Autoimmune haemolytic anaemia complicating haematopoietic cell transplantation in paediatric patients: high incidence and significant mortality in unrelated donor transplants for non‐malignant diseases

Abstract

SummaryHaemolytic anaemia is a recognized complication of haematopoietic cell transplantation (HCT) and can result from alloimmune-or autoimmunederived antibodies. Unlike alloimmune haemolytic anaemia, autoimmune haemolytic anaemia (AIHA) is poorly understood, particularly in the paediatric population where only case reports have been published. Between January 1995 and July 2001, 439 consecutive allogeneic HCT were performed in paediatric patients at the University of Minnesota, 31% (n ¼ 136) from related donors (RD) and 69% (n ¼ 303) from unrelated donors (URD). Nineteen cases of AIHA were identified with documented significant haemolysis and a positive direct antiglobulin test. All cases of AIHA occurred in URD transplants, yielding a cumulative incidence of AIHA post-transplant of 6% at 1 year. Patients transplanted for non-malignant disease, particularly metabolic diseases, had a higher incidence of AIHA post-HCT when compared with patients transplanted for malignancies (RR 4AE2 95% CI 1AE2-15AE4, P ¼ 0AE01). Mortality was high in our series of 19 patients with 10 (53%) dying following the onset of AIHA, three as a direct consequence of haemolysis. Fifty per cent of deaths occurred from infection while on immunosuppressive therapy to treat haemolysis. Alternative treatment strategies were employed, with the majority of patients demonstrating disease refractory to traditional steroid therapy.

Blood Group Discrepancy-First Sign of Autoimmune Hemolytic Anemia after Hematopoietic Stem Cell Transplantation in a Child

“…Patients with nonmalignant disease have a relatively competent immune system prior to HSCT as they have not been exposed to cytotoxic or immunosuppressive therapy. It is possible that a more 'intact' immune system during the period of immune reconstitution may contribute to the higher incidence of AIHA in this patient population [5]. The presence of concurrent cold and warm autoantibodies are associated with more severe clinical course in post-HSCT patients [6].…”

“…The underlying pathogenesis of AIHA in the post-HSCT setting is poorly understood but is probably related to immune dysregulation with the majority of patients demonstrating disease refractory to traditional steroid therapy [4,5]. The profound immune dysregulation may be explained by Daikeler and Tyndall hypothesis of either the imbalance between autoreactive and regulatory lymphocyte population or the loss of self-tolerance mechanisms; the presence of genetic difference in the major or minor HLA genes between the donor and the recipient; the transfer of autoimmunity from the donor to the recipient; and as a direct effect to the conditioning regimen for the HSCT [9].…”

“…In Fig. 1 Resolution of group discrepancy patients where post-HSCT AIHA is documented, there are no standard recommendations for management that can be made as a the result of the vast clinical variability of each patient, including time of post-HSCT, development of hemolysis, presence of GvHD and the status of immunosuppressive therapy at the time of presentation, all of which will impact therapeutic choices [5]. But there are an increasing number of reports on the successful treatment of refractory AIHA with rituximab in post-HSCT settings [4,11].…”

Dramatic response to rituximab in a child with severe cold autoimmune hemolytic anemia arising after allogeneic hematopoietic SCT

“…2,3 In the largest study of pediatric patients to date, published in 2004, the incidence of all types of AIHA was 6% at 1 year after transplant. 4 The cause for this increased incidence post transplant is poorly understood, but is likely because of an incomplete reconstitution of the immune system and immune dysregulation. As has been observed in the adult HSCT patient population, 2,3 the majority of the pediatric patients are refractory to standard therapy for AIHA.…”

“…As a result, the mortality rate is high (53%) because of hemolysis and infectious complications that develop as a consequence of the immunosuppressive treatments for AIHA. 4 Autoimmune hemolytic anemia following HSCT is usually mediated by warm reactive, IgG autoantibodies. Cold reactive, IgM autoantibodies that have reactivity at 30 1C or higher can also cause clinically significant hemolysis, but this has been rarely described in the HSCT setting, with only two pediatric cases reported in the literature to our knowledge.…”