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The frequency and prognostic relevance of translocations t(11;14) and t(4;14), the most common translocations involving the immunoglobulin heavy chain (IgH) gene in multiple myeloma (MM), were investigated in 128 patients treated with intensive chemotherapy and autologous stem cell transplant. Myeloma cells were identified by cytoplasmic light chain immunofluorescence combined with fluorescence in situ hybridization (cIg-FISH) for detection of translocations t(11;14) and t(4;14). Overall, t(11;14) was detected in 16 of 125 (12·8%) and t(4;14) in 15 of 120 (12·5%) patients. Progression-free and overall survivals were similar for patients with or without t(11;14). However, patients with t(4;14) had significantly shorter progression-free (median 9·9 months vs. 25·8 months; P = 0·0003) and overall survivals (median 18·3 months vs. 48·1 months; P < 0·0001) than patients without t(4;14). The t(4;14) was associated with IgA and t(11;14) with light chain MM. There was no association between the t(11;14) or t(4;14) and other biological parameters including age, gender, haemoglobin, β-2 microglobulin, C-reactive protein, calcium, creatinine, albumin, or the percentage of bone marrow plasma cells. Multivariate analysis identified t(4;14) as the only adverse prognostic factor for both progression-free survival and overall survival. Our results indicate that the t(4;14) detected by cIg-FISH is associated with a poor prognosis in MM patients receiving intensive chemotherapy and autotransplant. [ABSTRACT FROM AUTHOR]

Both single and tandem cycles of high dose therapy and autologous peripheral blood stem cell transplantation (ASCT) have been shown to improve survival in multiple myeloma (MM) patients. We report outcomes in 104 MM patients undergoing a single transplant after conditioning with a conventional myeloablative regimen, busulphan and cyclophosphamide. The patients were either in a first (71%), or subsequent remission (29%). Peripheral blood stem cells were mobilized using cyclophosphamide and granulocyte colony stimulating factor. The conditioning regimen consisted of busulphan 0·85 mg/kg given orally every 6 h (16 doses) and cyclophosphamide 60 mg/kg/d given intravenously for 2 d. The entire conditioning, transplant and post-transplant course were in the outpatient setting for 45% patients. At a median follow-up of 26 months (range 2–98 months), the median overall and progression-free survival were 57 months [95% confidence interval (CI) 47–68] and 26 months (95% CI 20–32) respectively. Younger age and higher CD34+ cell dose infused were independently predictive of improved overall and progression-free survival. Busulphan and cyclophosphamide is an effective and well-tolerated preparative regimen for ASCT that can be given to MM patients in the outpatient setting. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are potent antigen-presenting cells that can induce effective tumour-specific T-cell responses. This study investigated leucapheresis products as source of DC precursors in 48 patients undergoing autologous peripheral blood stem cell (PBSC) transplantation for haematological malignancies. Strikingly, high-dose cytarabine and etoposide plus granulocyte colony stimulating factor (G-CSF) mobilized PBSC harvests from acute myeloid leukaemia (AML) patients containing the highest number of myeloid linnegCD11cpos DC (mean: 7·04 × 106/kg, range: 1·46–19·67) which was 18·1-fold higher than in non-AML patients mobilized using chemotherapy (CT) regimens plus G-CSF. Clonality of purified linnegCD11cpos DC from CT plus G-CSF mobilized AML patients ( n = 8 ) was assessed using the human androgen-receptor locus methylation, disclosing a polyclonal pattern in five female patients. These cells displayed morphological and phenotypic features of myeloid DC precursors with expression of HLA-DR, HLA-ABC, CD86, CCR5 and CD54 molecules but lacking CD80, CD83, CD1a and CD40 antigens. Short-term culture with autologous leukaemic cell lysates plus tumour necrosis factor- α yielded maturated myeloid DC capable of triggering interleukin-2 and interferon- γ production by autologous T-lymphocytes. These findings suggest that the use of post-remission CT and G-CSF as mobilizing regimen in AML patients generates PBSC containing high doses of polyclonal myeloid linnegCD11cpos DC precursors, which could be used to design feasible immunotherapy protocols. [ABSTRACT FROM AUTHOR]

The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60–64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population-based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta-2-microglobulin and age <60 years vs. 60–64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0·001) and 60–64 years (median 50 months vs. 27 months; P = 0·001). We conclude that in a population-based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60–64 years but with less superiority than in younger patients. [ABSTRACT FROM AUTHOR]