Objective: To study the effect of alemtuzumab used in Reduced Intensity Conditioning prior to hematopoietic stem cell transplant (HSCT) on thyroid function.
Methods: This retrospective case review of 13 patients (9 male, 4 female) who underwent HSCT and had alemtuzumab based conditioning regimen. 5 patients had Acute lymphoblastic leukaemia, 3 severe a plastic anaemia, 1 acute myeloid leukaemia, 1 congenital bone marrow failure, 1 chronic granulomatous disease (GCD) 1 juvenile myelomonocytic leukaemia. Treatment age mean 7.6 years (range 117); mean age at follow up: 14.6 (Range: 818). 7 patients had Total body Irradiation (TBI) (dose 14.4 Gy), 1 had additional Cranial RT (3 Gy). The cumulative dose of alemtuzumab used was 1 mg/kg.
Results: Ten patients had TFT done post HSCT. 8 had normal thyroid function whereas 2 patients were on thyroxine replacement (25125 mg a day), antibody status unknown. None of the patient had thyrotoxicosis.1 TBI patient had papillary carcinoma, treated with surgery and RAI.
Discussion: Alemtuzumab is recombinant humanized IgG monoclonal antibody which depletes CD52+ cells used to in HSCT to reduce rate of graft versus host disease. 41% of patients with Multiple Sclerosis treated with alemtuzumab developed thyroid dysfunction with Graves (72%) being the most frequent thyroid disorder(1). In this small case review, this does not appear to be common phenomenon in patients receiving alemtuzumab before HSCT. The mechanism of alemtuzumab-induced autoimmunity has been attributed to a breakdown in self-tolerance during immune reconstitution(2) and differential lymphocyte reconstitution causing early hyper-repopulation of immature B lymphocytes(3). HCST may affect this immune reconstitution process. Or differences may be attributed to a dose effect. Thyroxine in this cohort is often started when TSH is within the normal range so diagnosis of hypothyroidism is not confirmed. We are currently looking at effect of alemtuzumab on thyroid function in a larger cohort.