
Akihiko Tanizawa ◽  
Hidemitsu Kurosawa ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Flow Cytometric Analysis ◽  
Chronic Phase ◽  
Predictive Tool ◽  
Flow Cytometric

The Association Between the Level of Leukemic Stem Cells and Treatment Response Among Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate

2020 ◽  
Vol 7 (2) ◽  
pp. 119-124
Author(s):  
Shinta Oktya Wardhani ◽  
Hani Susianti ◽  
Puji Rahayu ◽  
Yuyun Yueniwati
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Treatment Response ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Cross Sectional Study ◽  
Imatinib Therapy ◽  
Sectional Study ◽  
Cross Sectional ◽  
Blast Cells ◽  
Response Group

Background: The failure of imatinib therapy in patients with chronic myeloid leukemia (CML) is associated with the presence of leukemic stem cell (LSC), and the altered LSC level was reported to occur earlier in the progression of CML. Objective: The study aimed to assess the association between the level of LSC and treatment response among CML patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted in Saiful Anwar Hospital. All participants were divided into two groups, response and non-response group. To assess the level of LSC, flow cytometry was conducted conforming with BD Bioscience. The association and effect estimates were determined using multiple logistic regression. Results and Discussion: A total of 29 response and non-response CML patients treated with imatinib therapy were recruited for our study. After six months of imatinib therapy, we found that elevated levels of leukocytes, thrombocytes, basophils, and blast cells were associated with treatment failure among CML patients treated with imatinib. Moreover, we also found that the LSC level was observed significantly higher in the non-response group compared to the response group among CML patients treated with imatinib. Conclusion: Our study reveals that the elevated level of LSC is considered as an important factor to predict the failure of imatinib therapy among CML patients.

scholarly journals Proteomics Analysis Reveals Protein Panels That Are Associated with Prediction to Tyrosine Kinase Inhibitors Response, Bone Marrow Transplant, Survival and Disease Outcome of Chronic Myeloid Leukemia Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5434-5434
Author(s):  
Ayodele Alaiya ◽  
Mahmoud Aljurf ◽  
Zakia Shinwari ◽  
Fahad Z. Alsharif ◽  
Hazza A. Alzahrani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Personalized Medicine ◽  
Tyrosine Kinase ◽  
Treatment Response ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
The Other ◽  
Disease Outcome

Abstract Clinical and molecular diagnosis of most hematological malignancies including Chronic Myeloid Leukemia (CML) can be accurately made. However, prediction of treatment response and estimation of disease survival period eludes the currently available tools for patient care. Quantitative expression proteomics can potentially be developed as effective tool to monitor therapy response towards achieving personalized medicine for CML patients. We have over 10 years follow up period for some of the CML patients, and the majorities of them are alive and doing well on Imatinib. On the other hand, a small fraction of the patients were switched to alternative Tyrosine Kinase Inhibitors (TKI) and some underwent bone marrow transplants (BMT). Our follow up results stratified all 37 analyzed newly diagnosed CP-CML patients into 5 distinct cohorts including 52% on Imatinib, 12% on Nilotinib, 9% on Dasatinib, and 15% BMT, while 12% of the patients had disease-related mortality. Kaplan-Meier survival curve showed no significant difference between all patients on TKI and BMT that were alive under a follow up period of 4-11 years compared. On the other hand 3 of 4 patients had disease related deaths less than 2 years of diagnosis. Only one patient survived for almost 10 years (Figure 1). Besides survival analysis, peripheral blood samples obtained from the patients at time of diagnosis were subjected to expression proteome analysis using label-free quantitative liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A subset of significantly differentially expressed proteins was able to distinctively discriminate samples into their respective treatment response and disease outcome groups based on unique protein expression signatures (P<0.05 and > 2- ∞- fold change, (Figure 2). Some of the identified proteins were implicated in hematological diseases including CML as potential biomarkers using Ingenuity Pathway Analysis. These protein signatures once validated in larger sample cohorts might be capable of prediction of molecular response, choice of therapy and disease outcome for CML patients. Therefore; allowing for identification of would be high risk patients that might potentially benefit from aggressive treatment at point of diagnosis pre initiation of conventional therapy. Altogether our findings indicate that analysis of panel of protein markers have the potential of clinical utility for prediction of response to therapy, disease survival and objective prognostication of disease outcome, thus bringing personalized medicine closer to CML patients. Disclosures No relevant conflicts of interest to declare.

Chronic Myeloid Leukemia in Pediatrics — First Results From Study CML-PAED II.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 342-342 ◽  
Author(s):  
Meinolf Suttorp ◽  
Christian Thiede ◽  
Josefine T Tauer ◽  
Silja Roettgers ◽  
Petr Sedlacek ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Bone Metabolism ◽  
Treatment Response ◽  
Muscle Pain ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Response Rates ◽  
Longitudinal Growth ◽  
Molecular Response

Abstract Abstract 342 Background: Chronic myeloid leukemia (CML) is a rare malignancy in pediatrics. In this decade -like in adults- imatinib meyslate (IMA) has been established also as first line treatment for children with CML while allogeneic stem cell transplantation (SCT) as treatment option is postponed for those cases becoming intolerant or refractory to tyrosine kinase inhibitor (TKI) treatment. However, results from controlled trials in children are lacking so far. We here report an analysis of pediatric data from patients (pts) with newly diagnosed Philadelphia-chromosome positive (Ph+) CML on up-front treatment with IMA. Pts and Methods: According to protocol CML-PAED II pediatric pts with confirmed diagnosis of Ph+ CML were treated in CP with IMA 300 mg/sqm once daily, while in accelerated phase (AP) or in blastic phase (BC) the dose was increased to 400 mg/sqm and 500 mg/sqm (bis daily), respectively. Initial and long-term clinical and laboratory data, treatment response and side effects were reported to the study center on standardized forms by the treating physician. Specimen from peripheral blood (pB) and bone marrow (BM) were assessed by cytogenetics and by quantitative RT-PCR for BCR-ABL transcript rates in central laboratories for standardized monitoring in three months intervals. Results: From 1. Jan 2004 until 31. Mrch 2009 a total of 51 pts (21 female, 30 male; median age: 10.6 yrs [range:1-20 yrs]) were registered: 10 pts with ongoing IMA treatment were recruited and analyzed retrospectively while 41 pts were enrolled prospectively from centers in Austria (n=1), Czech Rep. (n=6), Germany (n=40), Italy (n=1), Netherlands (n=1), Slovak Rep. (n=2). Stages of disease were: CP n=47; AP n=1; BC n=3 (two myeloid). Those four pts diagnosed in AP and BC underwent early SCT. Observed side effects in the whole group included: nausea (n=9), muscle pain (n=7), edema (n=3), rhabdomyolysis (n=1, short interruption of IMA), reduced blood cell count (n=2, short interruption of IMA in one pt), biochemical alterations in bone metabolism [for details see: N Engl J Med 2006;354:2006] (n = 8), impaired longitudinal growth (n=1, [Haematologica 2009;94:1177]). Two pts experienced intolerance (muscle pain) or toxicity (hepatic), respectively, therefore stopped IMA and were put on dasatinib after 4 and 10 months, respectively. Having achieved complete cytogenetic response (CyR) and 2 log-fold reduction of BCR-ABL transcript rate, one pt opted for SCT from her HLA-identical brother after 15 mo of treatment. Response rates in advanced stages of CML were as follows: in BC (n=3) two pts became hematological responders (HR), one pt exhibited partial HR. The only one pt diagnosed in AC exhibited partial CyR but complete HR. A landmark analysis in pts entering CML-paed II in CP exhibited that 2/42 pts (5%) had no complete HR at month 3; 2/28 (7%) had no complete CyR at month 12, and 2/19 (15%) pts achieved no major molecular response (MMR, defined as >0.1% BCR-ABL [Blood 2006;108:28–37]) at month 18 after start of IMA. Each two of those four patients with incomplete response (one pt with no CyR at month 12, one pt with no MMR at month 18) underwent SCT from a sibling donor and the other two pts stopped IMA and were put on dasatinib. With a median follow-up of 19 months (range: 0-63 months) all 47 pts diagnosed in CP are alive. Of note none of the six pts (median age at diagnosis: 5 yrs; range 1–13 years) treated by imatinib meanwhile for >36 months have opted for SCT. Conclusion: Keeping in mind that the number of pediatric pts is still small, IMA treatment for children and adolescents with CML in CP is associated -like in adults- with high treatment response rates. Refractoriness to IMA is uncommon and side effects seem tolerable, as only 10% of the total cohort stopped imatinib and were put on 2nd generation TKI. However, disturbances of bone metabolism and longitudinal growth impairment may be of special concern in this not yet outgrown cohort [N Engl J Med 2006;354:2006, Blood 2008;111:2538; Haematologica 2008;93:1101; Lancet 2008;372:111; Int J Hematol; 2009;89:251; Haematologica 2009;94:1177]. Only 3/47 pts not diagnosed in advanced phases of CML so far underwent SCT thus underlining that also in pediatrics SCT has been shifted to a second-line strategy for high-risk patients and those who failed therapy with IMA. Disclosures: Suttorp: Novartis : Research Funding. Thiede:Novartis: Research Funding.

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