Association of corticosteroids is a trigger in the development of SCNT. MRI is recommended for the early identification of the transient brain lesions in patients with a prodromal phase. The more specific distribution of the lesions in the anastomotic border zones suggests vascular injury as a contributing factor in the pathology of SNCT.
Multiple myeloma (MM) represents a plasma cell (PC) disorder, associated with an accumulation of monoclonal terminally differentiated PCs in the bone marrow (BM) and, usually, the presence of a monoclonal immunoglobulin (Ig) in the blood and ⁄ or urine (1). It accounts for approximately 1% of all malignant diseases and it is the second most commonly diagnosed hematological malignancy, with an annual incidence in Europe of 23,000 new cases (2). The incidence is higher with increasing age (the median age at diagnosis is 67 yr) and about 3% of all patients are younger than 40 yr. The recorded incidence of myeloma has been increasing in many countries, but these reported increases are in part because of increasing diagnostic accuracy (3). EpidemiologyEpidemiological studies have shown that at least onethird of MM emerges from a pre-existing monoclonal PC disorder, being monoclonal gammopathy of undetermined significance (MGUS), suggesting that two types of MM could exist: MM secondary to MGUS and primary, de novo MM. MGUS represents a condition characterized by the presence of a monoclonal spike of serum Ig without evidence of end-organ damage (4). MGUS was recently found in 1.7%, 3%, 4.6%, and 6.6% of persons between 50 and 59 yr, 60 and 69 yr, 70 and 79 yr, and older than 80 yr, respectively (5). There is a risk of progression to malignant MM at a rate of 0.6-3% per year, depending on the concentration of serum monoclonal Ig (6). This malignant transformation of MGUS to MM seems to be a multi-step transformation process in which genetic changes, BM angiogenesis, various cytokines related to myeloma bone disease, and possibly infectious agents may be involved (7). At the time of diagnosis, one cannot distinguish a patient with a stable condition from a possible evolutive one. However, different parameters are useful for predicting the likelihood of progression from MGUS to MM: the size of serum M-protein, type of M-protein (IgM or IgA have an increased risk as compared with an IgG protein), percentage of BM cells, and an abnormal serum free light chain (FLC) ratio. AbstractMultiple myeloma is a plasma cell (PC) malignancy characterized by the accumulation of monoclonal PCs in the bone marrow and the production of large amounts of a monoclonal immunoglobulin or paraprotein. In the past years, new approaches in the diagnosis and treatment were introduced aiming to identify highrisk patients who need proper anti-myeloma treatment. Intensive therapy including autologous hematopoietic stem cell transplantation and the new agents bortezomib, thalidomide, and lenalidomide have improved patients' responses. Further optimalization of the different treatment schedules in well-defined patient groups may prolong their survival. Patient stratification is currently based on patient characteristics, extent of myeloma disease, and associated cytogenetic and laboratory anomalies. More and more gene expression studies are introduced to stratify patients and to individualize therapy.
Summary:We monitored levels of C-reactive protein (CRP) in 96 consecutive adult allogeneic BMT patients (age 15-50 years) transplanted in our unit. Major transplantrelated complications (MTC) occurred in 32% of cases and included: hepatic veno-occlusive disease, pneumonitis, severe endothelial leakage syndrome and >II acute GVHD. Transplant-related mortality (TRM) before day 100 post-BMT was 13.5%. Variables included in a stepwise logistic regression model were: gender, age, disease category, donor type, T cell depletion, TBI, use of growth factors, bacteremia, mean CRP-levels >50 mg/l between days 0 and 5 (CRP day 0-5) and >100 mg/l between days 6 and 10 (CRP day 6-10) post-BMT. Only high CRP-levels (for MTC and TRM) (P < 0.001) and donor-type (for TRM) (P ؍ 0.02) were independent risk factors. The estimated probability for MTC was 73% (CRP day 6-10 >100 mg/l) vs 17% (CRP day 6-10 <100 mg/l). Using the same cut-off levels, the probabilities for TRM were 36.5% vs 1% in the identical sibling donor situation and 88% vs 12.5% in other donor-type transplants. We conclude that the degree of systemic inflammation, as reflected by CRP-levels, during the first 5-10 days after BMT identifies patients at risk of MTC and TRM. Our data may be useful in selecting patients for clinical trials involving pre-emptive antiinflammatory treatment. Bone Marrow Transplantation (2002) 30, 441-446. doi:10.1038/sj.bmt.1703672 Keywords: C-reactive protein; severe complications; transplant-related mortality; allogeneic BMT Despite improvements in supportive care, the practice of allogeneic BMT remains limited by its toxicity. Overall
Summary:Patterns of C-reactive protein (CRP) release were derived from frequent CRP measurements in a cohort of 66 consecutive patients receiving allogeneic bone marrow transplants (BMT) in our unit. Based on a retrospective study of clinical events occurring within the first 40 days after BMT, patients with major transplant-related complications (MTC+ group, n = 22) could be separated from those with fever or mild complications only (MTC− group, n = 44). Treatment-related mortality in the MTC+ group was significantly higher: 32 vs 0% (P Ͻ 0.001). Major complications included veno-occlusive liver disease (VOD), severe endothelial leakage syndrome (ELS), pneumonitis and acute GVHD ϾII. The severity of complications was reflected by the patterns of CRP release with continuously high levels preceding the maximal signs and symptoms of MTC. Univariate analysis showed that, among other variables (sex, age, disease status at transplant, ؎TBI in the conditioning regimen, ؎ use of myeloid growth factors after BMT, time to reach PN Ͼ200/mm 3 ), three factors were significantly associated with MTC: maximal levels of CRP during the post-transplant episode (CRPmax) (296.6 ؎ 91.8 vs 88.9 ؎ 55.8 mg/100 ml, P Ͻ 0.001), the use of unmanipulated graft (no T depletion) (46.9 vs 12.5%, P Ͻ 0.009) and the CRP level on the day of BMT (CRPo) (42.7 ؎ 55.4 vs 18.2 ؎ 19.5, P = 0.045). In multivariate analysis, using a stepwise logistic regression model including the same variables, CRPmax appeared to be the strongest independent variable (P Ͻ 0.001) and a reliable (94% accuracy) parameter to assess the risk of MTC. Based on this model, CRP levels of 200 and 300 mg/100 ml are associated with a risk of 48 and 94% of developing MTC, respectively. We conclude that CRP monitoring after BMT identifies patients at risk of severe transplant-related complications and mortality. Keywords: CRP levels; severe complications; transplantrelated mortality; allogeneic BMT Correspondence: Dr R Schots, Dienst Medische Oncologie en Hematologie, Laarbeeklaan 101, 1090 Brussels, Belgium Received 6 November 1997; accepted 14 February 1998 Despite substantial improvement in supportive care after allogeneic bone marrow transplantation (BMT), early treatment-related complications still account for a 10-20% mortality in cases of HLA-compatible sibling and up to 40-50% in cases of volunteer unrelated donor (VUD) BMT. 1,2Severe complications during the early post-transplant episode include infections, acute graft-versus-host disease (AGVHD), veno-occlusive liver disease (VOD), endothelial leakage syndrome (ELS) and pneumonitis. 3 C-reactive protein (CRP) is an acute phase protein produced by the liver in several inflammatory states. 4 In marrow transplant recipients, CRP levels have been reported to increase in association with bacterial infections and to a lesser extent with aGVHD. 5 The value of CRP monitoring after BMT is unclear. Therefore, we performed a retrospective analysis in a large number of BMT patients consecutively transplanted in our unit. CRP was ...
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