EBMT Prospective Non-Interventional Study On Allogeneic Hematopoietic Stem Cell Transplantation In T-Prolymphocytic Leukemia (T-PLL). Preliminary Analysis Of 43 Patients
Authors: Jedrzejczak Wieslaw Wiktor , Iacobelli Simona , Hoek Jennifer D.C. , Drozd-Sokolowska Joanna E , Potter Michael , Wulf Gerald , Chevallier Patrice , Ljungman Per T. , Koc Yener , Schetelig Johannes , de Witte Theo , Kroeger Nicolaus , Dreger Peter 
Published: October 2019

Abstract
T-PLL is very rare disease with aggressive course and poor prognosis. Our earlier retrospective study (Wiktor-Jedrzejczak et al. Leukemia 2012;26:972-6) of 41 patients with T-PLL has shown that allogeneic stem cell transplantation (allo-SCT) may provide effective disease control in some of them. However, this study (similarly to many other retrospective studies) was based on very heterogeneous material and included mainly patients with advanced disease.

Methods
Since the extreme rarity of the disease and existing regulations preclude performance of prospective randomized trial in such a situation, we proposed another approach: After a careful review process expert recommendations for the diagnosis and treatment of T-PLL by allo-SCT were prepared and published on the EBMT website in 2007. Subsequently a non-interventional study on the outcome of allogeneic transplantation was initiated and continued to recruit patients until 2012. Inclusion criteria were: T-PLL diagnosed at least by immunophenotype, age between 18 and 65 years, Karnofsky performance status ≥ 60% with adequate renal and liver function, first or second-line therapy before transplantation, life-expectancy at the time of screening of at least 3 months.

Results
This preliminary analysis covers 43 patients with T-PLL confirmed by immunophenotyping. The median age was 54 years (30 years to 63 years) and the male to female ratio was 31/12. The median time from diagnosis to transplant was 7.8 months. Twenty-six patients were in complete remission (CR), nine in partial remission, seven patients in stable or progressive disease, and one patient in unknown disease status at SCT. In line with the recommendations, 37 patients had received alemtuzumab as part of initial treatment and 6 patients did not. Donors were HLA-identical siblings in 14 patients, a matched other relative in one patient, mismatched relatives in two patients, and matched unrelated donors in 26 patients. The source of stem cells was peripheral blood in 40 patients and cord blood in 3 patients. 25 patients (58 %) received reduced intensity conditioning. In 16 patients conditioning included total body irradiation.
With a median follow-up of 49.8 months in surviving patients, 3-year RFS and OS was 38% (95% CI, 25 to 57%) and 48% (95% CI, 35 to 66%), respectively. There was a tendency for better survival for patients transplanted in CR but the difference was not significant. However, non-relapse post-transplant mortality was significantly lower in this first group of patients. Other variables evaluated including use of alemtuzumab prior transplantation, type of the donor or conditioning also did not show significant differences for this number of patients. The three-year non-relapse mortality and relapse incidence were 32% and 30%, respectively.

Conclusion
These data confirm that allo-HSCT may provide effective disease control in selected patients with T-PLL. Preliminary results of our prospective study seem to be better than earlier reports of retrospective analyses. In part this could be due to better patient selection and compliance with EBMT recommendations to offer allogeneic SCT early in the course of disease.

Disclosures:
Off Label Use: alemtuzumab, use in the pretransplantation treatment of T cell prolymphocytic leukemia.