Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Liposomal drug delivery systems: from concept to clinical applications.

Background Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. Methods We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. Results After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 perce...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa022457

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

BackgroundIn a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. MethodsIn this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. ResultsAmong the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%)....

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Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa ...

/pdf/five-year-follow-up-of-patients-receiving-imatinib-for-2ejt1h30j2.pdf

Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia

Fluorescence in situ hybridization with a chromosome 12-specific alpha-centromeric probe and a 13q14 yeast artificial chromosome probe was performed on interphase cells from 100 patients with B-cell chronic lymphocytic leukemia. Thirty-one patients exhibited a 13q14 deletion. No correlation was found between 13q14 deletions and clinical stage, sex, or morphology. Sixteen patients had trisomy 12, including 6 (of 12) with an atypical morphology. Trisomy 12 and 13q14 abnormalities were detected concomitantly in three patients only. The analysis of patients with deletions clearly showed that in five cases a significant number of cells retained two signals with the yeast artificial chromosome probe, indicating a genetic heterogeneity among the leukemic population. Our data confirm that the 13q14 deletion is a frequent event, indicate that the concomitant occurrence of 13q14 deletion and trisomy 12 is rare but possible, and show that both abnormalities are secondary events in B-cell chronic lymphocytic leukemia.

https://clincancerres.aacrjournals.org/content/clincanres/2/10/1673.full.pdf

13q14 deletions are not primary events in B-cell chronic lymphocytic leukemia : A study of 100 patients using fluorescence in situ hybridization

BACKGROUND Impact of total-body irradiation (TBI) in conditioning regimen on outcome for patients with mantle cell lymphoma (MCL) remains unknown. METHODS Patients with MCL who underwent autologous stem-cell transplantation (ASCT) in our institution were eligible for the present study (n=73). We analyzed the impact of various biologic and clinical parameters, with and without TBI, on patient outcome. RESULTS All patients presented with chemosensitive disease at transplantation. Median follow-up from ASCT was 37.2 months. One- and three-year overall survival (OS) rates were 90.3% and 74.5%, progression-free survival (PFS) rates were 85% and 59%, respectively. Three-year OS and PFS rates in the non-TBI group versus TBI group were similar: 80% versus 72.5% and 60% versus 57%, respectively. In univariate analysis, the use of TBI did not modify OS or PFS (P=0.93 and P=0.48, respectively). This remains true for patients who underwent ASCT up front. According to multivariate analysis, OS tended to be shorter for patients presenting with high Mantle Cell Lymphoma International Prognostic Index or low hemoglobin level. CONCLUSIONS Absence of TBI in conditioning regimen modifies neither PFS nor OS. The present retrospective and monocentric analysis shows that transplant patients with MCL remain highly exposed to relapse.

Is ASCT with TBI superior to ASCT without TBI in mantle cell lymphoma patients

Background. Multiple lymphomatous polyposis (MLP) results from gastrointestinal involvement by a B-cell lymphoma that originates from the mantle zone of lymphoid follicles. This well described clinicopathologic entity has a poor prognosis : the rate of complete response after conventional chemotherapy is very low. High dose radiochemotherapy with autologous stem cell transplantation (ASCT), which is one of the most intensive treatments of lymphoma, to the authors' knowledge has not been evaluated in the treatment of MLP. Methods. Four consecutive patients with MLP were treated with high dose radiochemotherapy and ASCT while they were in partial response after conventional chemotherapy. Results. Three patients achieved a complete clinical and histologic response and one achieved a complete clinical resolution of symptoms, but with persistent histologic lesions. Progression free survival ranged from 11 to 35 months. Conclusions. Autologous stem cell transplantation for patients with MLP is feasible and may be more effective than conventional chemotherapy. However, further studies are needed to assess the actual place of this type of treatment in the management of MLP

High dose radiochemotherapy followed by autologous stem cell transplantation in four patients with multiple lymphomatous polyposis.

Treatment of acute non-lymphoblastic leukaemia in elderly patients

Bortezomib (BOR) and High Dose Melphalan (HDM) as Conditioning Regimen Before Autologous Stem Cell Transplantation (ASCT) for De Novo Multiple Myeloma (MM): Final Results of the IFM Phase II Study VEL/MEL

Jean Luc Harousseau

Papers

13q14 deletions are not primary events in B-cell chronic lymphocytic leukemia : A study of 100 patients using fluorescence in situ hybridization

Is ASCT with TBI superior to ASCT without TBI in mantle cell lymphoma patients

High dose radiochemotherapy followed by autologous stem cell transplantation in four patients with multiple lymphomatous polyposis.

Treatment of acute non-lymphoblastic leukaemia in elderly patients

Bortezomib (BOR) and High Dose Melphalan (HDM) as Conditioning Regimen Before Autologous Stem Cell Transplantation (ASCT) for De Novo Multiple Myeloma (MM): Final Results of the IFM Phase II Study VEL/MEL