Search

Acute myeloid leukemia (AML) is a heterogeneous disease increasing in frequency owing to an aging population. Decisions on intensive induction treatments, intensification and allografting rely on the ability to divide an apparently homogeneous group according to risk. A wide range of clinical, cytogenetic and molecular variables may be used to inform this task; here we examine those variables useful in assessing prognosis for a patient with non-acute promyelocitic AML focusing on core binding factor leukemia. In clinical practice, when counseling an individual patient with AML, a range of well-known clinical variables (age, performance status and tumor burden) and genetic variables (cytogenetic and gene mutation) must be considered to better define the prognostic risk.

Introduction Several studies have recently pointed out the adverse impact of KIT mutations (mutKIT) on relapse incidence (RI) and overall survival (OS) in AML pts with t(8;21). By contrast, the prognostic significance of mutKIT in pts with inv(16) remains unclear. Purpose of this study is to evaluate the prevalence and the prognostic impact of mutKIT in inv(16)(p13q22). Patients and Methods Fifty adults with inv(16) AML at diagnosis (median age 46.6 yrs, range: 17–88; M/F: 30 /20), were centrally analyzed for mutKIT in exon 2, 8, 10, 11 and 17. Mutations were detected using sequencing and other sensitive assays such as ARMS (amplification refractory mutation system) PCR for D816Y and D816H and enzymatic digestion with HINFI for D816V and with Tsp509I for N822K. Results Data showed a prevalence of KIT mutation of 34% (17/50 pts). Among the mutKIT cases, we detected mutations in exon 17 (n=12), exon 8 (n= 4) and exon 10 (n=1). There was no difference between the mutKIT vs the unmutated (KIT-) patients in the median of WBC count at presentation (WBC 13.9 x109/L, range 4.4 to 277.5 vs 19.4 x109/L, range 2.5 to 130; Mann-Whitney U test: p = 0.649). Of the 42 patients (age < 60 years) who received intensive chemotherapy, 13 resulted mutKIT upon mutational screening. Complete remission (CR) was achieved in 13/13 (100%) mutKIT vs 27/29 (93%) KIT- patients (Fisher’s exact test: p > 0.999). At a median follow-up of 26 months (range: 2–144), 9/13 (69%) mutKIT and 8/27 (29%)KIT- pts relapsed;the Kaplan-Meier plots revealed KIT mutations to be a significant factor adversely affecting RI (log-rank test: p = 0.017) but not OS (61% in mutKIT vs 75% in KIT-;log-rank test: p = 0.331). Conclusion KIT mutations are associated with a greater probability of relapse following CR, without affecting OS, in AML pts with inv(16) aged

α and β-tryptase genes cluster on the short arm of human chromosome 16 and encode lineage-associated serine proteases that are abundantly expressed in mast-cells and, in trace amounts, in basophils. Under physiologic conditions no other myeloid cells express tryptases. However, in several myeloid leukemia cell lines and in AML blasts, the level of tryptase is elevated. In an attempt at correlating the levels of tryptase with cytogenetic features and the KIT and FLT3 mutational status, we analyzed serum samples collected at diagnosis from 150 AML and 57 ALL adult patients. The total serum concentration was determined by UniCAP 100 and UniCAP Tryptase Fluorenzyme Immunoassay Kit (Pharmacia-Upjohn, Uppsala, Sweden). The median value of tryptase level in the control group (50 healthy people; mean age 35 y, range 20–50; M/F= 26/24) amounted to less than 5 ng/ml, ranging from 1 to 15 ng/ml. We detected elevated tryptase levels (more than 15 ng/ml) in 66 out of 150 AML-patients (44%) and in 1 out of 57 ALL-patients (1.75%; median value 1.2 ng/ml) (p = < 0.0005, Fisher’s exact test ). In AMLs data showed that elevated tryptase values are significantly bound to patients with t(8;21) (n = 26, p =

Introduction: Skeletal localizations is reported in approximately 10–20% of cases of advanced stage malignant lymphomas. Detection of osseous involvement can change clinical stage and consequently determine the choice of treatment. Computed tomography (CT) is considered the gold standard for lymphoma staging and evaluation of treatment response; this technique, however, has a limited sensitivity in identifying extra-nodal disease, especially skeletal localizations. Positron emission tomography (PET) using fluorine-18 (FDG) has a higher sensitivity in recognizing bone involvement and is now a well-recognized diagnostic tool, complementary to CT. Total body magnetic resonance (MR) may rapresent a useful technique for detection and better characterization of tumoral bone lesions. In this report total body MR is compared with conventional imaging procedures (CT and PET) in the evaluation of Hodgkin (HL) and non Hodgkin lymphomas (NHL) with suspected skeletal involvement. Patients and methods: In the last year, 4 patients with diagnosis of HL, and 8 patients with diffuse large B cell lymphoma, with clinical signs or radiological findings suggesting skeletal involvement, underwent total body MR in addiction to standard staging techniques (CT and PET). All patients showed at diagnosis a systemic disease with nodal involvement. Total body MR was performed with a body coil (1.5 Tesla) and images were obtained by using fast spin-echo (FSE) short time inversion recovery (STIR) and spin-echo single-shot (SE-EPI-SSH) sequences diffusion weighted. MR was performed at diagnosis in 6 cases, at restaging in 4 cases and in two cases both at the onset and after treatment, for a total of 14 examinations. MR images were compared with those obtained from conventional imaging performed at the same time. Results: At diagnosis a total of 8 MR were performed, and multifocal skeletal involvement was detected in all cases. On the contrast, CT was negative in 6/8 cases, showing a lower sensitivity (25% vs. 100%); moreover, when positive (2/8 cases), CT detected a lower number of osseous localizations. PET was performed at diagnosis in 5 patients and resulted positive in 4 cases, identifying a minor extension of osseous involvement. At restaging 6 MR were performed: in 4 cases no skeletal lesions were detected, accordingly to CT and PET results, confirming the complete remission obtained after treatment. In the remaining two patients MR was persistently positive at restaging. PET showed a concordant result in one of these two cases, but detected less sites of involvement. Discussion: These data suggest that total body MR may play a role in investigating patients affected by malignant lymphoma with suspected skeletal involvement. FSE-STIR and SE-EPI-SSH sequences diffusion weighted can accurately detect and characterize the hyper-intensity of lymphoma bone lesions. On the contrary, CT sensitivity was very low for skeletal involvement (25%); it derives that this technique alone is unable to correctly evaluate disease extension, possibly resulting in patients under-treatment. PET findings regarding skeletal involvement are often concordant with total body MR, but a lower number of bone lesions is detected in the majority of cases.

Α and β tryptase genes cluster on the short arm of human chromosome 16 and encode lineage-associated serine proteases that are abundantly expressed in mast cells and, in trace amounts, in basophils. Under physiologic conditions no other myeloid cells express tryptases. However, in several myeloid leukemia cell lines and in AML blasts, the level of tryptase is elevated. In vitro, AML blasts are capable to produce and release the α-protryptase constitutively. Recently, elevated levels of serum tryptase have been detected in certain FAB subtypes of AML, particularly in AML-M4eo. In an attempt at correlating the levels of tryptase with FAB classification and cytogenetics, we have analyzed serum samples collected at diagnosis, from 103 AML and 57 ALL patients referred to our Institution. The total serum concentration was determined by UniCAP 100 and UniCAP Tryptase Fluorenzyme Immunoassay Kit (Pharmacia-Upjohn, Uppsala, Sweden). The median value of tryptase level in the control group (50 healthy people; mean age 35 y, range 20–50; M/F= 26/24) amounted to less than 5 ng/ml. We found elevated tryptase levels (more than 15 ng/ml) in 46 out of 103 AML-patients (44.6%) and in 1 out of 57 ALL-patients (1.75%) (p = 89.3 ng/ml) (p = 0.0001), in comparison with other cytogenetic groups (diploid, n= 43; t(15;17), n=10; other, n=29). Our data suggest that elevated serum tryptase levels at diagnosis may play a role as a marker for CBF AML subtypes.