The risk of thrombosis in children with acute lymphoblastic leukemia (ALL) reportedly ranges between 1% and 37%. Epidemiologic studies have usually been hampered by small numbers, making accurate estimates of thrombosis risk in ALL patients very difficult. The aim of this study was to better estimate the frequency of this complication and to define how the disease, its treatment, and the host contribute to its occurrence. We made an attempt to combine and analyze all published data on the association between pediatric ALL and thrombosis, by using a meta-analytic method. The rate of thrombosis in 1752 children from 17 prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on several factors. Most of the events occurred during the induction phase of therapy. Lower doses of asparaginase (ASP) for long periods were associated with the highest incidence of thrombosis, as were anthracyclines and prednisone (instead of dexamethasone). The presence of central lines and of thrombophilic genetic abnormalities also appeared to be frequently associated with thrombosis. In conclusion, the overall thrombotic risk in ALL children was significant, and the subgroup analysis was able to identify high-risk individuals, a finding that will hopefully guide future prospective studies aimed at decreasing this risk. IntroductionAcute lymphoblastic leukemia (ALL) is more frequent in children than in adults; indeed, two thirds of all cases occur at pediatric age. 1 The risk of thrombosis is increased in ALL patients, 2 and its occurrence may complicate the treatment course with a negative prognostic impact. Its frequency reportedly ranges between 1.1% and 36.7%, a quite large variation related to several factors, such as different definitions of thrombosis (symptomatic vs asymptomatic), diagnostic methods for its detection, study design (prospective vs retrospective), and differences in treatment protocols. 2 The pathogenesis of this increased thrombotic risk is not fully understood, but includes a combination of variables related to the disease itself, its treatment, and the host. [3][4][5] Although many clinical and epidemiologic studies were performed in this field, the majority were either retrospective or prospective observations on small numbers of subjects. Thus, the results are contradictory and inconclusive, mainly due to lack of statistical power. However, a careful assessment of risk factors would be useful to improve the quality of treatment and to identify subgroups in which prophylactic interventions would be beneficial.The objective of the present study was to quantitatively combine and analyze the available data, by a meta-analytic approach, to obtain accurate estimates of the thrombotic risk in pediatric patients with ALL.Several subgroup analyses were carried out to control for possible biases arising from heterogeneous pieces of information and to sort out subpopulations at higher risk of thrombosis. Materials and methods Meta-analysisIn the PubMed database, all available articles were searched usin...

Hematopoiesis, the process by which the hematopoietic stem cells and progenitors differentiate into blood cells of various lineages, involves complex interactions of transcription factors that modulate the expression of downstream genes and mediate proliferation and differentiation signals. Despite the many controls that regulate hematopoiesis, mutations in the regulatory genes capable of promoting leukemogenesis may occur. The FLT3 gene encodes a tyrosine kinase receptor that plays a key role in controlling survival, proliferation and differentiation of hematopoietic cells. Mutations in this gene are critical in causing a deregulation of the delicate balance between cell proliferation and differentiation. In this review, we provide an update on the structure, synthesis and activation of the FLT3 receptor and the subsequent activation of multiple downstream signaling pathways. We also review activating FLT3 mutations that are frequently identified in acute myeloid leukemia, cause activation of more complex downstream signaling pathways and promote leukemogenesis. Finally, FLT3 has emerged as an important target for molecular therapy. We, therefore, report on some recent therapies directed against it.

PURPOSE: Primary testicular lymphoma (PTL) has poor prognosis with failures in contralateral testis, CNS, and extranodal sites. To prevent these events, we designed an international phase II trial (International Extranodal Lymphoma Study Group 10 [IELSG-10]) that addressed feasibility and activity of conventional chemoimmunotherapy associated with CNS prophylaxis and contralateral testis irradiation. The trial was conducted by the IELSG and the Italian Lymphoma Foundation. PATIENTS AND METHODS: Fifty-three patients (age 22 to 79 years) with untreated stage I or II PTL were treated with six to eight courses of rituximab added to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days (R-CHOP21); four doses of intrathecal methotrexate (IT-MTX) and radiotherapy (RT) to the contralateral testis (30 Gy) for all patients and to regional lymph nodes (30 to 36 Gy) for stage II disease. RESULTS: All patients received R-CHOP21, 50 received CNS prophylaxis, and 47 received testicular RT. With a median follow-up of 65 months, 5-year progression-free survival and overall survival rates were 74% (95% CI, 59% to 84%) and 85% (95% CI, 71% to 92%), respectively. Ten patients relapsed or progressed: two in lymph nodes, five in extranodal organs, and three in the CNS. The 5-year cumulative incidence of CNS relapse was 6% (95% CI, 0% to 12%). No contralateral testis relapses occurred. Ten patients died: lymphoma (n = 6), secondary leukemia (n = 2), heart failure (n = 1), and gastric cancer (n = 1). Grade 3 to 4 toxicities were neutropenia, 28%; infections, 4%; and neurologic, 13%. No deaths occurred as a result of toxicity. CONCLUSION: This international prospective trial shows that combined treatment with R-CHOP21, IT-MTX, and testicular RT was associated with a good outcome in patients with PTL. RT avoided contralateral testis relapses, but CNS prophylaxis deserves further investigation

We performed a multicenter study in order to validate the concept that a simple CGA can identify elderly DLBCL non-fit patients in whom curative treatment is not better then palliation and to analyse potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria.One-hundred-seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgment only were grouped according to CGA in fit (46%), unfit (16%) and frail (38%) categories. Two-yr OS was significantly better in fit than in non-fit patients (84% vs 47%; P <.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-yr OS in unfit (75% vs 44%), but not in frail patients (45% vs 39%).CGA was confirmed as very efficient in identifying elderly DLBCL patients who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients.3