Patients In Different Risk Groups Research Articles

Indicações em transplante de células-tronco hematopoéticas em pacientes adultos com leucemia linfoide aguda

Na leucemia linfoide aguda (LLA), a proliferação, acúmulo e infiltração de células imaturas caracterizam uma entidade heterogênea, apresentando ampla diversidade de aspectos clínicos e biológicos. Na LLA do adulto, a concentração de fatores prognósticos de alto risco, como o imunofenótipo B, alterações cromossômicas e, principalmente, a presença do cromossomo Ph positivo. Considerações a respeito da alta morbidade e mortalidade relacionadas ao transplante de células-tronco hematopoéticas (TCTH) têm gerado controvérsias quanto à indicação desta modalidade terapêutica, nos pacientes adultos com LLA em primeira remissão (1ª RC). Os resultados da terapia convencional com quimioterapia, diante dos diferentes grupos de risco em pacientes com LLA, têm sido utilizados para a indicação de TCTH. Apresentamos o algoritmo de indicações do transplante de células-tronco hematopoéticas em pacientes adultos com LLA.

Natural Rubber Latex Allergy in Pediatric Patients

During the last fifteen years better hygienic standards led to an increased consumption of natural rubber latex (NRL) gloves for the protection of medical staff. At the same time case reports about an IgE-mediated allergy to NRL sometimes causing life-threatening anaphylactic reactions came up. This allergy was different from the well-known type IV reactions caused by latex additives. Health care workers and patients with multiple surgery surgeries were identified as high risk groups. For unknown reasons patients with spina bifida (SB) showed the highest prevalence of NRL-specific IgE-antibodies. A pre-existing atopy increased the risk of latex sensitization. Allergic reactions were caused mainly by medical procedures, especially surgeries, if latex gloves and other latex containing devices were used. Meanwhile some allergenic proteins in NRL (named Hev b in accordance with the rubber tree Hevea brasiliensis) could be identified. Patients in different risk groups showed distinct prevalences of sensitization to these allergens. The way of the allergen uptake (aerogen or by direct mucosal contact during surgeries) played an important role in the sensitization to different allergens. Most of the latex allergens like Hev b 1, Hev b 3, Hev b 6.02 have been totally sequenced. Since the sequence of all registrated allergens (Hev b 1 - Hev b 13) is known, it was possible to localize in Hev b 1, Hev b 5 and Hev b 6.01 several IgE binding sites as well as T cell epitopes. Cross-reacting antibodies between NRL and numerous fruit were described and for some proteins structural homologies were well characterized. For the in vitro diagnosis of NRL allergy serologic tests with improved extracts and recombinant allergens (for instance ImmunoCAPTM system) are available. NRL protein extracts for skin prick tests were difficult to standardize. The use of natural extracts in combination with recombinant latex allergens could be one possible future perspective for skin testing. The problem of NRL allergy is still not resolved but significant progress has been made in its prevention. In high risk patients like persons with spina bifida a primary prophylaxis was performed with success, but also secondary or tertiary prophylaxis allows safe operations without symptoms of NRL allergy.

Some Old and Some New Statistical Tools for Outcomes Research

Outcomes research “seeks to understand the end results of particular health care practices and interventions”1 to inform the development of clinical practice guidelines, evaluate the quality of medical care, and foster effective interventions to improve the quality of care.2 Although randomized trial designs have been used to assess quality of care and to identify effective interventions in the real world,3,4 the empirical basis of outcomes research largely rests on data collected in the observational setting (eg, in the routine setting of everyday practice). With more emphasis placed on increasing the value of health care in terms of lives saved and morbidity avoided, outcomes researchers are making unprecedented demands of observational databases. This is evidenced by the increasing number of and participation in national registries. These include the National Cardiac Data Registry of the American College of Cardiology; the Implantable Cardioverter Defibrillator Registry launched jointly by the American College of Cardiology and the Heart Rhythm Society; the National Cardiac Surgery Database of the Society of Thoracic Surgeons; and the Interagency Registry of Mechanically Assisted Circulatory Support Devices funded by the National Heart, Lung, and Blood Institute, the Centers for Medicare and Medicaid Services, and others. Empirical analyses of these databases require statistical tools that can handle the complexity of the data: observational, sometimes hierarchical, often with multiple outcomes, and always with some missing data. The purpose of the present article is to review key statistical methods important to outcomes research and to introduce newer methodology. The article describes 4 methodological issues commonly present when observational data are analyzed; summarizes the primary assumptions associated with strategies to handle these common problems; demonstrates methods to assess the plausibility of the assumptions associated with each strategy; and illustrates these concepts using examples from cardiovascular outcomes research. Although the intent of the …

Liver Transplantation for Hepatocellular Carcinoma: Hangzhou Experiences

Liver transplantation (LT) has been the treatment of choice for patients with hepatocellular carcinoma (HCC). This study was designed to summarize our experience in LT for HCC patients and establish a new set of criteria for patient selection and prognosis prediction. Data of 195 patients with HCC were retrospectively analyzed and various clinical and pathological factors for survival and tumor-free survival were examined by univariate and multivariate analyses. Macrovascular invasion, preoperative serum alpha fetoprotein (AFP) level, tumor size, multifocality, histopathologic grading, distribution, and cirrhosis background were significant factors for survival and tumor-free survival by univariate analysis. Multivariate analysis identified macrovascular invasion, tumor size, preoperative AFP level, and histopathologic grading were prognostic factors independently associated with patient survival or tumor-free survival (RR=1.688-2.779, P=0.000-0.034). Based on the prognostic stratification of different risk groups of patients without macrovascular invasion, Hangzhou criteria was established, containing one of the two following items: (a) Total tumor diameter less than or equal to 8 cm; (b) total tumor diameter more than 8 cm, with histopathologic grade I or II and preoperative AFP level less than or equal to 400 ng/mL, simultaneously. The difference between survival curves of patients fulfilling Milan criteria (n=72) and patients fulfilling Hangzhou criteria (n=99) did not achieve statistical significance (5-year survival rates: 78.3% vs. 72.3%, P>0.05). Of the patients exceeding Milan criteria (n=123), those who fulfilled Hangzhou criteria (n=26) also had better prognosis than the others (n=97) (P=0.000). The results of this study show a reliable and feasible candidates selection and prognostic criteria of LT in HCC patients.

Efecto de AM3 en la calidad de vida de pacientes con enfermedad pulmonar obstructiva crónica en subgrupos de riesgo

AM3 is an immunomodulator that significantly improves the quality of life of patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of AM3 on the quality of life of patients in different risk groups and identified the factors associated with change in this variable. This was a randomized, double-blind, placebo-controlled trial involving parallel groups of patients. The duration of the trial was 6 months. The study involved 253 patients with a mean (standard deviation) age of 67.7 (8.1) years and a mean forced expiratory volume in one second (FEV1) of 49.7% (10.2%). Only 121 patients (47.8%) suffered at least one exacerbation during the 6 months period. At the end of the study period, the improvement in St. George's Respiratory Questionnaire (SGRQ) score in those patients who suffered an exacerbation but who received AM3 was significantly greater than that experienced by similar placebo-treated patients (-8.10 compared to -2.5 units; p=0.034). Patients treated with inhaled corticoids also improved more with AM3 than with placebo (-9.17 compared to -4.44; p=0.035). In the 108 patients with an FEV1 of <50%, the improvements were not significantly different (-9.57 vs. -6.57; p=0.23). The factors influencing the change in SGRQ score were baseline SGRQ (p<0.001), exacerbations (p<0.008), an FEV1 of <50% (p<0.032) and treatment with AM3 (p<0.004). Among the patients who experienced exacerbations, treatment with AM3 helped prevent the deterioration of their quality of life. Along with AM3 treatment, the factors that independently influenced the change in SGRQ score were suffering from an exacerbation and poorer pulmonary function.

Portal hypertension and variceal bleeding-Unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single-topic conference

Many randomized controlled trials (RCTs) have advanced the knowledge of the complications of portal hypertension, specifically in the management of varices and variceal hemorrhage. The endpoints in most of these trials have used definitions attained at international consensus workshops that have been published in medical journals since the first Baveno conference in 1992.1 Three more international consensus conferences have helped further define clinical endpoints and practice recommendations.2-5 This article summarizes the results of an Endpoints Single Topic Conference on “Portal Hypertension and Variceal Bleeding—Unresolved Issues” that took place in Atlanta, GA, in June 4-6, 2007 and that was sponsored jointly by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver and constitutes the 6th international consensus conference in the area of varices and variceal hemorrhage. As outcomes have improved and knowledge has been gained, it is necessary to prioritize areas that require further research, to define surrogate markers of outcome and to stratify patients in different risk groups. These were the objectives of this single-topic conference. For areas in the management of varices and variceal hemorrhage in which it was decided that no further trials were necessary or plausible, practice recommendations were put forward. In some instances, these differed from recommendations put forward at the most recent consensus conference in Baveno 20045 and were incorporated into the recently published AASLD/ American College of Gastroenterology (ACG)-sponsored recommendations.6,7 Recommendations were obtained by majority agreement defined as agreement by greater than 70%of 23 expert participants (listed at the end of the article).

Long-term follow-up of women enrolled in a randomized trial of adjuvant chemotherapy for early stage ovarian cancer (ICON1)

5509 Background: ICON1 and a meta-analysis of all relevant trials demonstrated an improvement in 5 year recurrence-free and overall survival (RFS and OS) for women with early-stage epithelial ovarian cancer (ES EOC) treated with adjuvant chemotherapy compared to no adjuvant chemotherapy. We aimed to determine if this initial benefit is maintained long-term and whether benefit is different with different risk groups of patients defined by stage, grade and histology. Method: 477 women with ES EOC were recruited from centres in Italy (271 women) UK (195) Switzerland (11) between August 1991 and January 2000. 5-year results were presented at ASCO 2001. Systematic long-term follow up was planned and completed in May 2006. Results: With a median follow-up of 9.2 years, 168 women have developed recurrent disease or died and 144 women have died. The Hazard Ratio (HR) for RFS of 0.70 in favour of adjuvant chemotherapy (95% CI 0.52–0.95 p= 0.023) translated into an improvement of 10-year absolute RFS of 10% from 57 to 67%. For OS, HR was 0.74 (95% CI 0.53–1.02 p= 0.066), a corresponding improvement in 10-year absolute OS of 8% from 64% to 72%. 26% of patients died from causes other than ovarian cancer. Stage I patients were grouped as low (Ia, grade 1), medium (Ia grade 2, Ib or Ic grade 1) and high risk (Ia, grade 3, Ib or IC grade 2 or 3, any clear cell). The test of interaction between risk groups and adjuvant treatment for RFS and OS was 0.055 and 0.13, respectively. The HR, 95%CI and p value are summarised in the table . Conclusions The long-term benefit of adjuvant treatment on RFS is confirmed. There is clear evidence that adjuvant chemotherapy reduces the risk of recurrence/death or death alone in high-risk patients but not in the low-risk group. [Table: see text] [Table: see text]

Risikoadaptierte Therapie der akuten myeloischen Leukämie

Genetic and molecular techniques have provided increasing insights into the biology of acute myeloid leukemia (AML). These investigations showed that AML is not a homogeneous disease but a heterogeneous group of biologically different subentities. These subentities are currently primarily defined by cytogenetics and molecular markers. They differ substantially in response to therapy and long-term outcome and hence allow different risk groups of patients to be defined. These will guide therapeutic decisions in future therapeutic strategies and may ultimately lead to an individualized treatment concept.

High Density Lipoprotein Associated Paraoxonase1 Activity in Relation to Oxidative Stress in CAD Patients

High density lipoprotein (HDL) has been considered to possess antioxidant properties in addition to its antiatherosclerotic effects. Paraoxonase1 (PON1) associated with HDL has been considered to be responsible for its antioxidant potential. Present investigation aimed to study PON1 activity in relation to oxidative stress in Indian (Punjabi) population suffering from coronary artery disease (CAD). Significantly reduced serum PON1 activity was observed in CAD patients compared to normal individuals. Reduced PON1 activity was also observed in CAD positive diabetics, hypertensives, smokers and alcoholics in comparison to CAD negative diabetics, hypertensives, smokers and alcoholics and controls. Activity of PON1 varies significantly among patients in different risk groups, may be leading to different susceptibility towards disease development and its progression in various CAD risk factors. Patients were also having increased oxidative stress as indicated by their significantly raised serum MDA levels. Significant variation in serum MDA levels was also observed in different risk groups. Of all the risk factors, smoking was associated with highly reduced PON1 activity and significantly raised serum MDA levels. A significant negative coefficient of correlation (r2 0.71) was observed between serum PON1 activity and serum MDA levels. Activity of another antioxidant enzyme i.e. superoxide dismutase (SOD) was also reduced in CAD patients. However SOD activity did not vary significantly among patients in different risk groups. Depressed PON1 activity in CAD patients may reduce their ability to protect LDL from oxidation. In conclusion, significantly reduced paraoxonase1 activity has been associated with CAD and its various risk factors in Indian (Punjabi) population. Smoke may extensively modify serum PON1 activity in a negative direction.

Prognostic factors in non-metastatic Ewing's sarcoma tumor of bone: An analysis of 579 patients treated at a single institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1998

We aimed to identify pretreatment and treatment factors that may influence the outcome of Ewing's sarcoma family tumors of bone and enable customized therapy for future studies with a retrospective analysis of 579 patients with non-metastatic Ewing's sarcoma treated with combined adjuvant or neoadjuvant chemotherapy at a single institution between 1972 and 1998. We evaluated the prognostic significance of gender, age, site and volume of tumor, serum level of LDH, type of local treatment, type of chemotherapy and histologic response to preoperative treatment. The 5- and 10-year disease-free survival rates were 56.9% and 49.2% respectively. Multivariate analyses showed that all the evaluated factors, with exclusion of the tumor site, were significantly correlated with the 5-year disease-free survival. We concluded that the outcome of non-metastatic ESF of bone tumors is influenced by many clinical and treatment-correlated variables. In order to gain the greatest benefit from treatment, while reducing the morbidity, appropriate therapeutic strategies for different risk groups of patients should be selected. Criteria to stratify patients according to the risk of local or systemic relapse should not be based on a single prognostic factor, but should include all the variables that showed prognostic significance.

Gene Expression Profiling of the Bone Marrow Mononuclear Cells from Patients with Melodysplastic Syndrome.

Myelodysplastic syndrome (MDS), a clonal disorder of hematopoietic stem cells, is characterized by cytopenia in at least one lineage of peripheral blood and dysplastic features in BM cells. It has been considered as a preleukemic condition for a high risk of transformation to AML. The FAB classification has divided MDS into five clinical categories: RA, RAS, RAEB, RAEB-t and CMML. To date, the key genes involved in the pathogenesis and its progression to acute leukemia has not been clearly identified. This was at least partially caused by a narrow scale of genes which could only been studied once a time by using traditional methods. The present study was to investigate the molecular mechanism of MDS by using cDNA microarray techniques. We have first applied total RNA of bone marrow monoculear cells (BMNCs) from 2 MDS patients (one RA and one RAS) to a BioStar H141 microarray ( United Gene Holdings Co. LTD, Shanghai, China) containing 13484 gene cDNA clones and ets. Based on the preliminary results of these assay, 500 genes which were shown most remarkably differentially expressed in MDS compare to normal control, and with known functions and potential involvement in hematopoiesis regulation, were selected to design and compose 10 cDNA chips. These arrays were then used to analyze the gene expression pattern of BMNCs from 10 patients with MDS, including 4 RA, 1 RTC, 4 RAEB, and 1 RAEBt. To confirm the microarray results and to evaluate the disease relevance of some selected genes from array results, a semiquantitative RT-PCR was performed to analyze gene expression in fifty addi-tional patients with MDS (28 RA, 15 RAEB, 7 RAEBt), 38 acute myeloid leukemia (7 M1, 12 M2, 4 M3, 4 M4, 5 M5, 6 M6), 15 atypical anaplastic anemia (AA), and 12 hypercellular anemia. Our results revealed that 95 genes were abnormally expressed in at least five MDS patients compared to normal controls, involving cell growth and differentiation regulation, cell cycle control, signaling, redox, such as thrombospondin 1 (THBS1), phosphatase and tensin homolog (PTEN), MAD, DNA-damage-inducible transcript 3 (DDIT3), ets variant gene 1 (ETV1), and G1 to S phase transition 1 (GSPT1). These MDS patients in different risk groups could be clustered into two groups overall by hierarchical clustering, wherein a case with isolated thrombocytopenia and other RA patients were clustered into two subgroups 5 genes (RNAHP, DDIT3, FOXO3A, GSPT1, and ETV1) which displayed a most marked differential expression pattern in most MDS patients, were selected as "candidate genes". Consistent expression patterns of 3 (60%) in 5 genes were confirmed by semiquantitative RT-PCR. Further analysis showed different transcript levels of RNAHP, DDIT3 among patients with MDS in different risk group, AML, and normal controls. Meanwhile, the transcript levels of five genes were also compared in the patients with RA, AA and other hypercelluler anemia patients. There was significant difference in RNAHP levels between RA and CAA, or other hypercelluler anemia (P<0.05), similar diversity also seen in ETV1 levels between RA and AA (P<0.01). However, significant differences in DDIT3, FOXO3A, and GSPT1 levels were not observed. Our study suggested that gene expression profiling of MDS patients may reveal a specific transcription patterns for BMNCs in MDS. The abnormal expression of RNAHP, DDIT3 and ETV1 may play roles in the patho-genesis of MDS and may provide useful biomarkers for the molecular diagnosis of MDS.

Rectal cancer: preoperative versus postoperative irradiation as a component of adjuvant treatment

The search for improved disease control and survival for resectable but high-risk rectal cancers has led to studies that combine all 3 modalities. For surgically resected, high-risk rectal cancers, postoperative chemoradiation has been shown to improve both disease control (local and distant) and survival (disease free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health Colorectal Cancer Consensus Conference. Three randomized studies showed improved overall survival (OS) and local control for patients treated with postoperative irradiation and chemotherapy when compared with surgery alone or surgery plus irradiation control arms. These include 2 US trials, Gastrointestinal Tumor Study Group and Mayo/North Central Cancer Treatment Group (NCCTG) and a Norway trial. Although most preoperative external beam radiation trials show reductions in local relapse with the addition of preoperative EBRT to resection, only the large Swedish trial of ∼1,100 patients showed a survival improvement when compared with a surgery alone control arm for resectable primary rectal cancers. In a recent pooled analysis of 3 postoperative adjuvant rectal cancer trials (NCCTG 794751, NCCTG 864751, and GI Intergroup 0114) survival and disease relapse were dependent on both TN and NT stage of disease (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more positive nodes), T substage influenced 5-year OS (T1-2, 69%; T3, 48%; and T4, 38%; P < .001). Ongoing randomized trials are being conducted for patients with high-risk, resectable primary rectal cancers. The intent is to help define optimal combinations of postoperative chemoradiation (US GI Intergroup), to test sequencing issues of preoperative versus postoperative chemoradiation (Germany trial), and to determine if concurrent and maintenance 5-FU and leucovorin add to the benefits found with preoperative irradiation (European Organization for Research and Treatment of Cancer). For subsequent trials, it may be preferable to perform separate studies, or a planned statistical analysis, for different risk groups of patients (low, intermediate, moderately high, and high), as defined in the rectal cancer pooled analysis.

How low is the α/β ratio for prostate cancer?

Purpose : It has been suggested recently that the α/β ratio for human prostate cancer is low (around 1.5 Gy), and much debate on the evidence for such a low value is ongoing. Analyses reported so far ignored the contribution of tumor repopulation. Extremely low α values and unrealistic cell numbers of tumor clonogens are found in these studies. In this paper, we present a comprehensive analysis of the updated clinical data to derive a self-consistent set of parameters for the linear-quadratic (LQ) model. Methods and Materials : The generalized LQ model, considering the effects of dose rate, sublethal damage repair, and clonogenic proliferation, was used to analyze the recently reported clinical data for prostate cancer using either external-beam radiotherapy or brachytherapy. Three LQ parameters, α, α/β, and the repair time, were determined based on the clinical finding that the external-beam radiotherapy and the 125I and 103Pd permanent implants are biologically equivalent. The tumor control probability model was used also to analyze the clinical data to obtain an independent relationship of α/β vs. α and to estimate clonogenic cell numbers for patients in different risk groups. Results : Based on the analysis of clinical data and a consideration of repopulation effect, we have derived a self-consistent set of LQ parameters for prostate cancer: α = 0.15 ± 0.04 Gy −1, α/β = 3.1 ± 0.5 Gy. Our analysis indicates the half-time of sublethal damage repair to be in the range from 0 to 90 min with a best estimate of 16 min. The best estimate of clonogenic cell numbers in prostate tumors is found to range from 10 6 to 10 7 according to the patient risk level. These values are more realistic than those derived previously (only 10–100). Conclusions : The effect of tumor repopulation is not negligible in determining the LQ parameters for prostate cancer, especially for the low-dose-rate permanent implants. Analysis of clinical data for prostate cancer with corrections for damage repair and repopulation effects results in a low α/β ratio of 3.1 Gy. Unrealistic clonogenic cell numbers and extremely small values of α reported in the literature can be resolved by correcting for repopulation effect. The LQ parameters derived presently from the clinical data are consistent with reports of intrinsic radiosensitivity in vitro.

RECENT CLINICAL TRIALS IN ACUTE LYMPHOCYTIC LEUKEMIA BY THE CANCER AND LEUKEMIA GROUP B

The Cancer and Leukemia Group B (CALGB) has performed a series of studies evaluating different aspects of remission induction and postremission treatment in adults with acute lymphocytic leukemia (ALL). In recent years, these clinical trials have been supplemented by systematic morphologic, immunophenotyping, cytogenetic, and molecular genetic studies leading to the identification of different risk groups of patients who may warrant individualized treatments. These protocols have enrolled all adult patients older than 15 years with ALL, without an upper age restriction, and did not exclude Philadelphia (Ph) chromosome-positive patients.

Multifactorial analysis of local recurrences in rectal cancer, including DNA ploidy studies: a predictive model.

DNA ploidy studies were performed in 188 patients operated on for rectal cancer. In order to define different risk groups of patients, a stepwise logistic regression was carried out in 138 patients who underwent abdominal "curative" resections. Thirty-seven variables were analyzed. Although several variables were significant, only three improved the prognostic value: (1) more than three positive lymph nodes (p = 0.0007); (2) macroscopic local tumor invasion (p = 0.01); and (3) DNA ploidy (p = 0.03). Standardized discriminant coefficients were used to obtain a model and format for predicting local recurrences. This is the first time that a predictive model for rectal cancer, using DNA ploidy as a variable, is reported. Based on calculated discriminant values (DV), patients can be divided into three subgroups: (1) low risk for local recurrences (DV < -1.9, n = 56)--local recurrences were observed in two patients (3.6%); (2) moderate risk (DV between -1.9 and -0.6, n = 55)--local recurrences occurred in nine patients (16.4%); and (3) high risk (DV > -0.6, n = 27)--local recurrences occurred in 14 patients (51.8%). This predictive model for local recurrences has much better prognostic value than Dukes' staging (p < 0.0001).

Large-cell lymphoma: a study of prognostic factors and assessment of five recently proposed predictive systems.

The main initial and evolutive variables of 133 patients with large-cell lymphoma treated with adriamycin-containing regimens were evaluated for prognostic significance. At the time of analysis, 66 patients had died with the median survival of the series being 48.9 months. Variables associated with poor prognosis in the univariate study were: lymphoma of immunoblastic subtype, advanced Ann Arbor stage, presence of B-symptoms, poor performance status, bulky disease (> or = 10 cm), involvement of two or more extranodal sites, bone marrow infiltration, and high serum LDH levels. In the multivariate analysis, Ann Arbor stage (p < 0.001), bulky disease (p = 0.004), performance status (p = 0.018), and histologic subtype (p = 0.021) retained their prognostic value. After excluding those patients with localized disease (stage I), the Ann Arbor staging system lost prognostic significance in favor of bone marrow infiltration (p = 0.009) and serum LDH (p < 0.001). However, when response to treatment was included in the regression model, it proved to be the most important prognostic factor (p < 0.001), followed by serum LDH (p = 0.004). On the other hand, when the analysis was restricted to complete responders, serum LDH at diagnosis was the only parameter useful to predict survival (p = 0.008). Finally, five recently proposed prognostic classifications were useful to separate different risk-groups of patients when applied to the series.

Presenting Features and Prognosis of Chronic Lymphocytic Leukemia in Younger Adults

Abstract We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.

Presenting features and prognosis of chronic lymphocytic leukemia in younger adults [see comments

We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.

Chronic myelomonocytic leukemia--clinicobiological characteristics: a multivariate analysis in a series of 70 cases.

In a series of 70 patients diagnosed according to the FAB criteria, 42 clinical and biological disease characteristics were analyzed in order to identify significant prognostic factors by means of univariate and multivariate analysis. The univariate analysis identified ten parameters associated with poor prognosis: Symptoms of anemia, WBC over 10 x 10(9)/l, presence of blast cells, myeloid precursors or erythroblasts in peripheral blood (PB), high bone marrow (BM) cellularity, severe dysthrombopoiesis, percent of blast cells in BM and high serum levels of bilirubin and LDH. The Cox proportional hazards regression method revealed that the combination of high leukocyte counts and BM percentage of blast cells had the strongest predictive relation to survival length (p = 0.002 and p = 0.060 respectively). A new multivariate analysis treating the presence of myeloid and erythroid precursors in PB as a single variable selected only this as the most significant prognostic factor (p = 0.001). Both regression models allowed us to discriminate two significantly different risk groups of patients.