Utilisation of Stem Cell Transplantation for Lymphoplasmacytic Lymphoma in the UK.
Authors: Gilleece Maria Helena , Pearce Rachel , Linch David C. , Wilson Marie , Towlson Keiren , Mackinnon Stephen , Potter Michael , Kamzi Majid , Gribben John G. , Marks David I. 
Published: October 2019

Lymphoplasmacytic Lymphoma (LL) is incurable by standard therapy (median survival 60m). Review of U.K. stem cell transplant (SCT) registry data 1984–2003 identified 19 cases of LL verified by histology reports. Median age at diagnosis was 49.6y (38.1–60.9). A median 3 lines of therapy (R1-7) given pre-SCT included alkylators, nucleoside analogs & rituximab. Ten patients received autologous peripheral blood stem cell transplant (APBSCT) at median time from diagnosis of 1.2y (R0.68–13.85). Disease state: Complete remission (CR) (2), partial remission (PR) (6), primary refractory (PRD) (1) & relapse (1). Median CD34+ cell dose was 2.4 (R0.7–6.5) × 106/kg. High dose therapy pre-APBSCT in 9/10 patients was mephalan (MEL) 200 mg/m2 (3); BiCNU 300 mg/m2, VP16 800 mg/m2, ARA-C mg/m2 & MEL 140 mg/m2, (BEAM) (5) or cyclophosphamide (CY) 120 mg/m2 & Total Body Irradiation (TBI) 13.2Gy (1). Neutrophil engraftment (0.5 × 109/l) occurred at a median 13.5d (R11–36) & platelet engraftment (20 × 109/l) at 12.5d (R7–33). Transplant Related Mortality (TRM) at 12 & 24m was 0 & 14% due to infection. Acute lymphoblastic leukaemia developed in 1 at 23m (15y post diagnosis of LL); death occurred three months post-induction & second APBSCT. Two patients remained in CR & 2 achieved CR post APBSCT; 3y disease progression rate (DPR) was 33% & actuarial overall survival (OS) post-ASCT was 71%. Karnofsky Performance status (KPS) is available in 7: 100% (5) & 80% (2). All 9 allograft patients received PBSC from a matched sibling (8) or unrelated (1) donor. Conditioning regimens incorporated CY 120 mg/kg + TBI (7.5/12 Gy) in 2 patients and were non-CY/TBI based in the remainder, four of which included alemtuzumab or anti-thymocyte globulin. Median age at SCT & time from diagnosis was 49y (R39.2–55.7) & 1.04y (R0.67–6.05). Disease state: PR (7) & PRD (2). Median CD34+ cell dose was 3.8 (R0.3–6.0) × 106/kg (available data in 8/9). Neutrophil engraftment occurred in 7 patients at 13d (R11–21) & platelet engraftment at 16d (R9–32) in 6 patients but 2 failed to engraft & died at d54 & d166 of infection, the latter despite a second PBSC infusion at d36. Two patients had Grade I–II acute Graft versus Host disease (aGVHD) & grade III–IV aGVHD affected 3 patients, 2 of whom died (d28 & d111). Limited chronic GVHD developed in 3 patients. TRM at d100 & 1 year post allograft was 23% & 44% & actuarial OS at 3y was 55%. CR was achieved by 3 patients post-SCT (2PRD & 1 PR pre-SCT) but 1 of these died at d111 of aGVHD. Three patients in PR pre-SCT had stable disease post-SCT but 2 then progressed, at 8.3 & 9m. Donor lymphocytes were given to 1 of these who survives at 65m post-SCT. KPS is available in 4/5 survivors:70, 80, 90 & 100%. SCT in LL salvages selected patients with refractory/multiply relapsing disease but optimal timing & allograft conditioning is uncertain. The rarity of LL requires international collaboration to design prospective studies with sufficient statistical power to benefit future patients.