Posttransplant Autoimmune Hemolytic Anemia and Other Autoimmune Cytopenias are Increased in Very Young Infants Undergoing Unrelated Donor Umbilical Cord Blood Transplantation

Abstract

Autoimmune cytopenias are a recognized complication of hematopoietic stem cell transplant (HSCT), and are considered to be a feature of chronic graft-versus-host disease (cGVHD). We report on a cohort of very young infants (≤3 months of age) receiving HSCT from unrelated donor umbilical cord blood for genetic disorders who developed posttransplant autoimmune cytopenias at an increased rate compared to older aged controls. These infants received a conditioning regimen consisting of busulfan, cyclophosphamide, and antithymocyte globulin (ATG). All infants received HLA mismatched unrelated umbilical cord blood as graft source. GVHD prophylaxis was either cyclosporine + methylprednisolone (n = 16) or cyclosporine + mycophenolate mofetil (n =3). Engraftment, acute GVHD (aGVHD) and cGVHD, survival, treatment-related mortality (TRM), and deaths were evaluated. Ten patients developed cGVHD manifesting as autoimmune cytopenias at a median 247 days posttransplant with a cumulative incidence of 44% (95% confidence interval [CI] 21%–68%) and 56% (95% CI 32%–80%) at 1 and 2 years, respectively. In 6 of 10 patients developing autoimmune cytopenias, cGVHD presented as autoimmune cytopenia de novo. The cytopenias observed included anemia (n =4), thrombocytopenia (n =1), anemia with thrombocytopenia (n =3), and pancytopenia (n =2). No graft factors were identified as being significant to development of cGVHD. All patients responded to treatment with methylprednisolone, azithioprine ± rituximab. One patient required splenectomy. We hypothesize that posttransplant immunosuppression interferes with normal immune ontogeny creating immune dysregulation and graft directed cell destruction. Alternative strategies to prevent GVHD should be considered for this unique patient population.

New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation

“…Most were organ-specific ADs such as cytopenias followed by ADs of the thyroid and a few cases of miscellaneous multisystemic AD. The diagnoses of ADs in our cohort are comparable to those after CBT reported in the literature [6][7][8][9][10][11][12] and to ADs after allogeneic HSCT. 1,14 AIHA, ITP, and, more rarely, autoimmune neutropenia have been reported after allogeneic, noncord-blood-derived SCT with an incidence of 3%-4.5% in 3 single-center studies [14][15][16] The published cases have been reviewed recently.…”

“…6 We previously identified younger age at transplantation as a risk factor for future development of an AD in patients having received autologous HSCT for an AD. 4 Therefore, younger age and diagnosis of a nonmalignant disease might both contribute to the development of ADs after HSCT.…”

“…Reports of ADs occurring after CBT are scarce and based on single case reports and small series, the largest including 10 patients. 6 The most prevalent ADs reported are AIHA, [6][7] Evans syndrome, 8 ITP, 6,9 thyroiditis, 10 and bullous dermatoses (pemphigus and pemphigoid). [11][12] This study was undertaken to characterize the nature, incidence, and risk factors for ADs developing after CBT in a large patient population.…”

Unrelated cord blood transplantation for thalassaemia: a single-institution experience of 35 patients

“…Post transplant immunosuppression might interfere with normal immune ontogeny and sequentially created immune dysregulation and graftdirected cell destruction. 22 In our studies, patients with transfusion-dependent thalassaemia received unrelated CBT after immunesuppression with CY (200 mg/kg over 4 days), and BU (14 mg/kg over 4 days) was administered in the preparatory regimen for myeloablative therapy. BU is an agent that has a good possibility of eradicating a diseased erythron, but when used alone is not likely to be sufficiently immunosuppressive to permit sustained allogeneic engraftment.…”

Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study

“…29 One toxicity deserving mention is autoimmune hemolytic anemia that occurred in 3 subjects and was severe enough to require the subjects to go off study and receive treatment with rituximab. Autoimmune hemolytic anemia after HSCT has been described both in adults and in children, 30,31 and one can hypothesize that the cause is the immune dysregulation from chronic GVHD, from the therapy for chronic GVHD, or both. Future chronic GVHD studies should be able to better separate the direct effects of the drug on the immune system from the underlying disease and its prior therapies.…”