Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

Prognostic value of cytologic parameters in acute myelogenous leukemia

The prognostic value of some current cytologic characteristics was assessed in 174 adult patients with acute myelogenous leukemia (AML) treated according to the AML‐5 protocol of the EORTC Leukemia and Hematosarcomas Group. A significantly higher rate of complete remission (CR) was observed in patients with low bone‐marrow (BM) cellularity, with BM blasts less than 80%, and with Auer rod positive cells more than 2.5% of the total blast cell population. A leukocyte count of less than 50 × 109/1 in the peripheral blood was also associated with a higher CR rate. No significant difference was found between the various French‐American‐British (FAB) subtypes, in spite of a trend towards a lower CR rate in patients with an M1, myeloblastic, poorly differentiated, subtype. The leukocyte count and the percentage of Auer rod positive cells were the only significant parameters for duration of survival from the beginning of maintenance treatment. However these features had no prognostic value for the duration of remission. It seems therefore that patients with a higher percentage of Auer‐rod‐positive cells and lower peripheral leukocyte counts can enter remission more easily, and can also more readily achieve subsequent remissions following relapse. The prognostic value of these routine cytologic features is probably related to their relationship with proliferative activity and tumor burden: the percentage of Auer‐rod‐positive cells correlates inversely with the leukocyte count, whereas leukocyte count, BM cellularity, and percentage of BM blasts are linked together. Copyright © 1984 American Cancer SocietySCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Pentostatin in T-cell malignancies - A phase II trial of the EORTC

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Quality of life in patients with acute myelogenous leukemia in prolonged first complete remission after bone marrow transplantation (allogeneic or autologous) or chemotherapy: A cross-sectional study of the EORTC-GIMEMA AML 8A trial

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Mitoxantrone-containing regimen for treatment of childhood acute leukemia (AML) and analysis of prognostic factors: results of the EORTC Children Leukemia Cooperative Study 58872.

The objective of this study was to evaluate the feasibility, the toxicity and the efficiency of a BFM-like treatment protocol for acute nonlymphoblastic leukemia (ANLL) of children in which mitoxantrone was substituted for conventional anthracycline. The chemotherapy called for induction (mitoxantrone, cytosine arabinoside, etoposide), consolidation (mitoxantrone, cytosine arabinoside, 6 thioguanine), followed by two intensification courses with cytosine arabinoside plus, respectively, mitoxantrone during the first and etoposide during the second courses. Maintenance therapy consisted of daily 6 thioguanine, four-weekly courses of cytosine arabinoside (s.c. daily during 4 days) and eight-weekly courses of mitoxantrone. The latter drug was pursued up to a total cumulative dose of 150 mg/sqm. Maintenance therapy was stopped at 2 years of diagnosis. Out of 108 patients, 84 (77%) achieved a complete remission, 10 died during induction of hemorrhage, sepsis or pulmonary infiltration by leukemic cells. A total of 32 relapses occurred. The median follow-up was 3.5 years. Actuarial event-free survival, disease-free survival and overall survival at 3 years as 41%, 52%, 56%, respectively. These results compare favorably with most reported data, and cytogenetic findings appear to be the most important prognostic factor.Clinical TrialJournal Articleinfo:eu-repo/semantics/publishe

Cytosine Arabinoside for Induction Salvage and Consolidation Therapy of Adult Acute Lymphoblastic Leukemia

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Pentostatin in prolymphocytic leukemia: Phase II trial of the European organization for research and treatment of cancer leukemia cooperative study group

Background: B-cell prolymphocytic leukemias or T-cell prolymphocytic leukemias are aggressive variants of chronic lymphoid leukemias. The small studies conducted to date have shown median survival durations of approximately 3 years for patients who have B-cell prolymphocytic leukemia and 7.5 months for those who have T-cell prolymphocytic leukemia, compared with about 8 years for patients who have chronic lymphocytic leukemia. In chronic lymphocytic leukemia, chemotherapy consisting of alkylating agents such as cyclophosphamide and chlorambucil combined with prednisone has achieved overall response rates of 50% to 70%, but this regimen has resulted in response rates of less than 25% in prolymphocytic leukemia. Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies. Purpose: This prospective phase II trial by the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer was performed to assess the activity and toxicity of DCF in prolymphocytic leukemia. Methods: Twenty patients with B-cell or T-cell prolymphocytic leukemia were given DCF at a dosage of 4 mg/m2 intravenously once a week for 3 weeks, then every other week for three doses. Patients who had at least partial response received maintenance therapy once a month for a maximum of 6 months. Fourteen patients had B-cell prolymphocytic leukemia, and six had T-cell prolymphocytic leukemia, as evidenced by morphologic and immunologic criteria; three were previously untreated, eight had been given one or two chemotherapeutic regimens, and nine had been given more than two. Results: One patient died of an unknown cause during the first 6 weeks of treatment, and one died of disseminated toxoplasmosis during the period of maintenance therapy, 5 months after achieving partial remission. Nine (45% response rate) of the 20 patients achieved partial remission, including seven (50%) of 14 with B-cell prolymphocytic leukemia and two (33%) of six with T-cell prolymphocytic leukemia. The median duration of response was 9 months (range, 2-30 months); for patients with B-cell prolymphocytic leukemia, the median remission duration was 12 months. No complete remission was observed. Toxic effects included nausea and vomiting (30%), infections (30%), and transient increase in liver enzymes (35%) and increatinine (20%) levels. Eight patients experienced thrombocytopenia, the major hematologic toxic effect; four had grade 3 or 4 toxic effects. Conclusion: DCF is active in prolymphocytic leukemia, even as salvage therapy in patients who had received multiple prior chemotherapeutic regimens. Implications: Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia. [J Natl Cancer Inst 85:658-662, 1993] © 1993 Oxford University Press.SCOPUS: ar.jinfo:eu-repo/semantics/publishe