Minimal residual disease and normalization of the bone marrow after long-term treatment with alpha-interferon2b in polycythemia vera. A report on molecular response patterns in seven patients in sustained complete hematological remission

被引:66
作者
Larsen, Thomas Stauffer [1 ]
Moller, Michael Boe [2 ]
de Stricker, Karin [2 ]
Norgaard, Peter [3 ]
Samuelsson, Jan [4 ]
Marcher, Claus [1 ]
Andersen, Morten T. [5 ]
Bjerrum, Ole Weis [6 ]
Hasselbalch, Hans Carl [7 ]
机构
[1] Odense Univ Hosp, Dept Hematol, Odense, Denmark
[2] Odense Univ Hosp, Dept Pathol, Odense, Denmark
[3] Herlev Hosp, Dept Pathol, Herlev, Denmark
[4] Stockholm S Hosp, Karolinska Inst, Sect Hematol, Dept Internal Med, Stockholm, Sweden
[5] Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark
[6] Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark
[7] Roskilde Hosp, Dept Hematol Oncol, Roskilde, Denmark
关键词
Polycythemia vera; JAK2; quantitative PCR; molecular responses; histomorphology; ALLELE BURDEN; JAK2; MUTATION; MYELOFIBROSIS;
D O I
10.1179/102453309X12473408860587
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Polycythemia vera (PV) is characterized by the presence of the JAK2V617F mutation in virtually all patients. Several studies have shown that the JAK2V617F mutational load decreases during treatment with alpha-interferon 2. We report on molecular and histomorphological bone marrow responses in seven PV patients with profound molecular responses during and after long-term treatment with alpha-interferon 2b. All patients obtained a major molecular response (MMR). Subsequently all patients discontinued alpha-interferon and sustained complete hematological remission with a follow-up period of median 10 months (range 4-30 months). Complete normalization of the bone marrow was seen in three of five patients. Long term treatment with IFN2b is able to induce 'minimal residual disease' with very low JAK2 V617F allele burden and may induce profound, and in some patients total, regression of histomorphological bone marrow features of PV. Finally, hematological remissions and major molecular responses can be sustained after discontinuation of long-term treatment with IFN2b.
引用
收藏
页码:331 / 334
页数:4
相关论文
共 16 条
[1]   JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis [J].
Barosi, Giovanni ;
Bergamaschi, Gaetano ;
Marchetti, Monia ;
Vannucchi, Alessandro M. ;
Guglielmelli, Paola ;
Antonioli, Elisabetta ;
Massa, Margherita ;
Rosti, Vittorio ;
Campanelli, Rita ;
Villani, Laura ;
Viarengo, Gianluca ;
Gattoni, Elisabetta ;
Gerli, Giancarla ;
Specchia, Giorgina ;
Tinelli, Carmine ;
Rambaldi, Alessandro ;
Barbui, Tiziano .
BLOOD, 2007, 110 (12) :4030-4036
[2]   Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders [J].
Baxter, EJ ;
Scott, LM ;
Campbell, PJ ;
East, C ;
Fourouclas, N ;
Swanton, S ;
Vassiliou, GS ;
Bench, AJ ;
Boyd, EM ;
Curtin, N ;
Scott, MA ;
Erber, WN ;
Green, AR .
LANCET, 2005, 365 (9464) :1054-1061
[3]   Myelofibrosis with myeloid metaplasia: The advanced phase of an untreated disseminated hematological cancer Time to change our therapeutic attitude with early upfront treatment? [J].
Hasselbalch, Hans Carl .
LEUKEMIA RESEARCH, 2009, 33 (01) :11-18
[4]   Recurrence of clonal hematopoiesis after discontinuing pegylated recombinant interferon-α 2a in a patient with polycythemia vera [J].
Ishii, T. ;
Xu, M. ;
Zhao, Y. ;
Hu, W-Y ;
Ciurea, S. ;
Bruno, E. ;
Hoffman, R. .
LEUKEMIA, 2007, 21 (02) :373-374
[5]   Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha [J].
Jones, AV ;
Silver, RT ;
Waghorn, K ;
Curtis, C ;
Kreil, S ;
Zoi, K ;
Hochhaus, A ;
Oscier, D ;
Metzgeroth, G ;
Lengfelder, E ;
Reiter, A ;
Chase, AJ ;
Cross, NCP .
BLOOD, 2006, 107 (08) :3339-3341
[6]   Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera [J].
Kiladjian, Jean-Jacques ;
Cassinat, Bruno ;
Chevret, Sylvie ;
Turlure, Pascal ;
Cambier, Nathalie ;
Roussel, Murielle ;
Bellucci, Sylvia ;
Grandchamp, Bernard ;
Chomienne, Christine ;
Fenaux, Pierre .
BLOOD, 2008, 112 (08) :3065-3072
[7]   High molecular response rate of polycythemia vera patients treated with pegylated interferon α-2a [J].
Kiladjian, Jean-Jacques ;
Cassinat, Bruno ;
Turlure, Pascal ;
Cambier, Nathalie ;
Roussel, Murielle ;
Bellucci, Sylvia ;
Menot, Marie-Laurence ;
Massonnet, Gerald ;
Dutel, Jean-Luc ;
Ghomari, Kamel ;
Rousselot, Philippe ;
Grange, Marie-Jose ;
Chait, Yasmina ;
Vainchenker, William ;
Parquet, Nathalie ;
Abdelkader-Aljassem, Lina ;
Bernard, Jean-Francois ;
Rain, Jean-Didier ;
Chevret, Sylvie ;
Chomienne, Christine ;
Fenaux, Pierre .
BLOOD, 2006, 108 (06) :2037-2040
[8]   Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera [J].
Larsen, T. S. ;
Bjerrum, O. W. ;
Pallisgaard, N. ;
Andersen, M. T. ;
Moller, M. B. ;
Hasselbalch, H. C. .
ANNALS OF HEMATOLOGY, 2008, 87 (10) :847-850
[9]   The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis - impact on disease phenotype [J].
Larsen, Thomas Stauffer ;
Pallisgaard, Niels ;
Moller, Michael Boe ;
Hasselbalch, Hans Carl .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2007, 79 (06) :508-515
[10]   The JAK2 V617F mutation involves B- and T-lymphocyte lineages in a subgroup of patients with Philadelphia-chromosome negative chronic myeloproliferative disorders [J].
Larsen, Thomas Stauffer ;
Christensen, Jacob Haaber ;
Hasselbalch, Hans Carl ;
Pallisgaard, Niels .
BRITISH JOURNAL OF HAEMATOLOGY, 2007, 136 (05) :745-751