Abstract
The aim of our study was to evaluate the prognostic impact of minimal residual disease (MRD) and high-risk cytogenetics (HRCs) on outcomes in multiple myeloma (MM) patients. We applied multiparameter flow cytometry (MFC) to detect MRD in 123 consecutive patients diagnosed with MM for the first time who achieved very good partial remission (VGPR) or better after bortezomib or thalidomide-based induction therapy. Moreover, we examined the cytogenetic features of MM patients using magnetic-activated cell sorting and interphase fluorescence in situ hybridization (MACS-iFISH) at diagnosis. In all 123 MM patients, progression-free survival (PFS) and overall survival (OS) were better in the MRD− group (n = 31) than in the MRD+ group (n = 92) (median PFS: not reached (NR) vs. 26 months (m), P = 0.0002; 4-year OS, 91.7% vs. 66.3%, P = 0.008). PFS and OS were significantly shorter for each increase of one log per MRD level (P < 0.0001 and P = 0.001). The median PFS of the four groups according to the ratio of aberrant plasma cells (less than 0.01%, 0.01–0.1%, 0.1–1%, and more than 1%) were NR, 37 m, 26 m, and 15 m, respectively, and the 4-year OS rates were 91.7%, 69.3%, 76.1%, and 54.0%, respectively. In addition, our results show that PFS and OS were better for the standard-risk cytogenetic (SRC) patients than the HRC patients (median PFS: NR vs. 26 m, P = 0.004; 3-year OS: 95.8% vs. 76.0%, P = 0.006). The independent predictors of PFS were HRC and MRD+, which had hazard ratios of 1.901 (95% CI 1.094–3.303) and 3.486 (95% CI 1.449–8.386), respectively; while those for OS were an LDH level ≥ 250 U/L, HRC, and MRD+, which had hazard ratios of 2.789 (95% CI 1.080–7.199), 2.697 (95% CI 1.053–6.907), and 7.714 (95% CI 1.040–57.227), respectively. Furthermore, for SRC patients or HRC patients, PFS and OS were all longer in MRD− than in MRD+ patients. Strikingly, there was no significant difference in PFS or OS between the MRD-HRC and MRD+SRC groups (median PFS 45 vs. 34 m, P = 0.300; 4-year OS 100% vs. 83.6%, P = 0.196). PFS was superior in MRD-SRC than in MRD-HRC (NR vs. 45 m, P = 0.035); however, there was no significant difference in the 4-year OS between MRD-SRC and MRD-HRC (87.5% vs 100%, P = 0.480). MRD+ and HRCs were both independent prognostic factors in MM patients. Moreover, achieving MRD− may ameliorate a poor prognosis in MM patients with HRCs.
Similar content being viewed by others
Abbreviations
- MFC:
-
Multiparameter flow cytometry
- BM:
-
Bone marrow
- MRD:
-
Minimal residual disease
- SRC:
-
Standard-risk cytogenetics
- HRCs:
-
High-risk cytogenetics
- HD:
-
Hyperdiploidy
- NHD:
-
Non-hyperdiploidy
- APCs:
-
Aberrant plasma cells
- NPCs:
-
Normal plasma cells
- MACS-iFISH:
-
Magnetic-activated cell sorting and interphase fluorescence in situ hybridization
- CR:
-
Complete remission
- sCR:
-
Stringent CR
- VGPR:
-
Very good partial remission
- Ig:
-
Immunoglobulin
- ISS:
-
International Staging System
- LC:
-
Light chain
- PFS:
-
Progression-free survival
- OS:
-
Overall survival
- NR:
-
Not reached
- IMWG:
-
International Myeloma Working Group
- PCR:
-
Polymerase chain reaction
- NGS:
-
Next-generation sequencing
References
Kyle RA, Rajkumar SV (2008) Multiple myeloma. Blood 111(6):2962–2972. https://doi.org/10.1182/blood-2007-10-078022
Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC (2010) Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 116(5):679–686. https://doi.org/10.1182/blood-2010-02-268862
Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG, Group T-MS (2016) Oral lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 374(17):1621–1634. https://doi.org/10.1056/NEJMoa1516282
Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P, Investigators P (2016) Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 375(14):1319–1331. https://doi.org/10.1056/NEJMoa1607751
Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29. https://doi.org/10.3322/caac.21254
Ocio EM, Richardson PG, Rajkumar SV, Palumbo A, Mateos MV, Orlowski R, Kumar S, Usmani S, Roodman D, Niesvizky R, Einsele H, Anderson KC, Dimopoulos MA, Avet-Loiseau H, Mellqvist UH, Turesson I, Merlini G, Schots R, McCarthy P, Bergsagel L, Chim CS, Lahuerta JJ, Shah J, Reiman A, Mikhael J, Zweegman S, Lonial S, Comenzo R, Chng WJ, Moreau P, Sonneveld P, Ludwig H, Durie BG, Miguel JF (2014) New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG). Leukemia 28(3):525–542. https://doi.org/10.1038/leu.2013.350
Cooke F, Bakkus M, Thielemans K, Pico JL, Apperley JF, Samson D (1999) Use of quantitative ASO-PCR to predict relapse in multiple myeloma. Br J Haematol 105(1):317–319
Ding C, Cantor CR (2003) A high-throughput gene expression analysis technique using competitive PCR and matrix-assisted laser desorption ionization time-of-flight MS. Proc Natl Acad Sci U S A 100(6):3059–3064. https://doi.org/10.1073/pnas.0630494100
Ladetto M, Bruggemann M, Monitillo L, Ferrero S, Pepin F, Drandi D, Barbero D, Palumbo A, Passera R, Boccadoro M, Ritgen M, Gokbuget N, Zheng J, Carlton V, Trautmann H, Faham M, Pott C (2014) Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders. Leukemia 28(6):1299–1307. https://doi.org/10.1038/leu.2013.375
Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M (2014) Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myelome. J Clin Oncol 32(25):2712–2717. https://doi.org/10.1200/JCO.2013.54.8164
Tembhare PR, Yuan CM, Venzon D, Braylan R, Korde N, Manasanch E, Zuchlinsky D, Calvo K, Kurlander R, Bhutani M, Tageja N, Maric I, Mulquin M, Roschewski M, Kwok M, Liewehr D, Landgren O, Stetler-Stevenson M (2014) Flow cytometric differentiation of abnormal and normal plasma cells in the bone marrow in patients with multiple myeloma and its precursor diseases. Leuk Res 38(3):371–376. https://doi.org/10.1016/j.leukres.2013.12.007
Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17(8):e328–e346. https://doi.org/10.1016/S1470-2045(16)30206-6
Rawstron AC, Child JA, de Tute RM, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Feyler S, Ross FM, Cook G, Jackson GH, Morgan GJ, Owen RG (2013) Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol 31(20):2540–2547. https://doi.org/10.1200/JCO.2012.46.2119
Rawstron AC, Gregory WM, de Tute RM, Davies FE, Bell SE, Drayson MT, Cook G, Jackson GH, Morgan GJ, Child JA, Owen RG (2015) Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction. Blood 125(12):1932–1935. https://doi.org/10.1182/blood-2014-07-590166
Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C (2007) Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 109(8):3489–3495. https://doi.org/10.1182/blood-2006-08-040410
Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G, Stoppa AM, Voillat L, Wetterwald M, Pegourie B, Voog E, Tiab M, Banos A, Jaubert J, Bouscary D, Macro M, Kolb B, Traulle C, Mathiot C, Magrangeas F, Minvielle S, Facon T, Moreau P (2012) Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol 30(16):1949–1952. https://doi.org/10.1200/JCO.2011.36.5726
Boyd KD, Ross FM, Walker BA, Wardell CP, Tapper WJ, Chiecchio L, Dagrada G, Konn ZJ, Gregory WM, Jackson GH, Child JA, Davies FE, Morgan GJ, Group NHOS (2011) Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival. Clin Cancer Res 17(24):7776–7784. https://doi.org/10.1158/1078-0432.CCR-11-1791
Korthals M, Sehnke N, Kronenwett R, Bruns I, Mau J, Zohren F, Haas R, Kobbe G, Fenk R (2012) The level of minimal residual disease in the bone marrow of patients with multiple myeloma before high-dose therapy and autologous blood stem cell transplantation is an independent predictive parameter. Biol Blood Marrow Transplant 18(3):423–431 e423. https://doi.org/10.1016/j.bbmt.2011.07.002
Paiva B, Vidriales MB, Cervero J, Mateo G, Perez JJ, Montalban MA, Sureda A, Montejano L, Gutierrez NC, Garcia de Coca A, de Las HN, Mateos MV, Lopez-Berges MC, Garcia-Boyero R, Galende J, Hernandez J, Palomera L, Carrera D, Martinez R, de la Rubia J, Martin A, Blade J, Lahuerta JJ, Orfao A, San Miguel JF, Groups GPCS (2008) Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood 112(10):4017–4023. https://doi.org/10.1182/blood-2008-05-159624
Paiva B, Gutierrez NC, Rosinol L, Vidriales MB, Montalban MA, Martinez-Lopez J, Mateos MV, Cibeira MT, Cordon L, Oriol A, Terol MJ, Echeveste MA, de Paz R, de Arriba F, Palomera L, de la Rubia J, Diaz-Mediavilla J, Sureda A, Gorosquieta A, Alegre A, Martin A, Hernandez MT, Lahuerta JJ, Blade J, San Miguel JF, Groups PGCS (2012) High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood 119(3):687–691. https://doi.org/10.1182/blood-2011-07-370460
Hu B, Thall P, Milton DR, Sasaki K, Bashir Q, Shah N, Patel K, Popat U, Hosing C, Nieto Y, Lin P, Delgado R, Jorgensen J, Manasanch E, Weber D, Thomas S, Orlowski RZ, Champlin R, Qazilbash MH (2018) High-risk myeloma and minimal residual disease postautologous-HSCT predict worse outcomes. Leuk Lymphoma:1–11. https://doi.org/10.1080/10428194.2018.1485908
Chakraborty R, Muchtar E, Kumar SK, Jevremovic D, Buadi FK, Dingli D, Dispenzieri A, Hayman SR, Hogan WJ, Kapoor P, Lacy MQ, Leung N, Gertz MA (2017) Impact of post-transplant response and minimal residual disease on survival in myeloma with high-risk cytogenetics. Biol Blood Marrow Transplant 23(4):598–605. https://doi.org/10.1016/j.bbmt.2017.01.076
Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Blade J, Lonial S, Dimopoulos M, Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG, International Myeloma Working G (2009) International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 23(2):215–224. https://doi.org/10.1038/leu.2008.307
Cordone I, Marchesi F, Masi S, Summa V, Pisani F, Merola R, Cigliana G, Orlandi G, Gumenyuk S, Palombi F, Romano A, Spadea A, Renzi D, Papa E, Canfora M, Conti L, Petti MC, Mengarelli A (2016) Flow cytometry remission by Ig light chains ratio is a powerful marker of outcome in multiple myeloma after tandem autologous transplant: a real-life study. J Exp Clin Cancer Res 35:49. https://doi.org/10.1186/s13046-016-0324-0
Ross FM, Avet-Loiseau H, Ameye G, Gutierrez NC, Liebisch P, O'Connor S, Dalva K, Fabris S, Testi AM, Jarosova M, Hodkinson C, Collin A, Kerndrup G, Kuglik P, Ladon D, Bernasconi P, Maes B, Zemanova Z, Michalova K, Michau L, Neben K, Hermansen NE, Rack K, Rocci A, Protheroe R, Chiecchio L, Poirel HA, Sonneveld P, Nyegaard M, Johnsen HE, European Myeloma N (2012) Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders. Haematologica 97(8):1272–1277. https://doi.org/10.3324/haematol.2011.056176
Chng WJ, Van Wier SA, Ahmann GJ, Winkler JM, Jalal SM, Bergsagel PL, Chesi M, Trendle MC, Oken MM, Blood E, Henderson K, Santana-Davila R, Kyle RA, Gertz MA, Lacy MQ, Dispenzieri A, Greipp PR, Fonseca R (2005) A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS. Blood 106(6):2156–2161. https://doi.org/10.1182/blood-2005-02-0761
Munshi NC, Avet-Loiseau H, Rawstron AC, Owen RG, Child JA, Thakurta A, Sherrington P, Samur MK, Georgieva A, Anderson KC, Gregory WM (2017) Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: a meta-analysis. JAMA Oncol 3(1):28–35. https://doi.org/10.1001/jamaoncol.2016.3160
Arroz M, Came N, Lin P, Chen W, Yuan C, Lagoo A, Monreal M, de Tute R, Vergilio JA, Rawstron AC, Paiva B (2016) Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytometry B Clin Cytom 90(1):31–39. https://doi.org/10.1002/cyto.b.21228
Rawstron AC, Paiva B, Stetler-Stevenson M (2016) Assessment of minimal residual disease in myeloma and the need for a consensus approach. Cytometry B Clin Cytom 90(1):21–25. https://doi.org/10.1002/cyto.b.21272
Paiva B, van Dongen JJ, Orfao A (2015) New criteria for response assessment: role of minimal residual disease in multiple myeloma. Blood 125(20):3059–3068. https://doi.org/10.1182/blood-2014-11-568907
de Tute RM, Rawstron AC, Gregory WM, Child JA, Davies FE, Bell SE, Cook G, Szubert AJ, Drayson MT, Jackson GH, Morgan GJ, Owen RG (2016) Minimal residual disease following autologous stem cell transplant in myeloma: impact on outcome is independent of induction regimen. Haematologica 101(2):e69–e71. https://doi.org/10.3324/haematol.2015.128215
Rosinol L, Oriol A, Teruel AI, Hernandez D, Lopez-Jimenez J, de la Rubia J, Granell M, Besalduch J, Palomera L, Gonzalez Y, Etxebeste MA, Diaz-Mediavilla J, Hernandez MT, de Arriba F, Gutierrez NC, Martin-Ramos ML, Cibeira MT, Mateos MV, Martinez J, Alegre A, Lahuerta JJ, San Miguel J, Blade J, Programa para el Estudio y la Terapeutica de las Hemopatias Malignas/Grupo Espanol de Mieloma g (2012) Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 120(8):1589–1596. https://doi.org/10.1182/blood-2012-02-408922
Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG, Zepeda VH, Mikhael JR, Leis JF, Bergsagel PL, Fonseca R, Stewart AK (2009) Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 23(7):1337–1341. https://doi.org/10.1038/leu.2009.26
Paiva B, Martinez-Lopez J, Vidriales MB, Mateos MV, Montalban MA, Fernandez-Redondo E, Alonso L, Oriol A, Teruel AI, de Paz R, Larana JG, Bengoechea E, Martin A, Mediavilla JD, Palomera L, de Arriba F, Blade J, Orfao A, Lahuerta JJ, San Miguel JF (2011) Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol 29(12):1627–1633. https://doi.org/10.1200/JCO.2010.33.1967
Liu H, Yuan C, Heinerich J, Braylan R, Chang M, Wingard J, Moreb J (2008) Flow cytometric minimal residual disease monitoring in patients with multiple myeloma undergoing autologous stem cell transplantation: a retrospective study. Leuk Lymphoma 49(2):306–314. https://doi.org/10.1080/10428190701813018
Paiva B, Cedena MT, Puig N, Arana P, Vidriales MB, Cordon L, Flores-Montero J, Gutierrez NC, Martin-Ramos ML, Martinez-Lopez J, Ocio EM, Hernandez MT, Teruel AI, Rosinol L, Echeveste MA, Martinez R, Gironella M, Oriol A, Cabrera C, Martin J, Bargay J, Encinas C, Gonzalez Y, Van Dongen JJ, Orfao A, Blade J, Mateos MV, Lahuerta JJ, San Miguel JF, Grupo Espanol de Mieloma/Programa para el Estudio de la Terapeutica en Hemopatias Malignas Cooperative Study G (2016) Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood 127(25):3165–3174. https://doi.org/10.1182/blood-2016-03-705319
Martinez-Lopez J, Lahuerta JJ, Pepin F, Gonzalez M, Barrio S, Ayala R, Puig N, Montalban MA, Paiva B, Weng L, Jimenez C, Sopena M, Moorhead M, Cedena T, Rapado I, Mateos MV, Rosinol L, Oriol A, Blanchard MJ, Martinez R, Blade J, San Miguel J, Faham M, Garcia-Sanz R (2014) Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood 123(20):3073–3079. https://doi.org/10.1182/blood-2014-01-550020
Perrot A, Lauwers-Cances V, Corre J, Robillard N, Hulin C, Chretien ML, Dejoie T, Maheo S, Stoppa AM, Pegourie B, Karlin L, Garderet L, Arnulf B, Doyen C, Meuleman N, Royer B, Eveillard JR, Benboubker L, Dib M, Decaux O, Jaccard A, Belhadj K, Brechignac S, Kolb B, Fohrer C, Mohty M, Macro M, Richardson PG, Carlton V, Moorhead M, Willis T, Faham M, Anderson KC, Harousseau JL, Leleu X, Facon T, Moreau P, Attal M, Avet-Loiseau H, Munshi N (2018) Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood 132:2456–2464. https://doi.org/10.1182/blood-2018-06-858613
van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM (2018) Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol 5(10):e479–e492. https://doi.org/10.1016/S2352-3026(18)30149-2
McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, Bringhen S, Musto P, Anderson KC, Caillot D, Gay F, Moreau P, Marit G, Jung SH, Yu Z, Winograd B, Knight RD, Palumbo A, Attal M (2017) Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol 35(29):3279–3289. https://doi.org/10.1200/JCO.2017.72.6679
Fukumoto K, Fujisawa M, Suehara Y, Narita KT, Usui Y, Takeuchi M, Matsue K (2016) Prognostic impact of immunophenotypic complete response in patients with multiple myeloma achieving better than complete response. Leuk Lymphoma 57(8):1786–1792. https://doi.org/10.3109/10428194.2015.1121262
Mei J, Zhai Y, Li H, Li F, Zhou X, Song P, Zhao Q, Yu Y, An Z, Wang L (2018) Prognostic impact of hyperdiploidy in multiple myeloma patients with high-risk cytogenetics: a pilot study in China. J Cancer Res Clin Oncol 144(11):2263–2273. https://doi.org/10.1007/s00432-018-2732-3
Kumar S, Fonseca R, Ketterling RP, Dispenzieri A, Lacy MQ, Gertz MA, Hayman SR, Buadi FK, Dingli D, Knudson RA, Greenberg A, Russell SJ, Zeldenrust SR, Lust JA, Kyle RA, Bergsagel L, Rajkumar SV (2012) Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood 119(9):2100–2105. https://doi.org/10.1182/blood-2011-11-390658
Pawlyn C, Melchor L, Murison A, Wardell CP, Brioli A, Boyle EM, Kaiser MF, Walker BA, Begum DB, Dahir NB, Proszek P, Gregory WM, Drayson MT, Jackson GH, Ross FM, Davies FE, Morgan GJ (2015) Coexistent hyperdiploidy does not abrogate poor prognosis in myeloma with adverse cytogenetics and may precede IGH translocations. Blood 125(5):831–840. https://doi.org/10.1182/blood-2014-07-584268
Acknowledgments
We sincerely thank all the doctors and nurses in the hematology department. In particular, we thank our colleagues who participated in this study. We thank all the patients who participated in this study and who sought care at our center.
Funding
This work is supported by projects from the National Natural Science Foundation of China for Young Scholars (grant number 81800126), the Six Talent Peak Project in Jiangsu Province (grant number 2015-WSN-011), and Hanqing Li received grant support from the Research Foundation of Jinling Hospital (grant number 2014017).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical statement
This study was approved by the Clinical Research Ethics Committee of Jinling Hospital, Nanjing, China. Written consent was waived by the Ethics Committee.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Li, H., Li, F., Zhou, X. et al. Achieving minimal residual disease-negative by multiparameter flow cytometry may ameliorate a poor prognosis in MM patients with high-risk cytogenetics: a retrospective single-center analysis. Ann Hematol 98, 1185–1195 (2019). https://doi.org/10.1007/s00277-019-03609-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-019-03609-x