Patients with AIHA treated with AIHA-directed pharmacologic therapy (Fig. 1)
Of the 33 patients with AIHA, only 16 (48.5%) were treated with new AIHA-directed pharmacologic therapy. Patients received a median of one AIHA-directed treatment (range: 1-4). Treatments included: corticosteroids (n=13), rituximab (n=6), intravenous immunoglobulin (n=2), mycophenolate (n=2), erythropoietin (n=2), bortezomib (n=2), cyclosporine (n=1), and plasmapheresis (n=1). Variable treatment responses were seen (Table 2). Six patients required corticosteroids only, 1 patient received rituximab only, 2 patients received an erythropoietin stimulating agent only, and 7 patients received more than one AIHA-directed treatment. First-line pharmacologic treatment was most commonly corticosteroids (n=11). The most common second line treatment was rituximab (n=4).
Corticosteroid only treatment . Of the 6 patients who were treated with corticosteroids only, the median time to development of AIHA after HSCT was 5.9 months (range: 3.7-29.7 months). These patients were a median age of 0.46 years (range: 0.14-3.88 years) at time of transplant. Five of these patients had received bone marrow (BM), and 1 had received peripheral blood stem cells (PBSC). All patients in this group had an immunodeficiency diagnosis, including CD40L deficiency (n=2), severe combined immunodeficiency (n=2), Wiskott-Aldrich Syndrome (n=1), and NFKB1 deficiency (n=1). Five patients received serotherapy with anti-thymocyte globulin and 5 received myeloablative conditioning. One patient had CMV while 2 had EBV concurrently or prior to the time of AIHA after transplant. At the time of AIHA diagnosis, these patients had a median hemoglobin of 6.4 g/dl (range 4 -10 g/dL). All patients received pRBC transfusions. Five patients (83.3%) had a partial response to corticosteroids at 1 month; one patient had a complete response. One of these patients was diagnosed with EBV 1 week after being diagnosed with AIHA and received rituximab for treatment of EBV. Five patients (83.3%) were in complete remission at last follow up while 1 patient had a partial remission.
Corticosteroids and rituximab treatment . Three patients received corticosteroids followed by rituximab for treatment of AIHA. The median time to AIHA after HSCT in these patients was 6.34 months (range 4.17-6.77 months) and were a median age of 4.98 years (range 1.29-8.04 years) at the time of transplant. Median hemoglobin was 4.8 g/dL (range 4.0-6.9 g/dL). These patients all had non-malignant diagnoses and received matched unrelated donor (MURD) BM transplants with myeloablative conditioning. One month after rituximab, 2 patients had a partial response and 1 patient had a complete response. Six months after AIHA diagnosis, 1 patient was in partial remission and 2 patients were in complete remission; all were in complete remission at last follow up.
Bortezomib treatment . Two patients required third- or fourth-line treatment with bortezomib. One patient developed AIHA at 4.73 months after MURD BM transplant with reduced intensity conditioning including alemtuzumab serotherapy for X-linked lymphoproliferative disease. Hemoglobin at time of diagnosis was 4 g/dL, and the patient received 10 pRBC transfusions in the first two weeks after diagnosis and required ICU care. The patient was started initially on corticosteroids, then rituximab, followed by mycophenolate with non-response and then received bortezomib with a partial response. The patient developed iron overload the year following AIHA diagnosed by T2* MRI. At the time of last follow up, the patient was alive and in complete remission.
The other patient developed AIHA at 3.19 months post-transplant after a matched related BM transplant with myeloablative conditioning for combined immunodeficiency. This patient had a history of AIHA pre-transplant. Hemoglobin at time of AIHA diagnosis was 7.1 g/dL, and the patient received 2 pRBC transfusions in the first two weeks after diagnosis. The patient received plasmapheresis after intravenous immunoglobulin with non-response, corticosteroids with partial response, and then bortezomib with non-response. This patient also had iron overload in the year following AIHA diagnosed by T2* MRI. This patient later developed pure red cell aplasia and graft failure and died after receiving a second transplant.