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Purpose: To assess the impact of lung dose on lethal pulmonary complications (LPCs) in a single-center group of patients with hematologic malignancies treated with total body irradiation (TBI) in the conditioning regimen for bone marrow transplantation (BMT)., Methods: The mean lung dose of 101 TBI-conditioned patients was assessed by a thorough (1 SD around 2%) in vivo transit dosimetry technique. Fractionated TBI (10 Gy, 3.33 Gy/fraction, 1 fraction/d, 0.055 Gy/min) was delivered using a lateral-opposed beam technique with shielding of the lung by the arms. The median lung dose was 9.4 Gy (1 SD 0.8 Gy, range 7.8--11.4). The LPCs included idiopathic interstitial pneumonia (IIP) and non-idiopathic IP (non-IIP)., Results: Nine LPCs were observed. LPCs were observed in 2 (3.8%) of 52 patients in the group with a lung dose < or = 9.4 Gy and in 7 (14.3%) of 49 patients in the >9.4 Gy group. The 6-month LPC risk was 3.8% and 19.2% (p = 0.05), respectively. A multivariate analysis adjusted by the following variables: type of malignancy (acute leukemia, chronic leukemia, lymphoma, myeloma), type of BMT (allogeneic, autologous), cytomegalovirus infection, graft vs. host disease, and previously administered drugs (bleomycin, cytarabine, cyclophosphamide, nitrosoureas), revealed a significant and independent association between lung dose and LPC risk (p = 0.02; relative risk = 6.7). Of the variables analyzed, BMT type (p = 0.04; relative risk = 6.6) had a risk predictive role., Conclusion: The mean lung dose is an independent predictor of LPC risk in patients treated with the 3 x 3.33-Gy low-dose-rate TBI technique. Allogeneic BMT is associated with a higher risk of LPCs.

Forty consecutive neutropenic patients with acute leukemia receiving oral ciprofloxacin (500 mg twice daily) and ketoconazole (200 mg daily) for selective intestinal decontamination were compared retrospectively with 33 comparable patients treated with polymyxin E (1,500,000 U x 3/day) and nystatin (1,000,000 U x 3/day). The incidence of febrile episodes was slightly lower in ciprofloxacin treated patients (87.5% vs 100%). No gram-negative sepsis was observed in this group compared with seven cases in patients receiving polymyxin E (p less than 0.01). Furthermore, eight patients in ciprofloxacin group (20%) had gram-positive sepsis, compared with five (15.5%) in the polymyxin E group. The incidence of documented fungal infections was similar in the two groups. Ciprofloxacin appears to be an effective agent for the prevention of gram-negative infections in granulocytopenic patients with acute leukemia, but may contribute to a shift in the type of infections in these patients towards those caused by gram-positive microorganisms, intrinsically fairly sensitive or with acquired drug resistance.

Sixteen adult patients with refractory acute non-lymphoblastic leukemia (ANLL) underwent reinduction therapy with idarubicin (12 mg/m2) i.v. on days 1-3) followed by cytosine arabinoside (120 mg/m2 every 12 h on days 4-10). Patients achieving complete remission (CR) received consolidation and early intensification courses which included idarubicin at lower dosage. CR was reached after a single course in 70% of the patients treated at first relapse, and two of the five subjects previously resistant to daunorubicin-containing regimens responded to the idarubicin protocol. The median duration of CR was 11 months. Gastrointestinal side-effects were not important; mild and reversible ECG changes were noted whereas delayed cardiac toxicity was not observed despite previous treatment with daunorubicin. These encouraging results confirm the efficacy of idarubicin in treating acute leukemia and suggest it may have a major role in the treatment of relapsed and refractory patients with ANLL.

Twelve patients affected by different types of acute leukemia received idarubicin (4-demethoxy-daunorubicin) by oral route at the total dosage of 45, 60 or 90 mg/m2 distributed over three consecutive days. Drug response was assessed by the decrease in blast cells in peripheral blood and showed some variations between the different types of leukemia. Acute myelogenous leukemia patients and those with blastic crisis of chronic myeloid leukemia appeared to be the more responsive groups; however, the lower dose schedule could explain the less satisfactory results obtained in lymphatic leukemia patients. Data suggest that idarubicin is absorbed rapidly after oral ingestion, in spite of nausea and vomiting, which appeared 3-4 h later and were easily controlled by antiemetic therapy. The purpose of fractionating the drug dosage over three consecutive days is to prolong in the blood an elevated concentration of the main idarubicin metabolite (13-dihydro-derivative), which presents in experimental models an antileukemic potency similar to the parent compound. This study confirms that idarubicin is effective in acute leukemia also by oral route. This formulation could offer some advantages for subjects who cannot tolerate parenteral chemotherapy and it could be proposed in maintenance leukemia protocols.

Multiresistant bacterial infections are a potentially life-threatening condition in acute leukaemia (AL) patients. We aimed to better define the very recent epidemiology and outcome of bloodstream infections (BSIs) in a real-life setting. We prospectively collected all consecutive febrile/infectious episodes occurring in AL patients admitted to 9 haematology units. In 293 AL patients, 433 BSIs were diagnosed. Gram-positive (GP) bacteria were isolated in 44.8 % BSI and Gram-negative (GN) in 38.3 %, while polymicrobial aetiology- or fungi-related events were identified in 15.7 and 1.1 % of the cases, respectively. GP was observed more frequently in patients not in complete remission (p = 0.04), while GN during consolidation cycles (p = 0.003). Extended spectrum β-lactamase-producing strains accounted for 23.2 % of enterobacteria. They were associated with previous antibiotic exposure, including fluoroquinolones prophylaxis (p = 0.01). Carbapenem-resistant (CR) strains occurred in 9 % of enterobacteria. Among Pseudomonas aeruginosa strains, 21.6 % were multiresistant. Overall 30-day mortality was 8.5 %. CR GN and multiresistant P. aeruginosa BSIs were independent predictors of death (p = 0.002), as well as relapsed/resistant AL (18.3 %; p = 0.0002) and the presence of pulmonary infiltrates (26.6 %; p < 0.001). Although GP still predominate over GN BSI, the percentage of antibiotic resistant GN strains is considerable in AL patients and it is associated with poor prognosis. [ABSTRACT FROM AUTHOR]

Bone marrow histology after bone marrow transplantation has rarely been studied. Here, we reviewed the pre- and post-transplant bone marrow biopsies (BMB) of 40 acute myelogenous leukemia (AML) patients autografted in our center, 28 with normal and 12 with delayed peripheral recovery. The two groups were comparable in terms of previous therapy, disease phase and the number of infused cells, and received the same conditioning regimen. In the former group, reduced bone marrow cellularity and mild reticulin abnormalities were usual histological findings; in the latter, five patients had the same pattern, but the other seven had an almost undetectable hematopoietic parenchyma and severe reticulin derangement. One of these seven patients died of reactivated hepatitis B virus infection; the others eventually achieved peripheral recovery, with none of them experiencing a relapse. Autografted AML patients are excellent subjects for histological investigations. They account for the majority of delayed engraftments, the contribution of extramedullary components to the timing of engraftment is minimal, and leukemia relapse cannot be ruled out. These results suggest that BMB is a useful investigation in the work-up of late engraftment. A high degree of reticulin derangement with an almost undetectable hematopoietic parenchyma appear to be the morphological hallmarks of late engraftment. Bone Marrow Transplantation (2000) 25, 837–841. [ABSTRACT FROM AUTHOR]