Rituximab in Auto-Immune Hemolytic Anemia

Inclusion Criteria:

1. Age > 18 years

2. AIHA defined at time of diagnosis by a Hgb level £ 10 g/dL, with a reticulocytes count > 120 109/L, signs of hemolysis (at least a haptoglobin level < 4 mg/L), and apositive direct antiglobulin test (DAT) ( IgG or IgG + complement pattern).

3. Disease duration equal or less than 6 weeks at time of inclusion --> removed byamendment n°4 and substituted by :First episode of AIHA to "hot" antibody previouslyuntreated or treated corticosteroids for less than 6 weeks.

4. Patients with an associated autoimmune thrombocytopenia (Evans' syndrome) will beeligible for the study if the platelet count is over 30 x 109/L at inclusion.

5. Normal level gammaglobulins in the serum (i.e. >5g/L) at inclusion.

6. Absence of detectable lymph nodes on a total body CT-scan (to be performed beforeinclusion if not performed at diagnosis).

7. Effective means of contraception during treatment and for six months after completionof treatment for all women of child bearing age

8. Negative serum pregnancy test within 14 days prior to study entry.

9. Written informed consent

Exclusion Criteria: Previous treatment with rituximab

1. AIHA diagnosed and treated more than 6 weeks prior to inclusion removed by amendmentn°4 and substituted by AIHA relapsed or newly diagnosed but treated withcorticosteroids for more than 6 weeks

2. Ongoing immunosuppressive therapy (other than corticosteroids) or previous treatmentadministered within 2 weeks prior to the beginning of the study treatment

3. Non-Hodgkin Lymphoma (NHL) other than stage A chronic lymphoid leukemia

4. Previous or concomitant malignancy other than basal cell or squamous cell carcinoma ofthe skin, carcinoma-in-situ of the cervix, or other malignancy for which the patienthad not been disease-free for at least 5 years.

5. Autoimmune disorder such as SLE with at least one extra-hematological manifestationrequiring a treatment with steroids and/or immunosuppressive drugs.

6. Any other associated cause congenital or acquired hemolytic anemia (except thalassemiatrait or heterozygous sickle cell anemia).

7. Negative DAT or DAT positive with isolated anti-C3d pattern related to the presence ofa monoclonal IgM with cold agglutinin properties.

8. Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virussurface antigen (HbsAg).

9. Neutrophils count < 1,000/mm 3 at inclusion.

10. Impaired renal function as indicated by a serum creatinine level > 2 mg/d

11. Inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/oran AST or ALT level > 2x upper limit of normal.

12. New York Heart Classification III or IV heart disease.

13. Previous history of severe psychiatric disorder or are unable to comply with study andfollow-up procedures

14. Pregnant or lactating women, or woman planning to become pregnant within 12 months ofreceiving study drug

15. Absence of written informed consent.