engleski

Addition of yttrium-90 ibritumomab tiuxetan to beam conditioning prior to autografting does not improve outcome of chemorefractory patients with agressive B-cell NHL

Background: The outcome of patients with aggressive B-NHL failing standard front-line and salvage chemotherapy is extremely poor even after autografting. Yttrium-90 ibritumomab tiuxetan (Zevalin ®) is a radioimmunoconjugate consisting of an anti-CD20 monoclonal antibody coupled to radioactive yttrium-90. Yttrium-90 ibritumomab tiuxetan is active against B-NHL, has mainly hematological toxicity and is not cross-resistant with chemotherapy. We therefore hypothesized that the addition of yttrium-90 ibritumomab tiuxetan to conditioning might improve the outcome of autografting in these patients. Aims: We performed this trial to investigate the feasibility and efficacy of the addition of standard-dose yttrium-90 ibritumomab tiuxetan to the standard pretransplant BEAM chemotherapy conditioning regimen consisting of carmustine, etoposide, cytarabine and melfalan (Z-BEAM) in patients with chemorefractory aggressive B-NHL. Methods: Patients with diffuse large B-cell (DLBCL) and mantle-cell lymphoma (MCL) were eligible for the trial provided they have failed front-line antracycline-based chemotherapy and the last salvage regimen, were transplant-eligible and did not have bone marrow infiltration with lymphoma. Yttrium-90 ibritumomab tiuxetan was given at a dose of 14.8 MBq/kg (but not more than 1.26 GBq) on day -10. BEAM was administered between days -7 and -2 and stem cells were reinfused on day 0. Results: We identified 18 patients with chemorefractory NHL potentially eligible for the trial, 16 with DLBCL and 2 with MCL. Stem cell collection was successful in 11, all with DLBCL. In 4 out of these 11, rapidly progressive disease precluded autografting. Seven patients received Z-BEAM. Three were men and 4 women ; median age was 47 years, range 33-62. All were previously exposed to rituximab. Median number of previous treatment lines was 2, range 2-4, and median disease duration 21 months, range 15-23. Two patients died before engraftment, one due to refractory ventricular fibrillation during stem-cell reinfusion, and the other due to pneumonia caused by a multiresistant Pseudomonas strain. Time to platelet engraftment was 12-39 days (median 18) and time to granulocyte engraftment 8-18 days (median 10). One patient died after engraftment due to multiorgan failure. There were no other cases of serious non-hematological, non-infectious toxicity. None of the four patients surviving to discharge responded and all died within 5 months of transplantation due to tumor progression or complications of further treatment. The trial was stopped prematurely because of lack of efficacy and toxicity. Conclusions: In this small series of very high-risk patients with chemorefractory aggressive B-NHL the addition of yttrium-90 ibritumomab tiuxetan to BEAM conditioning prior to autografting was toxic and did not improve outcomes.

autologous hematopoietic stem cell transplantation; Ibritumomab tiuxetan; Non-Hodgkin's lymphoma

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