IS ALLOGENEIC TRANPLANTATION AN OPTION IN PATIENTS AFFECTED BY CONCURRENT MYELOFIBROSIS AND CHRONIC MYELOID LEUKEMIA (CML)?
Main Article Content
Keywords
chronic myeloid leukemia, myelofibrosis, JAK2, allogeneic transplantation
Abstract
Abstract
Classification of myeloproliferative neoplasms is based on hematologic, histopathologic and molecular characteristics including the presence of the BCR-ABL1 and JAK2 V617F or MPL and CALR. Although the different gene mutations ought to be mutually exclusive, a number of cases with co-occurring BCR-ABL1 and JAK2 V617F or CALR, have been identified with a frequence of 0.2-2.5%in European population .The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission whereas the JAK2V617F clone either persisted or clinically expanded after major response of Ph+-clone.
Allogeneic stem cell transplantation is at the present the only potentially curative therapy for these patients after therapy with ruxolitinib and TKI inhibitor. We describe the case of 3 young people treated in our institution for coexistence of BCR/ABL chronic myeloid leukemia and another Philadelphia chromosome negative (Ph−) CMPD. They received ruxolitinib, imatinib/nilotinib and allogeneic transplantation with a safe and efficient results.
Downloads
Abstract 713
PDF Downloads 307
HTML Downloads 77
References
2. Hussein K, Bock O, Seegers A, Flasshove M, Henneke F, Büsche G et al. Myelofibrosis evolving during Imatinib treatment of a chronic myeloproliferative disease with co-existing BCR–ABL translocation and JAK2V617F mutation. Blood 2007; 109: 4106–4107.
3. Kramer A, Reiter A, Kruth J, Erben P, Hochhaus A, Muller M et al. JAK2-V617F mutation in a patient with Philadelphia-chromosome-positive chronic myeloid leukaemia. Lancet Oncol 2007; 8: 658–660.
4. Bornhauser M, Mohr B, Oelschlaegel U, Bornhauser P, Jacki S, Ehninger G et al. Concurrent JAK2(V617F) mutation and BCR–ABL translocation within committed myeloid progenitors in myelofibrosis. Leukemia 2007; 21: 1824–1826.
5. Inami M, Inokuchi K, Okabe M, Kosaka F, Mitamura Y, Yamaguchi H et al. Polycythemia associated with the JAK2V617F mutation emerged during treatment of chronic myelogenous leukemia. Leukemia 2007; 21: 1103–1104.
6. Iurlo A, Gianelli U, Rapezzi D, Cattaneo D, Fermo E, Binda F et al. Imatinib and ruxolitinib association: first experience in two patients. Haematologica. 2014;6:e76-7.
7. Soderquist CR, Ewalt MD, Czuchlewski DR, Geyer JT, Rogers HJ, Hsi ED et al. Myeloproliferative neoplasms with concurrent BCR-ABL1 translocation and JAK2 V617F mutation: a multi-institutional study from the bone marrow pathology group.Mod Pathol. 2018;5:690-704.
8. Zhou A, Knoche EM, Engle EK, Fisher DA, Oh ST.Concomitant JAK2 V617F-positive polycythemia vera and BCR-ABL-positive chronic myelogenous leukemia treated with ruxolitinib and dasatinib. Blood Cancer J. 2015; 10:e351.
9. Martin-Cabrera P, Haferlach C, Kern W, Schnittger S, Haferlach T. BCR-ABL1-positive and JAK2 V617F-positive clones in 23 patients with both aberrations reveal biologic and clinical importance. Br J Haematol. 2017 Jan;1:135-139
10. 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.
11. Harrison C, Kiladjian J, Haifa K, Gisslinger H, Waltzman R, Stalbovskaya V et al.JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis N Engl J Med 2012; 366:787-798
12. Sora F, Grazia CD, Chiusolo P, Raiola AM, Bregante S, Mordini N,et al. Allogeneic Hemopoietic Stem Cell Transplants in Patients with Acute Myeloid Leukemia (AML) Prepared with Busulfan and Fludarabine (BUFLU) or Thiotepa, Busulfan, and Fludarabine (TBF): A Retrospective Study. Biol Blood Marrow Transplant. 2020 Apr;26(4):698-703.
13. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809–20.
14. Makishima H, Jankowska AM, McDevitt MA, O'Keefe C, Dujardin S, Cazzolli H, et al. CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood. 2011;21:e198-206
15. Pieri L, Spolverini A, Scappini B, Occhini U, Birtolo S et al. Concomitant occurrence of BCR-ABL and JAK2V617F mutation. Blood. 2011 22;12:3445-6.
16. Dogliotti I, Fava C, Serra A, Gottardi E, Daraio F, Carnuccio F, et al CALR-positive myeloproliferative disorder in a patient with Ph-positive chronic myeloid leukemia in durable treatment-free remission: a case report. Stem Cell Investig. 2017 Jun 23;4:57
17. Bader G, Dreiling B.Concurrent JAK2-Positive Myeloproliferative Disorder and Chronic Myelogenous Leukemia: A Novel Entity? A Case Report With Review of the Literature. J Investig Med High Impact Case Rep. 2019Jan-Dec;7:2324709619832322
18. Jain T, Mesa RA, Palmer JM.Allogeneic Stem Cell Transplantation in Myelofibrosis. Biol Blood Marrow Transplant. 2017 ;9:1429-1436.
19. Tiribelli M, Palandri F, Sant'Antonio E, Breccia M, Bonifacio M. The role of allogeneic stem-cell transplant in myelofibrosis in the era of JAK inhibitors: a case-based review. Bone Marrow Transplant. 2020 ;4:708-716.