Abstract

Introduction

Transfusion plays a major role in the management of sickle cell disease (SCD). Delayed haemolytic transfusion reaction (DHTR) is frequent in SCD patients and may have a lethal outcome. DHTR is characterized by recurrence of clinical symptoms related to SCD with a marked haemoglobin (Hb) drop, rapid disappearance of HbA, within 5 to 15 days after transfusion. DHTR is mainly caused by a secondary immune response to an allo-antigen (Ag) on transfused RBCs, but some cases are described without significant antibodies (Abs) or detectable Abs. The increased rate of alloAbs in SCD patients is the result of blood groups polymorphisms between recipients (mainly of Afro-Caribbean’s origin) and donors (Caucasians). Inhibition of a primary or secondary immune response to blood group antigens is therefore a major goal for these patients. B cell depletion therapy with anti-CD20 is commonly used to treat auto-antibodies mediated diseases. Thus, one can speculate that rituximab could be helpful in preventing alloimmunization in SCD patients. Here, we report 8 cases of SCD patients previously allo-immunized, in whom a new transfusion was indicated, and treated with rituximab in order to prevent further immunization and DHTR.

Patients and rituximab protocol

Patients treated with rituximab were already highly immunized (high responders). All but one had a previous history of life threatening DHTR characterized by severe clinical vaso-occlusive crisis (VOC), acute chest syndrome (ACS) and/or multi organ failure (MOF) and a marked decrease of Hb compared to immediate post-transfusion level, ranging from 2 to 6 g/dl. Treatment with rituximab was given according 2 different regimens depending on the patient’s condition as follows: 1) at a fixed dose of 1,000 mg 2 weeks apart, 1 month and 2 weeks before the procedure in case of a planned surgery requiring a transfusion or 2) a single infusion of 1,000 mg in acute situations of life-threatening VOC with ACS and/or MOF. In all cases, a premedication by low dose of methyprednisolone (10 mg) was administered to limit the risk of secondary VOC. All patients were transfused with leucodepleted RBCs units with matched phenotype for the known antibodies and the most immunogenic blood groups (Rh/Kell/Duffy/Kidd/MNS).

Outcome

Following rituximab and after transfusion, 4 patients had a non eventful clinical course. Four patients presented a mild DHTR, with a drop of Hb ranging from 2 to 3 g/dl from baseline. Among them, 2 had mild clinical symptoms of intravascular hemolysis and/or exacerbation of VOC, but none of them had an ACS or a MOF, or needed new admission in intensive care unit. In all patients, the post transfusional immunological screening tests remained identical to the pre transfusion screening test without any newly detectable allo-Abs. None of the patients experienced a severe adverse event related to rituximab.

Conclusion

This retrospective analysis of 8 cases from the French referral centre for SCD suggests that rituximab may at least prevent the occurrence of newly formed antibodies in highly immunized patients and potentially minimize the risk of severe DHTR This study confirms that the mechanisms of DHTR are complex in SCD, and does not rely only on the classical conflict between red blood cell Ag and Abs. Thus, rituximab may be considered when a new transfusion seems inevitable in SCD patients with a previous history of DHTR linked to immunization.

Disclosures:

Off Label Use: administration of rituximab in a off-label setting.

Author notes

*

Asterisk with author names denotes non-ASH members.