Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study

被引：81

作者：

Kulagin, Alexander ^{[1
]}

Lisukov, Igor ^{[1
]}

Ivanova, Maria ^{[1
]}

Golubovskaya, Irina ^{[1
,2
]}

Kruchkova, Irina

Bondarenko, Sergey ^{[1
]}

Vavilov, Vladimir ^{[1
]}

Stancheva, Natalia ^{[1
]}

Babenko, Elena ^{[1
]}

Sipol, Alexandra ^{[1
]}

Pronkina, Natalia ^{[2
]}

Kozlov, Vladimir ^{[2
]}

Afanasyev, Boris ^{[1
]}

机构：

[1] First Pavlov State Med Univ St Petersburg, St Petersburg 197022, Russia

[2] Inst Clin Immunol, Novosibirsk, Russia

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2014年 / 164卷 / 04期

关键词：

Aplastic anaemia; Paroxysmal nocturnal haemoglobinuria; immunosuppressive therapy; bone marrow failure; flow cytometry; RABBIT ANTITHYMOCYTE GLOBULIN; BONE-MARROW-TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; MINOR POPULATION; PREDICTING RESPONSE; ANCHORED PROTEIN; CELLS; CYCLOSPORINE; DIAGNOSIS; THERAPY;

D O I：

10.1111/bjh.12661

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Paroxysmal nocturnal haemoglobinuria (PNH) clones are frequently detected in patients with aplastic anaemia (AA). To evaluate the prognostic role of PNH clone presence we conducted a prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST). Seventy-four patients (59%) had a PNH clone (PNH+ patients) at diagnosis, with a median clone size of 060% in granulocytes and 015% in red blood cells. The response rate at 6months was higher in PNH+ patients than that in PNH- patients, both after first- and second-line IST: 68% vs. 45%, P=00164 and 53% vs. 13%, P=00502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH- patients (P=00029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 256, P=00180) and baseline absolute reticulocyte count (ARC) 30x10(9)/l (odds ratio 519, P=00011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC 30x10(9)/l showed significant distinctions for cumulative incidence of response, overall and failure-free survival. The results of this prospective study confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.

引用

页码：546 / 554

页数：9

共 38 条

[11] Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia [J].

Frickhofen, N ;

Heimpel, H ;

Kaltwasser, JP ;

Schrezenmeier, H .

BLOOD, 2003, 101 (04) :1236-1242

[12] APLASTIC-ANEMIA AND PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA - SEARCH FOR A PATHOGENETIC LINK [J].

GRISCELLIBENNACEUR, A ;

GLUCKMAN, E ;

SCROBOHACI, ML ;

JONVEAUX, P ;

VU, T ;

BAZARBACHI, A ;

CAROSELLA, ED ;

SIGAUX, F ;

SOCIE, G .

BLOOD, 1995, 85 (05) :1354-1363

[13]

HEIMPEL H, 1987, BLOOD, V70, P1718

[14]

Kulagin A, 2013, BONE MARROW TRANSPL, V48, pS43

[15]

KULAGIN A, 2011, HAEMATOLOGICA, V96, P351

[16] Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade:: a report from the European Group for Blood and Marrow Transplantation [J].

Locasciulli, Anna ;

Oneto, Rosi ;

Bacigalupo, Andrea ;

Socie, Gerard ;

Korthof, Elisabeth ;

Bekassy, Albert ;

Schrezenmeier, Hubert ;

Passweg, Jakob ;

Fuhrer, Monika .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2007, 92 (01) :11-18

[17] Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones [J].

Maciejewski, JP ;

Rivera, C ;

Kook, H ;

Dunn, D ;

Young, NS .

BRITISH JOURNAL OF HAEMATOLOGY, 2001, 115 (04) :1015-1022

[18] Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome [J].

Maciejewski, JP ;

Follmann, D ;

Nakamura, R ;

Saunthararajah, Y ;

Rivera, CE ;

Simonis, T ;

Brown, KE ;

Barrett, JA ;

Young, NS .

BLOOD, 2001, 98 (13) :3513-3519

[19] Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: A report from the European blood and marrow transplant (EBMT) severe aplastic anaemia working party [J].

Marsh, J ;

Schrezenmeier, H ;

Marin, P ;

Ilhan, O ;

Ljungman, P ;

McCann, S ;

Socie, G ;

Tichelli, A ;

Passweg, J ;

Hows, J ;

Raghavachar, A ;

Locasciulli, A ;

Bacigalupo, A .

BLOOD, 1999, 93 (07) :2191-2195

[20] Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party [J].

Marsh, Judith C. ;

Bacigalupo, Andrea ;

Schrezenmeier, Hubert ;

Tichelli, Andre ;

Risitano, Antonio M. ;

Passweg, Jakob R. ;

Killick, Sally B. ;

Warren, Alan J. ;

Foukaneli, Theodora ;

Aljurf, Mahmoud ;

Al-Zahrani, H. A. ;

Schafhausen, Philip ;

Roth, Alexander ;

Franzke, Anke ;

Brummendorf, Tim H. ;

Dufour, Carlo ;

Oneto, Rosi ;

Sedgwick, Philip ;

Barrois, Alain ;

Kordasti, Shahram ;

Elebute, Modupe O. ;

Mufti, Ghulam J. ;

Socie, Gerard .

BLOOD, 2012, 119 (23) :5391-5396

← 1 2 3 4 →