ABSTRACT
Human tryptase is a serine protease expressed in mast-cells. We previously observed that AML blast cells, cultured in vitro from a KIT D816Y patient, give rise to adherent cells with mast-cell like phenotype and tryptase was released in the serum-free medium. To correlate total serum tryptase (ts-try) levels with cytogenetic features and KIT mutational status, we analyzed serum samples from AML patients at diagnosis. In 70 out of 155 patients (45%) we detected elevated ts-try (>15 ng/mL), significantly linked to t(8;21) (P < .001) and inv(16) (P = .007). In patients that achieved complete remission the ts-try decreased to normal values. In 75 patients screened for KIT mutation, we found a clear relationship between elevated ts-try and mutated patients with t(8;21) (P < .001). In conclusion, we propose that checking for ts-try at diagnosis of AML may be a simple tool to select patients to be addressed to KIT mutation screening.
Subject(s)
Biomarkers, Tumor/blood , Leukemia, Myeloid, Acute/genetics , Mutation , Proto-Oncogene Proteins c-kit/genetics , Adolescent , Adult , Aged , Culture Media, Serum-Free , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Post-transplant lymphoproliferative disorders (PTLDs) are heterogeneous severe complications occurring in 1-10% of transplanted patients. In most cases, PTLDs are associated with Epstein-Barr virus (EBV) infection but, recently, some clinical studies have reported an increasing number of EBV-negative PTLDs. Several studies have emphasized the critical role of the early identification of patients at risk for PTLD, in prompting the adoption of either pre-emptive strategies or timely treatment. To this purpose, monitoring of EBV DNA load in peripheral blood mononuclear cells is considered to be a useful test. Moreover, recently, the role of interleukin (IL)-10 in EBV-related diseases has been remarked, and high levels of IL-10 have been detected in PTLD patients. In this study, both EBV load and IL-10 were monitored in 38 PTLD patients at diagnosis and during follow-up, as well as in a control group, in order to establish the diagnostic role of the two tests, their relationship with the different PTLD subsets (EBV-positive and EBV-negative) and their behaviour during treatment. Results of our study suggest that the usefulness of IL-10 assay for early diagnosis of PTLD is similar to that of EBV load quantification, and its clinical diagnostic value is lower in EBV-negative than in EBV-positive PTLDs.
Subject(s)
Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/isolation & purification , Interleukin-10/blood , Lymphoproliferative Disorders/diagnosis , Organ Transplantation , Adult , Biomarkers/blood , DNA, Viral/blood , Follow-Up Studies , Humans , Lymphoproliferative Disorders/immunology , Lymphoproliferative Disorders/virology , Sensitivity and Specificity , Viral LoadABSTRACT
PURPOSE: To evaluate the natural history of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), identify early predictors of evolution, and assess whether associated conditions correlate with disease progression. PATIENTS AND METHODS: A total of 1,231 consecutive patients with either MGUS (n = 1,104) or SMM (n = 127) diagnosed from July 1975 to March 1998 were included in the study. Cumulative survival probability and cumulative probability of transformation into lymphoproliferative disease were calculated by means of the Kaplan-Meier estimator. Univariate and multivariate Cox models were used to identify possible predictors of malignant evolution. RESULTS: Cumulative transformation probability at 10 and 15 years was 14% and 30%, respectively. At a median follow-up of 65 months (range, 12 to 239 months), 64 MGUS cases (5.8%) evolved to multiple myeloma (MM) (n = 43), extramedullary plasmacytoma (n = 1), primary amyloidosis (n = 1), Waldenström's macroglobulinemia (n = 12), non-Hodgkin's lymphoma (n = 6), and B-chronic lymphocytic leukemia (n = 1). At a median follow-up of 72 months (range, 12 to 247 months), 25 SMMs (19.7%) evolved to overt MM. A lower evolution risk was observed in MGUS than in SMM (P <.0001). Greater than 5% marrow plasmacytosis, detectable Bence Jones proteinuria, polyclonal serum immunoglobulin reduction, and high erythrocyte sedimentation rate (ESR) were independent factors influencing MGUS transformation. SMM progression correlated with greater than 10% marrow plasma cells, detectable Bence Jones proteinuria, and immunoglobulin (Ig) A isotype. Neither concomitant diseases nor immunosuppression correlated with progression. CONCLUSION: Careful evaluation of marrow plasmacytosis, urinary paraprotein, background immunoglobulins, ESR, and paraprotein isotype might help identify at presentation patients with benign monoclonal gammopathies requiring stricter monitoring.