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

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.

Association between Hasford Scoring System and Hematologic Response in Chronic and Accelerated Phase of Chronic Myelocytic Leukemia Patient with Imatinib for Three Months

Background: Hasford score is a scoring system which was made in interferon treatment era to assess chronic myelocytic leukemia (CML) prognosis. Complete hematologic response (CHR) is the milestone of prognosis evaluation. CHR achievement will significantly increase survival. Imatinib is a revolutionized treatment that change the prognosis of CML. With the advent of Imatinib, lessened the prognostic impact of the Hasford score to predict prognosis.Materials and Methods: An observational analytic with prospective cohort study conducted in oncology outward division Dr. Soetomo hospital Surabaya, from July until October 2018. Hasford score determined in 32 patients at the beginning of the study, given imatinib and followed up regularly for 3 months to know the hematologic response. Data were analyzed using Fisher exact test which was considered significant if p<0.05.Results: Median age was 39 years old, male 37.5% and female 62.5%, the median spleen was 18 cm, median hemoglobin was 9.1 g/dL, median leukocyte was 180x109 /L, median thrombocyte was 645x109 /L, median eosinophil was 2.9%, median basophil was 4.6%, median myeloblast was 6%. Hasford score showed 3.1% in low risk, 25% in intermediate risk and 71.9% in high risk. As much as 78.1% complete hematologic response was found in patient, and 21.9% was incomplete.Conclusion: There was no association between Hasford scoring system and hematologic response in chronic and accelerated phase of chronic myelocytic leukemia patient with imatinib for three month. Hasford score had no impact in hematologic response with imatinib.Keywords: Hasford score, hematologic response, CML, imatinib

CML patients presenting with priapism: Is there any disparity in outcome?

e18545 Background: Priapism, a urological emergency that needs prompt treatment, is an uncommon presenting feature of chronic myeloid leukemia (CML). CML frequently occurs in younger males and adolescents in developing countries. Occurrence of erectile dysfunction (ED) in this particular age group can severely decrease the quality of life. It is known that immediate treatment of priapism preserves erectile function. The data on the outcome of priapism in CML patients from developing world is limited. Methods: We analysed the CML patients treated at PGIMER Chandigarh from January 2003 to December 2018. Baseline spleen and liver size, hematological parameters, Sokal and Hasford score were documented. Duration of priapism, treatment received by the patients, and response to Imatinib were recorded. The severity of ED was assessed by SHIM (Sexual Health Inventory for Men) score. Results: Twenty-three patients (1.7%) out of total 1350 male CML-CP patients had priapism at diagnosis. The median age was 24 years (range 13 – 50 years); 60.8% patients belonged to 21 – 40 years age group. Median duration of priapism was 8 days (range 2 – 25 days). Splenomegaly and hepatomegaly were found in 91.3% and 56.5% patients, respectively. Baseline median hemoglobin was 9.9 g/dL; TLC was 283000/mm3 and platelet count was 352000/mm3. Based on Sokal score, 4/23, 16/23 and 3/23 patients belonged to low, intermediate and high risk categories, respectively. According to Hasford score, 7/23, 14/23 and 2/23 patients belonged to low, intermediate and high risk categories, respectively. All patients received cytoreductive therapy [hydroxyurea and Imatinib]; 21 patients underwent penile aspiration, 13 patients underwent therapeutic leucapheresis and 8 patients underwent distal penile shunt surgery. Majority of the patients (78.2%) achieved CHR at 6 weeks and 21 patients achieved MMR at 12 months. ED could be assessed in 14 patients on follow up. As per SHIM score, 2/14 and 12/14 patients had moderate and severe ED, respectively. The occurrence and severity of ED was unaffected by leucapheresis or shunt surgery. Conclusions: We found severe ED on follow up among majority of CML-CP patients with priapism at presentation. Despite favourable response to Imatinib, long duration of symptoms and hyperleucocytosis probably contributed to ischemic priapism and severe ED in the study cohort. We conclude that prolonged and untreated priapism in CML-CP patients is a major risk factor for ED. There is a need to sensitise the primary care physicians and surgeons in the developing world regarding this grave complication in CML patients.

Outcome of CML patients with de novo bleeding complications: Do they behave differently?

e18546 Background: Chronic myeloid leukemia (CML) is a clonal hematopoietic neoplasm. A subset of CML patients present may present with unusual bleeding manifestations. There is limited data on the incidence and outcome of such patients on treatment with imatinib. Methods: We analysed the CML patients treated at PGIMER Chandigarh from January 2003 to December 2018. Baseline spleen and liver size, hematological parameters, Sokal and Hasford score, site and severity of bleeding (as per WHO classification) were recorded. The treatment response, occurrence of cytopenias and need for second line TKI were analyzed. Results: Sixty-six patients (2.8%) out of 2350 adult CML patients had bleeding at diagnosis. The median age was 35 years (range 15 – 66 years); 56.1% were males. The median duration of follow up was 79 months (range 6 – 123 months). Splenomegaly and hepatomegaly was found in 89.3% and 65.1% patients, respectively. Baseline median hemoglobin was 9.5 g/dL; TLC was 151600/mm3 and platelet count was 301000/mm3. Based on Sokal score, 15/66, 26/66 and 25/66 patients belonged to low, intermediate and high risk categories, respectively. According to Hasford score, 22/66, 36/66 and 8/66 patients belonged to low, intermediate and high risk categories, respectively. Based on WHO grading, 33/66, 30/66 and 3/66 patients had grade 1, 2 and 3 bleed, respectively. 48 patients had mucocutaneous bleeding [cutaneous 17, gum bleed 16, epistaxis 15], 4 had psoas haematoma, 7 had vaginal bleeding, 3 had ocular bleeding, 6 had GI bleed [upper GI 3, lower GI 3], 3 had hematuria. 74.2% achieved CHR at 6 weeks and 83.3% achieved MMR at 12 months with Imatinib. 18 developed cytopenias which required Imatinib interruption or dose reduction. 18 required Imatinib dose escalation for suboptimal response, 5 patients received second line TKI. Six patients progressed to advanced phase CML (AP/BC) after a median duration of 32 months (range 21 – 49 months). Bleeding manifestations resolved in all patients and there was no recurrence of bleeding on follow up. Conclusions: Bleeding is an uncommon presentation of CML. It might be a harbinger of an increased risk of cytopenias, suboptimal treatment response and disease progression on Imatinib.

Correlation between Hasford Score with Early Molecular Response in Patients with Chronic Myeloid Leukemia in Chronic Phase Treated with Imatinib

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.

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

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.

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

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.