ITP: The Past Decade

2006-2015

Ming Hou

Qilu Hospital, Shandong University

Nomenclature

Idiopathic Thrombocytopenic Purpura (ITP)

Immune Thrombocytopenia (ITP)

2007

International ITP working group. Blood. 2009, 113(11):2386-93.

Phases of ITP

International ITP working group. Blood. 2009, 113(11):2386-93.

0 6 Months

Chronic ITPAcute ITP

2007

0 3 Months 12 Months

Newly ITP Persistent ITP Chronic ITP

USA

UK

Japan

Epidemiology and incidence of ITP

France Danmark

Pathogenesis of ITP

Decreased productionIncreased destruction

Humoral immunity Cell immunity

SpleenRES

Liver Desialya

tion

CTLlysis

Liver Desialya

tion

J Immunol. 2015 Jun 15;194(12):5579-5587.Br J Haematol. 2014 Apr;165(2):248-58

Loss of Immune tolerance

Dysmegakaryocytopoiesis

Differentiation

Aapoptosis

Loss of T cell tolerance

• Anergy T cell

• Tregs

• Apoptotic T cell

• Th1/Th2

T cell-mediated cytotoxicity

Dysmegakaryocytopoiesis

Desialyation

Hepatocytes

PLT PLT

Platelet desialylation

Qiu J, ASH Annual Meeting Abstracts, 2014Ni H, Nat Communication, 2015

Laboratory Diagnosis of ITP

Curr Hematol Rep. 2005 Mar;4(2):160-5. Br J Haematol. 2009 Sep;146(6):585-96. Eur J Haematol. 2011 Apr;86(4):339-46. Br J Haematol. 1998 Jun;101(3):420-4.

• Treatment not indicated

• platelet > 30×109/L

• no bleeding symptom

• no increased risk of bleeding

International ITP working group. Blood. 2009, 113(11):2386-93.

ITP therapy

• Conventional PDN

• HD-DXM

International ITP working group. Blood. 2009, 113(11):2386-93.

First-line treatment

short-term application

Conventional PDN vs HD-DXM

• One or two courses of HD-DXM demonstrated higher CR rate,

shorter time to response and less adverse events than PDN.

Wei Y, et al, Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial, 2014 ASH abstract, 1455

NCT01356511

N Engl J Med. 2007; 357(22):2237-47. Lancet. 2008;371(9610):395-403.Lancet. 2009;373(9664):641-8. N Engl J Med. 2010;363(20):1889-99.Int J Hematol. 2012;96(2):222-8. Blood. 2015;125(10):1541-7.

Second-line treatment - 1

• Rituximab

• long TTR

• high sustained response rate

Blood. 2001;98(4):952-7. Ann Intern Med. 2007;146(1):25-33.Haematologica. 2008; 93(6):930-3. Blood. 2012;119(25):5989-95.Blood. 2015;125(10):1541-7. Lancet. 2015;385(9978):1653-61.

Second-line treatment - 2

• Splenectomy

• 32% sustained response

• surgical risk

• post-splenectomy state

Blood. 2004;104(9):2623-34. Blood. 2013;121(23):4782-90.

Second-line treatment - 3

• DXM plus Rituximab

• DXM plus Eltrombopag

• rhTPO plus Rituximab

• DXM, Rituximab and Cyclosporin

Blood. 2015;125(10):1541-7.

Blood. 2010;115(14):2755-62.

David GA. ASH Annual Meeting Abstracts, 2013

Blood. 2015 May 13. Epub ahead of print

Combined therapy

Definition of response

• CR: platelet count > 100×109/L and absence of bleeding

• R: platelet count > 30×109/L and at least 2-fold increase the baseline

count and absence of bleeding

• NR: platelet count < 30×109/L or less than 2-fold increase of baseline

ITP: The Next Decade

• Restoration of immune tolerance

• Tregs/Bregs

• BAFF/BAFF-R antagonist

• MSC/Thalidomide

• MDSC

• DANA/Oseltamivir

• Anti-inflammatory macrophages/dasatinib

Thank you