Allogeneic Stem Cell Transplantation of Mantle Cell Lymphoma - Results of the Prodpective Trials OSHO #060 and OSHO #074

Mantle cell lymphoma (MCL) has a poor prognosis under conventional therapy. Allo-SCT after conventional or reduced-intensity conditioning is here a promising approach.

Two prospective trials were conducted to investigate the efficacy of chemotherapy-based conditioning followed by allo-SCT for treatment of MCL: Trial #074 was open for patients with de-novo MCL and #060 for patients requiring salvage therapy. At least a pR to (re)-induction therapy was mandatory for proceeding to allo-SCT. Conditioning consisted of treosulfan (12g/m²) and fludarabin (150mg/m²). Busulphan (16mg/kg) and cyclophosphamide (120mg/kg) was optional for younger patients. ATG was given prior to mismatched or mud SCT. Assessment of minimal residual disease was performed with real-time PCR-amplification of t(11;14) or of specific CDR3-sequences.

39 patients have been recruited into both trials (#060: n=15, #074: n=24). 31 patients are male and 8 are female with a median age of 59y (33–69). In de-novo patients the median MIPI was 5 (2–9). Salvage patients were pre-treated with 8 (6–13) cycles chemotherapy. (Re)-Induction prior to TX consisted mainly of R-CHOP or R-DHAP. 33 patients proceeded to allo-TX from mrd or mud. 2 patients died from progressive disease prior to TX, 1 patient had no suitable stem cell donor, in one case the diagnosis was revised and 2 patients were withdrawn. 26 patients (79%) were conditioned with Treo/Flu and 7 (21%) with Bu/Cy. 76% (n=25) of patients received a graft from an unrelated donor. Toxicity was moderate and incidence of acute GvHD was 51%. The median follow-up after allogeneic stem cell transplantation was 18 months with a range from 0,26 to 113,7 months. The median disease-free and median overall survivals have not been reached. Three patients have relapsed after transplantation between 5,4 and 26,7 months after transplantation. One of these suffered from blastic variant of MCL. 26 patients are alive with a median KI of 100% (range 50%-100%) after SCT with a median follow-up of 18 months (0,3–114) without differences between both trials (p=0,67). 6 patients have died from infections and cerebral bleeding (n=1) and one from infection related to an acute GvHD IV° due to DLI for relapse (blastic variant) ten months after SCT in CR of MCL. Molecular analyses showed a 2–4log reduction of circulating lymphoma cells after chemotherapy alone. Blood became negative by qPCR after allo-SCT in all 5 patients analysed so far. An intermediate increase of circulating lymphoma cells in 4 patients was successfully treated by rituximab, withdrawal of Cy-A and DLI.

Allo-SCT is a standard salvage therapy for suitable patients and an option for patients with de-novo MCL. Long-term remissions can be reached and negativity of mrd analyses by qPCR strongly supports curative potential of allo-SCT. GvL-effect has curative potential even in the case of relapsed blastic variant of MCL.

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