Reduced-Intensity Conditioning Regimen in Allogeneic Haematopoietic Stem Cell Transplantation for Follicular Lymphoma and Chronic Lymphocytic Leukemia

Reduced-intensity conditioning (RIC) regimens is being increasingly used for allogeneic haematopoietic stem cell transplantation (HSCT) in recent years for follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). The lower risk of transplant related toxicity associated with RIC regimens makes allogeneic transplantation applicable to patients (pt) with haematological malignancies resistant to conventional therapy and/or in poor medical condition, while preserving the putative graft-versus-tumour effect (GVT). From May 99 to January 07, 31 recipients were studied. Twenty two pt (71%) with FL: 14pt CR2; 4pt PR; 2pt resistant relapse; 1pt graft failure; 1pt advanced disease and 9pt with CLL in PR, underwent to allogeneic HSCT from HLA-matched (31) sibling donors, after treatment with fludarabine 30 mg/m2/d iv × 5 + busulfan 4 mg/Kg/d × 2 ± anti-T lymphocyte globuline (10 mgKg/d) × 4 or fludarabine 30 mg/m2/d iv × 5 + cyclophosphamide (1g/m2/d) × 3 + alentuzumab 20mg/d × 5 (pt with graft failure). Stem cell source was unmanipulated peripheral blood progenitor cells. Median number of CD34+ cells infused: 6,0 × 10⁶/Kg (3,3–12,0). CsA 3 mg/kg/d was given from day-1 until day +90 then tapered progressively, associated with Micophenolate mofetil d0 until d+84.

Results: In 31 evaluable pt hematological recovery have a median time to neutrophils ≥0.5×10⁹/L of 13d. (3–37+) and platelets ≥20 × 10⁹/L of 11 d. (9–105+). Transfusion requirements: median: 4 RBC units and 2 platelet transfusions per pt. Median day of discharge: d.15. Hepatic veno-occlusive disease and severe mucositis did not occur. Chimerism analysis (day +28) showed donor engraftment in all pts–mixed in 5 and full in 26 (full in graft failure pt after second transplant). 36±9,2% pts developed clinical grade 2–4 aGvHD and 68,9±10,8% developed cGvHD. Four pt had relapsed/progressive disease. Non relapse mortality occurred in 3 pts with low performance status and chemotherapy resistant disease. At 3,6 years median overall survival (OS) is 85.2±6.9%. Twenty eight pts are alive with a median follow-up of 3.6 years. Progression free survival (PFS) at 3 years is 84,1±7,1 %. Aimed to induce GvT effect, one pt with progressive disease, without GvHD was assigned to receive donor lymphocyte infusions (DLI) at regular intervals achieved stable disease. These results show that RIC regimen are well tolerated, have a low risk of transplant related mortality and are able to ensure a sustained engraftment. RIC is becoming the standard approach in allogeneic HSCT for FL/CLL and the increased risk of late disease progression might be manipulated with GvT effect associated with posterior DLI.