Age,severe comorbidity and functional impairment independently contribute to poor survival in cancer patients

Purpose With the increasing number of elderly patients suffering from cancer, comorbidity and functional impairment become common problems in patients with cancer. Both comorbidity and functional impairment are associated with a shorter survival time in cancer patients, but their independent role has rarely been addressed before. Methods Within a prospective trial we recruited 427 cancer patients, irrespective of age and type of cancer, admitted as inpatients prior to the start of chemotherapy. Comorbidity was assessed with the cumulative illness rating scale (CIRS-G), functional impairment with WHO performance status (WHO-PS), basal (ADL) and instrumental (IADL) activities of daily living. Results Median follow-up was 34.2 months. A total, 61.4%. of patients died. Median survival time was 21.0 months. Age, kind of tumour (solid vs. haematological), treatment approach (non-curative vs. curative), WHO-PS (2–4 vs. 0–1), IADL (<8 vs. 8), and severe comorbidity (CIRS-level 3–4 vs. none) were significantly associated with shorter survival time in univariate analysis. In a multivariate Cox-regression-analysis, age (HR 1.019; 95%-CI 1.007–1.032; P = 0.003), kind of tumour (HR 1.832; 95%-CI 1.314–2.554; P < 0.001), WHO-PS (HR 1.455; 95%-CI 1.059–2.000; P = 0.021), and comorbidity level 3–4 (HR 1.424; 95%-CI 1.012–2.003; P = 0.043) maintained their significant association. Conclusions Age, severe comorbidity, functional impairment, and kind of tumour are independently related to shorter survival time in cancer patients.     

Therapy with statins and aspirin enhances long-term outcome of percutaneous coronary intervention

Aspirin is the standard therapy applied after coronary intervention, and statins are also prescribed to prevent secondary coronary heart disease. We assessed the ability of a combination of statins and aspirin to improve the longterm prognosis of patients after percutaneous coronary intervention (PCI). We collected data from 575 consecutive patients who underwent PCI. The patients were divided into groups depending on the presence or absence of statin or aspirin therapy as follows: both statin and aspirin (Group B: n = 190; 33%); aspirin only (Group A: n = 236; 41.1%); statin only (Group S: n = 53; 9.2%S); neither drug (Group N: n = 96; 16.7%). Data were statistically assessed using the Cox proportional hazard model for multivariate analysis with adjustment of baseline convariates. Sixty-eight patients died during follow-up (11 ± 3 years). Multivariate analysis showed that compared with group N, both groups S and A were independent predictors for survival from all causes [group S: hazards ratio (HR) 0.29, 95% confidence interval (CI) 0.10–0.81, P = 0.019; group A: HR 0.31, 95% CI 0.17–0.56, P < 0.0001] and cardiovascular (CV) death (group S: HR 0.16, 95% CI 0.04–0.73, P = 0.018; group A: HR 0.12, 95% CI 0.05–0.30, P < 0.001). risk for all causes and CV death was significantly lower in Group B (HR 0.25, 95% CI 0.12–0.53, P < 0.0001 and HR 0.10, 95% CI 0.03–0.31, P < 0.0001, respectively). Therapy with statins plus aspirin improves long-term clinical outcome in patients after PCI.     

Factors Associated with Progression to Hepatocellular Carcinoma and to Death from Liver Complications in Patients with HBsAg-Positive Cirrhosis

Background and Aims Hepatitis B viral markers and liver tests were used as predictors for development of hepatocellular carcinoma and progression to end-stage liver disease in 128 cirrhosis patients with hepatitis B. Results During a median follow-up of 63.5 months, 28 patients (21.9%) developed HCC and 36 (28.1%) died from non-HCC liver deaths. By multivariate analysis, independent predictors of HCC development and their hazard ratios were high alfa-fetoprotein (HR2.83, 95% CI 1.60–5.00, P = 0.0003), negative HBeAg (HR2.33, 95% CI 1.04–5.29, P = 0.04), and low alanine aminotransferase value (HR1.42, 95% CI 1.08–1.89, P = 0.02). Independent predictors of non-HCC liver deaths were HBeAg positivity (HR3.39, 95% CI 1.16–9.93, P = 0.02), decrease albumin (HR1.61, 95% CI 0.99–2.63, P = 0.05), decrease platelet count (HR2.54, 95% CI 1.03–6.25, P = 0.04), high ALT value (HR1.22, 95% CI 1.03–1.43, P = 0.02), and onset of encephalopathy (HR3.34, 95% CI 1.21–9.27, P = 0.02). Concusions HBeAg negativity, elevated AFP, and low ALT values predicted HCC development, while HBeAg positivity, abnormal liver tests, and low platelet counts identified patients with non-HCC liver deaths.     

Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population‐based series of acute myeloid leukaemia

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population‐based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high‐risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five‐year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis.     

Therapy related‐chronic myelomonocytic leukemia (CMML): Molecular,cytogenetic, and clinical distinctions from de novo CMML

Therapy related myeloid neoplasms (t‐MN) including therapy related myelodysplastic syndromes (t‐MDS) and acute myeloid leukemia (t‐AML) are associated with aggressive disease biologies and poor outcomes. In this large (n = 497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t‐CMML. T‐CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t‐CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t‐MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (<2%) were uncommon. Molecularly integrated CMML prognostic models were not effective in risk stratifying t‐CMML patients and responses to hypomethylating agents were dismal with no complete responses. Median overall (OS) and leukemia free survival (LFS) was shorter for t‐CMML in comparison to d‐CMML (Median OS 10.9 vs 26 months and median LFS 50 vs 127 months) and t‐CMML independently and adversely impacted OS (P = .0001 HR 2.1 95% CI 1.4‐3.0). This prognostic impact was retained in the context of the Mayo Molecular Model (P = .001, HR 2.4, 95% CI 1.5‐3.7) and the GFM prognostic model (P < .0001, HR 2.15, 95% CI 1.5‐3.7). In summary, we highlight the unique genetics and independent prognostic impact of t‐CMML, warranting its inclusion as a separate entity in the classification schema for both CMML and t‐MN.     

Cytogenetic risk score maintains its prognostic significance in AML patients with detectable measurable residual disease undergoing transplantation in remission: On behalf of the acute leukemia working party of the European society for blood and marrow transplantation

While evidence for measurable residual disease (MRD) is a harbinger of inferior outcome in acute myeloid leukemia (AML) patients referred for allogeneic stem cell transplantation (allo-SCT), the exact clinical trajectory of specific patient subsets in this clinical setting is undefined. Using a recently published prognostic cytogenetic model (Canaani et al. Leukemia 2019) we evaluated whether this model applied also to studies of patients with positive MRD. The analysis comprised MRD⁺ patients in first complete remission undergoing allo-SCT from a matched sibling donor or unrelated donor. Seven hundred and seventy-five patients were evaluated with a median follow-up duration of 22 months. Cytogenetic risk score was favorable, intermediate/FLT3^wt intermediate/FLT3-ITD3, and adverse in 15%, 28.3%, 37% and 19.7% of the patients, respectively. Favorable and intermediate/FLT3^wt risk patients had 2-year leukemia-free survival rates of 78% and 61%, respectively, compared with only 50% and 37% for intermediate/FLT3-ITD3 and adverse risk patients, respectively (P < .001). In multivariate analysis adverse and intermediate/FLT3-ITD3 risk patients were more likely to experience disease relapse compared with favorable risk patients [hazard ratio (HR) = 3.9, 95% confidence interval (CI), 2.1-7.3; P < .001, and HR = 4.4, CI 95%, 2.4-7.8; P < .001, respectively]. The European society for blood and marrow transplantation cytogenetic risk score is a valuable adjunct for risk stratification of MRD⁺ AML patients.     

Allogeneic bone marrow transplantation compared to peripheral blood stem cell transplantation for the treatment of hematologic malignancies: a meta-analysis based on time-to-event data from randomized controlled trials

Controversy remains regarding the transplant outcomes of human leukocyte antigen-identical related bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) for the treatment of patients with hematological malignancies. To provide an estimate of the effect of BMT and PBSCT on clinical outcomes in patients with hematological malignancies, we conducted a meta-analysis based on time-to-event data from 17 randomized controlled trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), from 1972 through July 2010, and conference proceedings through July 2009 and reference lists, without any language restriction, of randomized trials that compared the transplant outcomes after BMT and PBSCT in patients with hematological malignancies were searched for details. Two independent reviewers extracted the data. The outcomes examined were engraftment, graft-versus-host disease (GVHD), relapse, transplant-related mortality (TRM), leukemia-free-survival (LFS), and overall survival (OS). Compared to PBSCT, BMT had lower neutrophil (HR, 2.08; 95% CI, 1.80 to 2.42; p < 0.00001) and platelet (HR, 2.77; 95% CI, 1.78 to 4.30; p < 0.00001) engraftment. BMT was associated with a significant decrease in the development of grades II–IV (HR, 0.75; 95% CI, 0.63 to 0.90; p = 0.002) and III–IV (HR, 0.63; 95% CI, 0.47 to 0.84; p = 0.001) acute GVHD as well as overall (HR, 0.70; 95% CI, 0.59 to 0.83; p < 0.0001) and extensive (HR, 0.60; 95% CI, 0.39 to 0.91; p = 0.002) chronic GVHD. BMT was associated with a higher incidence of relapse (HR, 1.91; 95% CI, 1.34 to 2.74; p = 0.0004). Comparable TRM (1.08; 95% CI, 0.56 to 2.10; p = 0.81), LFS (HR, 1.04; 95% CI, 0.83 to 1.30; p = 0.73), and OS (HR, 1.06; 95% CI, 0.81 to 1.39; p = 0.65) were demonstrated for both treatments. An inverse linear relationship was observed between the acute GVHD difference (PBSCT minus BMT) and the outcome of OS (p = 0.016). Our meta-analysis suggest that BMT leads to slower hematological recovery, increasing rates of relapse, and a lower risk of GVHD, but no significant difference in LFS and OS. A lower incidence of acute GVHD is associated with a superior OS.     

Daunorubicin,cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety,tolerance and early outcome—Polish Adult Leukemia Group (PALG) pilot study

In 1992–1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m⁻² day⁻¹ iv on days 1–3 and fludarabine 25 mg m⁻² day⁻¹ iv on days 1–5 given before cytarabine 200 mg m⁻² day⁻¹ in ci on days 1–7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for 1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI] 36–52%) and 69% (95% CI 55–83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22–54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.     

Predictors of uptake and adherence to the use of hip protectors among nursing-home residents

The aim of the present study was to identify predictors for initial uptake and adherence with the use of hip protectors when offering hip protectors free of charge to nursing-home residents. An 18 months prospective follow up study was carried out in 18 Norwegian nursing homes. One thousand two hundred and thirty-six residents were included in the study of which 604 started to use a hip protector. A multivariate logistic regression model was used to identify predictors for the initial uptake. A Cox proportional hazard model was used to identify predictors for adherence. A stepwise backward strategy was used in both the logistic and in the Cox regression. The effect of nursing homes as clusters was adjusted for in the analysis. The uptake rate among all residents was 46% and the adherence was approximately 75% after 3 months, and approximately 60% after 18 months. Female gender [odds ratio (OR): 1.54, 95% CI: 1.06–2.24, P = 0.022], previous fractures (OR: 1.67, 95% CI: 1.02–2.75, P = 0.043), previous falls (OR: 2.08, 95% CI: 1.35–3.19, P < 0.001) and memory (not able to memorise: OR: 3.71, 95% CI: 2.09–6.59, P < 0.001, large problems with memorising: OR: 2.85, 95% CI: 1.81–4.49, P < 0.001, medium problems with memorising: OR: 2.45, 95% CI: 1.39–4.33, P = 0.002, some problems with memorising: OR: 1.99, 95% CI: 1.14–3.48, P = 0.016) seemed to be important predictors for uptake. Among those who took up the offer male gender (HR: 1.71, 95% CI: 1.00–2.91, P = 0.049), memory (not able to memorise: HR: 0.26, 95% CI: 0.14–0.50, P < 0.001, large problems with memorising: HR: 0.32, 95% CI: 0.22–0.45, P < 0.001, medium problems with memorising: HR: 0.46, 95% CI: 0.30–0.73, P < 0.001, some problems with memorising: HR: 0.49, 95% CI: 0.32–0.73, P = 0.001) and bowel incontinence (HR: 0.41, 95% CI: 0.25–0.66, P < 0.001) were predictors for a lower probability of ending hip protector use. Factors related to a high risk of falling were important predictors for both uptake and adherence. The fact that neither memory impairments nor incontinence (bowel) seemed to be barriers to hip protector use is important since these characteristics are common among nursing-home residents and tertiary prevention such as the use of hip protectors is probably the most feasible intervention to prevent hip fractures in this group.     

Emergency department admissions,older people,functional decline,and length of stay in hospital

Objective: Early identification of patients at risk of a prolonged admission to the hospital may allow targeted management decisions and discharge planning to begin in the emergency department. The aim of this study was to evaluate the effect of recent decline in function, measured in the emergency department, on length of stay (LOS) in the hospital. Methods: A total of 469 patients with a mean age of 79.4 years presenting to the emergency department of a tertiary hospital were comprehensively assessed by a nurse practitioner. The Modified Barthel Index (MBI) was used to measure recent decline in function (MBI‐change, the decline in MBI in the month before the emergency visit). Other measures included recent decline in instrumental activities of daily living (IADL‐change, using the Lawton IADL Scale), Folstein Mini Mental State Examination, Geriatric Depression Scale (GDS), Waterlow Scale, Social Support Instrument (SSI), principal medical diagnosis, living arrangement, care needs, and self‐rated health. Using multivariate survival analysis, the influence of MBI‐change on LOS was modelled in 249 randomly selected patients, and validated in the remaining 220. Results: In total, 327 patients (69.7%) were admitted to the hospital, for a median LOS of 10 days. In the modelling sample, variables significantly associated with LOS included MBI‐change (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.85–0.98), IADL‐change (HR 1.14, 95% CI 1.02–1.28), whether known to the Aged Care Assessment Team (ACAT) (HR 1.65, 95% CI 1.04–2.59) and Waterlow score (HR 0.95, 95% CI 0.90–0.99). MBI‐change (HR 0.94, 95% CI 0.88–0.99) and Waterlow score (HR 0.95, 95% CI 0.91–0.99) were also significant predictors of LOS in the validation sample. Conclusions: Recent decline in function predicts LOS in the hospital, is easy to measure in the emergency department, and may prove useful across the full spectrum of disease. It should be considered when formulating diagnostic and management plans, and when developing funding models.     

Prognostic impact of complex and/or monosomal karyotypes in post-transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach

To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT-CI score ≥3 (HR, 1.23), non-remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post-HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post-HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics.     

TP53 mutation in patients with high‐risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation

Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse‐risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three‐year probabilities of overall survival (OS) and event‐free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53‐mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML.     

Survival analysis of patients with dermatomyositis and polymyositis

To estimate the mortality rate and identify factors predicting survival in patients with polymyositis (PM) and dermatomyositis (DM). The medical records of 192 PM/DM patients who were treated at Chang Gung Memorial Hospital from 1999 through 2008 were retrospectively reviewed. The Taiwan National Death Registry (1999–2008) was used to obtain their survival status. Thirty-one (16.1%) of the 192 patients with PM/DM had an associated malignancy; 41 (21.4%) had interstitial lung disease (ILD). During the follow-up period, 55 (28.6%) patients died and the overall cumulative survival rate was 79.3% at 1 year, 75.7% at 2 years, 69.9% at 5 years, and 66.2% at 10 years. In univariate analysis, older age at PM/DM onset, anemia, thrombocytopenia, leukopenia, diabetes mellitus, ILD, cancer, and non-use of azathioprine were associated with higher mortality (p = 0.0172, 0.0484, <0.0001, 0.0008, 0.0001, 0.0036, 0.0010, and 0.0019, respectively). In multivariate Cox regression analysis, thrombocytopenia (hazard ratio [HR] 4.94, 95% confidence interval [CI] 2.60–9.37, p < 0.0001), diabetes mellitus (HR 2.57, 95% CI 1.38–4.80, p < 0.0001), cancer (HR 2.30, 95% CI 1.26–4.22, p = 0.0030), and ILD (HR 1.98, 95% CI 1.11–3.51, p = 0.0182) were positively associated with mortality. Use of azathioprine (HR 0.35, 95% CI 0.16–0.74, p = 0.0064) was negatively associated with mortality. This study confirmed the high mortality rate (28.6%) in PM/DM patients. Survival time was significantly reduced in patients with thrombocytopenia, diabetes mellitus, ILD, and cancer patients than in those without these conditions.     

Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3A(mutant) AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3A(wild-type) AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3A(mutant) AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3A(wild-type) AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.     

Presence of a high-grade component in gastric mucosa-associated lymphoid tissue (MALT) lymphoma is not associated with an adverse prognosis

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL) show a spectrum of disease characterized by varying proportions of low-grade and high-grade components. While the natural history and optimum treatment for low-grade gastric MALT lymphoma and DLBCL is well established, the prognosis and optimal treatment of patients with both low- and high-grade components is not well established. The purpose of our study was to evaluate the clinical characteristics, survival outcomes, and prognostic factors of patients with gastric MALT lymphoma and gastric DLBCL. A retrospective review of patients with gastric MALT lymphoma, gastric DLBCL, or MALT lymphoma with a high-grade component treated at our centers from 1994 to 2006 was performed. Patients were divided into three categories: “pure MALT lymphoma,” “MALT lymphoma with high-grade component” (mixed), and “pure DLBCL.” Seventy-six patients were included in our study—26 with pure MALT, 22 with MALT with high-grade component (“mixed”), and 28 with pure DLBCL. Pure MALT lymphoma and mixed lymphoma patients had similar clinical characteristics, whereas pure DLBCL patients had less favorable disease characteristics with significantly poorer performance status, higher number of extranodal sites of disease, higher stage, and larger proportion of bone marrow involvement and international prognostic index (IPI) scores compared with mixed lymphoma. The majority of mixed lymphoma (72.7%) and DLBCL patients (71.4%) were treated with chemotherapy. Of patients receiving chemotherapy, a higher proportion of mixed lymphoma and DLBCL patients received anthracycline-based combination chemotherapy regimens compared with MALT lymphoma (73% vs 71% vs 8%) whereas the proportion of mixed lymphoma and DLBCL patients was similar (p = 0.919). At a median follow-up of 37 months, the 5-year overall survival was 66.9%. The 5-year overall survival was 78% for MALT lymphoma, 84% for mixed lymphoma, and 45% for DLBCL. On univariate analysis, DLBCL histology, age, performance status, serum albumin, lactate dehydrogenase, bone marrow, number of extranodal sites, stage, and IPI score were prognostic for inferior survival. On multivariate analysis, DLBCL histology remained significantly prognostic for inferior survival, independent of chemotherapy regimen (hazard ratio (HR) 6.66, 95% confidence interval (CI) 2.01–21.41, p = 0.001). Mixed histology was not prognostic for inferior survival (HR 1.13, 95% CI 0.28–4.54, p = 0.868). Other factors prognostic for inferior survival were serum albumin <37 g/L (HR 3.22, 95% CI 1.11–13.22, p = 0.034) and treatment with non-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy (HR 4.89, 95% CI 1.67–14.36, p = 0.004). In conclusion, the clinical characteristics of mixed histology MALT lymphoma are similar to low-grade MALT lymphoma and significantly different from pure DLBCL. The prognosis of mixed histology MALT lymphoma is significantly better than pure DLBCL, independent of IPI and chemotherapy regimen, and pure DLBCL histology is independently prognostic of inferior survival outcome.     

Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia

Acute myeloid leukemia (AML) is more common and more lethal among patients over the age of 60. Increased body mass index (BMI) has been associated with a higher incidence of various malignancies, including AML. We sought to determine whether patient BMI at the time of AML diagnosis is related to overall survival (OS) among elderly patients. We identified 97 patients with AML diagnosed after the age of 60 and treated with cytarabine‐based induction chemotherapy. The median age was 68 years (range 60–87); 52% of patients were male, and our study population was predominantly white (89% of patients). The median OS for all patients was 316 days (95% CI 246–459). The hazard ratio for mortality was increased among patients with a BMI < 25 compared to BMI ≥ 30 (HR 2.14, P = 0.009, 95% CI 1.21–3.77), as well as with older age (HR 1.76, P = 0.015, 95% CI 1.12–2.79) and with secondary versus de novo disease (HR 1.95, P = 0.006, 95% CI 1.21–3.14). After multivariable analysis, we did not find a significant association between OS and other potential confounders such as coronary artery disease or diabetes among these patients. We conclude that increased BMI was independently associated with improved OS among older AML patients at our institution. Am. J. Hematol. 88:642–646, 2013. © 2013 Wiley Periodicals, Inc.     

The prognostic factors of systemic sclerosis for survival among Koreans

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by fibrosis of the skin and internal organs, which can cause significant morbidity and mortality. The prognostic factors for survival were not fully evaluated in Asian population. We investigated the prognostic factors for survival of SSc among Korean patients. A total of 243 SSc patients were enrolled from Seoul National University Hospital between 1972 and 2007. Age at onset, gender, cutaneous subset, autoantibody status, major organ involvement, and occurrence of malignancy were evaluated with all-cause mortality as the end point. A multivariate Cox proportional hazard model was used to retrieve the prognostic factors for survival. During the follow-up of 1,967 person-years, 33 patients died. Old age at onset (hazard ratio [HR] 7.4, 95% confidence interval [95% CI] 1.9–28.1), diffuse cutaneous subset (HR 2.5, 95% CI 1.1–5.9), presence of anti-Scl-70 antibody (HR 3.0, 95% CI 1.2–7.1), forced vital capacity less than 70% (HR 2.8, 95% CI 1.3–6.2), and heart involvement (HR 4.2, 95% CI 1.7–10.2) were found to be significant risk factors for mortality in multivariate analysis. In Korean SSc patients, old age, diffuse cutaneous involvement, anti-Scl-70 antibody, and internal organ involvement are risk factors for mortality.     

QT<Subscript>c</Subscript> interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

Aims/hypothesis We evaluated the association of QT interval corrected for heart rate (QT_c) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. Methods We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 ± 0.6 years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. Results In subjects with type 1 diabetes QT_c, but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10 ms increase in QT_c, 95% CI 1.02–1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02–1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03–1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QT_c was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15–1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18–1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19–1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21–1.90, p < 0.001). Effect modification of QT_c by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). Conclusions/interpretation QT_c is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabetes.     

Interferon alpha-2c therapy of patients with chronic myelogenous leukemia: long-term results of a multicenter phase-II study

 In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN)α-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2–90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n=19) and untreated (n=58) patients were 51 months (95% confidence interval [CI], 30–72) and 77 months (95% CI, 43–111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n=6), PHR (n=34), and less than PHR (n=35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-α treatment identifies patients with a favorable long-term prognosis. Received: 26 October 1995 / Accepted: 3 January 1996     

Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database

Aims/hypothesis Risk estimates for stroke in patients with diabetes vary. We sought to obtain reliable risk estimates for stroke and the association with diabetes, comorbidity and lifestyle in a large cohort of type 2 diabetic patients in the UK.Materials and methods Using the General Practice Research Database, we identified all patients who had type 2 diabetes and were aged 35 to 89 years on 1 January 1992. We also identified five comparison subjects without diabetes and of the same age and sex. Hazard ratios (HRs) for stroke between January 1992 and October 1999 were calculated, and the association with age, sex, body mass index, smoking, hypertension, atrial fibrillation and duration of diabetes was investigated.Results The absolute rate of stroke was 11.91 per 1,000 person-years (95% CI 11.41–12.43) in people with diabetes (n = 41,799) and 5.55 per 1,000 person-years (95% CI 5.40–5.70) in the comparison group (n = 202,733). The age-adjusted HR for stroke in type 2 diabetic compared with non-diabetic subjects was 2.19 (95% CI 2.09–2.32) overall, 2.08 (95% CI 1.94–2.24) in men and 2.32 (95% CI 2.16–2.49) in women. The increase in risk attributable to diabetes was highest among young women (HR 8.18; 95% CI 4.31–15.51) and decreased with age. No investigated comorbidity or lifestyle characteristic emerged as a major contributor to risk of stroke.Conclusions/interpretation This study provides risk estimates for stroke for an unselected population from UK general practice. Patients with type 2 diabetes were at an increased risk of stroke, which decreased with age and was higher in women. Additional risk factors for stroke in type 2 diabetic patients included duration of diabetes, smoking, obesity, atrial fibrillation and hypertension.