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Hereditary anemias (HAs) embrace a heterogeneous group of chronic disorders with a highly variable clinical picture. Within HAs, congenital dyserythropoietic anemias (CDAs) are a large group of hypo-productive anemias that result from various kinds of abnormalities during late stages of erythropoiesis. Among them, CDAI is characterized by relative reticulocytopenia, and congenital anomalies. It is caused by biallelic mutations in CDAN1 and C15orf41. Differential diagnosis, classification, and patient stratification of CDAs and related HAs are often difficult, particularly between CDAI-II and enzymatic defects, such as pyruvate kinase deficiency (PKD). The classical diagnostic workflow for these conditions includes different lines of investigation, in which genetic testing by next generation sequencing (NGS) approaches has become the frontline system. Indeed, the primary aim of this study was to analyze a large cohort of HAs patients (n=244), by our (t)-NGS RedPanel, to identify the proper molecular diagnosis despite their clinical suspicion. Indeed, only 16.3% of patients originally suspected to suffer from CDA (14/86) showed a matched genotype. Conversely, 64% of patients (72/86) initially suspected for CDA were diagnosed as other HAs, mainly PKD. In agreement with this observation, the analysis of the main erythroid markers demonstrated that PKD patients showed a dyserythropoietic component that may underlie the frequent misdiagnosis with CDAI-II. Beyond achieving a definitive diagnosis, knowing the genetic basis of these patients is valuable also for guiding treatment. Indeed, in our cohort of patients, we identified a novel case of syndromic CDA due to a novel variant in CAD gene, leading to a specific treatment with uridine supplementation. Finally, we described three cases of CDAI, identifying two novel variants in the DNA binding domain of C15orf41, Y94S and P20T, and another one in the nuclease domain of the protein, H230P. Functional characterization of the

Conventional transbronchial needle aspiration for the staging of lung cancer

BACKGROUND. The objective of the current study was to evaluate a salvage chemotherapy regimen consisting of mitoxantrone, carboplatin, cytosine arabinoside, and methylprednisolone (MiCMA) for the treatment of patients with primary refractory or recurrent non-Hodgkin lymphoma (NHL). METHODS. From September 1991 to August 2002, 94 consecutive patients ages 16-60 years who had either recurrent or refractory NHL (mainly diffuse large-cell lymphomas) were treated on the MiCMA protocol. Patients had peripheral blood stem cells collected successfully for autologous stem cell transplantation after two or three cycles of MiCMA. RESULTS. Sixty-four of 85 evaluable patients achieved a response to the MiCMA regimen: 24 patients (26%) achieved a complete response and 40 patients (44%) achieved a partial response, for a total response rate of 70%. Sixty-two patients underwent autologous stem cell transplantation. After a median follow-up of 58 months, 47 patients (55%) remained alive; among these patients, 32 were free of disease (37%). No toxic deaths related to MiCMA were observed. Three patients, died of infectious complications after transplantation. CONCLUSIONS. The current results suggested that MiCMA chemotherapy is an effective therapeutic alternative salvage regimen for patients with primary refractory or recurrent NHL. Response rates, overall survival, and freedom from disease progression were found to be associated significantly with response to MiCMA. Peripheral blood stem cell transplantation was feasible in virtually all patients, and its outcome was influenced strongly by chemosensitivity. © 2006 American Cancer Society.