Association of CD117 and HLA‑DR expression with shorter overall survival and/or progression‑free survival in patients with multiple myeloma treated with bortezomib and thalidomide combination treatment without transplantation

Wang,Huan; Zhou,Xin; Zhu,Jian‑Wei; Ye,Jian‑Nan; Guo,Hong‑Feng; Sun,Chao

doi:10.3892/ol.2018.9365

Association of CD117 and HLA‑DR expression with shorter overall survival and/or progression‑free survival in patients with multiple myeloma treated with bortezomib and thalidomide combination treatment without transplantation

Authors:
- Huan Wang
- Xin Zhou
- Jian‑Wei Zhu
- Jian‑Nan Ye
- Hong‑Feng Guo
- Chao Sun
View Affiliations

Affiliations: Department of Hematology, Affiliated Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
Published online on: August 24, 2018 https://doi.org/10.3892/ol.2018.9365
Pages: 5655-5666
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Certain immunophenotypes in multiple myeloma (MM), including CD56 and CD117, have been reported to be associated with overall survival (OS). However, previous reports have ignored the impact of different treatment regimens and the long‑term prognostic value of immunophenotyping in MM when treated with novel agents, including thalidomide and bortezomib, in the absence of transplantation for autologous stem cell transplantation and allo‑hematopoietic stem cell transplantation. To further understand the long‑term prognostic value of immunophenotyping in MM, when treated with bortezomib combined with thalidomide‑based regimens without transplantation, 80 patients who were newly diagnosed between January 2007 and December 2015, were analyzed retrospectively. In contrast to previous studies, no significant survival time difference was observed between CD56+/CD117+ and CD56‑/CD117‑ groups. Multivariate analysis suggested that human leukocyte antigen‑antigen D‑related (HLA‑DR)+ was independently associated with shorter OS and progression‑free survival (PFS), while CD117+ was an independent prognostic factor for decreased PFS. In addition, the myeloma prognostic index (MPI), defined by HLA‑DR+, age ≥65 years and international staging system stage III, was suitable for risk stratification of patients treated with novel agents for OS and PFS. The results of the current study suggested that HLA‑DR+ patients had a shorter OS and PFS and CD117+ patients had shorter PFS. HLA‑DR+ or CD117+ was sufficient to affect survival. Evaluating these markers may reveal valuable prognostic factors for MM in patients receiving bortezomib combined with thalidomide‑based regimens without autologous stem cell transplantation and allo‑hematopoietic stem cell transplantation). MPI may describe an accessible tool to predict the prognosis of patients with MM.

View Figures

View References

1	Cejalvo MJ and de la Rubia J: Which therapies will move to the front line for multiple myeloma? Expert Rev Hematol. 10:383–392. 2017. View Article : Google Scholar : PubMed/NCBI
2	Palumbo A and Anderson K: Multiple myeloma. N Engl J Med. 364:1046–1060. 2011. View Article : Google Scholar : PubMed/NCBI
3	Anderson KC, Alsina M, Bensinger W, Biermann JS, Cohen AD, Devine S, Djulbegovic B, Faber EA Jr, Gasparetto C, Hernandez-Illizaliturri F, et al: Multiple myeloma, version 1.2013. J Natl Compr Canc Netw. 11:11–17. 2013. View Article : Google Scholar : PubMed/NCBI
4	Tadmor T: Do lymphocytes count in myeloma? Are we absolutely sure? Leuk Lymphoma. 56:1193–1194. 2015. View Article : Google Scholar : PubMed/NCBI
5	Kim DS, Yu ES, Kang KW, Lee SR, Park Y, Sung HJ, Choi CW and Kim BS: Myeloma prognostic index at diagnosis might be a prognostic marker in patients newly diagnosed with multiple myeloma. Korean J Intern Med. 32:711–721. 2017. View Article : Google Scholar : PubMed/NCBI
6	Gertz MA and Buadi FK: Utility of immunophenotyping of plasma cells in multiple myeloma. Leuk Lymphoma. 28:1–2. 2015.
7	Li HQ and Zhai YP: Research progress on multiple myeloma immunophenotyping and minimal residual disease detected by flow cytometry. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 23:241–245. 2015.(In Chinese). PubMed/NCBI
8	Pan Y, Wang H, Tao Q, Zhang C, Yang D, Qin H, Xiong S, Tao L, Wu F, Zhang J and Zhai Z: Absence of both CD56 and CD117 expression on malignant plasma cells is related with a poor prognosis in patients with newly diagnosed multiple myeloma. Leuk Res. 40:77–82. 2016. View Article : Google Scholar : PubMed/NCBI
9	Ceran F, Falay M, Dagdas S and Ozet G: The assessment of CD56 and CD117 expressions at the time of the diagnosis in multiple myeloma patients. Turk J Haematol. 34:226–232. 2017.PubMed/NCBI
10	International Myeloma Working Group, . Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report of the international myeloma working group. Br J Haematol. 121:749–757. 2003. View Article : Google Scholar : PubMed/NCBI
11	Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, et al: International staging system for multiple myeloma. J Clin Oncol. 23:3412–3420. 2005. View Article : Google Scholar : PubMed/NCBI
12	Cavo M, Rajkumar SV, Palumbo A, Moreau P, Orlowski R, Blade J, Sezer O, Ludwig H, Dimopoulos MA, Attal M, et al: International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 117:6063–6073. 2011. View Article : Google Scholar : PubMed/NCBI
13	Palumbo A, Rajkumar SV, San Miguel JF, Larocca A, Niesvizky R, Morgan G, Landgren O, Hajek R, Einsele H, Anderson KC, et al: International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol. 32:587–600. 2014. View Article : Google Scholar : PubMed/NCBI
14	Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, et al: International uniform response criteria for multiple myeloma. Leukemia. 20:1467–1473. 2006. View Article : Google Scholar : PubMed/NCBI
15	Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, et al: Revised international staging system for multiple myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 33:2863–2869. 2015. View Article : Google Scholar : PubMed/NCBI
16	Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, et al: Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 371:906–917. 2014. View Article : Google Scholar : PubMed/NCBI
17	Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, Siniscalchi A, Magarotto V, Pour L, Carella A, et al: Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial. Lancet Oncol. 16:1617–1629. 2015. View Article : Google Scholar : PubMed/NCBI
18	Jimenez-Zepeda VH, Reece DE, Trudel S, Chen C, Franke N, Winter A, Tiedemann R and Kukreti V: Absolute lymphocyte count as predictor of overall survival for patients with multiple myeloma treated with single autologous stem cell transplant. Leuk Lymphoma. 56:2668–2673. 2015. View Article : Google Scholar : PubMed/NCBI
19	Suriu C, Akria L, Azoulay D, Shaoul E, Barhoum M and Braester A: Absolute lymphocyte count as a prognostic marker in newly diagnosed multiple myeloma patients. Int J Lab Hematol. 38:e56–59. 2016. View Article : Google Scholar : PubMed/NCBI
20	Bataille R, Jego G, Robillard N, Barille-Nion S, Harousseau JL, Moreau P, Amiot M and Pellat-Deceunynck C: The phenotype of normal, reactive and malignant plasma cells. Identification of ‘many and multiple myelomas’ and of new targets for myeloma therapy. Haematologica. 91:1234–1240. 2006.PubMed/NCBI
21	Dahl IM, Rasmussen T, Kauric G and Husebekk A: Differential expression of CD56 and CD44 in the evolution of extramedullary myeloma. Br J Haematol. 116:273–277. 2002. View Article : Google Scholar : PubMed/NCBI
22	Bataille R, Pellat-Deceunynck C, Robillard N, Avet-Loiseau H, Harousseau JL and Moreau P: CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis. Leuk Res. 32:379–382. 2008. View Article : Google Scholar : PubMed/NCBI
23	Sahara N, Ohnishi K, Ono T, Sugimoto Y, Kobayashi M, Takeshita K, Shigeno K, Nakamura S, Naito K, Tamashima S, et al: Clinicopathological and prognostic characteristics of CD33-positive multiple myeloma. Eur J Haematol. 77:14–18. 2006. View Article : Google Scholar : PubMed/NCBI
24	Qiu Q, Zhu P, Wang MJ, Lu XZ, Dong YJ, Sun YH, Wang LH, Zhang Y, Bu DF, Wang WS, et al: Expression of CD56 and CD19 in patients with newly diagnosed multiple myeloma and their relationship with karyotypes and prognosis. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 24:1071–1078. 2016.(In Chinese). PubMed/NCBI
25	Tang HL, Shu MM, Dong BX, Gu HT, Liang R, Bai QX, Yang L, Zhang T, Gao GX and Chen XQ: Influence of CD117 expression on response of multiple myeloma patients to chemotherapy. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 23:1346–1351. 2015.(In Chinese). PubMed/NCBI
26	Mateo G, Montalban MA, Vidriales MB, Lahuerta JJ, Mateos MV, Gutierrez N, Rosinol L, Montejano L, Blade J, Martinez R, et al: Prognostic value of immunophenotyping in multiple myeloma: A study by the PETHEMA/GEM cooperative study groups on patients uniformly treated with high-dose therapy. J Clin Oncol. 26:2737–2744. 2008. View Article : Google Scholar : PubMed/NCBI
27	Hundemer M, Klein U, Hose D, Raab MS, Cremer FW, Jauch A, Benner A, Heiss C, Moos M, Ho AD and Goldschmidt H: Lack of CD56 expression on myeloma cells is not a marker for poor prognosis in patients treated by high-dose chemotherapy and is associated with translocation t(11;14). Bone Marrow Transplant. 40:1033–1037. 2007. View Article : Google Scholar : PubMed/NCBI
28	Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium. Nature. 401:921–923. 1999. View Article : Google Scholar : PubMed/NCBI
29	Hasan ZN, Zalzala HH, Mohammedsalih HR, Mahdi BM, Abid LA, Shakir ZN and Fadhel MJ: Association between human leukocyteantigen-DR and demylinating Guillain-Barre syndrome. Neurosciences. 19:301–305. 2014.PubMed/NCBI
30	Nada AM and Hammouda M: Immunoregulatory T cells, LFA-3 and HLA-DR in autoimmune thyroid diseases. Indian J Endocrinol Metab. 18:574–581. 2014. View Article : Google Scholar : PubMed/NCBI
31	Diao J, Xia T, Zhao H, Liu J, Li B and Zhang Z: Overexpression of HLA-DR is associated with prognosis of glioma patients. Int J Clin Exp Pathol. 8:5485–5490. 2015.PubMed/NCBI
32	Sconocchia G, Eppenberger-Castori S, Zlobec I, Karamitopoulou E, Arriga R, Coppola A, Caratelli S, Spagnoli GC, Lauro D, Lugli A, et al: HLA class II antigen expression in colorectal carcinoma tumors as a favorable prognostic marker. Neoplasia. 16:31–42. 2014. View Article : Google Scholar : PubMed/NCBI
33	Rimsza LM, Leblanc ML, Unger JM, Miller TP, Grogan TM, Persky DO, Martel RR, Sabalos CM, Seligmann B, Braziel RM, et al: Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP. Blood. 112:3425–3433. 2008. View Article : Google Scholar : PubMed/NCBI
34	Yamamoto W, Nakamura N, Tomita N, Takeuchi K, Ishii Y, Takahashi H, Watanabe R, Takasaki H, Motomura S, Kobayashi S, et al: Human leukocyte antigen-DR expression on flow cytometry and tumor-associated macrophages in diffuse large B-cell lymphoma treated by rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: Retrospective cohort study. Leuk Lymphoma. 55:2721–2727. 2014. View Article : Google Scholar : PubMed/NCBI
35	Nemec P, Zemanova Z, Kuglik P, Michalova K, Tajtlova J, Kaisarova P, Oltova A, Filkova H, Holzerova M, Balcarkova J, et al: Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: Results of CMG2002 trial. Leuk Lymphoma. 53:920–927. 2012. View Article : Google Scholar : PubMed/NCBI
36	Chen SY: Clinical effect of bortezomib combined with dexamethasone and thalidomide on treatment of multiple myeloma. J Clin Med Practice. 18:1–126. 2014.