Clinical Outcome of Stem Cell Transplantation(SCT) in Patients with T Cell Prolymphocytic Leukaemia(T-PLL) Previously Treated with Alemtuzumab: A Multicentre Experience.
Authors: Krishnan Biju , Swansbury John , Cazin Bruno , Ireland Robin , Ketterer Nicolas , Lakhani Anil , Parreira Antonio , Rassam Saad , Catovsky Daniel , Matutes Estella , Dearden Claire 
Published: April 2020

Abstract
T-PLL is a rare aggressive malignancy with poor response to conventional chemotherapy. In our previously published data on a series of mostly relapsed refractory disease patients treated with the anti CD 52 monoclonal antibody Campath -1H (alemtuzumab),60% of the patients achieved complete remission (CR) with an overall response rate of 76%. Median disease free interval (DFI) of 7 months (range 4–45 months). Therapy naive patients had higher CR rates (86%) rates than those who had received prior therapy. However, patients inevitably relapse. Consolidation with a SCT may prolong survival for patients able to undergo such procedures. We update here our experience of 16 patients, 10 males and 6 females, median age of 58 years (range 40–67 yrs), who had SCT following alemtuzumab therapy. 11 patients had an autograft and 5 patients had an allograft including 4 from sibling donors and 1 from an unrelated donor. Disease status at SCT showed 10 patients in 1st CR, 3 in 2nd CR and 2 patients in partial remission (PR). The conditioning regimen for autografts included melphalan/TBI, Cyclo/TBI and BEAM or BEAC. Of the allograft patients, 3 received full intensity Cyclo/TBI conditioning and the 2 remaining cases received reduced intensity Fludarabine/Melphalan/Campath conditioning. 7 patients remain alive with a median follow up of 60 months (24–78 months). Among the patients who underwent an autograft, 55% (6/11) remain alive. Of these, 62% had SCT in 1st CR and 33% in 2nd CR. Median disease free interval was 20 months (8–78 months). 4 out of the 5 deaths were disease related (36%). 2 of these patients showed initial PR to subsequent therapy but eventually died from progressive disease.1 patient had CNS relapse which was fatal. 1 patient relapsed with CD52 negative disease and failed further alemtuzumab therapy, dying from rapid disease progression. 1 patient died from pneumocystis pneumonia whilst her disease was in remission. In the 5 patients who had an allograft median DFI was 26 months (21 days-60 months). Only 1 patient is alive in CR at 60 months follow up. Transplant related mortality (TRM) in this series was 40 %( 2/5 pts), both receiving full intensity conditioning. 1 patient died of infection on D+21 and the other of severe graft versus host disease (GVHD). 2 patients had fulminant relapses, with one case of extramedullary bone disease and another of acute splenic rupture. We conclude that alemtuzumab therapy is able to induce remission in the majority of T-PLL patients with minimal toxicity enabling selected patients to proceed to consolidation with a SCT. Our results indicate that autograft increases the DFI, especially if performed in 1st CR. However, one third of these patients have relapsed. Allograft is an attractive option but is not often feasible in view of the older age group of patients with T-PLL. High rates of TRM were seen in patients receiving full intensity conditioning. Reduced intensity conditioning could offer better results and this need to be explored. For patients without an available donor, cord blood transplant may provide an alternative.