Extracorporeal light chain elimination: high cut-off (HCO) hemodialysis parallel to chemotherapy allows for a high proportion of renal recovery in multiple myeloma patients with dialysis-dependent acute kidney injury.

Acute kidney injury (AKI) is frequent in multiple myeloma (MM) patients and strongly affects prognosis, with particularly poor outcomes in patients requiring hemodialysis. Introduction of the novel therapeutic agents to MM therapy has improved myeloma response and renal outcome. This case series reviews the efficacy of combined systemic and extracorporeal therapy to further optimize time to light chain (serum-free light chain (sFLC)) reduction and renal recovery in MM patients with dialysis-dependent AKI (n = 19). High cut-off (HCO) hemodialysis for extracorporeal sFLC removal was initiated in parallel to chemotherapy. Combined therapy resulted in early sFLC response after a median of 13 (range 4-48) days and 6 (3-22) HCO hemodialysis sessions. Time to sFLC response was shorter in patients recovering renal function. Median time to dialysis independence was 15 (4-64) days. By intent-to-treat analysis, sustained renal recovery was achieved in 73.7% (77.8% adjusted for death) of patients. In multivariate analysis, duration of AKI prior to initiation of therapy was an independent predictor of renal functional outcome. Combining HCO hemodialysis for extracorporeal sFLC elimination and effective chemotherapy is a novel treatment strategy allowing for early and sustained sFLC reduction and a high proportion of renal recovery in these patients. Timely diagnosis and onset of therapy is essential for improving renal outcome.

Hantavirus infection: a neglected diagnosis in thrombocytopenia and fever?

Thrombocytopenia, fever, and acute renal failure are characteristic features of nephropathia epidemica, the predominant hantavirus infection in Europe. However, clinical presentation and blood cell counts may point to other disorders, such as a hematologic disease, particularly when impairment of renal function is not evident. This differential diagnosis often results in further extensive and unnecessary testing. We describe 3 patients with hantavirus infection with no renal failure, in whom a hematologic disorder was initially suspected. Serologic testing of hantavirus finally unraveled the mystery, and outcome of the patients was excellent. It is conceivable that similar cases often remain undiagnosed. Thus, testing for hantavirus should always be considered in cases of thrombocytopenia and fever of unknown origin, especially in areas endemic for the infection.

The benefit of using whole-body, low-dose, nonenhanced, multidetector computed tomography for follow-up and therapy response monitoring in patients with multiple myeloma.

BACKGROUND: The objectives of this study were to assess the status and clinical course of patients with multiple myeloma based on the direct visualization of changes in medullary, extramedullary, and focal osteolytic myeloma involvement by using whole-body, low-dose, multidetector computed tomography (WBLD-MDCT) and to compare those results with an assessment based on conventional hematologic parameters. METHODS: Between June 2002 and December 2005, WBLD-MDCT scans were obtained from 131 consecutive multiple myeloma patients with or without therapy, resulting in a total of 439 examinations. The number and size of osteolytic lesions and the number, size, and density of focal or diffuse medullary and extramedullary lesions were analyzed. Those results and the results at follow-up were related to current laboratory tests for myeloma. Validation was achieved by the combined reading of both hematologic and radiologic parameters at follow-up. RESULTS: Association between both diagnostic modalities was assessed by using European Group for Blood and Marrow Transplantation response criteria, resulting in an agreement of kappa = 0.70. Hematologic parameters proved correct in 84% of all examinations, whereas WBLD-MDCT resulted in correct assessment in 94% of all examinations. Among 91 of 439 examinations that produced discrepant findings (21%), WBLD-MDCT proved correct in 68 of 91 examinations (75%), as determined at further follow-up (95% confidence interval, 66-83%; P = .000003; sign test). The combination of WBLD-MDCT with conventional, laboratory-based follow-up resulted in significantly greater diagnostic accuracy compared with laboratory testing alone. CONCLUSIONS: The results from this study indicated that WBLD-MDCT represents a reliable, imaging-based method for the direct monitoring of the course of patients with myeloma under specific therapy, and it showed good concordance with established hematologic parameters. It is noteworthy that, in the current investigation, WBLD-MDCT proved to be even more reliable than conventional, laboratory-based follow-up.

Interferon-alpha, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a clonal disease of hematopoietic stem cells caused by a reciprocal translocation of the long arms of chromosomes 9 and 22. In human leukocyte antigen A*0201(+) (HLA-A*0201(+)) individuals, response after interferon-alpha (IFN-alpha) was shown to be associated with the emergence of CML-specific cytotoxic T cells that recognize PR-1, a myeloblastin (MBN)-derived nonapeptide. In contrast, imatinib potently induces remissions from CML by specific inhibition of the ABL tyrosine kinase. Here, we explored molecular regulations associated with CML responses under different treatment forms using cDNA-array. Expression of MBN was found to be down-regulated in remission under imatinib therapy (0 of 7 MBN(+) patients). In contrast, MBN transcription was readily detectable in the peripheral blood in 8 of 8 tested IFN-alpha patients in complete remission (P =.0002). IFN-alpha-dependent MBN transcription was confirmed in vitro by stimulation of peripheral blood mononuclear cells (PBMCs) with IFN-alpha and by IFN-alpha-mediated activation of the MBN promoter in reporter gene assays. Finally, with the use of HLA-A*0201-restricted, MBN-specific tetrameric complexes, it was demonstrated that all of 4 IFN-alpha-treated patients (100%), but only 2 of 11 imatinib patients (19%), in complete hematological or cytogenetic remission developed MBN-specific cytotoxic T cells (P =.011). Together, the induction of MBN expression by IFN-alpha, but not imatinib, may contribute to the specific ability of IFN-alpha to induce an MBN-specific T-cell response in CML patients. This also implies that the character of remissions achieved with either drug may not be equivalent and therefore a therapy modality combining IFN-alpha and imatinib may be most effective.