Abstract

There are few treatment options for pts with multiply relapsed or refractory lymphoma. Allogeneic stem cell transplantation has historically been limited in this group by high transplant-related mortality (TRM) rates, and evidence for a clinically relevant graft-versus-lymphoma (GvL) effect has been limited. We evaluated reduced-intensity transplantation (RIT) in these pts with the aim of reducing TRM while exploiting the GvL effect. Between 12/00 and 02/05, 31 pts with an HLA-identical sibling were enrolled, 18 with non-Hodgkin (NHL) and 13 with Hodgkin (HL) lymphoma. Main characteristics were: median age = 33 years (range, 17–60); male gender = 20; histology = diffuse large B cell (9), T-cell anaplastic large cell (2), transformed-large cell (2), mantle cell, lymphoplasmacytic, T-peripheral, diffuse mixed large and small cell (1 each), and Hodgkin lymphoma (13). At study entry, 19 pts (36% NHL, 92% HL) had previously failed autologous transplantation (AT) and even patients who had not received high-dose chemotherapy had failed a median of 4+ lines of therapy. Five patients were in partial remission, 2 in untreated relapse post-AT and 24 had chemorefractory disease. Conditioning consisted of fludarabine (25 mg/m2 x 5 d) and cyclophosphamide (60 mg/kg x 2 d). Twenty nine pts received peripheral blood and 2 received marrow stem cells. GVHD prophylaxis comprised cyclosporin and mini-methotrexate. Early death occurred in 3 pts from aspergillosis, pulmonary fibrosis and cardiac failure. All other patients engrafted, 1 with a progressively autologous pattern of chimerism. The overall incidende of grades II, III and IV acute GVHD was 50%, 10% and 7%, respectively. Chronic extensive GVHD occurred in 7/23 (30%) of evaluable pts. Eight pts (25%) died of progressive disease and 9 (29%) of non-relapse causes at a median of 2.5 (range, 1–12) months. Median overall and disease-free survival for all pts is 15.3 months and 7.9 months, respectively. Differences in overall and disease-free survival were not statistically significant between pts with NHL and HL (15.3 vs 25.2 months, p = 0.7; 5.9 vs 8.1, p = 0.44; respectively). Seven pts remain alive and disease-free (HL = 2/13 [15%]; NHL = 5/18 [27%]; p = 0.66) at median follow-up of 33.7 (range, 13.2 – 54.5) months. Allogeneic RIT is a reasonable therapeutic alternative for pts with relapsed NHL or HL, even those who have relapsed after AT. Mortality rates were acceptable for this heavily pretreated group of patients.

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