Hasford Score

The aim of the study is to to determine correlation Hasford score and early molecular response in chronic phase BCR-ABL-Positive CML patients treated with imatinib. This is an longitudinal observational study in newly diagnosed patients of CML chronic phase BCR-ABL-Positive treated imatinib from Januari 2017 to September 2017. Patients were stratified according to Hasford score at diagnosis. Q-PCR(Quantitative RT-PCR) were used to monitor BCR-ABL transcription levels after 3 months of imatinib treatment. Correlation between Hasford score with early molecular response were analyzed using Koefisien Kontingensi’s correlation test. Results: Thirty five patients were enrolled in this study consist of 13 male and 22 female. After 3 months of imatinib treatment, EMR were 5 patients (83.3%), 11 patients (61.1%) and 2 patients (18.2%) in low, intermediate, and high risk group patients, respectively. Koefisien kontigensi test showed that there was significant correlation between Hasford score and EMR (p=0.018; r=0.431). The Hasford score correlated to early molecular response in chronic phase BCR-ABL-positive CML patients received imatinib.

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Hasford Score Is Correlated with 18 Month Molecular Response for Chronic Myeloid Leukemia Patients Treated with Second Generation Tyrosine Kinase Inhibitors and It May be Useful to Differentiate Low and Intermediate Risk Patients: A Single Institution Experience

Blood ◽

10.1182/blood.v126.23.5163.5163 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5163-5163

Author(s):

Jaroslaw Dybko ◽

Olga Haus ◽

Bozena Jazwiec ◽

Tomasz Lonc ◽

Mateusz Sawicki ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Molecular Response ◽

Intermediate Risk ◽

Risk Patients ◽

Hasford Score

Abstract BACKGROUND: Chronic myeloid leukemia (CML) has been a model disease for a variety of studies concerning scoring systems, graft versus leukemia effect or tyrosine kinase inhibitors (TKI) treatment for many years. Scoring systems playing an important role in modern medicine to establish risk-adjusted optimal therapy [1] have been always essential for CML changing treatment modalities [1-3]. The three principal risk scores : Sokal [2], Hasford [1] and European Treatment and Outcome Study (EUTOS) [3] were established in different eras of CML therapy with implications for prognosis and disease outcome [4]. Hasford metric was designed based on data of patients treated with interpheron alpha [1] and it failed to differentiate patients who achieved low and intermediate risk scores according to CCyR, MMR, and 5 years EFS [5]. However in our previous study we found Hasford score to be correlated with the long-term molecular response in patients treated with imatinib [6]. This study presents the analysis of patients treated with second generation tyrosine kinase inhibitors (2G-TKI) due to their loss of MMR on imatinib. Hasford score still distinguish patients with low and intermediate risk and correlates with 18 month molecular response. PATIENTS AND RESULTS: The original group of 88 CML patients (F/M:42/46, median age 51 (21-83), 57 low risk and 31 intermediate risk assessed by Hasford risk score) in first chronic phase without any additional chromosomal abnormalities receiving standard dose imatinib was described in our previous study [6]. Of these, 42 patients lost MMR in a median time of 47 months. Within this group we identified 20 low risk (LR) and 22 intermediate risk (IR) patients. All 42 patients were switched to 2G-TKI. The observation after 3 months of 2G-TKI treatment was also previously described. After 18 months of 2G-TKI treatment median bcr-abl transcript levels in the LR group were 0.002 (0.000-0.02) but in the IR group bcr-abl levels were 0.03 (0.000-21.1) (p=0.03, Figure 1). All 20 low risk patients achieved major molecular response (MMR). In the intermediate risk group the response rate (MMR) was approximately 73% (16/22) and there is a significant difference in a probability of achieving MMR in both groups (Fig.2, p=0.0002). CONCLUSIONS: We are aware of Hasford score limited usefulness in predicting MMR in large studies. However in our study it is still a tool to distinguish low and intermediate risk patients by their molecular response on 2G-TKI after imatinib failure. We find our results relevant to the discussion on optimizing scoring systems and first line treatment of CML patients. REFERENCES: 1. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. Journal of the National Cancer Institute. 1998;90:850-8. 2. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood. 1984;63:789-99. 3. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118:686-92. 4. Hu B, Savani BN. Impact of risk score calculations in choosing front-line tyrosine kinase inhibitors for patients with newly diagnosed chronic myeloid leukemia in the chronic phase. European journal of haematology. 2014;93:179-86. 5. Yahng SA, Jang EJ, Choi SY, Oh YJ, Bang JH, Park JE, Jeon HL, Lee SE, Kim SH, Byun JY, Kim DW. Comparison of Sokal, Hasford and EUTOS Scores in Terms of Long-Term Treatment Outcome According to the Risks in Each Prognostic Model: A Single Center Data Analyzed in 255 Early Chronic Phase Chronic Myeloid Leukemia Patients Treated with Frontline Imatinib Mesylate. Blood 2012;120:Abstract 2794 6. Dybko J, Medras E, Haus O, Jazwiec B, Wrobel T, Kuliczkowski K. The Hasford Score Correlates with the Long-Term Molecular Response to Imatinib Treatment for Chronic Myeloid Leukemia Patients and May be Useful for Differentiating Low and Intermediate Risk Patients: A Single Institution Experience. Blood 2014;124:Abstract 3152 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

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Clinicohematological study of spectrum of myeloproliferative neoplasms in a tertiary care hospital

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i3.2535 ◽

2020 ◽

Vol 11 (3) ◽

pp. 3710-3718

Author(s):

Sonal Gupta ◽

Sujata R. Kanetkar

Keyword(s):

Bone Marrow ◽

High Risk ◽

Tertiary Care Hospital ◽

Risk Group ◽

Myeloproliferative Neoplasms ◽

Tertiary Care ◽

Care Hospital ◽

Trephine Biopsy ◽

Maximum Serum ◽

Hasford Score

Myeloproliferative neoplasms (MPNs) are a group of disorders of hematopoietic stem cells which were initially recognised by William Dameshek in 1951. Objectives of the study were to diagnose and classify cases of myeloproliferative neoplasms according to 2016 revision of WHO classification of myeloid neoplasms and acute leukaemias, to study various haematological parameters of cases of MPNs (Peripheral smear findings, bone marrow aspirate and trephine biopsy) and their clinical manifestations, to record the cytogenetic/molecular genetic abnormalities of the cases and to categorise CML patients according to Hasford Risk Score as a predictor of prognosis. This study was a prospective study carried out in the Department of Pathology of a tertiary care hospital over two years from June 2016 to September 2018. The study included a total of 41 cases of MPNs. The cases of CMLs were diagnosed on peripheral blood findings, Bone marrow aspiration, Trephine biopsy Serum LDH and uric acid. CML was the most common MPN encountered (37/41; 90.24%) in the present study. Maximum serum LDH elevation was observed in CML cases with a mean value of 1396.6 U/L. Of the 37 CML cases, as per Hasford score, 17 cases were categorised into a low-risk group, 17 cases into an intermediate-risk group and 3 cases into a high-risk group. In the present study of Hasford score in CML cases, it was found that it helps in making a better-informed decision about the adaption of alternative high-risk treatment, and was of value in oncology practice.

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Results of Imatinib Therapy In Patients with Early and Late Chronic-Phase Chronic Myeloid Leukemia In a South Brazilian Cohort.

Blood ◽

10.1182/blood.v116.21.4487.4487 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4487-4487

Author(s):

Marcelo Capra ◽

Mariza Shaan ◽

Katia Fassina ◽

Mario Sérgio Fernandes ◽

Marco Antônio Schilling ◽

...

Keyword(s):

Myeloid Leukemia ◽

Chronic Phase ◽

Cytogenetic Response ◽

Molecular Response ◽

Imatinib Treatment ◽

Second Line Therapy ◽

Line Therapy ◽

Sokal Score ◽

Hasford Score

Abstract Abstract 4487 Background: Imatinib treatment for Chronic Myeloid Leukemia (CML) was first introduced in Brazil in 2001, initially used as second line therapy for patients resistant or intolerant to interferon (IFN). In 2008 imatinib was adopted as front-line therapy for chronic-phase (CP-CML) and clinical experience is improving since then, but little is known about the result of its introduction in our clinical practice. Aims: To evaluate the impact of imatinib treatment in the outcomes of a cohort of CP-CML and the prognostic significance of Sokal and Hasford scores and late-onset treatment. Methods: We conducted a retrospective study in a cohort of patients with CP-CML from a south Brazilian database. All patients received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the European LeukemiaNet. The outcomes were response to treatment, event-free survival (EFS) and overall survival (OS). Results: We analyzed data from 185 pts with CP-CML diagnosed since 1990. The median age at diagnosis was 48 years (4 – 85). The median time from diagnosis to imatinib was 7 months (0 – 178) and 29% of pts had more than 12 months lapse. Prior therapy with IFN was used in 70% pts. All pts had a minimum follow-up of 12 months. At baseline, 57 pts (31%) were in complete hematological response (CHR) due to the use of previous treatment. Of the 127 pts not in CHR at baseline, 98% achieved CHR early during imatinib treatment. 177 pts had cytogenetic evaluation during treatment and 9 pts were in complete cytogenetic response (CCyR) due to the use of previous IFN. Of the 168 pts not in CCyR at baseline, 86,4% achieved a major cytogenetic response (MCyR) during imatinib treatment (84% had a CCyR and 2,4% had a partial cytogenetic response). The rate of pts achieving MCyR any point during treatment differed significantly in the low, intermediate and high risk Sokal score groups (97%, 81% and 78% respectively, P=0,04), but not in the Hasford score groups (90%, 85% and 72%, P=0,22). Minor cytogenetic response was seen in 3,6% of pts, minimal cytogenetic response in 6% and 9,5% had no cytogenetic response. The median time to a MCyR was 9 months, with 62% of pts achieving MCyR at 12 months. The rate of pts achieving MCyR in 12 months differed significantly between pts who start imatinib before 12 months from diagnosis (68%) and those late treated (47%, P=0,02). Evaluation of minimal residual disease at the molecular level was available for 155 pts: 25,5% of pts had a complete molecular response (CMR), 43% had a major molecular response (MMR) and 2 pts were in MMR at baseline due to previous IFN. The projected EFS and OS rates at 4 years were, respectively, 68% and 92% after a median follow-up time of 4 years. The rate of EFS differed significantly in the low, intermediate and high risk Sokal score groups (80%, 66% and 52% respectively, P=0,04), but not in the Hasford score groups (78%, 62% and 44%, P=0,09). During treatment with imatinib, 120 pts (65%) had a register of any grade hematologic adverse event (21% being grades 3 or 4) and 165 pts (90%) had a register of any grade nonhematologic adverse event (9,3% being grades 3 or 4). Of the 185 pts who received treatment, 134 (72%) continue to receive imatinib and 51 (28%) discontinued treatment. The reasons for discontinuation were: 11 (6%) pts had drug-related adverse events (3 [1,6%] hematologic and 8 [4,3%] nonhematologic), 17 (9,2%) had disease progression (5 [2,7%] loss of CHR, 10 [5,4%] loss of CCyR, 2 [1%] had progression to accelerate or blastic phase), 22 (11,9%) had treatment failure (3 [1,6%] had no CHR, 13 [7%] had no CCyR and 6 [3,2%] had no MMR), 1 pt (0,5%) discontinued due to comorbidity. For the 51 (100%) pts that discontinued imatinib, 31 (61%) switched to dasatinib, 17 (33%) to nilotinib, 1 (2%) to hydroxyurea, 1 (2%) to other treatment and 1 (2%) remained without treatment. Sixteen pts (8,6%) died during imatinib treatment or during long-term follow-up after discontinuation of imatinib. Conclusions: In our population of CP-CML pts treated with imatinib, a majority of patients achieved complete cytogenetic and major molecular responses, with a prolonged of OS and EFS and good safety profile. Sokal score showed better prognosis prediction than Hasford. Early onset of imatinib therapy led to better outcomes and justifies imatinib as front-line treatment of our patients. Disclosures: No relevant conflicts of interest to declare.

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Impact Of Major Molecular Response On Overall Survival and Its Time Of Achievement On Complete Molecular Response Incidence In Chronic Myeloid Leukemia Patients Treated By Tyrosine Kinase Inhibitors In First Chronic Phase

Blood ◽

10.1182/blood.v122.21.2721.2721 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2721-2721

Author(s):

Mauricette Michallet ◽

Mohamad Sobh ◽

Helene Labussiere ◽

Lila Gilis ◽

Fiorenza Barraco ◽

...

Keyword(s):

Overall Survival ◽

Median Time ◽

Research Funding ◽

Kinase Inhibitors ◽

Molecular Response ◽

Line Treatment ◽

First Line ◽

Sokal Score ◽

Hasford Score ◽

First Line Treatment

Abstract Most patients with CML treated with Tyrosine Kinase Inhibitors (TKIs) achieve a major molecular response (MMR), that is, the absence of detectable Philadelphia chromosome. Even after this threshold is achieved, the disease burden continues to progressively decrease with continued treatment. Therefore, more sensitive polymerase chain reaction (PCR)–based molecular methods are required to detect and quantify levels of minimal residual disease leading to complete molecular response (CMR), especially at long time points after TKI initiation. Low levels of minimal residual disease, as measured by real-time quantitative PCR, have been shown to be an excellent surrogate marker for long-term prognosis. The objective of the present study is to describe the different clinical and therapeutic characteristics of chronic myeloid leukemia (CML) patients consecutively treated in first chronic phase (CP1) using tyrosine-kinase inhibitors (TKI) as first line treatment, followed at our centre between years 2001 and 2011, and at a second time to assess response to TKI with the incidence of major molecular response (MMR) and then its evolution to reach complete molecular response (CMR). Among 253 consecutive CML patients treated in CP1 at our centre, we analysed 183 (72%) who received TKI as first line treatment, 117 males and 66 females with a median age at diagnosis of 50 years (17-81)]. Among 135 patients evaluated for Sokal score, 41 (30%) were low, 63 (47%) were intermediate and 31 (23%) were high. According to hasford score (125 evaluated), 57 (46)% were low, 61 (49%) intermediate and 7 (5%) were high. First line treatment was imatinib for 161 (88%) patients, dasatinib for 14 (8%) patients and nilotinib for 8 (4%) patients. Overall, 167 (91%) patients obtained MMR [134 (80%) after first line treatment, 26 (16%) after second line treatment and 7 (4%) after third line treatment] within a median time of 13 months (range: 2-88); and 16 (9%) patients never reached MMR. Non-MMR patients, were as follow: 53% had high sokal score 33% intermediate and 14% low; 6% had high hasford score, 47% intermediate and 47% low; they received a median of 3 TKI-based treatment lines during a median follow-up of 37 months; 6 (37.5%) of them died after disease progression and 10 still under treatment. The median time to obtain MMR was correlated with sokal score: 9 months (range: 2-84) in patients with low score; 13 months (range: 3-78) in patients with intermediate score and 17 months (range: 3-63) in patients with high score, p=0.03, same according to hasford score with 11 months, 13 and 20 months respectively, p=0.05. Among MMR patients, 18 (11%) lost their MMR after a median time of 28 months (range: 3-65) while 57 (34%) achieved a CMR after a median time of 36 months (range: 0-73) from MMR. Interestingly, response enhancement from MMR to CMR was significantly impacted by the time to have a MMR, thus the 5 years incidence of CMR was 67% in patients who had MMR in ≤ 3 months, 56% in patients with MMR > 3 and ≤ 12 months, 28% in patients with MMR > 12 and ≤ 24 months, and 12% in patients with MMR > 24 months, p=0.01 (Figure 1). After a median follow-up of 62 months (range: 6-135), patients who were in MMR at 24 months had 5 years probability of overall survival of 99% compared to 64% for those who did not have it at that time nor later, p <0.001 (Figure 2).Figure 1CMR incidence according to time to obtain MMRFigure 1. CMR incidence according to time to obtain MMRFigure 2Overall survival for patients in MMR at 24 months vs. those never in MMRFigure 2. Overall survival for patients in MMR at 24 months vs. those never in MMR We showed that MMR is a very significant factor predicting patient overall survival independently of treatment line number and delay of its achievement. In addition, we demonstrated that patients with low Sokal and Hasford scores have significant faster time to achieve MMR and that CMR incidence was significantly related to shorter time to obtain MMR. Disclosures: Michallet: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding.

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The Hasford Score May Predict Molecular Response in Chronic Myeloid Leukemia Patients: A Single Institution Experience

Disease Markers ◽

10.1155/2016/7531472 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Jarosław Dybko ◽

Bożena Jaźwiec ◽

Olga Haus ◽

Donata Urbaniak-Kujda ◽

Katarzyna Kapelko-Słowik ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Molecular Response ◽

Single Center ◽

Single Center Study ◽

Significant Difference ◽

Hasford Score ◽

Tki Treatment ◽

Eutos Score

The Sokal, Hasford, and EUTOS scores were established in different treatment eras of chronic myeloid leukemia (CML). None of them was reported to predict molecular response. In this single center study we tried to reevaluate the usefulness of three main scores in TKI era. The study group included 88 CML patients in first chronic phase treated initially with standard imatinib dose. All of them achieved major molecular response (MMR) in time points defined by European LeukemiaNet (ELN). 42 patients lost MMR in a median time of 47 months and we found a significant difference in MMR maintenance between intermediate-risk (IR) and low-risk (LR) patients assessed by Hasford score. All 42 patients were switched to second-generation TKI (2G-TKI) treatment. At 18 months of 2G-TKI therapy we have still found a significant difference in BCR-ABL transcript levels and MMR rate between IR and LR groups. We did not find any of the described differences discriminating patients by Sokal or EUTOS score. In this retrospective single center analysis we found Hasford score to be useful in predicting molecular response in first chronic phase of CML patients.

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Validation of the Hasford score in a demographic study in chronic granulocytic leukaemia

Journal of Clinical Pathology ◽

10.1136/jcp.54.6.491 ◽

2001 ◽

Vol 54 (6) ◽

pp. 491-493 ◽

Cited By ~ 6

Author(s):

M J Thomas

Keyword(s):

Chronic Granulocytic Leukaemia ◽

Demographic Study ◽

Hasford Score

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Both Higher Level of (bcr,abl) Transcripts and High Hasford Risk Score Are Associated with Cytogenetic Response but Absence of Molecular Remission during First Line Use of Imatinib Mesilate(IM): A Finding Not Observed Following Use among Interferon Failures.

Blood ◽

10.1182/blood.v104.11.4671.4671 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4671-4671

Author(s):

Selami K. Toprak ◽

Klara Dalva ◽

Dilsa Mizrak ◽

Mutlu Arat ◽

Muhit Ozcan ◽

...

Keyword(s):

Risk Score ◽

Prognostic Score ◽

Response To Treatment ◽

Quantitative Detection ◽

Molecular Response ◽

First Line ◽

Group 2 ◽

Hasford Score ◽

Group 1

Abstract Factors that predict response to treatment in CML has been defined for busulphan and Interferon. Search for prognostic parameters in the imatinib era are still continuing. Very recently a new prognostic scoring of CML patients has been defined by Kantarjian et al (Blood, 2004; 10: 1182).The value of these scoring systems in prediction of molecular response to first line use of IM has not been published yet. With this aim, we have evaluated the hematological and molecular response of all CML patients chronic (n: 74)/accelerated (n: 9) treated with IM in this prospective study. Since IM has been approved for secondary ( May 2001)and primary (May 2003) treatment in Turkey, we have evaluated 22 patients- first line use (Group 1) and 61 Interferon failures (Group 2) following a median follow-up of 9–35 months. Hasford prognostic score was available and calculated in 67 of these patients online at www.pharmacoepi.de/cmlscore.html. Scores were: Group 1 low:8 /medium:5 /high:2; Group 2:low:16 /medium:29 /high:7. In group 2, time from diagnosis to IM treatment was 29 m(3–144). Method: RNA was isolated from blood or marrow (High Pure RNA isolation kit, Roche) and used for quantitative detection of bcr-abl transcripts with “LightCycler t(9;22) Quantification Kit”. Results were expressed as ratio to G6PD standarts. Results: Age and Hasford distribution were comparable in group 1 and 2. The tumor burden (median)according to scoring was Group1: low: 0.014 /high: 0.0453 and Group 2: low: 0.0035 /high: 0.012. Level of bcr-abl transcripts were higher in group1 vs 2(0.03 vs 0.009) and Hasford-high vs low, regardless of previous treatment. We could not show any correlation between Hasford score and transcript level at diagnosis (Pearson, r=.314, p=0.255). 20% of the Group 1-high and 60% of Group 1-low patients achieved major and complete CR at 6m and 12m. Similar evaluation revealed a weaker response rate in Group-2: 21–30% depending on risk score and time (6–12m). Time to mol CR (less than 10e5) occurred at a median of 6 (6–12) months in 26.7% (6m) of Group1 and 9m (3–12) in 7.7% (6m) of Group 2. Resistance developed both in Group 1(2/22) and Group 2 (7/61). Among scored patients, mol CR was achievable in Group-1(only low risk). However in Group 2, molCR could be obtained both in low (n:17) and high (n:17) risk patients. The median levels of bcr,abl transcript were: Group1:0.029 (molCR+) vs 0.059(molCR-) and Group 2: 0.0498 (molCR+) vs 0.0988(molCR−). Conclusion: In accordance with previous reports both molecular and cytogenetic remissions were observed earlier and more frequently among patients who received IM as a first line agent compared to second line use. Among patients being treated after Interferon, Hasford scoring at diagnosis did not have an impact on the prediction of response to IM. This finding is in paralel to Kantarjian’s results. However, in our study de novo CML patients’ bcr,abl transcript levels and the Hasford score showed an association with response. The shorter median follow-up in Group 1 may also have an impact on these results and updates are warranted. Like ours, the recent publications (Brummendorf 2003 and Drummond, 2004) on the correlation of telomere length with Hasford score and the response to treatment with IM support the value of this score in previously untreated patients with CML.

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Risk Score at Diagnosis and the Dynamics of Response to TKI Therapy In Chronic Myeloid Leukemia.

Blood ◽

10.1182/blood.v116.21.1236.1236 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1236-1236

Author(s):

Tom Lenearts ◽

Fausto Castagnetti ◽

Arne Traulsen ◽

Jorge M Pacheco ◽

Gianantonio Rosti ◽

...

Keyword(s):

High Risk ◽

Computational Model ◽

Risk Score ◽

Response To Therapy ◽

The Self ◽

Self Renewal ◽

Number Of Patients ◽

High Risk Disease ◽

Hasford Score ◽

The Impact

Abstract Abstract 1236 Background: Although most patients with early chronic phase CML (ECP-CML) respond to TKI therapy, the depth and speed of response can be different. While it is known that both the Sokal and Hasford scores have an impact on the speed and depth of response, no mechanisms explaining these differences have been identified. Objective: To provide explanations for any potential differences in CML response as a function of the Sokal and Hasford score using a computational model. Methods: We utilize a computational model of hematopoiesis and CML, together with serial quantitative data of disease burden under nilotinib therapy to determine the fraction of CML cells responding to therapy (z) and the impact of TKI on the self-renewal probability of CML cells (e) under therapy. Patients were stratified at diagnosis on both the Sokal and Hasford scoring system. A non-linear least squares method was used to separately fit the model to serial Q-RT-PCR data for BCR-ABL in response to therapy in each cohort. Results: A total of 73 patients were studied. The number of patients with low, intermediate and high risk disease based on the Sokal score was 34, 29 and 10 respectively while the respective distribution of patients on the Hasford score was 29, 43 and 1. Although the impact of nilotinib on the self-renewal probability of CML progenitor cells was similar across all risk groups (there were substantial differences in the fraction of cells responding to therapy: For the Sokal groups, the fraction of cells (z) responding to therapy decreased from 0.09 to 0.086 and 0.069 respectively for low, intermediate and high risk disease. In the case of the Hasford score, the difference in z between low and intermediate categories becomes more pronounced, i.e. z is 0.093 for low and 0.08 for intermediate risk disease. Conclusions: The risk score at diagnosis of CML has a direct impact on the dynamics of response to TKI therapy. Patients with a lower risk score respond faster to the same therapy when compared to high risk patients. The impact of TKI on the self renewal of CML cells appears to be the same regardless of the risk score but the fraction of cells responding decreases as the risk score increases. This suggests that subclones that may be less sensitive to TKI therapy may be emerging. Strategies that increase the fraction of cells responding to therapy in patients with higher risk disease may be indicated. Disclosures: Rosti: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau.

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