Surgical resection of persistent pulmonary fungus nodules and secondary prophylaxis are effective in preventing fungal relapse in patients receiving chemotherapy or bone marrow transplantation for leukemia.

Antifungal therapy may be unable to eradicate invasive mycosis in leukemia patients. The presence of persisting pulmonary nodules owing to mycosis seems to increase the risk of fungal relapse after chemotherapy and transplant procedures. Between 1997 and 2004, 10 acute leukemia patients underwent pulmonary surgery for invasive mycosis. The median time from diagnosis of mycosis to surgery was 135 days (range 21-147). Three patients underwent emergency surgery, owing to hemoptysis. In the other seven patients with nodule/cavitation remaining after antifungal treatment, surgery (three wedge resections, four lobectomies) was scheduled before transplant. Pathologic examination confirmed two aspergillosis and three zygomycosis. The only side effect was pneumothorax in one case. Nine patients were considered cured. Six patients underwent bone marrow transplantation (three allogeneic, three autologous) with antifungal prophylaxis without relapse during the transplant procedure. In selected patients scheduled for bone marrow transplantation, surgical resection of localized pulmonary fungus nodules combined with antifungal prophylaxis seem to be an effective treatment for preventing mycotic relapse.

T-cell receptor gene rearrangement in Epstein-Barr virus infectious mononucleosis.

This report describes the case of a previously healthy young man who presented with fever, pharyngitis, cervical lymphadenopathy, lymphocytosis, and severe thrombocytopenia. Serological tests for Epstein-Barr virus were diagnostic of a primary Epstein-Barr virus infectious mononucleosis but severe thrombocytopenia aroused the suspicion of a lymphoproliferative disease. T-cell receptor gene analysis performed on peripheral and bone marrow blood revealed a T-cell receptor γ-chain rearrangement without the evidence of malignancy using standard histologic and immunophenotype studies. Signs and symptoms of the infectious disease, blood count, and T-cell receptor gene rearrangement resolved with observation without the evidence of emergence of a lymphoproliferative disease. In the contest of a suspected lymphoproliferative disease, molecular results should be integrated with all available data for an appropriate diagnosis.

Beta-2-microglobulin as a tumor marker in solid malignancies.

Beta-2-microglobulin (beta 2-MG) and CEA were measured in the sera of 186 cancer patients divided into two groups: at diagnosis (D) and at follow-up (F). Four groups of patients at diagnosis (D-I, D-II, D-III and D-IV according to TNM classification) and two at follow-up (in remission, F-RS, and in relapse, F-RP) were considered. All patients had normal serum creatinine and urea concentrations. beta 2-MG values in D-I were significantly (p less than 0.01) lower than those for D-II and D-III, while in D-IV they overlapped those of group D-I. No significant difference was observed between F-RS and F-RP patients. Patients with serum CEA concentration greater than 100 ng/ml revealed beta 2-MG values close to those of groups D-I and D-IV. In 10% of patients in stage IV or with CEA greater than 100 ng/ml beta 2-MG was lower than the mean value of the healthy population. From data beta 2-MG is probably produced by an aspecific reaction to the tumor and the decrease in advanced stages could express a decreased immunologic response. On the other hand, high serum beta 2-MG in the initial stages of the neoplasia may reflect an elevated cell turnover, while low beta 2-MG during the final stages may be due to a weak expression of the protein by highly undifferentiated cells.

Detection of malignant pleural effusions by tumor marker evaluation.

Cytologic examination and determination of tumor markers (PHI, LDH, alpha-1-glycoprotein, alpha-2-HS-glycoprotein, beta 2-microglobulin, ferritin [corrected], sialic acid, IgE, fetoprotein, CEA, beta HCG and beta 1-SP-glycoprotein) were carried out in pleural fluid samples obtained from 70 patients with suspected neoplasia. Tumor markers were also determined in sera. The protein content of all pleural effusions was greater than or equal to 3 g/dl. Patients were grouped according to diagnosis as follows: (a) 42 with neoplastic diseases (7 mesotheliomas and 19 lung, 4 ovarian, 3 breast and 8 miscellaneous cancers), (b) 22 with benign inflammations and (c) 6 with congestive effusions. Of the parameters examined, only CEA and beta-HCG [corrected] gave information that the effusion was probably malignant. Using 6 ng/ml as cut-off for CEA and 10 mIU/ml for beta HCG, the sensitivity was 57.1% and 45.2%, respectively, specificity was 92.8% for both parameters and test efficiency 0.75 and 0.69, respectively. When CEA and beta HCG were considered together sensitivity increased to 73.8% and efficiency to 0.78. CEA and/or beta HCG were positive in the pleural effusions of 19 of the 20 malignant pleural effusions, all with a negative cytologic examination, which subsequently became positive in 8. Because of their high specificity, these two parameters are a useful tool and can be routinely measured to evaluate pleural effusions of dubious origin, even if CEA and beta HCG cannot, on [corrected] their own, define the primary malignancy.

Invasive aspergillosis in haematological malignancies: clinical findings and management for intensive chemotherapy completion.

Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acute lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, eight non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteristics, to ascertain the factors that influenced the outcome from mycotic infections, and whether early diagnosis and prolonged therapy permitted completion of scheduled intensive chemotherapy and bone marrow transplantation (BMT) without fungal recurrence. The patients were divided into three diagnostic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbiology) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of proven or probable aspergillosis was 7.1%. At onset of infection 92% of patients were neutropenic (< 0.5 x 10(9)/L). The most frequent site of infection was the lung (90%); disseminated disease was present in 20 patients. Among 44 assessable patients, 12 (27%) failed to respond to early antifungal therapy and died. Thirty-two patients were cured with antifungal treatment, three of five nonneutropenic with only itraconazole, the others with amphotericin B 1 mg/Kg/day with or without itraconazole subsequently or with liposomal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 neutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined with medical treatment in two cases before scheduled BMT. After infection nine patients were submitted to BMT (six allo, one marrow unrelated donor (MUD), two auto) with Ambisome or itraconazole as secondary prophylaxis without fungal relapse (follow-up: 25-99 months). The median time from fungal infection to transplant was five months, range 3-10. Thirteen of 29 surviving patients had leukemia relapse, but only three (23%) of these showed also fungal infection recurrence. In conclusion, a high index of suspicion and careful clinical and radiological examinations are the key to identifying infected patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifungal agents seems to improve the outcome of invasive fungal disease and to permit intensive chemotherapy completion and transplant.