Does donor-recipient ABO incompatibility protect against relapse after allogeneic bone marrow transplantation in first remission acute myeloid leukemia?

It is not known if donor-recipient ABO blood group incompatibility contributes to graft-versus-leukemia after allogeneic BMT. One hundred and nineteen patients with acute myeloid leukemia in first remission underwent non-T cell-depleted marrow allografts from HLA-identical siblings after TBI and cyclophosphamide (n = 72) or melphalan (n = 47). GVHD prophylaxis comprised cyclosporine alone or cyclosporine-methotrexate. Twenty-two patients relapsed at 3-46 months (median 7): 18 of 76 patients with ABO-matched donors and four of 43 patients with ABO-mismatched donors (actuarial 5-year probabilities 33 +/- 6% vs 12 +/- 6%; P = 0.028). The incidence of acute and chronic GVHD was not affected by ABO mismatch. The following factors were studied in Cox analysis for effect on outcome: gender, age, FAB subtype, ABO mismatch, CR-transplant interval, conditioning, TBI dose, nucleated cell dose, lymphocyte recovery, acute GVHD, and chronic GVHD. Donor-recipient ABO match was the only factor independently associated with a higher risk of relapse (RR = 3.7; 95% Cl, 1.1-12.6; P = 0.04). ABO mismatch was also associated with superior overall and disease-free survivals. We conclude that ABO incompatibility may influence relapse rates and survival favorably after allogeneic BMT. It is not known if this holds true for allogeneic blood stem cell transplants.     

The extent of perfusion-F18-fluorodeoxyglucose positron emission tomography mismatch determines mortality in medically treated patients with chronic ischemic left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to assess the determinants of mortality in a large group of patients with ischemic cardiomyopathy who are treated medically and the impact of the extent of viable tissue on prognosis. BACKGROUND: Whether the presence of viability drives mortality in patients with ischemic cardiomyopathy who are treated medically and whether the extent of viability is important are issues that are currently unclear. METHODS: Two hundred sixty-one patients with ischemic cardiomyopathy underwent positron emission tomography (PET) for assessment of viability. Prospective follow-up was obtained. RESULTS: Ninety-four patients were revascularized and 167 were not. The cardiac death rate was significantly less in the revascularized patients as compared with medically treated patients (13% vs. 24%, p < 0.05). In the revascularized patients, there was a trend toward better survival in patients with viable myocardium as compared with nonviable myocardium (3.5-year survival, 85% and 75% respectively, p = NS). In the medically treated group, age (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.2 to 3.7), presence of left bundle branch block (HR 3.4, 95% CI 1.6 to 7.2) and extent of perfusion-metabolism mismatch on PET (HR 1.36, 95% CI 1.1 to 1.6) predicted cardiac death during a median follow-up period of 2.1 years. The risk of cardiac death was not significantly increased when the extent of mismatch was < or =20% (HR 0.97, 95% CI 0.46 to 2.05) but was significantly increased when the extent of mismatch was >20% (HR 3.21, 95% CI 1.38 to 7.49). CONCLUSIONS: Medically treated patients with ischemic cardiomyopathy and large areas of viable myocardium on PET are at high risk for cardiac death.     

Chronic bronchitis in an elderly population

BACKGROUND: in order to describe the prevalence and prognostic implications of chronic bronchitis in individuals 65 years or older we analysed data from The Copenhagen City Heart Study. METHODS: the population was studied in 1976-1978 resurveyed in 1981-1983 and 1991-1994 and followed with regard to survival for up to 12 years. Approximately 3,700 elderly participants with a mean age of 76 years were available for analyses. RESULTS: the prevalence of chronic bronchitis was 13.0% in women and 18.6% in men. Multiple logistic regression yielded the following predictors for chronic bronchitis: male gender (odds ratio with 95% confidence interval = 1.1 (0.9-1.3)), previous smoking odds ratio = 1.7 (1.2-2.2), present smoking odds ratio = 2.1 (2.1-3.8), previous exposure to dusts and fumes (odds ratio = 2.2 (1.7-2.7)), chest infections in childhood (odds ratio = 2.1 (1.6-2.9)), more than 6 chest infections in previous 10 years (odds ratio = 6.2 (4.1-9.2)) and alcohol consumption of more than 3 drinks a day (odds ratio = 1.8 (1.3-2.3)). Chronic bronchitis was a significant predictor of both subsequent respiratory infections and survival. After adjustment for age, smoking and lung function, a Cox regression showed that chronic bronchitis was significantly related to mortality from all causes with a hazard ratio with 95% confidence interval = 1.3 (1.1-1.4), all benign respiratory diseases (hazard ratio = 2.0 (1.6-2.7)), obstructive lung disease (hazard ratio = 2.5 (1.7-3.6)) and lung cancer (hazard ratio = 2.0 (1.4-2.9)). CONCLUSIONS: in an elderly population, chronic bronchitis is a prevalent condition with important prognostic implications.     

Donor T-lymphocyte infusion for unrelated allogeneic bone marrow transplantation with CD3+ T-cell-depleted graft

In T-cell-depleted allogeneic bone marrow transplantation (TCD-BMT) using unrelated donors, the role of donor lymphocyte infusion (DLI) for survival and disease control has not been defined. In a study of 116 patients (92 matched, 24 mismatched) who received CD3+ T-cell-depleted marrow graft, sequential infusions of escalated doses of donor T lymphocytes up to 1 x 10(6) CD3+ cells/kg were prospectively investigated. T cells were administered while patients were on cyclosporine, provided >or=grade II acute graft-versus-host-disease (GVHD) had not occurred. Acute GVHD of >or=grade II occurred in 27 of 110 (25%) patients before DLI and in 39 of 79 (49%) patients after DLI. In total, 12 of 27 (44%) patients without DLI and 44 of 72 (61%) patients who received DLI developed chronic GVHD. A total of 19 patients died of GVHD, with 17 of acute and two of chronic GVHD. Overall survival (OS) and event-free survival (EFS) at 5 years were 27 and 21%, respectively. The 2-year incidence of relapse was 14%. In multivariate analysis, only chronic GVHD was a good prognostic factor for both OS: hazard ratio (HR) 1.4, P=0.04, and EFS: HR 1.6, P=0.01. Both acute and chronic GVHD were favorable prognostic factors for relapse probability: HR 1.9 for both, P=0.02, 0.01, respectively. The 1-year cumulative incidence of transplant-related mortality (TRM), excluding cases of GVHD, was 42%. The two most common causes of 1-year non-GVHD death were viral infection (9%) and idiopathic pneumonia syndrome (12%). Although the incidence of relapse was low, the study suggests that the current scheme of DLI in unrelated TCD-BMT would not improve survival unless TRM decreases significantly.     

Allogeneic bone marrow transplantation for leukemia with marrow grafts depleted of lymphocytes by counterflow centrifugation

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI) with a low (4.1 +/- 0.3 cGy/min) or high (13.1 +/- 1.6 cGy/min) midline average dose rate. In 43 patients, cytosine-arabinoside or anthracyclines were added to the conditioning regimen. Immunoprophylaxis posttransplant consisted of methotrexate (MTX) alone, cyclosporine A (CsA) in combination with MTX, or CsA alone; two patients received no immunoprophylaxis at all. Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) greater than or equal to grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. Only three patients died of cytomegalovirus-interstitial pneumonitis. The projected 3-year probability of relapse was 30% (95% confidence interval [CI], range 8% to 53%) in transplants for AML in first complete remission (CR1), 35% (95% CI, 1% to 69%) after transplantation for ALL in CR1, and 38% (95% CI, 2% to 74%) after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% (95% CI, 35% to 77%) after transplantation for AML-CR1, 42% (95% CI, 16% to 69%) in patients transplanted for ALL-CR1, and 49% (95% CI, 18% to 80%) after transplantation for CML-CP1. After transplantation for AML-CR1, ALL-CR1, or CML-CP1, the median follow-up time for leukemia-free survivors was 31+, 30+, and 21+ months, respectively. Probabilities of relapse, survival, and LFS in AML-CR1 and ALL-CR1 transplants were comparable with those reported in recipients of untreated grafts. In patients transplanted for CML-CP1, probability of relapse was higher and probability of LFS was lower than in recipients of untreated grafts. In transplants for leukemia in CR1 and CP1, preparative regimen and immunoprophylaxis posttransplant were not associated significantly with the probability of acute GVHD greater than or equal to grade 2, extensive chronic GVHD, relapse, survival, or LFS. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD.(ABSTRACT TRUNCATED AT 400 WORDS)     

Administration of cyclosporine for 24 months compared with 6 months for prevention of chronic graft-versus-host disease: a prospective randomized clinical trial.

This study compared the incidence of clinical extensive chronic graft-versus-host disease (GVHD), transplantation-related mortality, survival, and relapse-free survival among recipients randomly assigned to receive a 24-month or a 6-month course of cyclosporine prophylaxis after transplantation of allogeneic marrow from an HLA-identical sibling or alternative donor. Patients who did not have clinical manifestations of chronic GVHD on day 80 after transplantation were eligible for the study if they previously had acute GVHD or if a skin biopsy showed histologic evidence of chronic GVHD. Clinical extensive chronic GVHD developed in 35 of the 89 patients (39%) in the 24-month group and 37 of the 73 patients (51%) in the 6-month group. The hazard of developing chronic GVHD was not significantly different in the 2 groups (hazard ratio = 0.76; 95% confidence interval, 0.48-1.21; P =.25). In addition, there were no significant differences between the 2 groups in transplantation-related mortality, survival, or disease-free survival.     

Predictors of ten-year event-free survival in patients with acute myocardial infarction (from the Adria, Bassano, Conegliano, and Padova Hospitals [ABC] study on myocardial infarction)

The long-term event-free survival (EFS) after acute myocardial infarction (AMI) is largely uninvestigated. We analyzed noninvasive clinical variables in association with long-term EFS after AMI. The present prospective study included 504 consecutive patients with AMI at 3 hospitals from 1995 to 1998 (Adria, Bassano, Conegliano, and Padova Hospitals [ABC] study). Thirty-seven variables were examined, including demographics, cardiovascular risk factors, in-hospital characteristics, and blood components. The end point was 10-year EFS. Logistic and Cox regression models were used to identify the predictive factors. We compared 3 predictive models according to the goodness of fit and C-statistic analyses. At enrollment, the median age was 67 years (interquartile range 58 to 75), 29% were women, 38% had Killip class >1, and the median left ventricular ejection fraction was 51% (interquartile range 43% to 60%). The 10-year EFS rate was 19%. Both logistic and Cox analyses identified independent predictors, including young age (hazard ratio 1.2, 95% confidence interval 1.1 to 1.3, p = 0.0006), no history of angina (hazard ratio 1.4, 95% confidence interval 1.1 to 1.8, p = 0.009), no previous myocardial infarction (hazard ratio 1.4, 95% confidence interval 1.1 to 1.7, p = 0.01), high estimated glomerular filtration rate (hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p = 0.001), low albumin/creatinine excretion ratio (hazard ratio 1.2, 95% confidence interval 1.1 to 1.3, p <0.0001), and high left ventricular ejection fraction (hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p = 0.006). These variables had greater predictive power and improved the predictive power of 2 other models, including Framingham cardiovascular risk factors and the recognized predictors of acute heart damage. In conclusion, 10-year EFS was strongly associated with 4 factors (ABC model) typically neglected in studies of AMI survival, including estimated glomerular filtration rate, albumin/creatinine excretion ratio, a history of angina, and previous myocardial infarction. This model had greater predictive power and improved the power of 2 other models using traditional cardiovascular risk factors and indicators of heart damage during AMI.     

Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation

Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.     

Risk and prognostic factors for Japanese patients with chronic graft-versus-host disease after bone marrow transplantation

The incidence and prognostic factors for chronic graft-versus-host disease (cGVHD) were evaluated for 255 Japanese patients who survived more than 100 days after bone marrow transplantation, and of whom 119 (47%) developed cGVHD. Prior acute GVHD (grade 2-4) and use of an unrelated donor were significantly associated with the onset of cGVHD. Presence of cGVHD did not have an impact on mortality (hazard ratio (HR) = 0.89; 95% confidence interval (CI), 0.59-1.3). Three factors at diagnosis were associated with cGVHD-specific survival: presence of infection (HR = 4.1; 95% CI, 1.6-10.3), continuing use of corticosteroids at the onset of cGVHD (HR = 3.9; 95% CI, 1.7-9.1), and a Karnofsky performance score <80 (HR = 4.7; 95% CI, 2.0-11.3). The probability of cGVHD-specific survival at 4 years was 79% (95% CI, 70-86%). The severity and death rate of Japanese patients with cGVHD was lower than those for populations in Western countries, which might be the result of greater genetic homogeneity of Japanese ethnics. Our patients could not be accurately classified when the proposed prognostic models from Western countries were used, thus indicating the need for a different model to identify high-risk patients.     

Prophylactic T cell infusion after T cell-depleted bone marrow transplantation in patients with refractory lymphoma

Fifty-two patients with refractory lymphoma were prospectively treated with prophylactic T lymphocyte infusion after T cell-depleted allogeneic bone marrow transplantation, to induce graft-versus-lymphoma effect. Thirty-three patients had related donors; 19 had unrelated donors. After transplantation with marrow that had 0.8 +/- 0.4 x 10(5)CD3(+) cells/kg, T cells up to 1.75 x 10(6) CD3(+) cells/kg were given over 3 months provided > or = grade II acute graft-versus-host disease (GVHD) was not seen. The cumulative incidence of grades II-IV acute GVHD was 69%. Twenty of 32 evaluable patients (63%) developed chronic GVHD. Ten patients (19%) died of GVHD. The Kaplan-Meier 5-year overall survival of all patients was 34%. On multivariate analyses, chronic GVHD was significant for relapse (hazard ratio of 1.7, P < 0.05), and for overall survival (hazard ratio 1.4, P < 0.001). Chemosensitivity was significant for relapse only on univariate analysis. Patients who developed chronic GVHD had 4 years median survival, compared with 9 months in patients without chronic GVHD, P < 0.001. The study shows that patients with chronic GVHD have superior survivals, most probably related to a graft-versus-lymphoma effect, which could be modulated by prophylactic T cell infusion.     

Graft-versus-leukaemia effect in children: chronic GVHD has a significant impact on relapse and survival

To examine whether graft-versus-host-disease (GVHD) is associated with a graft-versus-leukaemia (GVL) effect that also influences the outcome of allogeneic stem cell transplantation (SCT) in childhood acute leukaemia, we evaluated all consecutive (n=169) children who had undergone SCT for ALL and AML at our centre. Median follow-up was 7 years. The 5-year probability of chronic GVHD was 34%. Median time to relapse was 24 months in children with chronic GVHD and 6 months in those without. The corresponding 5-year probabilities of relapse were 30 and 45% (P=0.01). The 5-year probability of survival was 54%. Patients with chronic GVHD had a significantly better survival, 77 vs 51% (P=0.01). In a Cox regression model, chronic GVHD independently decreased the risk of relapse (RR 0.44) and further predicted an increased chance of relapse-free survival (RR 1.7) and survival (RR 2.6). The impact of chronic GVHD on survival was most apparent in late-stage disease and in ALL. Acute GVHD was not an independent predictor for relapse or death in this study. This study is in support of a GVL effect in childhood leukaemia related to chronic GVHD, reducing the risk of relapse and improving survival.     

Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death

Interferon therapy for chronic hepatitis C reduces the risk of hepatocellular carcinoma, especially among virological and biochemical responders. However, little is known about the effect of interferon therapy on mortality. We studied the long-term effect of interferon therapy on mortality in patients with chronic hepatitis C. For this retrospective cohort study, 2954 patients with chronic hepatitis C were recruited, of whom 2698 received interferon therapy and 256 did not. The effect of interferon therapy on survival was assessed by standardized mortality ratio (SMR) based on published mortality data for the general Japanese population and by risk ratio calculated by proportional hazard regression. Over 6.0 +/- 2.2 years follow-up, death from liver-related diseases was observed in 69 (68%) of 101 deaths among interferon-treated patients and in 42 (81%) of 52 deaths among untreated patients. Compared with the general population, overall mortality was high among untreated patients (SMR: 2.7; 95% CI: 2.0-3.6) but not among interferon-treated patients (SMR: 0.9; 95% CI: 0.7-1.1). Liver-related mortality was extremely high among untreated patients (SMR: 22.2; 95% CI: 16.0-30.0) and less among interferon-treated patients (SMR: 5.5; 95% CI: 4.3-6.9). The risk of death from all causes was lower for interferon-treated than untreated patients (risk ratio: 0.47; 95% CI: 0.261-0.836; P = 0.01). The risk of death from liver-related diseases was significantly lower for sustained virological responders (risk ratio: 0.04; 95% CI: 0.005-0.301; P = 0.002) compared with untreated patients, but not for nonsustained virological responders. Sustained biochemical responders (risk ratio: 0.03; 95% CI: 0.004-0.230; P < 0.001) and transient biochemical responders (risk ratio: 0.18; 95% CI: 0.063-0.532; P = 0.002) showed a significantly reduced risk of death from liver-related death, whereas biochemical nonresponders did not. Hence interferon treatment improved survival in chronic hepatitis C patients showing a biochemical as well as a virological response by preventing liver-related deaths.     

Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants.

OBJECTIVE: The aim of this study was to analyze bone marrow lymphocyte subsets and CD34 cell dose and their influence on the outcomes of bone marrow transplantation. MATERIALS AND METHODS: Forty-eight patients (median age 30 years, range 5-54) receiving HLA-identical sibling bone marrow transplantation for hematologic malignancies were analyzed. RESULTS: Median number (range) of nucleated cells and CD34+ cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, time to neutrophil recovery was shortened when a higher number of CD3/CD8 cells was infused (> or =1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalovirus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). The incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. Infusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54%. Risk of death was increased in patients receiving <3.5 x 10(6)CD34 infused/kg (HR = 0.37, p = 0.02). Only six patients relapsed. CONCLUSIONS: A high cell dose of CD3/CD8 is associated with faster neutrophil recovery, whereas a high cell dose of CD4+ cells increases the incidence of acute GVHD. A high number of nucleated cells and CD34+ cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively.     

Pneumocystis prophylaxis and survival in patients with advanced human immunodeficiency virus infection treated with zidovudine. The Zidovudine Epidemiology Group.

BACKGROUND--Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and mortality in persons with advanced human immunodeficiency virus (HIV) infection. We assessed the impact of prophylaxis for PCP on survival in patients with advanced HIV disease who were treated with zidovudine. METHODS--A cohort of 1048 patients with prior PCP (N = 437), another acquired immunodeficiency syndrome-defining diagnosis (N = 168) or acquired immunodeficiency syndrome-related complex (N = 443) and with less than 0.250 x 10(9)/L CD4 cells initiated zidovudine treatment between April 1987 and April 1988. They were then followed up for 24 months. Morbidity and mortality outcomes were assessed every 2 months. A time-dependent, Cox proportional hazards model was used to identify factors associated with new episodes of PCP and with survival. RESULTS--Three hundred thirty-six patients (32%) developed PCP after beginning treatment with zidovudine, with a 24-month actuarial rate of 41%. Patients with prior PCP were more likely to develop PCP during follow up (40%) than those without a history of PCP at entry (27% with PCP at follow-up). Other factors associated with developing PCP were baseline acquired immunodeficiency syndrome vs acquired immunodeficiency syndrome-related complex, and dose interruptions of zidovudine. Thirty-six (17%) of 210 patients who received trimethoprim-sulfamethoxazole prophylaxis developed PCP vs 299 (36%) of 838 who never received trimethoprim-sulfamethoxazole (odds ratio, 0.48). One hundred seven (22%) of 483 patients who ever received aerosol pentamidine prophylaxis developed PCP vs 228 (40%) of 565 who did not receive aerosol pentamidine (odds ratio, 0.55). In a time-dependent Cox proportional hazards analysis, trimethoprim-sulfamethoxazole (relative hazard, 0.21; 95% confidence interval [CI], 0.11 to 0.4) and aerosol pentamidine prophylaxis (relative hazard, 0.25; 95% CI, 0.16 to 0.39) were associated with decreased risk of PCP. Pneumocystis carinii pneumonia during follow-up was strongly associated with death when controlling for other factors (odds ratio, 1.8). For all patients, aerosol pentamidine prophylaxis was associated with a reduced risk of death during follow-up (relative hazard, 0.59; 95% CI, 0.44 to 0.78), while trimethoprim-sulfamethoxazole showed a weaker association (relative hazard, 0.74; 95% CI, 0.54 to 1.1). However, there was a significantly reduced risk of death overall for patients who consistently used trimethoprim-sulfamethoxazole (relative hazard, 0.55; 95% CI, 0.35 to 0.88) or aerosol pentamidine (relative hazard, 0.57; 95% CI, 0.42 to 0.77) and this was most pronounced in patients with a baseline history of PCP. DISCUSSION AND CONCLUSIONS--Pneumocystis carinii pneumonia was common in advanced HIV infection treated with zidovudine. Prophylaxis with trimethoprim-sulfamethoxazole and aerosol pentamidine both were associated with a decreased likelihood of PCP, and consistent use of each was associated with improved survival. Prophylaxis for PCP is associated with prolonged survival for patients with advanced HIV disease.     

Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning

To analyze the incidence, characteristics and risk factors of hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning (allo-RIC), we conducted a retrospective study in three Spanish centers. We analyzed 452 consecutive patients receiving allo-RIC. Of these, 92 patients (20%) developed marked hyperbilirubinemia (>4?mg/day or >68.4?μM) after allo-RIC. The main causes of marked hyperbilirubinemia after transplant were cholestasis due to GVHD or sepsis (n=57, 62%) and drug-induced cholestasis (n=13, 14%). A total of 22 patients with marked hyperbilirubinemia (24%) underwent liver biopsy. The most frequent histological finding was iron overload alone (n=6) or in combination with other features (n=6). In multivariate analysis, the risk factors for marked hyperbilirubinemia after allo-RIC were non-HLA-identical sibling donors (hazard ratio (HR) 2.2 (95% confidence interval (CI) 1.4-3.6) P=0.001), female donors to male recipients (HR 2.1 (95% CI 1.3-3.3) P=0.003) and high levels of bilirubin and γ-glutamyl transpeptidase before transplant (HR 4.5 (95% CI 2.5-8.4) P<0.001 and HR 4.6 (95% CI 2.6-8.1) P<0.001, respectively). Patients with marked hyperbilirubinemia showed higher 4-year nonrelapse mortality (HR 1.3 (95% CI 1-1.7), P=0.02) and lower 4-year OS (HR 1.4 (95%CI 1.3-1.7), P<0.001) than patients without. In conclusion, we confirm that marked hyperbilirubinemia is frequent and diverse after allo-RIC. Development of marked hyperbilirubinemia after allo-RIC is associated with worse outcome of the procedure.     

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation

The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P =.001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P =.046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P <.001) and treatment failure (HR, 5.2; P <.001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome.     

One-year cyclosporine prophylaxis reduces the risk of developing extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation

BACKGROUND AND OBJECTIVES: Chronic graft-versus-host disease (GVHD) remains the most common late complication of allogeneic stem cell transplantation, producing significant long-term morbidity and contributing to a substantial risk of late mortality. Chronic GVHD may be more common, more protracted and less responsive to current treatments after peripheral-blood stem cell (PBSC) transplantation than after bone marrow transplantation. The purpose of this retrospective cohort study was to determine whether the hazard of extensive chronic GVHD after allogeneic PBSC transplantation could be decreased by prolonging cyclosporine A (CsA) prophylaxis over 12 months. DESIGN AND METHODS: Fifty-seven consecutive patients with hematologic malignancies who had received a PBSC transplant from an HLA-identical sibling were evaluable for chronic GVHD. All patients began CsA tapering at day 50 but 2 different durations of immunosuppression were used: the first 36 patients were allocated to receive a 6-month course with tapering by 5% at weekly intervals (group A), while the following 21 received a 12-month course with tapering by 5% every 2 weeks (group B). RESULTS: The cumulative incidence of extensive chronic GVHD at 2 years was 69% (95% CI, 53-85%) for group A and 25% (95% CI, 3-47%) for group B with a significantly lower hazard in group B than in group A (HR=0.2; 95% CI, 0.07-0.57; p=0.0009). In multivariate analysis, the 12-month CsA tapering schedule was associated with a significantly decreased risk of extensive chronic GVHD (HR=0.2; 95% CI, 0.06-0.66; p=0.008). The hazard of transplant-related mortality, relapse and failure to survive in remission was not significantly different among the 2 groups. INTERPRETATION AND CONCLUSIONS: One-year CsA prophylaxis seems to be more effective than the standard six-month CsA regimen at preventing extensive chronic GVHD after PBSC transplant from an HLA-identical sibling. Conclusive assessment of the benefits of such prolonged immunosuppression, in terms of better quality of life and minor morbidity, requires both long-term follow-up to evaluate the rates of relapse and secondary tumors and a randomized setting.     

Supervivencia de pacientes ambulatorios con insuficiencia cardiaca crónica del área mediterránea. Un estudio de base poblacional

Introduction and objectives

Scarce research has been performed in ambulatory patients with chronic heart failure in the Mediterranean area. Our aim was to describe survival trends in our target population and the impact of prognostic factors.

Methods

We carried out a population-based retrospective cohort study in Catalonia (north-east Spain) of 5659 ambulatory patients (60% women; mean age 77 [10] years) with incident chronic heart failure. Eligible patients were selected from the electronic patient records of primary care practices from 2005 and were followed-up until 2007.

Results

During the follow-up period deaths occurred in 950 patients (16.8%). Survival after the onset of chronic heart failure at 1, 2, and 3 years was 90%, 80%, 69%, respectively. No significant differences in survival were found between men and women (P=.13). Cox proportional hazard modelling confirmed an increased risk of death with older age (hazard ratio=1.06; 95% confidence interval, 1.06-1.07), diabetes mellitus (hazard ratio=1.53; 95% confidence interval, 1.33-1.76), chronic kidney disease (hazard ratio=1.73; 95% confidence interval, 1.45-2.05), and ischemic heart disease (hazard ratio=1.18; 95% confidence interval, 1.02-1.36). Hypertension (hazard ratio=0,73; 95% confidence interval, 0,64-0,84) had a protective effect.

Conclusions

Service planning and prevention programs should take into consideration the relatively high survival rates found in our area and the effect of prognostic factors that can help to identify high risk patients.Full English text available from:www.revespcardiol.org/en     

Survival rate and the determinants of progression from HIV to AIDS and from AIDS to the death in Iran: 1987 to 2016

Objective: To examine the prognostic factors of progression from HIV to AIDS and AIDS to the death in people living with HIV/AIDS in Iran.Methods: In this registry-based retrospective cohort study, we recruited 28 873 HIV-infected people from 158 Behavioral Diseases Counseling Centers of Iran.Two outcomes of interest included survival rates from HIV diagnosis to AIDS and from AIDS to the death.We used Kaplan-Meier and Cox regression model to investigate survival rate and factors affecting on survival controlling effect of confounding factors.Results: The one, three, five, and ten-year survival rate from HIV to AIDS were 85%, 73%, 61% and 32%, and for AIDS to death were 90%, 81%, 74% and 55%, respectively.Multivariate Cox regression analysis indicated that the risk of progression from AIDS phase toward death in individuals with CD4 less than 200/mm~3, infected with tuberculosis(TB) and not treated by antiretroviral therapy(ART) was 2.17(95% CI: 1.62-2.90), 1.49(95% CI: 1.01-2.20) and 4.88(95% CI: 3.42-6.96) times higher respectively.The risk of progression to AIDS in patients with baseline CD4 less than 200/mm~3 was 2.32(95% CI: 2.14, 2.51) times higher than patients with CD4 200/mm~3(P=0.001).On the other hand, tuberculosis increases the risk of death by 49.0%(P=0.04).The hazard ratio of death in patients who did not receive ART was 4.88(95% CI: 3.42, 6.96) times higher than patients who received ART(P0.001).Conclusion: The early detection of HIV, the screening and treatment of TB and receiving the ART improve the survival of HIV/AIDS patients significantly, and prevent the transmission of HIV to other people.     

Prognostic value of pharmacologic stress echocardiography in patients with left bundle branch block

PURPOSE: Although coronary artery disease is a frequent cause of left bundle branch block, the prognostic value of myocardial ischemia in patients with this conduction abnormality has not been defined. We investigated the value of pharmacologic stress echocardiography in risk stratification of patients with left bundle branch block. PATIENTS AND METHODS: Three hundred eighty-seven patients [230 men and 157 women, mean (+/- SD) age, 64 +/- 9 years] with complete left bundle branch block on the resting electrocardiogram underwent dobutamine (n = 217) or dipyridamole (n = 170) stress echocardiography to evaluate suspected or known coronary artery disease. A summary wall motion score (on a one to four scale) was calculated. The primary end points were cardiac death and nonfatal myocardial infarction. RESULTS: A positive echocardiographic result (evidence of ischemia) was detected in 109 (28%) patients. During a mean follow-up of 29 +/- 26 months, there were 21 cardiac deaths and 20 myocardial infarctions, 63 patients underwent coronary revascularization, and 1 patient received a heart transplant. In a multivariate analysis, four clinical and echocardiographic variables were associated with increased risk of cardiac death: resting wall motion score index [hazard ratio (HR) = 7.5 per unit; 95% confidence interval (CI), 2.8 to 20; P = 0.001], previous myocardial infarction (HR = 2.9; 95% CI, 1.1 to 7.3; P = 0.02), diabetes (HR = 2.7; 95% CI, 1.1 to 6.6; P = 0.03), and the change in wall motion score index from rest to peak stress (HR = 3.0 per unit; 95% CI, 1.0 to 8.6; P = 0.04). The 5-year survival was 77% in the ischemic group and 92% in the nonischemic group (P = 0.02). Four variables were associated with increased risk of cardiac death or infarction: previous myocardial infarction (HR = 3.4; 95% CI, 1.7 to 6.8; P = 0.0005), diabetes (HR = 2.4; 95% CI, 1.2 to 4.6; P = 0.01), resting wall motion score index (HR = 2.2 per unit; 95% CI, 1.1 to 4.1; P = 0.02), and positive echocardiographic result (HR = 2.2; 95% CI, 1.1 to 4.5; P = 0.03). The 5-year infarction-free survival was 60% in the ischemic group and 87% in the nonischemic group (P < 0.0001). Stress echocardiography significantly improved risk stratification in patients without previous myocardial infarction (P = 0.0001), but not in those with previous myocardial infarction (P = 0.08). In particular, it provided additional value over clinical and resting echocardiographic findings in predicting cardiac events among patients without previous infarction. CONCLUSIONS: Myocardial ischemia during pharmacologic stress echocardiography is a strong prognostic predictor in patients with left bundle branch block, particularly in those without previous myocardial infarction.