Review articleNew treatment options for immune-mediated hematological disorders
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
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Immune-mediated hematological disorders are associated with a significant morbidity and mortality.
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Besides conventional therapy, new treatment options including monoclonal antibodies and small molecules have become available.
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Rituximab, a humanized chimeric anti-CD20 monoclonal antibody, seems to be a promising and safe treatment option, but randomized prospective trials are needed.
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Second-generation thrombopoietic growth factors have shown very encouraging results in the treatment of ITP, and
References (75)
- et al.
Immunohematologic disorders
J Allergy Clin Immunol
(2003) - et al.
Autoimmune pathogenesis and autoimmune hemolytic anemia
Semin Hematol
(2005) - et al.
Treatment of autoimmune hemolytic anemia
Semin Hematol
(2005) - et al.
Rituximab: mechanism of action and resistance
Semin Oncol
(2002) - et al.
Treatment of childhood autoimmune haemolytic anaemia with rituximab
Lancet
(2001) - et al.
Rituximab for the treatment of refractory autoimmune hemolytic anemia in children
Blood
(2003) - et al.
Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome
Mayo Clin Proc
(2003) - et al.
Rituximab in cold agglutinin disease
Rev Med Interne
(2003) - et al.
Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients
Blood
(2004) - et al.
How I treat idiopathic thrombocytopenic purpura (ITP)
Blood
(2005)
Autoimmune thrombocytopenia
J Thromb Haemost
Treatment of immune thrombocytopenic purpura in adults
Semin Hematol
Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura
Blood
Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura
Blood
Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura
Blood
Recombinant human thrombopoietin: basic biology and evaluation of clinical studies
Blood
Thrombocytopenia caused by the development of antibodies to thrombopoietin
Blood
Thrombotic thrombocytopenic purpura: aetiology, pathophysiology and treatment
Blood Rev
A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders
Kidney Int
Structure of von Willebrand factor cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura
J Biol Chem
Rituximab therapy for refractory thrombotic thrombocytopenic purpura
Blood Cells Mol Diseases
Rituximab in patients with refractory thrombotic thrombocytopenic purpura
J Thromb Haemost
Rituximab prevents recurrence of thrombotic thrombocytopenic purpura: a case report
Blood
Autoimmune hemolytic anemia
Am J Hematol
The immune haemolytic anaemias: a century of exciting progress in understanding
Br J Haematol
Management of Evans syndrome
Br J Haematol
Rituximab-based chemotherapy for steroid-refractory autoimmune hemolytic anemia of chronic lymphocytic leukemia
Leukemia
Rituximab chimeric anti-CD20 monoclonal antibody treatment for refractory hemolytic anemia in patients with lymphoproliferative disorders
Haematologica
Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients
Leuk Lymphoma
Rituximab therapy for chronic lymphocytic leukemia-associated autoimmune hemolytic anemia
Am J Hematol
Rituximab for warm-type idiopathic autoimmune hemolytic anemia: a retrospective study of 11 adult patients
Eur J Haematol
The effect of treatment with Campath-1H in patients with autoimmune cytopenias
Br J Haematol
Immune thrombocytopenic purpura
N Engl J Med
Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children, and in pregnancy
Br J Haematol
The pathogenesis of immune thrombocytopaenic purpura
Br J Haematol
ITP in the 21st century
Hematology Am Soc Hematol Educ Program
Rituxan in the treatment of chronic idiopathic thrombocytopenia purpura (ITP)
Blood
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2010, Seminars in HematologyCitation Excerpt :We focus here on the three conditions that comprise most of the published literature: primary immune thrombocytopenia (previously referred to as idiopathic thrombocytopenic purpura or ITP), autoimmune hemolytic anemia (AIHA), and thrombotic thrombocytopenic purpura (TTP). The results in less common autoimmune hematologic diseases are reviewed in recent articles to which the reader is referred.40–42 A search of PubMed was conducted with each disease name and abbreviation combined with “rituximab” up to June 2009.
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