Review article
New treatment options for immune-mediated hematological disorders

https://doi.org/10.1016/j.ejim.2007.08.012Get rights and content

Abstract

In recent years, there has been a tremendous increase in the number of clinical studies with monoclonal antibodies and small molecules in the treatment of hematological malignancies. Clinical observations have shown that some of these molecules may also aid in the treatment of immune-mediated hematological disorders. Moreover, immunotherapy has become an important treatment cornerstone in other, non-hematological, auto-immune diseases. This paper reviews the current state of the use of these new molecules in the treatment of the most frequently encountered immune-mediated hematological disorders: auto-immune hemolytic anemia (AIHA), idiopathic thrombocytopenic purpura (ITP), and thrombotic thrombocytopenic purpura (TTP).

Introduction

Auto-immune hemolytic anemia (AIHA), idiopathic thrombocytopenic purpura (ITP), and thrombotic thrombocytopenic purpura (TTP) are well-defined, immune-mediated conditions with significant morbidity and mortality. Except for TTP, where therapeutic plasma exchange substantially reduces mortality rates, the optimal treatment of these disorders has not yet been established. Although several treatment options are available for these disorders, treatment-related complications remain a major concern and relapse/refractory disease is frequently encountered. Recently, responses to rituximab, a chimeric monoclonal anti-CD20 antibody, have been reported in some patients. In ITP, another promising therapeutic approach consists of thrombopoietic agents.

Section snippets

Definition and diagnosis

AIHA is an auto-immune disorder caused by the formation of auto-antibodies directed against self red blood cells (RBCs), eventually leading to extravascular and/or intravascular hemolysis. Diagnosis of AIHA requires two criteria: (a) serological evidence of a RBC antibody and (b) laboratory and/or clinical evidence of hemolysis. Serological evidence is provided by a positive direct anti-globulin test (DAT, direct Coombs' test), whereas manifestations of hemolysis include anemia with

Definition and diagnosis

ITP is characterized by reduced platelet counts due to immune-mediated platelet destruction in the mononuclear phagocytic system. As with warm AIHA, platelets are coated with IgG auto-antibodies, which are recognized by Fc receptors on macrophages and subsequently predominantly cleared in the spleen. However, antibodies are not detectable in up to 50% of the patients [19], [20].

Pathogenesis

As in AIHA and other immune-mediated disorders, the pathogenetic process underlying ITP is complex, involving

Definition

TTP is a life-threatening disease that is characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and the formation of hyaline microthrombi in different organs [51], [52].

The term TTP encompasses several conditions and etiologies. TTP is also frequently referred to as hemolytic uremic syndrome (HUS). Both diagnostic terms are based on historical and overlapping clinical descriptions. Although the distinction between these two entities remains controversial, both possess the same

Conclusion

In the past decade, the role of monoclonal antibodies and small molecules in the treatment of hematological malignancies has become well established. Apart from these indications, some of these molecules also show promising results in the treatment of hematological and non-hematological immune-mediated disorders.

Rituximab, a chimeric anti-CD20 monoclonal antibody, has proven to be efficacious in the treatment of AIHA, ITP, and TTP in several publications. Unfortunately, prospective, randomized

Learning points

  • Immune-mediated hematological disorders are associated with a significant morbidity and mortality.

  • Besides conventional therapy, new treatment options including monoclonal antibodies and small molecules have become available.

  • Rituximab, a humanized chimeric anti-CD20 monoclonal antibody, seems to be a promising and safe treatment option, but randomized prospective trials are needed.

  • Second-generation thrombopoietic growth factors have shown very encouraging results in the treatment of ITP, and

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