Durable response to lenalidomide in a patient with myelodysplastic syndrome associated with isolated 5q deletion and JAK2 V617F mutation despite discontinuation of treatment

Hatzimichael,Eleftheria; Lagos,Konstantinos; Vassou,Amalia; Gougopoulou,Dora; Papoudou‑Bai,Alexandra; Briasoulis,Evangelos

doi:10.3892/mco.2016.866

July-2016 Volume 5 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

July-2016 Volume 5 Issue 1

Full Size Image

Article

Durable response to lenalidomide in a patient with myelodysplastic syndrome associated with isolated 5q deletion and JAK2 V617F mutation despite discontinuation of treatment

Authors:
- Eleftheria Hatzimichael
- Konstantinos Lagos
- Amalia Vassou
- Dora Gougopoulou
- Alexandra Papoudou‑Bai
- Evangelos Briasoulis
View Affiliations / Copyright

Affiliations: Department of Hematology, University of Ioannina, 45110 Ioannina, Greece, Department of Pathology, University Hospital of Ioannina, 45500 Ioannina, Greece
Pages: 23-26
|
Published online on: April 20, 2016

https://doi.org/10.3892/mco.2016.866
Expand metrics +

Abstract

Loss of a section of the long arm of chromosome 5, as a sole cytogenetic abnormality, characterizes a rare type of myelodysplastic syndrome [del(5q) MDS] and the co‑existence of the JAK2 V617F mutation occurs in a small subset of these cases. Patients with isolated del(5q) MDS have a relatively favorable prognosis, with transformation to acute myeloid leukemia occurring in <10%, and their disease responds well to lenalidomide. However the optimal therapeutic approach for patients with del(5q) MDS in coexistence with the JAK2 V617F mutation, which is common to myeloproliferative neoplasms, remains to be elucidated. The present study reports a 77‑year‑old, transfusion-dependent female patient diagnosed with del(5q) MDS and a concomitant JAK2 V617F mutation. The patient was started on 10 mg lenalidomide daily for 21 days in a 28 day‑cycle and within the first month of treatment, the patient became transfusion‑independent. The only toxicity observed was grade 3 neutropenia, which was managed with transient treatment discontinuation and dose reduction on restart (5 mg). The patient achieved a complete cytogenetic and molecular response (normal karyotype and undetected JAK2 V617F mutation) within 6 months of treatment. However, 12 months post treatment initiation and while on hematological, cytogenetic and molecular response, the patient was unwilling to continue on treatment and lenalidomide was discontinued. The patient remains in hematological response, which lasts for >5 years despite treatment discontinuation. The present case highlights the coexistence of the JAK2 V617F mutation in del(5q) MDS and suggests that lenalidomide treatment is beneficial and effective for these patients, leading to complete hematological, cytogenetic and molecular response. Hematological response may be sustained for long periods of time, even following the discontinuation of the treatment.

View Figures

View References

1	Bejar R, Levine R and Ebert BL: Unraveling the molecular pathophysiology of myelodysplastic syndromes. J Clin Oncol. 29:504–515. 2011. View Article : Google Scholar : PubMed/NCBI
2	Cazzola M: Myelodysplastic syndrome with isolated 5q deletion (5q-syndrome). A clonal stem cell disorder characterized by defective ribosome biogenesis. Haematologica. 93:967–972. 2008. View Article : Google Scholar : PubMed/NCBI
3	List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, Powell B, Greenberg P, Thomas D, Stone R, et al: Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 355:1456–1465. 2006. View Article : Google Scholar : PubMed/NCBI
4	Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, et al: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 365:1054–1061. 2005. View Article : Google Scholar : PubMed/NCBI
5	Scott LM, Campbell PJ, Baxter EJ, Todd T, Stephens P, Edkins S, Wooster R, Stratton MR, Futreal PA and Green AR: The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders. Blood. 106:2920–2921. 2005. View Article : Google Scholar : PubMed/NCBI
6	Ingram W, Lea NC, Cervera J, Germing U, Fenaux P, Cassinat B, Kiladjian JJ, Varkonyi J, Antunovic P, Westwood NB, et al: The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow. Leukemia. 20:1319–1321. 2006. View Article : Google Scholar : PubMed/NCBI
7	Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J and Vardiman JW: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press. Lyon, France: 2008.
8	Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, et al: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 89:2079–2088. 1997.PubMed/NCBI
9	Azaceta G, Calasanz MJ, Dourdil V, Bonafonte E, Izquierdo I and Palomera L: Response to lenalidomide in a patient with myelodysplastic syndrome with isolated del(5q) and JAK2 V617F mutation. Leuk Lymphoma. 51:1941–1943. 2010. View Article : Google Scholar : PubMed/NCBI
10	Nomdedeu M, Maffioli M, Calvo X, Martínez-Trillos A, Baumann T, Díaz-Beyá M, Aguilar JL, Rozman M, Costa D, Esteve J, et al: Efficacy of lenalidomide in a patient with myelodysplastic syndrome with isolated del(5q) and JAK2V617F mutation. Leuk Res. 35:1276–1278. 2011. View Article : Google Scholar : PubMed/NCBI
11	Musto P, Simeon V, Guariglia R, Bianchino G, Grieco V, Nozza F, La Rocca F, Marziano G, Lalinga AV, Fabiani E, et al: Myelodysplastic disorders carrying both isolated del(5q) and JAK2 (V617F) mutation: Concise review, with focus on lenalidomide therapy. Onco Targets Ther. 7:1043–1050. 2014.PubMed/NCBI
12	Sokol L, Caceres G, Rocha K, Stockero KJ, Dewald DW and List AF: JAK2 (V617F) mutation in myelodysplastic syndrome (MDS) with del(5q) arises in genetically discordant clones. Leuk Res. 34:821–823. 2010. View Article : Google Scholar : PubMed/NCBI
13	Giagounidis A, Fenaux P, Mufti GJ, Muus P, Platzbecker U, Sanz G, Cripe L, Von Lilienfeld-Toal M and Wells RA: Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes. Ann Hematol. 87:345–352. 2008. View Article : Google Scholar : PubMed/NCBI
14	Adès L, Le Bras F, Sebert M, Kelaidi C, Lamy T, Dreyfus F, Eclache V, Delaunay J, Bouscary D, Visanica S, et al: Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the groupe francophone des myelodysplasies. Haematologica. 97:213–218. 2012. View Article : Google Scholar : PubMed/NCBI
15	Pisani F, Orlandi G and Merola R: Long-term response in a patient with del(5q) myelodysplastic syndrome who discontinued lenalidomide and obtained a good response and tolerance to rechallenge. Case Rep Oncol. 7:277–284. 2014. View Article : Google Scholar : PubMed/NCBI