[Current treatment of follicular lymphoma]. / Traitements actuels du lymphome folliculaire.

After diffuse large B-cell lymphoma, follicular lymphoma is the most frequent non-Hodgkin's lymphoma. It remains incurable, except for localized diseases. Advanced disease has to be treated only in the presence of clinical and/or biology aggressiveness. These patients should be treated by rituximab (Mab-Thera) associated to polychemotherapy comprising cyclophosphamide, vincristine and prednisone. After this therapy, the benefit of rituximab in maintenance has to be confirmed. Autologous stem cell transplantation is now reserved for young patients in first relapse. Allogenic stem cell transplantation is also an interesting option. The other therapeutic options comprise radio-immunotherapy with 90Y ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade).

Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC.

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.

MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies of 11q23.

We here report the clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data on 14 patients with a myeloid malignancy and structural aberration of chromosome band 11q23 associated with overrepresentation or amplification of the MLL gene. The number of copies of MLL varied from three (two cases) to a cluster consisting of multiple hybridization spots. Together with previous reports, available data indicate that amplification of 11q23/MLL is a recurrent genetic change in myeloid malignancy. It affects mainly elderly patients and is often associated with dysplastic bone marrow changes or with complex karyotypic aberrations, suggestive of genotoxic exposure. It is associated with a poor prognosis. In addition, FISH analysis of nine cases with additional 11q probes showed that the overrepresented chromosomal region is generally not restricted to MLL, and Southern blot analysis indicated that amplification does not involve a rearranged copy of this gene. The significance of MLL amplification and the mechanisms by which it could play a role in leukemogenesis and/or disease progression remain to be elucidated.

High-dose cytotoxic therapy with autologous bone marrow or peripheral blood progenitor cell transplantation in malignant lymphomas.

The present paper is an attempt to assess the efficiency of high-dose cytotoxic therapy followed by autologous bone marrow or peripheral progenitor cell rescue with hematopoietic growth factor support given in a group of 27 patients (16 men, 11 women) at the Department of Hematology of the Mont Godinne University Clinics, mainly in the same interval 1990-1994. The reasons for introducing such a therapy in these patients (6 with Hodgkin's disease, 14 with intermediate or high grade, aggressive non Hodgkin lymphomas and 7 with low grade follicular non Hodgkin lymphomas) were relapse of disease after conventional therapy (11 cases), resistance to initial therapy (5 patients) or because of histologically proven transformation to a more aggressive form (one case); in 10 patients with extended, poor prognosis forms, the procedure was used as part of the first line therapy. The conditioning high dose chemotherapy was given according to various regimens, most of them containing Cyclophosphamide, BCNU and Etoposide, with or without total body irradiation. In 14 patients, bone marrow (BM) graft was used, while peripheral blood progenitor cells (PBPC) were infused in the remaining 13 patients. The number of infused granulocyte-macrophage colony forming units (CFU-GM) ranged between 7,650 and 3,900,000/kg, with a mean value of 461,000/kg. The median time intervals required to reach an absolute neutrophil count > 500/microliter, a platelet count > 50,000/microliter and a hematocrit > 30% were 13 days, 20 days and 23 days respectively. Growth factors (GM-CSF and G-CSF) and PBPC use shortened the time for neutrophil recovery as well as neutropenia-related complications. No procedure-related death was observed and complete remission was achieved in 22 cases (81.4%); after a mean follow-up of 32.6 months, 14 patients (55.5%) are alive and free of disease, while in 7 patients (31% of the complete responders) relapse occurred at an average time interval of 8.2 months since the procedure.