Long Term Outcomes of Adults Undergoing Alemtuzumab-Based Reduced Intensity Conditioning Haematopoietic Stem Cell Transplantation.
Authors: Ceesay M. Mansour , Lim ZiYi , Kenyon Michelle , Ho Aloysius Y.L. , Devereux Stephen , Schey Steve , Mijovic Aleksandar , Pagliuca Antonio , Mufti Ghulam J. 
Published: April 2020

Abstract
The use of reduced intensity conditioning regimens (RIC) has facilitated the allografting of older patients while concurrently reducing the transplant-related mortality associated with allogeneic haematopoietic stem cell transplantation. At present, there is limited data available on the longer-term efficacy and safety of RIC HSCT. We performed a retrospective study on the long term outcomes of patients with haematological malignancies who received RIC HSCT at our center over an 8 year period from Jan 1997 to Dec 2005. A total of 263 adult patients received RIC HSCT, of which 135 patients (51%) survived for 2 or more years and were analysed for long-term outcomes and complications. The median recipient age among our long term survivors at HSCT was 49 years (range: 24–66), with an M: F ratio of 1.6:1 and median follow-up of 51.8 months (range 23.9–100.3). All patients received alemtuzumab (CAMPATH 1H) based RIC regimens with cyclosporin A as post-transplant GvHD prophylaxis. 61 were sibling donor and 74 were volunteer unrelated donor (VUD) transplants. 90 patients (66%) had a myeloid malignancy (mainly AML and MDS), 35 (26%) had lymphoid malignancy and 9 (7%) had myeloma. The stem cell source was PBSC in 98(73%) and bone marrow in 37(27%) cases. Using a 2-year landmark analysis, the actuarial survival at 3 and 5 years was 96% (95% CI: 94.3–97.7) and 91.6% (95% CI: 88.6- 94.6) respectively. There were 8 deaths in the cohort. Four deaths (50%) were due to late relapses, with 4 others due to respiratory failure(1), HBV reactivation with fulminant hepatic failure(1), adenovirus infection(1), chronic GvHD with invasive pulmonary aspergillosis(1). 44 patients had prior acute GvHD (33%). 20(15%) developed chronic GvHD (13 cutaneous involvement, 1 hepatic, 2 hepatic and cutaneous, 5 bronchiolitis obliterans). 18 other patients developed GvHD post donor lymphocytes infusion (DLI). The cumulative incidence of active cGvHD at 3 years and 5 years was 8% and 4% respectively. Significant infectious complications occurred in 38 patients (28%) of which 20 had VZV reactivation most commonly involving the trigeminal nerve. A further 14 had pulmonary problems (9-recurrent chest infections, 2-pneumocystis carinii pneumonia, 2-IPA, 1-TB). Endocrine complications included hyperthyroidism (2 cases) and hypothyroidism (14 cases). In addition, there were 4 cases (8% incidence) of premature menopause and 4 cases (5% incidence) of erectile dysfunction. Secondary malignancy occurred only in 1 patient who developed squamous cell carcinoma of the skin. In addition there were 4 cases of moderate renal impairment, 2 cases of cerebral ischaemic attacks, 8 reports of immune thrombocytopenia/ autoimmune haemolytic anemia. Patients who survive beyond 2 years following alemtuzumab-based RIC HSCT have an excellent overall survival, with a low incidence of chronic GvHD. Nevertheless, late complications of HSCT are still frequent in this cohort. Our data suggests that late effect in patients following RIC HSCT is different from those seen in patients following myeloablative HSCT. Prospective studies are warranted in long-term survivors of RIC HSCT in order to guide appropriate longer-term follow-up.