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ORIGINAL ARTICLE  
Year : 2013  |  Volume : 56  |  Issue : 3  |  Page : 216-220
A comparative study of Hasford score and Sokal index in prognostication of the novo chronic myeloid leukemia patients and a search for new prognostic markers


Department of Pathology, Medical College, Saroj Gupta Cancer Centre and Research Institute, Kolkata, West Bengal, India

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Date of Web Publication24-Oct-2013
 

   Abstract 

Introduction: Chronic myeloid leukemia (CML) is a common myeloproliferative disorder. Based on clinical and hematological parameters, two prognostic scoring systems, i.e., Hasford and Sokal index scoring systems are available to predict survival duration of CML patients on imatinib therapy. Aims and Objectives: Our study's objective is to compare Hasford score with Sokal index for the prognostication of de novo CML patients on therapy and find out new prognostic markers. Materials and Methods: This is a retrospective study. The study population comprised 66 patients who were followed up for 60 months. For each patient, at presentation, scoring was performed as per Hasford and Sokal index and Philadelphia chromosome analysis was carried out by conventional cytogenetics. Thereafter, hematological parameters were assessed 3 monthly and conventional cytogenetics was done yearly. Results: Out of these 66 patients, the number of patients belonging to low, intermediate and high risk categories are 21, 33 and 12 respectively by Hasford score and 12, 32 and 22 respectively by Sokal index. Eight patients, who had been categorized into high risk group by Sokal index but intermediate risk group by Hasford score, have shown better survival possibility as monitored by hematological and cytogenetic parameters. Ten cases, categorized into intermediate risk group by Sokal index but low risk group by Hasford score, is doing well till date. Conclusions: This study shows that Hasford score predicts survival of the patients better than Sokal index. However, multicentric study over a large population is needed to give the final verdict.

Keywords: Chronic myeloid leukemia, cytogenetics, Hasford score, Sokal index

How to cite this article:
Sinha SK, Sinha S, Mandal PK, Bhattacharyya NK, Pandey A, Gupta P. A comparative study of Hasford score and Sokal index in prognostication of the novo chronic myeloid leukemia patients and a search for new prognostic markers . Indian J Pathol Microbiol 2013;56:216-20

How to cite this URL:
Sinha SK, Sinha S, Mandal PK, Bhattacharyya NK, Pandey A, Gupta P. A comparative study of Hasford score and Sokal index in prognostication of the novo chronic myeloid leukemia patients and a search for new prognostic markers . Indian J Pathol Microbiol [serial online] 2013 [cited 2020 Oct 24];56:216-20. Available from: https://www.ijpmonline.org/text.asp?2013/56/3/216/120369



   Introduction Top


Chronic myeloid leukemia (CML) is a classic chronic myeloproliferative disorder. Hematopoiesis in CML is clonal, derives from a self-renewing, hematopoietic pluripotent stem cell and is fairly normal with respect to cellular maturation and function. The genetic hallmark of CML is the breakpoint cluster region and abelson (BCR-ABL) fusion gene-product. Its acquisition, presumably during division of a pluripotent stem cell, is part of the molecular and cellular defects that ultimately produce CML. Imatinib, a tyrosine kinase inhibitor, inhibits the proliferation of CML lines by inhibiting BCR-ABL kinase activity and is currently being used for the treatment of CML. [1]

For proper treatment, it is important to stratify CML patients according to the risk profile. The risk profile at diagnosis is more important for survival of CML patients, than therapy. [2] There are various prognostic scoring systems are available to predict the survival of CML patients. They are the Hasford score, Sokal index and the European Treatment and Outcome Study (EUTOS) score for risk assessment of CML patients before allogeneic blood or marrow transplantation. This study attempts to compare Hasford score with Sokal index only for prognostication of de novo CML patients on imatinib therapy and find out new prognostic markers. [3],[4],[5],[6]


   Materials and Methods Top


The study was a retrospective one, with a study period of 60 months. 89 CML patients who came to the Pathology Department of our institute during the period of 01-06-2005 to 01-06-2006 were selected for the study. A total of twenty patients had come with some therapy; hence 69 de novo CML patients were included in this study. Three patients were lost during follow-up. So the study population consisted of 66 de novo patients of CML, who were followed up for 60 months.

All the patients were diagnosed initially by a thorough clinical examination, a complete hemogram, a bone marrow examination and cytogenetic study from aspirated marrow.

At presentation, Philadelphia (Ph) chromosome analysis was done for each patient by conventional cytogenetics. Those with clinical or morphologic clues of CML but Ph chromosome negative by conventional cytogenetics, were further evaluated by fluorescent in situ hybridization (FISH) technique [Figure 1]. In this study, three patients amongst the 66 patients were initially Ph negative by conventional cytogenetics but positive by FISH. Each of the 66 patients were then scored as per Hasford score and Sokal index and categorized into low-risk, intermediate risk or high risk group, separately for each scoring system.
Figure 1: Breakpoint cluster region and abelson positive by fluorescent in situ hybridization but negative by conventional cytogenetics at presentation for a chronic myeloid leukemia patient-categorized as
intermediate risk by Hasford but high-risk by Sokal


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Parameters included in Hasford score are: [3] (1) Age of the patient at presentation, (2) spleen size below the left costal margin, (3) peripheral blood blast percentage, (4) eosinophil percentage, (5) basophil percentage and (6) total platelet count. [3]

Hasford risk score in patients with CML

Total score calculation:

1. Age × 0.6666 if age > or = 50 else 0 _________

2. 0.042 × spleen size _________

3. 1.0956 if platelet count > or = 1500 × 10 3 /μl else 0 _________

4. 0.0584 × myoblast percentage _________

5. 0.0413 × eosinophil percentage _________

6. Basophil percentage × 0.2039 if basophils >3% _________

Total (summation of above scores)

Relative risk = Total × 1000.

As per Hasford score, a CML patient is categorized as low risk if he/she has a relative risk <780, intermediate risk if relative risk 781-1479, high risk if relative risk > or = 1480.

Parameters included in Sokal index [4] are: (1) Age of patient at presentation, (2) spleen size below the left costal margin, (3) peripheral blood blast percentage and (4) total platelet count. [4]

Sokal index in patients with CML

exp[0.116 (age-43.4)] + 0.0345(spleen size-7.51) + 0.188[(platelets/700) 2 – 0.563] + 0.0887(% blasts - 2.1).

As per Sokal score, a patient is categorized as low risk if Sokal index <0.8, intermediate risk if Sokal index is 0.8-1.2 and high risk if Sokal index >1.2.

Patients were put on imatinib therapy and followed up. Hematological parameters including a complete blood count and spleen size were assessed 3 monthly to assess hematological response. A complete hematological response is said to have been achieved if total white blood cell (WBC) count becomes less than 10,000/μl, a platelet count of less than 4.5 lakh/μl, no immature cells in the peripheral blood and no palpable splenomegaly. [7] Conventional cytogenetics was done yearly to assess cytogenetic response. A patient was said to have achieved a minimal response if he/she had 66-95% Ph +ve cells in metaphase preparations, a minor response if 36-65% Ph +ve cells in metaphase preparations were present, a partial response if 1-35% Ph +ve cells in metaphase preparations were present, a complete response if 0% Ph +ve cells in metaphase preparations were present. A major response indicated if 0-35% Ph +ve cells were seen in metaphase preparations (patients under partial and complete response). For patients who could afford, reverse transcriptase-polymerase chain reaction was performed yearly to monitor minimal residual disease. [8] But, the number was negligible and were done irregularly and hence, not considered in our study.


   Results Top


For the 66 de novo CML patients, as per Hasford score: 21 patients were categorized into the low risk, 33 into the intermediate risk and 12 patients into the high risk group whereas according to Sokal index 12 patients were categorized into the low risk group, 32 into the intermediate risk and 22 into the high risk group [Table 1].
Table 1: No. of patients in different risk groups as per calculated scores of both

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Similarity in scoring was seen for 44 patients, with both Hasford score and Sokal index, categorizing 10 patients into low risk, 22 into intermediate risk and 12 into the high risk group.

Disparity in scoring was seen for the remaining 22 patients [Table 2]. Out of these 22 patients, Hasford categorized 11 patients into the low-risk and 11 patients into the intermediate risk group.
Table 2: Comparative study of both scores for actual response noted

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Out of the 11 patients who were categorized by Hasford score as low-risk, Sokal index categorized 10 of them as intermediate risk and one of them as high risk. However, all these eleven patients have achieved a complete hematological response by 3 months, complete cytogenetic response by 24 months and all of them are doing well till date. Thus the actual prognosis noted for these eleven patients have corroborated better with the Hasford score than Sokal index.

The remaining 11 patients who were categorized by Hasford score as intermediate risk, Sokal index categorized two of them into the low risk and nine of them into the high risk group.

Both of these two patients, who were categorized as low risk by Sokal but, intermediate risk by Hasford, have achieved a complete hematological response within 3 months. One has achieved a partial cytogenetic response [Figure 2]. However, one achieved a complete cytogenetic response by 24 months and has corroborated better with the Sokal index than Hasford score.
Figure 2: A total of 40% positivity for Philadelphia-chromosome (minor response) but complete hematological response in the same patient after 5 years of therapy-prognosis corroborated with Hasford score

Click here to view


Eight out of the remaining nine patients, who were categorized as high risk by Sokal but intermediate risk by Hasford, have achieved a complete hematological response by 6 months. Of these eight patients, six have achieved a partial cytogenetic response and two have achieved a minor cytogenetic response. Thus prognosis of these eight patients have corroborated better with the Hasford score than Sokal index.

The remaining one out of nine patients, who was categorized as intermediate risk by Hasford but high risk by Sokal, has actually shown poor prognosis and progressed to myeloid sarcoma thereby corroborating better with the Sokal index. [9]

In this study, we can see that Hasford score has predicted prognosis accurately in 96.9% cases (64 out of 66 patients) and Sokal index has predicted prognosis accurately in 69.7% cases (46 out of 66 patients). So, we can conclude that Hasford score is a better indicator of prognosis than Sokal index with a significant P value of 0.0006 and 95% confidence interval (CI) between 3.0978 and 62.4874, using the Z-test statistics. This observation is further confirmed by a "fair" agreement between the Hasford score and Sokal index using the weighted kappa scale (κ = 0.552, standard error = 0.0795, 95% CI = 0.396-0.708).


   Discussion Top


The Hasford score and Sokal index includes variables, which are routinely measured in clinical practice and their measurement is highly reliable. [3] So in this study, we intended to stratify CML patients by these two simple scoring systems and find out, which is a better prognostic indicator.

All patients have been initially evaluated for the Ph chromosome by conventional cytogenetics in this study and not FISH though the latter is more sensitive. A conventional cytogenetic study is advantageous because the entire chromosomal complement is evaluated for the presence of additional abnormalities to the Ph chromosome, which has prognostic significance. [10] However, this technique is limited in its resolution, in its sensitivity to detect an abnormal clone, and in its requirement for viable and dividing cells. [11] In this study, approximately 5% of the cases appeared to be "Ph-negative" by conventional cytogenetics. These cases required FISH for further evaluation.

The results showed that Hasford score identified more low risk patients (21) and few high risk patients (12) while Sokal index identified more high risk patients (22) and few low risk patients. [12] This observation is in keeping with a similar observation made by the Italian co-operative study group on CML. [12]

Forty four patients out of the total study population of 66 patients, showed similarity in scoring and in the 5 year follow-up period their prognosis corroborated with the prediction by both scoring systems. However, 22 patients showed a disparity in scoring. Out of these 22 patients, the prognosis of majority of the patients in the forthcoming 5 year period corroborated better with the Hasford score than Sokal index:

Patients categorized as low-risk group by Hasford score but intermediate and high risk group by Sokal index have all shown good prognosis as indicated by their hematological and cytogenetic response.

Eight patients were categorized as intermediate risk group by Hasford score but high risk group by Sokal index have shown complete hematological response and some degree of cytogenetic response and are surviving till date.

This is probably because of certain distinct differences between the two systems. The main differences concern age (more important in Hasford score than the Sokal index), spleen size and myeloblast percentage in peripheral blood (more important in Sokal index than in Hasford score). [12]

Also, Hasford score includes two additional important prognostic factors (i.e., eosinophil percentage, basophil percentage), while Sokal index does not. Basophil percentage and eosinophil percentage are two important prognostic factors in CML patients treated with conventional treatment, in addition to age, spleen size, platelet count, blood blast percentage and cytogenetic abnormalities beside Ph chromosome. [10],[13],[14]

The results of this study corroborate with the results of the study made by Thomas et al. which say that Sokal index is no longer the best method of reliably predicting length of survival of CML patients, [15] when being treated by interferons.

Although majority patients have shown a better correlation with Hasford score, two patients have shown better correlation with Sokal index than Hasford score. Nevertheless, all patients were classified as low risk by Hasford, have shown good prognosis, indicating Hasford score may be useful in identifying patients with a good prognosis using standard treatments. [15]

It was also noted in our study that patients who had an initial low total WBC count of less than 1 lakh/μl and hemoglobin (Hb) of more than 10 g/dl, performed better than those with initial total count of greater than 1 lakh/μl and Hb less than 10 g/dl, [14],[16] though these observations required more supports from other study groups.


   Conclusion Top


It can be concluded from the study that Hasford score is a better predictor of prognosis of CML patients on imatinib therapy than Sokal index. So Hasford score may help CML patients and their physicians in making better informed decisions about the adoption of alternative higher risk treatment options and may help in the analysis of outcome in studies of newer, experimental drug regimens. [15] We have purposefully omitted EUTOS to make our study simpler.

However, a multicentric study over a large number of CML patients is required to give the final verdict. Also, incorporation of parameters like the initial total WBC count and the initial Hb percentage could further help in increasing the accuracy in prediction of prognosis.

 
   References Top

1.Lyseng-Williamson K, Jarvis B. Imatinib. Drugs 2001;61:1765-74.  Back to cited text no. 1
    
2.Hehlmann R, Ansari H, Hasford J, Heimpel H, Hossfeld DK, Kolb HJ, et al. Comparative analysis of the impact of risk profile and of drug therapy on survival in CML using Sokal's index and a new score. German chronic myeloid leukaemia (CML)-study group. Br J Haematol 1997;97:76-85.  Back to cited text no. 2
    
3.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. J Natl Cancer Inst 1998;90:850-8.  Back to cited text no. 3
    
4.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.  Back to cited text no. 4
    
5.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.  Back to cited text no. 5
    
6.Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 1998;352:1087-92.  Back to cited text no. 6
    
7.Kantarjian HM, O'Brien SM, Keating M, Beran M, Estey E, Giralt S, et al. Results of decitabine therapy in the accelerated and blastic phases of chronic myelogenous leukemia. Leukemia 1997;11:1617-20.  Back to cited text no. 7
    
8.Mensink E, van de Locht A, Schattenberg A, Linders E, Schaap N, Geurts van Kessel A, et al. Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukaemia patients using real-time quantitative RT-PCR. Br J Haematol 1998;102:768-74.  Back to cited text no. 8
    
9.Liu PI, Ishimaru T, McGregor DH, Okada H, Steer A. Autopsy study of granulocytic sarcoma (chloroma) in patients with myelogenous leukemia, Hiroshima-Nagasaki 1949-1969. Cancer 1973;31:948-55.  Back to cited text no. 9
    
10.Hernández-Boluda JC, Cervantes F. Prognostic factors in chronic myeloid leukaemia. Best Pract Res Clin Haematol 2009;22:343-53.  Back to cited text no. 10
    
11.Garcia-Isidoro M, Tabernero MD, Garcia JL, Najera ML, Hernandez JM, Wiegant J, et al. Detection of the Mbcr/abl translocation in chronic myeloid leukemia by fluorescence in situ hybridization: Comparison with conventional cytogenetics and implications for minimal residual disease detection. Hum Pathol 1997;28:154-9.  Back to cited text no. 11
    
12.Bonifazi F, De Vivo A, Rosti G, Tiribelli M, Russo D, Trabacchi E, et al. Testing Sokal's and the new prognostic score for chronic myeloid leukaemia treated with alpha-interferon. Italian Cooperative Study Group on Chronic Myeloid Leukaemia. Br J Haematol 2000;111:587-95.  Back to cited text no. 12
    
13.Braga GW, Chauffaille ML, Moncau JE, Souto EX, Silva MR, Kerbauy J. Chronic myeloid leukemia (CML): Prognostic factors and survival analysis. Sao Paulo Med J 1996;114:1083-90.  Back to cited text no. 13
    
14.Gan DY, Chen Y. Prognostic analysis of chronic myeloid leukemia with Cox model and the Sokal, Hasford score. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006;14:662-6.  Back to cited text no. 14
    
15.Thomas MJ, Irving JA, Lennard AL, Proctor SJ, Taylor PR, on behlaf of the Northern Region Haematology Group. Validation of the Hasford score in a demographic study in chronic granulocytic leukaemia. J Clin Pathol 2001;54:491-3.  Back to cited text no. 15
    
16.Jootar S, Chuncharunee S, Ongphiphaphadhanakul B, Atichartakarn V. Multivariate analysis of prognostic factors in chronic myelogenous leukemia. J Med Assoc Thai 1990;73:662-9.  Back to cited text no. 16
    

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Correspondence Address:
Nirmal Kumar Bhattacharyya
Flat-4A, Shanti Apartment, 7/3 Motijheel Avenue, Kolkata - 700 074, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.120369

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    Figures

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