Minimal Identifiable Disease and the Role of Conditioning Intensity in Hematopoietic Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Evolving from Myelodysplastic Syndrome

被引:43
作者
Festuccia, Moreno [1 ,2 ]
Deeg, H. Joachim [1 ,2 ]
Gooley, Theodore A. [1 ,2 ]
Baker, Kelsey [1 ]
Wood, Brent L. [1 ,2 ]
Fang, Min [1 ,2 ]
Sandmaier, Brenda M. [1 ,2 ]
Scott, Bart L. [1 ,2 ]
机构
[1] Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,Mail Stop D1-100,POB 19024, Seattle, WA 98109 USA
[2] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
MDS; minimal residual disease; minimal identifiable disease; Allogeneic transplantation; Conditioning regimen; PROGNOSTIC SCORING SYSTEM; ACUTE MYELOID-LEUKEMIA; RESIDUAL DISEASE; ADULT PATIENTS; CLASSIFICATION; MALIGNANCIES; CYTOGENETICS; MUTATIONS; REGIMENS; OUTCOMES;
D O I
10.1016/j.bbmt.2016.03.029
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Allogeneic hematopoietic cell transplantation (HCT) is the only known treatment with curative potential for myelodysplastic syndrome, but relapse is a major cause of failure. We studied results in 289 patients transplanted between June 2004 and December 2013. Minimal identifiable disease (MID) markers pre-HCT were determined by multiparameter flow cytometry (MFC) and cytogenetics on marrow aspirates. The impact of MID on outcome after low- and high-intensity conditioning HCT was determined. Among 287 assessable patients, 68 (23.7%) had more than 5% marrow blasts at HCT; 219 patients were in morphologic remission but 154 (53.7%) were MID positive, whereas 65 (22.6%) were MID negative. The impact of MID on outcome was significantly different between patients who received low-intensity conditioning and patients who received a high-intensity regimen. The impact of conditioning intensity differed across the various MID categories. In particular, the risk of overall mortality was higher with low-intensity than with high-intensity regimens for patients who were positive for MID by cytogenetics regardless of positivity by MFC (HR, 1.67 if MFC positive/cytogenetics positive, HR, 7.23 if MFC negative/cytogenetics positive). On the other hand, patients who were MID negative by both MFC and cytogenetics had similar risks of mortality with low- and high-intensity regimens (HR,.99). The main factor responsible for mortality after low-intensity conditioning in MID-positive patients was relapse. The presence of MID should be considered when deciding on conditioning intensity because it identifies subgroups of patients who may benefit from high- or low-intensity conditioning. (C) 2016 American Society for Blood and Marrow Transplantation.
引用
收藏
页码:1227 / 1233
页数:7
相关论文
共 32 条
[1]   Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning [J].
Baron, F ;
Baker, JE ;
Storb, R ;
Gooley, TA ;
Sandmaier, BM ;
Maris, MB ;
Maloney, DG ;
Heimfeld, S ;
Oparin, D ;
Zellmer, E ;
Radich, JP ;
Grumet, FC ;
Blume, KG ;
Chauncey, TR ;
Little, MT .
BLOOD, 2004, 104 (08) :2254-2262
[2]   Somatic Mutations Predict Poor Outcome in Patients With Myelodysplastic Syndrome After Hematopoietic Stem-Cell Transplantation [J].
Bejar, Rafael ;
Stevenson, Kristen E. ;
Caughey, Bennett ;
Lindsley, R. Coleman ;
Mar, Brenton G. ;
Stojanov, Petar ;
Getz, Gad ;
Steensma, David P. ;
Ritz, Jerome ;
Soiffer, Robert ;
Antin, Joseph H. ;
Alyea, Edwin ;
Armand, Philippe ;
Ho, Vincent ;
Koreth, John ;
Neuberg, Donna ;
Cutler, Corey S. ;
Ebert, Benjamin L. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (25) :2691-+
[3]   Clinical Effect of Point Mutations in Myelodysplastic Syndromes [J].
Bejar, Rafael ;
Stevenson, Kristen ;
Abdel-Wahab, Omar ;
Galili, Naomi ;
Nilsson, Bjoern ;
Garcia-Manero, Guillermo ;
Kantarjian, Hagop ;
Raza, Azra ;
Levine, Ross L. ;
Neuberg, Donna ;
Ebert, Benjamin L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (26) :2496-2506
[4]   Relation of Clinical Response and Minimal Residual Disease and Their Prognostic Impact on Outcome in Acute Myeloid Leukemia [J].
Chen, Xueyan ;
Xie, Hu ;
Wood, Brent L. ;
Walter, Roland B. ;
Pagel, John M. ;
Becker, Pamela S. ;
Sandhu, Vicky K. ;
Abkowitz, Janis L. ;
Appelbaum, Frederick R. ;
Estey, Elihu H. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (11) :1258-+
[5]   Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia [J].
Cheson, Bruce D. ;
Greenberg, Peter L. ;
Bennett, John M. ;
Lowenberg, Bob ;
Wijermans, Pierre W. ;
Nimer, Stephen D. ;
Pinto, Antonio ;
Beran, Miloslav ;
de Witte, Theo M. ;
Stone, Richard M. ;
Mittelman, Moshe ;
Sanz, Guillermo F. ;
Gore, Steven D. ;
Schiffer, Charles A. ;
Kantarjian, Hagop .
BLOOD, 2006, 108 (02) :419-425
[6]   Haematopoietic stem cell transplantation for patients with myelodysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) [J].
de Witte, T ;
Hermans, J ;
Vossen, J ;
Bacigalupo, A ;
Meloni, G ;
Jacobsen, N ;
Ruutu, T ;
Ljungman, P ;
Gratwohl, A ;
Runde, V ;
Niederwieser, D ;
van Biezen, A ;
Devergie, A ;
Cornelissen, J ;
Jouet, JP ;
Arnold, R ;
Apperley, J .
BRITISH JOURNAL OF HAEMATOLOGY, 2000, 110 (03) :620-630
[7]   Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS [J].
Deeg, H. Joachim ;
Scott, Bart L. ;
Fang, Min ;
Shulman, Howard M. ;
Gyurkocza, Boglarka ;
Myerson, David ;
Pagel, John M. ;
Platzbecker, Uwe ;
Ramakrishnan, Aravind ;
Radich, Jerald P. ;
Sandmaier, Brenda M. ;
Sorror, Mohamed ;
Stirewalt, Derek L. ;
Wilson, Wendy A. ;
Storb, Rainer ;
Appelbaum, Frederick R. ;
Gooley, Ted .
BLOOD, 2012, 120 (07) :1398-1408
[8]   Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome [J].
Deeg, HJ ;
Storer, B ;
Slattery, JT ;
Anasetti, C ;
Doney, KC ;
Hansen, JA ;
Kiem, HP ;
Martin, PJ ;
Petersdorf, E ;
Radich, JP ;
Sanders, JE ;
Shulman, HM ;
Warren, EH ;
Witherspoon, RP ;
Bryant, EM ;
Chauncey, TR ;
Getzendaner, L ;
Storb, R ;
Appelbaum, FR .
BLOOD, 2002, 100 (04) :1201-1207
[9]   Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R [J].
Della Porta, Matteo G. ;
Alessandrino, Emilio Paolo ;
Bacigalupo, Andrea ;
van Lint, Maria Teresa ;
Malcovati, Luca ;
Pascutto, Cristiana ;
Falda, Michele ;
Bernardi, Massimo ;
Onida, Francesco ;
Guidi, Stefano ;
Iori, Anna Paola ;
Cerretti, Raffaella ;
Marenco, Paola ;
Pioltelli, Pietro ;
Angelucci, Emanuele ;
Oneto, Rosi ;
Ripamonti, Francesco ;
Bernasconi, Paolo ;
Bosi, Alberto ;
Cazzola, Mario ;
Rambaldi, Alessandro .
BLOOD, 2014, 123 (15) :2333-2342
[10]   Prognostic impact of discordant results from cytogenetics and flow cytometry in patients with acute myeloid leukemia undergoing hematopoietic cell transplantation [J].
Fang, Min ;
Storer, Barry ;
Wood, Brent ;
Gyurkocza, Boglarka ;
Sandmaier, Brenda M. ;
Appelbaum, Frederick R. .
CANCER, 2012, 118 (09) :2411-2419