|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 May 2002, Vol. 99, No. 9, pp. 3478-3479
CORRESPONDENCE
To the editor:
Mixed warm and cold autoimmune hemolytic anemia: complete
recovery after 2 courses of rituximab treatment
Mixed warm and cold autoimmune hemolytic anemia (AHIA) is
characterized by the presence in the serum of both an IgG warm
autoantibody and a cold-active IgM antibody with wide thermal
amplitude.1-2 The disease presents with severe
hemolysis, responds to steroids, but usually runs a chronic course with
intermittent exacerbations.1-2 Rituximab is a monoclonal
antibody against CD20 antigen, which has been introduced recently for
the treatment of some autoimmune disorders related to a B-cell
clone.3-5 We report here the use of rituximab to treat for
the first time a patient with mixed warm and cold AIHA who relapsed
after tapering off corticosteroids. A 68-year-old white woman was referred to the hospital
because of weakness and dyspnea. At admission, laboratory
investigations showed severe normochromic, normocytic anemia
(hemoglobin level of 6.4 g/dL and hematocrit of 16.5%), with a
reticulocyte count of 12.2%. The white blood cell count (WBC) was
4500/µL, with neutrophils, 81%; lymphocytes, 12%; and monocytes,
3%. The platelet count was 273 000/µL. Biochemical evidence of
hemolysis was supported by bilirubin level of 2.5 mg/dL, lactate
dehydrogenase (LDH) of 2140 IU/L, and haptoglobin below 7 mg/dL
(Figure 1). The direct antiglobulin test was positive for polyvalent serum (++-), complement (C3d) (++-),
and IgG (++-). Cold agglutinins of IgM type have a titer of
1:1024. Serologies for human immunodeficiency virus, hepatitis B and C
viruses, and Mycoplasma pneumoniae were negative.
Rheumatoid factor and antinuclear antibodies were undetectable. Total
body computed tomography showed neither adenomegaly nor splenomegaly. Bone marrow biopsy examination revealed erythroid hyperplasia and scant
lymphocytic infiltrates (< 5% of total cellularity). Prednisone
therapy was started at a dose of 1 mg/kg intravenously, daily.
Hemoglobin level rose to 11 g/dL, concomitantly with the improvement of
hemolytic signs. A reduction of positivity of both direct and indirect
antiglobulin tests (polyvalent serum + ; C3d
+; IgG+), as well as a reduction of
cold agglutinin titers (1:128), was observed 8 weeks after
corticosteroid therapy. Three months later, corticosteroids were
tapered to a maintenance dose of 25 mg daily. Hemolysis
subsided with the fall of hemoglobin to 7 g/dL. The direct
antiglobulin test recurred positive for polyvalent serum (+++),
complement (+++), and IgG (+++), while cold agglutinin titers again
became strongly positive (1:256). Immunophenotyping of bone marrow
cells showed that 10% of all the cells were CD20 and CD19 positive.
Rituximab was started at the dose of 375 mg/mq once weekly, for a total
of 4 doses (Figure 1). Hemoglobin value reached 13.5 g/dL just before
the third dose, although biochemical signs of hemolysis remained
substantially unaltered. One month after the first cycle of therapy, a
second course of rituximab was administered, at the same dosage
schedule. At the end of therapy, the hemolytic signs disappeared, the
direct and indirect antiglobulin tests became negative, and cold
agglutinin titers fell to 1:32 (Figure 1). Immunophenotyping of bone
marrow cells showed the absence of CD20 and CD19 B cells. The patient did not experience side effects during rituximab treatment. Actually, 7 months after the last administration of rituximab, the patient is in
complete remission and out of therapy.
View larger version (28K):
[in this window]
[in a new window]
| Figure 1.
Clinical course of the patient and response to
treatment.
Changes in hemoglobin, LDH, haptoglobin levels, and reticulocyte count
after initial rituximab therapy. Rectangle represents treatment with
corticosteroids. Black arrows represent single rituximab
infusions.
|
|
This is the first reported case of mixed warm and cold AIHA not
associated with an overt malignant lymphoproliferative disease responding to rituximab therapy. The notable finding is represented by
the complete recovery of the disease, which has been obtained by 2 courses of rituximab. To our knowledge, rituximab, often in association
with corticosteroids and/or chemotherapy, has so far shown efficacy in
only a few cases of cold agglutinin disease.6-11 A single
course of rituximab also has been used in combination with
corticosteroids for the treatment of one case of idiopathic warm
hemolytic anemia, leading only to a partial improvement of the
hemoglobin level and hemolytic signs.12 Although further studies are warranted on larger series of patients with longer follow-up, rituximab may represent a decisive therapeutic option in the
treatment of mixed warm and cold AIHA. The possibility of a second
course of rituximab also should be considered in partial responders.
Monica Morselli, Mario Luppi, Leonardo Potenza, Luca Facchini, Stefania Tonelli, Daniele Dini, Giovanna Leonardi, Amedea Donelli, Franco Narni, and Giuseppe Torelli
Correspondence: Mario Luppi, Dept of Oncology and
Hematology, Section of Hematology, University of Modena and Reggio
Emilia, Modena, Italy; e-mail: mluppi{at}unimo.it
Acknowledgments
Supported by a research grant from Associazione Italiana per la
Ricerca sul Cancro (AIRC, Milan, Italy) to M.L.
References
1.
Sokol RJ, Hewitt S, Stamps BK, et al.
Autoimmune hemolysis: an 18-year study of 865 cases referred to a regional transfusion centre.
Br Med J.
1981;282:2023-2027.
2.
Shulman IA, Branch DR, Nelson JM, Thompson JC, Saxena S, Petz LD.
Autoimmune hemolytic anemia with both cold and warm autoantibodies.
JAMA.
1985;253:1746-1748[Abstract/Free Full Text].
3.
Weide R, Heymanns J, Koppler H.
The polyneuropathy associated with Waldenström's macroglobulinaemia can be treated effectively with chemotherapy and the anti-CD20 monoclonal antibody rituximab.
Br J Haematol.
2000;109:838-841[CrossRef][Medline]
[Order article via Infotrieve].
4.
Zecca M, De Stefano P, Nobili B, Locatelli F.
Anti-CD20 monoclonal antibody for the treatment of severe, immune-mediated, pure red cell aplasia and hemolytic anemia.
Blood.
2001;97:3995-3996[Abstract/Free Full Text].
5.
Stasi R, Pagano A, Stipa E, Amadori S.
Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura.
Blood.
2001;98:952-957[Abstract/Free Full Text].
6.
Lee EJ, Kueck B.
Rituxan in the treatment of cold agglutinin disease [letter].
Blood.
1998;92:3490-3491[Free Full Text].
7.
Layios N, Van Den Neste E, Jost E, Deneys V, Scheiff JM, Ferrant A.
Remission of severe cold agglutinin disease after Rituximab therapy [letter].
Leukemia.
2001;15:187-188[CrossRef][Medline]
[Order article via Infotrieve].
8.
Bauduer F.
Rituximab: a very efficient therapy in cold agglutinins and refractory autoimmune haemolytic anemia associated with CD-20 positive, low-grade non-Hodgkin lymphoma [letter].
Br J Haematol.
2001;112:1085-1086[CrossRef][Medline]
[Order article via Infotrieve].
9.
Berentsen S, Tjonnfiord GE, Brudevold R, et al.
Favourable response to therapy with the anti-CD20 monoclonal antibody rituximab in primary chronic cold agglutinin disease.
Br J Haematol.
2001;115:79-83[CrossRef][Medline]
[Order article via Infotrieve].
10.
Zaja F, Russo D, Fuga G, et al.
Rituximab in a case of cold agglutinin disease [letter].
Br J Haematol.
2001;115:232[CrossRef][Medline]
[Order article via Infotrieve].
11.
Seipelt G, Bohme A, Koschmieder S, Hoelzer D.
Effective treatment with rituximab in a patient with prolymphocytoid transformation of B chronic lymphocytic leukaemia and Evans syndrome.
Ann Hematol.
2001;80:170-173[CrossRef][Medline]
[Order article via Infotrieve].
12.
Ahrens N, Kingreen D, Seltsam A, Salama A.
Treatment of refractory autoimmune haemolytic anaemia with anti-CD20 (Rituximab) [letter].
Br J Haematol.
2001;114:244-245[CrossRef][Medline]
[Order article via Infotrieve]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Granel, P. Rossi, F. Bernard, I. Dettori, R. Costello, A. L. Demoux, D. Bagneres, P. Lafforgue, and Y. Frances
Good outcome after rituximab treatment for a mixed warm and cold autoimmune haemolytic anaemia
BMJ Case Reports,
March 6, 2009;
2009(mar05_2):
bcr0920080857 - bcr0920080857.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Zecca, B. Nobili, U. Ramenghi, S. Perrotta, G. Amendola, P. Rosito, M. Jankovic, P. Pierani, P. De Stefano, M. R. Bonora, et al.
Rituximab for the treatment of refractory autoimmune hemolytic anemia in children
Blood,
May 15, 2003;
101(10):
3857 - 3861.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
