Gemtuzumab ozogamicin (Mylotarg) as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: final results of AML-15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell'Adulto Leukemia Groups.

The therapeutic activity and toxicity profile of gemtuzumab ozogamicin were assessed in 40 patients >60 years of age with acute myeloid leukemia (AML) who were not considered eligible for conventional chemotherapy because of advanced age or poor performance status. The drug was administered at the dose of 9 mg/m2 as a single 2-h i.v. infusion on days 1 and 15. Patients who achieved a complete remission (CR/CRp) were to receive a consolidation with two additional injections of the immunotoxin at the same dose. The overall CR/CRp rate was 17% (95% CI, 8-32%). The CR/CRp rate in patients 61-75 years old was 33% (6/18), and 5% (1/22) in patients older than 75 years. Induction death occurred in seven patients (17%), all aged above 75 years. Overall survival was significantly longer in patients aged 61-75 years than in older individuals (P=0.05), and in CD33+ cases than in CD33- cases (P=0.05). We conclude that the dose/schedule of gemtuzumab ozogamicin used in this trial is too toxic in the age group over 75 years. For these patients, additional studies with reduced doses of the immunotoxin are warranted.

Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation.

Hepatitis B virus/hepatitis C virus (HBV/HCV) positive patients undergoing haemopoietic stem cell transplantation (HSCT) are at risk of hepatitis reactivation and fatal liver failure: we have conducted a retrospective study to assess the risk in 20 Italian transplant centres. A total of 90 patients infected with HBV (n=33) or HCV (n=57) receiving allogeneic (n=36) or autologous (n=54) haemotopoietic stem cell transplant (HSCT) between 1996 and 2000 were reviewed. The biochemical profiles and outcomes of infection-related liver disease were also analysed. The risk of death at 2 years was comparable when considering type of infection (3% for HBV vs 8% for HCV, P=0.6) or type of HSCT (7% for allogeneic vs 5% for autologous HHSCT, P=0.34). Hepatitis reactivation followed by resolution was more frequent in HCV+ than in HBV+ patients receiving an allograft (100% vs 16%, P=0.004). In HBV+ cases, risk of reactivation was comparable after autologous or allogeneic transplantation (66 vs 81%, P=0.3), but liver disease was more severe and occurred earlier in the autologous group. Our results indicate that HBV and HCV infection should not be taken as an absolute contraindication for HSCT and the risk of life-threatening liver complications are similar after allogeneic or autologous transplants.

Relationship between Daunorubicin dosage delivered during induction therapy and outcome in adult acute lymphoblastic leukemia.

The long-term results of a therapeutic regimen for adult acute lymphoblastic leukemia (ALL) have been analysed with the main purpose to evaluate the impact of Daunorubicin (DNM) dosage given during the induction. The files of 86 consecutive adult ALL patients treated in our institution between 1974 and 1988 were reviewed. They received the same induction regimen based on Vincristine, DNM and Prednisone, consolidation with L-Asparaginase, central nervous system prophylaxis, and 3-year maintenance with 6-mercaptopurine and Methotrexate with periodic cycles of reinduction. We analysed the overall and disease-free survival (DFS) in relation to various prognostic factors, focusing on the dosage of DNM actually received during the induction period. Complete remission (CR) was achieved in 68 (79%) patients and the overall DFS was of 32 months (median follow-up 37 months); 22 patients (25.6%) are off-therapy and disease-free. The actual dosage of DNM received during induction turned out to be an independent DFS prognostic factor. In fact, patients who received more or less than 175 mg/sqm in induction had a median DFS of 44 and 12 months, respectively (p = 0.05). The plateau of DFS in the two groups was 44% and 21%, respectively. Similar data were found analyzing the dose-intensity (mg/sqm/week) of DNM given in induction. Our data suggest that the actual dosage of DNM given in induction plays a role in the long term DFS of adult ALL.

Ceftazidime and amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with hematological malignancies. Report of 171 consecutive episodes.

One hundred and seventy-one consecutive febrile episodes occurring in 130 neutropenic adult patients with hematological malignancies (mainly acute leukemia) were empirically treated with a combination antibiotic therapy consisting of ceftazidime (100 mg/kg/day) + amikacin (15 mg/kg/day). Of these, 161 were evaluable. In the majority of episodes (75 per cent) documented infections were identified as a cause of fever. There were 73 bacteremias (34 Gram-negative, 29 Gram-positive, 10 polymicrobial). One third of patients had pneumonia. Cure without change of the initial regimen was achieved in 45/73 (62 per cent) bacteremic episodes and in 12/13 episodes of microbiologically documented infections without bacteremia. There were 35 clinically documented infections and 26 (74 per cent) of these were cured. Of the 40 patients presenting with possible infections 26 (65 per cent) were cured. Overall, cure without modification of the initial antibiotic combination was achieved in 109/161 episodes (68 per cent). In spite of the frequent occurrence of persistent neutropenia (82 per cent), the infectious mortality was low (8.6 per cent), and often due to superinfection. The deaths due to primary infections were 6/161 (3.7 per cent). Side effects were mild and rare. In our experience ceftazidime + amikacin was an effective and safe empirical regimen for this population of hematologic patients with persistent neutropenia and severe documented infections.