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01 juni 2012, Item does not contain fulltext, The most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group.

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To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT). the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: ave in resistant disease, 14 during relapse and 19 in CR2, ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six: (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P = 0.01, RR 0.78, 95% confidence interval 0.63-0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P= 0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.

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Purpose: In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients.Patients and Methods: Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m(2) plus high-dose cytarabine (HDARA-C) 2 g/m(2) every 12 hours plus dexamethasone 4 mg/m(2) every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 mu g/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both.Results: Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved ct CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34(+) cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CF-UGM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median rimes to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L.Co

The correlation between the bromodeoxiuridine (BrdU)-labelling index (LI) of plasma cells and a new proliferation marker, the Argyrophilic Nucleolar Organizer Regions (AgNORs), was investigated in 44 myeloma patients at diagnosis. A preliminary analysis was made to verify the reproducibility of the assessment of plasma cell infiltration (PC%) in bone marrow aspirates, used to collect cells for LI determination, and in bone marrow biopsies, used for AgNORs evaluation. Although an overall good correlation was observed between PC% in biopsies and aspirates (r=0.58, p=0.001), the ratio between PC% in biopsies and in aspirates ranged form 0.35 to 7.5. Only 17 patients (38.6%) were within the 0.5-1.5 range. A positive correlation between LI and AgNORs was observed in these patients (r=0.68, p=0.003), whereas the correlation was lost in patients with higher ratio between PC% in biopsies and in aspirates (r=0.08, p=0.69). The prognostic significance of AgNORs was confirmed by survival analysis, showing a reduced survival for patients with high (>4.4) AgNOR counts (14 months vs 35 months, p=0.004). The AgNORs analysis therefore allows the simultaneous evaluation of myeloma cell infiltration, degree of differentiation and kinetics of growth in bone marrow biopsies. AgNOR counts deserve to be included in the procedures for diagnosis and prognostic evaluation of myeloma patients.

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In January 1987 we started a multicenter study in order to evaluate in adult ALL patients the results of an intensive chemotherapy effected early after CR, and to compare the efficacy of allogeneic BMT vs autologous BMT vs prolonged intensive chemotherapy in the attempt to eradicate minimal residual leukemia. To September 1990 ninety-six patients entered this study; of the 87 evaluable for induction 25 were at low risk and 62 at high risk; 67 (77%) achieved CR by an induction chemotherapy including vincristine, adriamycin, cyclophosphamide, dexamethasone. Fifty-six out of 67 remitters were enrolled for the early intensification, which consisted of HDAra-C+amsacrine (or IDAra-C+mitoxantrone) followed by vincristine+adriamycin+cyclophosphamide and etoposide+Ara-C. During the early intensification an unexpectedly high number of relapses (10/56) was observed, showing that very intensive treatment with myelosuppressive agents is not useful at this point of the post-remission therapy. One patient suffered toxic death. Out of 45 patients who completed the early intensification 16 had a related well-matched donor and were selected for allogeneic BMT (performed in 11); of the remaining 29 patients, 14 were randomized for autologous BMT (performed in 9) and 15 for a second intensification. The overall DFS at 3 years is 35%. The high number of early relapses makes it difficult to draw conclusions from the comparison of the three eradication modalities. The best results, although without statistical significance, were obtained after allogeneic BMT; in high-risk patients this procedure should be effected as soon as possible after attainment of CR. Autologous BMT and prolonged intensive chemotherapy gave results similar to each other; both were sometimes followed by delayed relapses.

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