Study of mutation profile in myelofibrosis and response to low dose ruxolitinib: a tertiary care experience
DOI:
https://doi.org/10.18203/2349-3933.ijam20250342Keywords:
Myelofibrosis, Ruxolitinib, Splenomegaly, Anaemia, JAK2Abstract
Background: Myelofibrosis is a rare myeloid neoplasm characterized predominantly by anaemia and splenomegaly. Mutations in Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukaemia (MPL) play key roles. This study aimed to examine the demographic profile, transfusion dependency, and mutations (JAK2, CALR, and MPL) associated with myelofibrosis and to evaluate the response to Ruxolitinib treatment in these patients.
Methods: This retrospective study included 30 patients at Madras Medical College, Chennai, from January 2022 to August 2024. Patients aged between 20 and 70 years at the time of diagnosis, primary myelofibrosis (PMF) or secondary myelofibrosis confirmed by clinical findings, laboratory tests, bone marrow biopsy, and genetic mutation such as JAK2 V617F, CALR, MPL, or triple-negative were included.
Results: The mean age was 52.37±13.08 years, with splenomegaly and anaemia being common. Of the 30 patients, 73.3% were on Ruxolitinib and 59.1% were transfusion-dependent. CALR-positive and triple-negative patients were entirely transfusion-dependent, whereas JAK2-positive patients were predominantly non-transfusion-dependent (p<0.0001). Ruxolitinib treatment showed mild reduction on spleen size but significantly improved quality of life (p=0.031). Non-transfusion-dependent patients had better quality of life scores (p<0.0001).
Conclusions: Genetic testing, including both driver and non-driver mutations, plays a crucial role in the diagnosis, prognosis, and treatment of myelofibrosis. Transfusion dependency and anaemia severity are negative prognostic factors, while Ruxolitinib improves the quality of life.
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References
Passamonti F, Mora B. Myelofibrosis. Blood. 2023;141:1954-70. DOI: https://doi.org/10.1182/blood.2022017423
Chifotides HT, Verstovsek S, Bose P. Association of myelofibrosis phenotypes with clinical manifestations, molecular profiles, and treatments. Cancers (Basel). 2023;15:3331. DOI: https://doi.org/10.3390/cancers15133331
Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS plus: A refined dynamic international prognostic scoring system for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29:392-7. DOI: https://doi.org/10.1200/JCO.2010.32.2446
Gerds AT, Mesa RA, Tkacz J, Moore-Schiltz L, Schinkel J, Phiri K, et al. Anemia and transfusion dependency are important prognostic factors for overall survival in patients with myelofibrosis: Results of a real-world analysis of Medicare patients. Blood. 2023;142:6418. DOI: https://doi.org/10.1182/blood-2023-178012
Patel KP, Newberry KJ, Luthra R, Jabbour E, Pierce S, Cortes J, et al. Correlation of mutation profile and response in patients with myelofibrosis treated with Ruxolitinib. Blood. 2015;126:790-7.
Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of Ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799-807. DOI: https://doi.org/10.1056/NEJMoa1110557
Cervantes F, Pereira A. Does Ruxolitinib prolong the survival of patients with myelofibrosis? Clinical Trials & Observations. Blood. 2017;129:832-7. DOI: https://doi.org/10.1182/blood-2016-11-731604
Rumi E, Trotti C, Vanni D, Casetti IC, Pietra D, Sant’Antonio E. The genetic basis of primary myelofibrosis and its clinical relevance. Int J Mol Sci. 2020;21:8885. DOI: https://doi.org/10.3390/ijms21238885
Gerds AT, Lyons RM, Colucci P, Kalafut P, Paranagama D, Verstovsek S. Disease and clinical characteristics of patients with a clinical diagnosis of myelofibrosis enrolled in the MOST study. Clin Lymphoma Myeloma Leuk. 2022;22:e532-40. DOI: https://doi.org/10.1016/j.clml.2022.02.001
Gerds AT, Harrison C, Thompson S, Snopek F, Pemmaraju N. The burden of illness and the incremental burden of transfusion dependence in myelofibrosis in the United States. Blood. 2022;140:3974-5. DOI: https://doi.org/10.1182/blood-2022-162657
Chen J, Pan L, Qu S, Qin T, Xiao Z, Xu Z. Intra-abdominal Streptococcus agalactiae infection associated with myelofibrosis treated with Ruxolitinib: a case report of an atypical clinical presentation. Curr Med Res Opin. 2022;38:371-4. DOI: https://doi.org/10.1080/03007995.2021.2022420
Drofenik A, Blinc A, Bozic Mijovski M, Pajic T, Vrtovec M, et al. Relation of JAK2 V617F allele burden and coronary calcium score in patients with essential thrombocythemia. Radiol Oncol. 2024;58:565-72. DOI: https://doi.org/10.2478/raon-2024-0036
Polverelli N, Hernández-Boluda JC, Czerw T, Barbui T, D’Adda M, Deeg HJ, et al. Splenomegaly in patients with primary or secondary myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT. Lancet Haematol. 2023;10:e59-70. DOI: https://doi.org/10.1016/S2352-3026(22)00330-1
Mauro G. Ruxolitinib improves spleen volume, TSS in myelofibrosis irrespective of anemia, transfusion status. ASCO and EHA Meeting Reporter. 2023. Available at: https://www.onclive.com/view/ruxol itinib-improves-spleen-volume-tss-in-myelofibrosis-irrespective-of-baseline-anemia-transfusion-status. Accessed on 28 October 2024.
Patel KP, Newberry KJ, Luthra R, Jabbour E, Pierce S, Cortes J, et al. Correlation of mutation profile and response in patients with myelofibrosis treated with Ruxolitinib. Blood. 2015;126(6):790-7. DOI: https://doi.org/10.1182/blood-2015-03-633404
Verma T, Papadantonakis N, Peker Barclift D, Zhang L. Molecular genetic profile of myelofibrosis: Implications in the diagnosis, prognosis, and treatment advancements. Cancers (Basel). 2024;16:514. DOI: https://doi.org/10.3390/cancers16030514
Yang Y, Luo H, Zheng Y. Low-dose Ruxolitinib shows effective in treating myelofibrosis. Ann Hematol. 2020;8. DOI: https://doi.org/10.1007/s00277-020-04311-z
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