Molecular Monitoring of BCR-ABL Transcripts after Allogeneic Stem Cell Transplantation for Chronic Myeloid Leukemia

被引:25
作者
Arpinati, Mario [1 ]
Tolomelli, Giulia [1 ]
Bochicchio, Maria Teresa [1 ]
Castagnetti, Fausto [1 ]
Amabile, Marilina [1 ]
Bandini, Giuseppe [1 ]
Bonifazi, Francesca [1 ]
Stanzani, Marta [1 ]
Rosti, Gianantonio [1 ]
Martinelli, Giovanni [1 ]
Baccarani, Michele [1 ]
机构
[1] Univ Bologna, Dept Hematol & Oncol Sci Seragnoli, I-40138 Bologna, Italy
关键词
Allogeneic hematopoietic stem cell transplantation (HSCT); Chronic myeloid leukemia (CML); BCR-ABL; Minimal residual disease (MRD); BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; INTERFERON-ALPHA THERAPY; VERSUS-HOST-DISEASE; QUANTITATIVE RT-PCR; CYTOGENETIC REMISSION; PERIPHERAL-BLOOD; RELAPSE; CML;
D O I
10.1016/j.bbmt.2013.01.007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The monitoring of minimal residual disease (MRD) through low sensitivity real-time (RT) polymerase chain reaction (PCR) analysis of BCR-ABL transcripts allows early detection of chronic myeloid leukemia (CML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT). The introduction of more sensitive techniques, such as RT quantitative (Q)-PCR, may lead to an overestimation of the risk of CML relapse. In this study, we reviewed the results of peripheral blood RT Q-PCR in CML patients who underwent allogeneic HSCT from 1983 to 2007. In our laboratory, RT Q-PCR analysis was routinely performed since 2002. Eighty-seven of 189 patients had available RT Q-PCR data; 63 patients had at least 3 RT Q-PCR analyses assessable. Fifty-two of 63 patients (83%) had, at least once, detectable transcript levels, but with an BCR-ABL/ABL ratio <.1% defined as <MR3 (molecular remission <0,1%), whereas 11 (17%) had persistent undetectable BCR-ABL transcripts. Six of 52 patients with <MR3 relapsed, defined as BCR-ABL transcript numbers >.1% confirmed by the finding of Ph+ cells in bone marrow. No patients with persistent undetectable transcripts relapsed (P = .19). Relapse did not correlate with the number of occurrences of <MR3 or with the time to the first <MR3 result. Finally, of 46 patients with detectable transcripts who did not relapse, 35 had undetectable transcripts at last contact. RT Q-PCR analysis had low specificity (19%) and low positive predictive value (12%) in predicting relapse of CML patients after allogeneic HSCf. Our data suggest that detection of low BCR-ABL transcript levels by RT Q-PCR analysis has a poor accuracy in defining the risk of CML relapse and should not be considered as the unique indication to treatment. Fluctuation of BCR-ABL transcripts levels is common as late as >= 10 years post-transplantation, possibly suggesting the long-term persistence of CML stem cells. (C) 2013 American Society for Blood and Marrow Transplantation.
引用
收藏
页码:735 / 740
页数:6
相关论文
共 41 条
[1]   Prediction of relapse by day 100 BCR-ABL quantification after allogeneic stem cell transplantation for chronic myeloid leukemia [J].
Asnafi, V ;
Rubio, MT ;
Delabesse, E ;
Villar, E ;
Davi, F ;
Damaj, G ;
Hirsch, I ;
Dhédin, N ;
Vernant, JP ;
Varet, B ;
Buzyn, A ;
Macintyre, E .
LEUKEMIA, 2006, 20 (05) :793-799
[2]   Peripheral blood vs. bone marrow for molecular monitoring of BCR-ABL1 levels in chronic myelogenous leukemia, a retrospective analysis in allogeneic bone marrow recipients [J].
Ballestrero, A. ;
Cirmena, G. ;
Dominietto, A. ;
Garuti, A. ;
Rocco, I. ;
Cea, M. ;
Moran, E. ;
Nencioni, A. ;
Miglino, M. ;
Raiola, A. M. ;
Bacigalupo, A. ;
Patrone, F. .
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 2010, 32 (04) :387-391
[3]   Reduced incidence of GVHD without increase in relapse with low-dose rabbit ATG in the preparative regimen for unrelated bone marrow transplants in CML [J].
Bonifazi, F ;
Bandini, G ;
Rondelli, D ;
Falcioni, S ;
Stanzani, M ;
Bontadini, A ;
Tazzari, PL ;
Arpinati, M ;
Giannini, B ;
Conte, R ;
Baccarani, M .
BONE MARROW TRANSPLANTATION, 2003, 32 (03) :237-242
[4]   The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: Biologic significance and implications for the assessment of minimal residual disease [J].
Bose, S ;
Deininger, M ;
Gora-Tybor, J ;
Goldman, JM ;
Melo, JV .
BLOOD, 1998, 92 (09) :3362-3367
[5]   Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-α therapy or allogeneic bone marrow transplantation [J].
Chomel, JC ;
Brizard, F ;
Veinstein, A ;
Rivet, J ;
Sadoun, A ;
Kitzis, A ;
Guilhot, F ;
Brizard, A .
BLOOD, 2000, 95 (02) :404-409
[6]   The Use of Imatinib Mesylate as a Lifesaving Treatment of Chronic Myeloid Leukemia Relapse after Bone Marrow Transplantation [J].
Conchon, Monika ;
Sanabani, Sabri S. ;
Bendit, Israel ;
Dinardo, Carla Luana ;
Dias, Lucia ;
Fischer Chamone, Dalton de Alencar ;
Dorlhiac-Llacer, Pedro Enrique ;
Dulley, Frederico Luiz .
JOURNAL OF TRANSPLANTATION, 2009, 2009
[7]   Management of chronic myeloid leukaemia in relapse following donor lymphocyte infusion induced remission: a retrospective study of the clinical trials committee of the British Society of Blood & Marrow Transplantation (BSBMT) [J].
Cummins, M ;
Cwynarski, K ;
Marktel, S ;
Dazzi, F ;
Cavenagh, J ;
Clark, RE ;
Holyoake, TL ;
Milligan, D ;
Parker, A ;
Russell, NH ;
Marks, DI .
BONE MARROW TRANSPLANTATION, 2005, 36 (12) :1065-1069
[8]   Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited [J].
Deol, Abhinav ;
Lum, Lawrence G. .
CANCER TREATMENT REVIEWS, 2010, 36 (07) :528-538
[9]   Accurate and rapid analysis of residual disease in patients with CML using specific fluorescent hybridization probes for real time quantitative RT-PCR [J].
Emig, M ;
Saussele, S ;
Wittor, H ;
Weisser, A ;
Reiter, A ;
Willer, A ;
Berger, U ;
Hehlmann, R ;
Cross, NCP ;
Hochhaus, A .
LEUKEMIA, 1999, 13 (11) :1825-1832
[10]   Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia -: A Europe Against Cancer Program [J].
Gabert, J ;
Beillard, E ;
van der Velden, VHJ ;
Bi, W ;
Grimwade, D ;
Pallisgaard, N ;
Barbany, G ;
Cazzaniga, G ;
Cayuela, JM ;
Cavé, H ;
Pane, F ;
Aerts, JLE ;
De Micheli, D ;
Thirion, X ;
Pradel, V ;
González, M ;
Viehmann, S ;
Malec, M ;
Saglio, G ;
van Dongen, JJM .
LEUKEMIA, 2003, 17 (12) :2318-2357