Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet.

In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-up, the 3-year overall survival (OS) and cumulative incidence of second relapse were 68% and 41% in hematological relapse, 66% and 48% in molecular relapse and 90 and 11% in extramedullary relapse, respectively. After allogeneic or autologous transplantation in second CR (n=93), the 3-year OS was 80% compared with 59% without transplantation (n=55) (P=0.03). Multivariable analysis demonstrated the favorable prognostic impact of first remission duration ⩾1.5 years, achievement of mCR and allogeneic or autologous transplantation on OS of patients alive after induction (P=0.03, P=0.01, P=0.01) and on leukemia-free survival (P=0.006, P<0.0001, P=0.003), respectively.

Autologous stem-cell transplantation in diffuse large B-cell non-Hodgkin's lymphoma not achieving complete response after induction chemotherapy: the GEL/TAMO experience.

BACKGROUND: Here we evaluate the results of high-dose chemotherapy and autologous stem-cell transplantation (HDC/ASCT) in 114 patients included in the GEL/TAMO registry between January 1990 and December 1999 with diffuse large B-cell lymphoma who failed to achieve complete remission (CR) with front-line conventional chemotherapy. PATIENTS AND METHODS: Sixty-eight per cent had a partial response (PR) and 32% failed to respond to front-line therapy. At transplant, 35% were chemoresistant and 29% had two to three adjusted International Prognostic Index (a-IPI) risk factors. RESULTS: After HDC/ASCT, 57 (54%) of 105 patients evaluable for response achieved a CR, 16 (15%) a PR and 32 (30%) failed. Nine patients were not assessed for response because of early death due to toxicity. With a median follow-up of 29 months for alive patients, the survival at 5 years is 43%, with a disease-free survival for complete responders of 63%. The lethal toxicity was 8%. Multivariate analysis revealed a-IPI and chemoresistance to be predicting factors. CONCLUSIONS: Our results show that one-third of patients who do not obtain a CR to front-line chemotherapy may be cured of their disease with HDC/ASCT. However, most chemoresistant patients pretransplant failed this therapy. For this population, as well as for those who presented with adverse factors of the a-IPI, pretransplant novel therapeutic modalities need to be tested.

High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience.

BACKGROUND: T-cell immunophenotype constitutes an unfavorable prognostic factor in aggressive non-Hodgkin's lymphomas. High-dose chemotherapy with autologous stem-cell rescue (HDC/ASCT) is the best salvage therapy for patients with aggressive B-cell lymphomas. However, results with this therapy in peripheral T-cell lymphoma (PTCL) are not well defined. PATIENTS AND METHODS: From January 1990 to December 1999, 115 patients with PTCL underwent HDC/ASCT inside the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) registry. At diagnosis the median age was 41 years and 60% of patients presented with two or three risk factors from the adjusted International Prognostic Index (a-IPI). Thirty-two per cent of patients were transplanted in first complete response (CR), 62% in chemosensitive disease and 5% in refractory disease. RESULTS: Eighty-six per cent of the patients attained a CR and 5% a partial response (PR). With a median follow-up of 37 months (range 1-133), overall survival (OS), time-to-treatment failure (TTF) and disease-free survival (DFS) at 5 years was 56%, 51% and 60%, respectively; for the 37 patients transplanted in first CR, OS and DFS at 5 years were 80% and 79%, respectively. Lactase dehydrogenase (LDH), a-IPI and disease status pre-transplant were associated with outcome. CONCLUSIONS: More than half of patients with chemosensitive disease who were transplanted are expected to be alive at 5 years. We confirm the utility of the pre-transplant IPI system in predicting outcome. Salvage treatment results with HDC/ASCT in PTCL are similar to those found in corresponding aggressive B-cell lymphomas.

[Surgical risk assessment using multivariate analysis]. / Estimación del riesgo quirúrgico por medio del análisis multivariante.

INTRODUCTION: Over and above the risk of a disease itself, surgical treatment implies additional risk involving possible temporary or permanent deterioration in a patient's health. Most studies of anesthetic-surgical risk are based on mortality or serious morbidity (severe, permanent deterioration). They may therefore be of limited applicability in hospitals where such outcomes are rare due to the types of patients treated. In order to compare and classify patients as well as improve outcome in such health care settings other parameters must be evaluated. PATIENTS AND METHODS: Indicators presaging adverse situations related directly to surgery in our postoperative intensive care units involve blood transfusion and perioperative events. By applying multivariate (regression) analysis we can determine the factors that condition these unfavorable situations. RESULTS: In the setting we studied, the main determinants of unfavorable events after surgery are patient health as shown by ASA classification, duration of operation and type of surgery. CONCLUSIONS: 1) Peripheral surgery in patients in good health is very safe. 2) Easily obtained parameters can be used to obtain a fairly efficient prediction of risk. 3) Single-setting risk studies are easy to carry out and useful for providing information about a specific hospital center.

Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine.

OBJECTIVE: To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: An open randomized clinical trial. PATIENTS AND METHODS: HIV-infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment. RESULTS: The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii. CONCLUSIONS: Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

Prophylaxis against infection. Single-dose cefonicid compared with multiple-dose cefamandole.

A total of 1489 patients were included in a prospective, randomized study that compared the efficacy of a single dose of cefonicid in 474 patients (Group I) with that of three doses of cefamandole in 510 patients (Group II) and five doses of cefamandole in 505 patients (Group III), for prophylaxis against infection after an operation on bone. The operations involved the insertion of a Moore prosthesis, an Ender and Küntscher nail, a bone-plate, or another device for internal fixation. Patients who had an open fracture or a total joint replacement were not included in the study. The three groups were similar with regard to mean age, sex ratio, duration of preoperative hospitalization, underlying risk factors, and type of operation. The rates of wound infection were not significantly different in the three groups (p = 0.8) or when the rates were stratified according to the type of operation (p greater than 0.3). Staphylococcus aureus and gram-negative bacilli were the most common infecting microorganisms. The rate of mortality related to infection was similar in all three groups (p = 0.2). No adverse side-effects of drugs were encountered. A single preoperative dose of cefonicid, three doses of cefamandole, and five doses of cefamandole were equally effective prophylaxis against infection of the wound in these patients.

Immunological markers in a coexisting chronic lymphocytic leukemia and Hodgkin's disease.

A 57 year old patient in whom Hodgkin's disease (HD) and Chronic Lymphocytic Leukemia (CLL) was simultaneously diagnosed is described. The infiltration of peripheral blood and bone marrow by mature lymphocytes, with special immunological phenotype (SIg negative, mouse rosette positive and monoclonal antibodies B1+, B4+) consistent with B-CLL and histological findings of lymphnode and axillary mass biopsies were typical of HD. The immunological study of the cell suspension from the axillary mass displayed a phenotype similar to that of the peripheral blood lymphocytes. Whether HD and CLL are two processes of fortuitous association, or a single clinical entity remains to be elucidated. The immunological findings in our patient suggest a common origin for both disorders and that HD could sometimes be the result of a B cell proliferation.

Perioperative cefamandole prophylaxis against infections.

Seven hundred and seventeen patients were included in a prospective randomized double-blind trial comparing the efficacy of five doses of cefamandole (group I, 335 patients) with that of a single preoperative dose (group II, 382 patients) for prophylaxis against sepsis in patients who had an operation using either a Moore prosthesis, Ender or Küntscher nails, a bone plate, or another internal-fixation device. Patients who had an open fracture or total joint replacement were not included in the study. The two groups were similar in terms of mean age, sex ratio, duration of preoperative hospital stay, underlying risk factors, and type of surgical procedure. A wound infection developed in none of the seventy-four patients in group I and in five (6.6 per cent) of the seventy-six in group II (p = 0.03) who required a Moore prosthesis. A wound infection developed in three patients (1 per cent) in group I and in fifteen (5 per cent) in group II (p = 0.006) who required an internal fixation device other than a Moore prosthesis. Staphylococcus aureus, Staphylococcus epidermidis, and gram-negative bacilli were the most common infecting organisms. The rate of mortality was similar in both groups, while the percentage of postoperative urinary-tract infections was lower in group I (p = 0.04). No adverse side effects of the drug were encountered.

Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides.

Risk factors predisposing to auditory toxicity of aminoglycosides were analyzed from records of 187 patients enrolled in three prospective randomized trials comparing the toxicity of netilmicin, tobramycin, and amikacin. Patients were eligible if they received three or more days of therapy and at least two serial audiograms were available. The overall auditory toxicity rate was 9.6% (18 of 187). Auditory toxicity was detected in 4.4, 10.8, and 23.5% of patients given netilmicin, tobramycin, and amikacin, respectively (P = 0.05). In the univariate analysis, patients who developed auditory toxicity were significantly older (P = 0.01) and had a significantly higher (P = 0.04) percentage of trough levels of netilmicin or tobramycin above 2 mg/liter or amikacin above 5 mg/liter. In the final logistic regression model, only age was retained as independently influencing the development of auditory toxicity (P less than 0.00001). Conversely, factors that did not add significantly to the prediction of auditory toxicity were aminoglycoside serum levels, total aminoglycoside dose, duration of therapy, sex, peak temperature, presence of bacteremia, shock, liver cirrhosis, dehydration, previous otic pathology or renal failure, and development of renal toxicity. At least in certain populations, age is the most important predisposing factor for the development of auditory toxicity in patients receiving aminoglycosides.

Tobramycin and amikacin nephrotoxicity. Value of serum creatinine versus urinary concentration of beta-2-microglobulin.

108 patients who received tobramycin or amikacin could be evaluated for nephrotoxicity in a prospective randomized trial. Both groups had similar illnesses, and causative agents, concurrent drug administration, ages, sex ratios, initial serum creatinine and aminoglycoside levels and total dose and duration of therapy. Using urinary concentration of beta 2 microglobulin (beta 2m) as a marker, nephrotoxicity was detected in 13 (22.4%) of 58 patients given tobramycin and 13 (26%) of 50 given amikacin (n.s.). Using serum creatinine as a marker, nephrotoxicity was detected in 3 (5.2%) of 58 patients given tobramycin and in 7 (14%) of 50 given amikacin (n.s.). The whole group of 108 patients was used to compare the usefulness of serum creatinine levels versus urinary concentration of beta 2m. An elevation of serum creatinine was detected in 10 of 108 patients (9.3%). In 5 of these 10 patients the beta 2m remained normal, suggesting a functional renal failure. In 21 of the 108 patients (19.4%) the beta 2m increased while the serum creatinine remained normal, suggesting an aminoglycoside nephrotoxicity which would have remained undetected if only serum creatinine had been measured. In the remaining patients (77 of the 108; 71.3%) serum creatinine and urinary concentration of beta 2m both remained normal throughout the treatment. In conclusion no statistically significant differences were found between tobramycin and amikacin nephrotoxicity. Urinary beta 2m is more sensitive than serum creatinine and furthermore it allows one to differentiate aminoglycoside nephrotoxicity from functional renal failure.

Prospective randomized double-blind comparison of nephrotoxicity and auditory toxicity of tobramycin and netilmicin.

Netilmicin or tobramycin was administered to 197 patients in a prospective randomized double-blind trial. Of these patients, 140 recipients of nine or more doses of netilmicin or tobramycin could be evaluated for nephrotoxicity. Fifty-five patients were able to cooperate in the administration of serial audiograms. Nephrotoxicity of similar severity developed in 7 of 73 (9.6%) recipients of tobramycin and in 7 of 67 (10.4%) recipients of netilmicin (P greater than 0.05). Mild or slight auditory toxicity developed in 5 of 28 (17.8%) recipients of tobramycin and in 2 of 27 (7.4%) recipients of netilmicin (P greater than 0.05).

Prophylactic cefamandole in orthopaedic surgery.

Three hundred patients were included in a prospective randomized double-blind trial comparing the efficacy of cefamandole with that of a placebo for prophylaxis of sepsis in operations using Ender or Küntscher nails, bone plates, or other internal fixation devices. Patients with an open fracture, total joint replacement, or direct operation on the hip were not included in the study. Sixteen patients were excluded because the trial protocol was not followed exactly, so a total of 284 patients participated, 134 of whom were given cefamandole and 150, a placebo. The two groups were similar in terms of mean age, sex ratio, duration of preoperative hospital stay, underlying risk factors, and type of surgical procedure. A superficial wound infection developed in none of the 134 patients who were given cefamandole and in seven of those in the control group (p less than 0.05). Two deep-wound infections developed in the cefamandole-treated group and four, in the control group (p greater than 0.05). Staphylococcus aureus, Staphylococcus epidermidis, and gram-negative bacilli were the most common infecting organisms. The rates of infection-related mortality and abscopal infection were similar in both groups. No adverse side effects of the drug were encountered.

Mesenteric hyaline plasma cell lymph node hyperplasia with amyloid deposits.

Lymph node hyperplasia (mixed hyaline vascular and plasma cell type) of mesenteric localization in a young woman was accompanied by noticeable systemic manifestations--fever, highly increased sedimentation rate, anemia, and hypergammaglobulinemia--that disappeared after the tumor was removed. Perivascular deposits of amyloid material were found within the tumor and in the spleen. To our knowledge, this finding has not been previously reported. On the basis of earlier studies in the literature and other considerations, an immunologic disorder is proposed as the cause of both the general symptoms and the amyloid deposits.