We report 17 cytopenic patients with myelodysplastic syndrome (MDS) of refractory anaemia (RA) subtype with hyper‐, normo‐ or hypo‐cellular bone marrow (BM), who were treated with cyclosporin A (CyA). Substantial haematological response was observed in 14 patients (82%): their anaemia improved and all transfusion‐dependent patients achieved transfusion independence. Complete trilineage recovery was observed in four patients (23%). The CyA therapy has not yet failed in any of the 14 successfully treated patients during follow‐up times ranging from 5 to 30 months. CyA was well tolerated in 14 patients; serious side‐effects required termination of the therapy in three patients in whom the blood count rapidly deteriorated to former levels upon cessation of therapy. Two patients benefited from a combination therapy of CyA and erythropoietin. Six patients experienced various autoimmune phenomena. CyA could thus offer an alternative treatment for certain MDS patients with RA regardless of hyper‐, normo‐ or hypo‐cellularity of bone marrow (BM). The mechanism of the beneficial effect of CyA is discussed and remains the subject of an ongoing study.
Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m(2) and granulocyte colony-stimulating factor (G-CSF) 10 microg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was >or=2.0x10(6) CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3x10(6) CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.
Summary:A 48-year-old male with CLL and concomitant AIHA unresponsive to chlorambucil was treated with fludarabine. The remission of CLL and improvement of the AIHA was achieved, but the patient remained steroid dependent. Therefore, high-dose chemotherapy followed by CD34-selected autologous peripheral blood stem cells transplantation was performed and this led to long-term clinical, immunophenotypic and molecular remission with disappearance of AIHA. Twenty-three months later, the CLL recurred with signs of AIHA. In this patient with AIHA, HDC and selected CD34 ؉ cells completely, though temporarily, controlled both CLL and associated immune complications. This case illustrates the potential application of this approach in the management of CLL patients with immune complications.
Summary:Increasing age has been reported to be associated with worse outcome and higher occurrence of complication after allogeneic bone marrow transplantation. We analysed a cohort of 39 patients between the ages of 45 and 57 (median 49 years) with different hematologic malignancies who had undergone BMT in our institution over the preceeding 4 years. Pretransplant conditioning consisted of Bu/CY2, GVHD prophylaxis of a combination of cyclosporine and 'short' methotrexate. At present 54% of patients remain alive (with a median follow-up 44 months), the probability of survival at 5 years is 53% (5-year DFS 78%). The 5-year survival probability in the control group of younger patients is 53% (P = 0.8003). Main causes of death were GVHD (4 patients, 10%), relapse (5 patients, 13%) and infection (6 patients, 15%). The incidence of acute GVHD grade II-IV was 51% (grade III-IV 0% patients), the incidence of chronic GVHD 49% (limited 18% and extensive 31% patients). Our results suggest that allogeneic BMT can be performed in patients above the age of 45 years with acceptable morbidity and mortality, especially if a family HLA matched donor is available. Bone Marrow Transplantation (2001) 27, 723-726.
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