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Bendt Nielsen

Publications and source records attributed to Bendt Nielsen.

4 recordsLinked to original sources

Autologous stem cell transplantation in multiple myeloma: outcome in patients with renal failure.

The impact of renal failure on prognosis of multiple myeloma patients treated with high-dose chemotherapy and stem cell support is incompletely studied. A total of 137 patients received high-dose chemotherapy with autologous transplantation at our centre. The patient population was divided into three groups based on their estimated creatinine clearance (Ccr); renal failure defined as Ccr < 60 mL/min: Group A: normal renal function both at diagnosis and at transplant (n = 78), Group B: renal failure at diagnosis but normal renal function at transplant (n = 30), Group C: renal failure both at diagnosis and at transplant (n = 29). There were no differences in the number of stem cells harvested, time to engraftment or response to transplantation between the groups. Ten of the patients in Group C had a normalisation of renal function post-transplant. Significantly longer hospitalisation, increased use of blood products and increased number of infections were seen in Group C compared to Groups A and B. The transplant-related mortality was 17% in Group C compared to 0% and 1% in Groups B and A respectively. Eight patients were on dialysis during transplant and four of these died within the first 100 d post-transplant. Disease response was similar in the three groups. Overall survival was significantly longer in Group A than in Groups B and C. High-dose chemotherapy with autologous transplantation is feasible in MM with renal failure. Whereas patients with moderate renal insufficiency seem to benefit from this treatment, patients in need for dialysis at the time of transplant must be carefully evaluated before proceeding to high-dose chemotherapy.

Adult↗

A narrow deletion of 7q is common to HCL, and SMZL, but not CLL.

To further characterise the genetic background of the two closely related B-lymphocytic malignancies hairy cell leukaemia (HCL), and splenic marginal zone lymphoma (SMZL) we have identified characteristic copy number imbalances by comparative genomic hybridisation (CGH). Based on these findings, areas of special interest were fine mapped, and relevant probes constructed for use in interphase-fluorescence in situ hybridisation (FISH) investigations. Thus, using the CGH data from 52 HCL and 61 SMZL patients, we identified the characteristic profiles of copy number imbalances for both diseases. These were a gain of 5q13-31 (19%) and loss of 7q22-q35 (6%) for HCL, and gain of 3q25 (28%), loss of 7q31 (16%), and gain of 12q15 (16%) for SMZL. A partial loss of 7q unusual for low-malignant B-cell diseases was found to be common to the two diseases. This loss was therefore fine mapped with BAC/PAC clones. Fine mapping revealed that in SMZL the minimal lost region covers 11.4 Mb spanning from 7q31.33 to 7q33 located between sequence tagged site (STS)-markers SHGC-3275 and D7S725. This area was distinct from the commonly deleted 7q region of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML). A FISH probe specific for the 7q region was constructed. Using this probe in an interphase-FISH investigation we showed the minimal lost 7q-region of HCL and SMZL to be one and the same. In one HCL case, this investigation furthermore showed the extent of the deleted region to be below the detection limit of CGH, whereas interphase-FISH screening of 36 chronic lymphocytic leukaemia (CLL) cases showed no deletion of the 7q area. In conclusion, we have identified characteristic profiles of copy number imbalances in HCL and SMZL and fine mapped the minimal extent of a commonly lost 7q area of special interest. We hypothesise that this region may contain (a) gene(s) important for the pathology of HCL and SMZL.

Biopsy↗

Expression levels of hsc70 and hsp60 are developmentally regulated during B-cell maturation and not associated to childhood c-ALL at presentation or relapse.

Heat shock proteins are potent regulators of apoptosis, and so they may also be involved in normal cellular differentiation and cancerogenesis. We used quantitative two-dimensional gel electrophoresis for determining whether either the constitutive chaperonic heat shock cognate protein 70 (hsc70) or heat shock protein 60 (hsp60) contribute to B-cell differentiation and leukemogenesis. We compared the expression of these hsps in normal peripheral blood (PB) CD19+ B-cells, in pediatric bone marrow (BM) CD19+ CD10+ B-cell precursors (BCPs) from normal donors, and in BCPs from common acute lymphoblastic leukemia (c-ALL) patients at diagnosis and at relapse. We found that the mean levels of hsc70 in c-ALL BCPs at initial presentation and at relapse failed to differ significantly. Likewise, they failed to differ significantly from the level in high-expressing normal BM BCPs or from that in low-expressing PB B-cells. Mean levels of hsp60 expression in c-ALL BCPs at initial presentation and at relapse were similar and not distinguishable from that in normal BM BCPs, however, elevated (by a factor of 2-3) compared with that in PB B-cells. Hsc70 and Hsp60 expressions were increased (by a factor of 2 of mean levels) in populations of normal BM BCPs as compared with populations of PB B-cells. Thus, no abnormal levels of hsc70 and hsp60 were detectable in populations of pediatric c-ALL BCPs neither at diagnosis nor at relapse. In contrast, our data were in support of developmentally regulated levels of hsc70 and hsp60 expression during B-cell ontogenesis.

B-Lymphocytes↗