Cochrane Haematological Malignancies Group Research Articles

An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data

The management of patients with chronic lymphocytic leukaemia is currently undergoing improvements due to novel therapies and a plethora of biological and genetic variables that add prognostic information to the classic clinical staging systems. We established an international consortium with the aim to create an international prognostic index for chronic lymphocytic leukaemia (CLL-IPI) that integrates the major prognostic parameters. We used results from a systematic search of the Cochrane Haematological Malignancies Group of MEDLINE, Embase, and Central databases for prospective, clinical phase 2 and 3 trials of chronic lymphocytic leukaemia, published between Jan 1, 1950, and Dec 31, 2010, which identified 13 trials. We contacted the principal investigators of these 13 trials, of which eight agreed to include individual patient data. We used the individual patient data from these phase 3 trials from France, Germany, Poland, the UK, and the USA to create the full analysis dataset. The full analysis dataset was randomly divided, using a random sample procedure, into training and internal-validation datasets. We did a univariate analysis and multivariate analyses using 27 baseline factors and overall survival as an endpoint. We assigned weighted risk scores to each factor included in the final multivariable model. We assessed the discriminatory value using C-statistics and also the validity and reproducibility of the CLL-IPI by subgroup analysis. We used two additional datasets from the Mayo Clinic (Rochester, MN, USA; MAYO cohort) and the SCALE Scandinavian population-based case-control study (SCAN cohort) as the external-validation datasets. 3472 treatment-naive patients were included in the full analysis dataset; 2308 were randomly segregated into the training dataset and 1164 into the internal-validation dataset. 838 patients were included in the MAYO cohort and 416 in the SCAN cohort. Median age of patients in the full analysis dataset was 61 years (range 27-86). Five independent prognostic factors were identified in the training dataset: TP53 status (no abnormalities vs del[17p] or TP53 mutation or both), IGHV mutational status (mutated vs unmutated), serum β2-microglobulin concentration (≤3·5 mg/L vs >3·5 mg/L), clinical stage (Binet A or Rai 0 vs Binet B-C or Rai I-IV), and age (≤65 years vs >65 years). Using a weighted grading of the independent factors, a prognostic index was derived that identified four risk groups within the training dataset with significantly different overall survival at 5 years: low (93·2% [95% CI 90·5-96·0]), intermediate (79·3% [75·5-83·2]), high (63·3% [57·9-68·8]), and very high risk (23·3% [12·5-34·1]; log-rank test comparing survival across the four risk groups p<0·0001; C-statistic, c=0·723 [95% CI 0·684-0·752]). These risk groups were confirmed in the internal-validation and external-validation datasets. The CLL-IPI combines genetic, biochemical, and clinical parameters into a prognostic model, discriminating four prognostic subgroups. The CLL-IPI will allow a more targeted management of patients with chronic lymphocytic leukaemia in clinical practice and in trials testing novel drugs. José Carreras Leukaemia Foundation.

Chinese External Validation of the Cochrane Haematological Malignancies Group Prognostic Index for Chronic Lymphocytic Leukemia Patients

Objection:Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disease characterized by highly clinical and biological heterogeneity. A number of biomarkers have been identified in predicting the overall survival (OS) over the last decades besides the traditional clinical staging. Recently, an international prognostic index (IPI) combing clinical staging and biomarkers was developed by the investigators of the Cochrane Haematological Malignancies Group. Due to genetic differences between Caucasic and Chinese CLL patients, our study was to validate the guiding function of IPI on Chinese CLL cases.Method:We performed a validation of the IPI proposed by the Cochrane Haematological Malignancies Group to stratify Chinese CLL patients prognostically in 225 CLL cases registered at our center. The five parameters (age, TP53 abnormalities, IGHV mutation status, b2-microglobulin and Binet stage) involved in the IPI were collected by clinical data, serum test, PCR and fluorescence in situ hybridization (FISH). Chi-square test, survival analysis, log-rank test and cox hazard regression analysis were utilized in the validation.Result:In the 225 Chinese CLL cases analysed in the validation, all five parameters involved in the IPI were associated with overall survival (OS) independently. The multivariate analysis demonstrated that age above 65 years old (HR 2.22; [1.15-4.30]; P=0.018), b2-microglobulin over 3.5 mg/L (HR 2.46; [1.22-4.94]; P=0.001), Binet staging B/C (HR 3.40; [1.02-11.33]; P=0.046), TP53 abnormalities (HR 2.72; [1.50-4.94]; P=0.012) and IGHV unmutation (HR 5.19; [2.51-10.77]; P<0.001) were OS related risk factors respectively. Then a total point score was calculated for each patient according to the grading system proposed by the Cochrane Haematological Malignancies Group investigators. There were 60 (26.7%) patients at low-risk (scoring 0-1), 57 (25.3%) patients at intermediate-risk (scoring 2-3), 65(28.9%) patients at high-risk (scoring 4-6) and 43 (19.1%) patients at very high-risk (scoring 7-10). The IPI allowed different prediction of time to treatment (TTT) in all groups (Fig. 1). The estimated median TTT were: 102 months for low-risk, 12 months for intermediate-risk and 1 month for high-risk group. However, the low-risk and intermediate-risk groups showed similar overall survival (P=0.424). Beyond that, significant difference was found between the intermediate, high and very high-risk groups. We combined the low-risk and the intermediate-risk groups into one to accommodate to the Chinese CLL cases. 117 (52%) patients were at low & intermediate-risk (scoring 0-3), thus leading to the significantly different prognostic value between groups (Fig. 1) . The estimated median survival times were: not reached for low&intermediate-risk, 63 months for high-risk and 128 months for very high-risk group.Conclusion:Our results basically validated the IPI proposed by the Cochrane Haematological Malignancies Group to prognostically stratify CLL patients in China, which confirmed the value of the novel prognostic index externally. However, a slight adaption was made to accommodate the Chinese cases better via the combination of the low-risk and intermediate-risk groups. We considered that a universally recognized prognostic model would be utilized to predict the disease progression and guide the treatment when initially diagnosed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Sixteenth biannual report of the Cochrane Haematological Malignancies Group: focus on Non-Hodgkin's lymphoma.

This sixteenth biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials (RCTs) in the field of hemato-oncology, with special focus on non-Hodgkin's lymphoma. The report covers the publication period June 2012 to July 2013. Trials are selected regarding their methodology and implication for clinical practice. Studies were identified by electronic search of MEDLINE using a broad search filter that covers all topics in hemato-oncology combined with a highly sensitive search filter for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions). Four RCTs are presented in detail, followed by two further RCTs of high importance in a short version. The report is finalized with an overview of new and updated Cochrane Reviews.

Fifteenth Biannual Report of the Cochrane Haematological Malignancies Group--Focus on Non-Hodgkin's Lymphoma

This fifteenth biannual report of the Cochrane Haematological Malignancies Group (CHMG) highlights recently published randomized controlled trials (RCTs) in the field of hemato-oncology, covering the publication period from October 2011 to May 2012. Implications for clinical practice and methodological aspects are the main principles for selecting trials for this report. Studies were identified by electronic search of MEDLINE using a broad search filter that covers all topics in hemato-oncology combined with a highly sensitive search filter for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions).

Interdisciplinary Evidence-Based Guideline for Diagnosis, Therapy and Follow-up of Adult Hodgkin Lymphoma Patients

Abstract 4230 Background:Hodgkin Lymphoma (HL) is one of the most common malignancies in young adults and has become curable for the majority of patients even in advanced stage. Nowadays, the main challenges are to develop strategies that decrease secondary malignancies and mortality, as well as to retain fertility after treatment. So far, there is no national or international evidence-based guideline giving recommendations for clinical practice in the treatment of HL patients. For this reason, various medical societies, clinical experts from the German Hodgkin Study Group (GHSG) and methodological experts from the Cochrane Haematological Malignancies Group (CHMG) have developed and consented a clinical practice guideline to improve and standardize diagnosis, treatment and follow-up for HL patients. This project was funded by the German Program for Guidelines in Oncology Implementation. Aims:To emphasize the clinically most relevant guideline recommendations related to diagnostics, treatment and follow-up of adult HL patients. Methods:Randomized controlled trials, systeamtic reviews, cohort studies and specific sensitive data included from systematic literature searches in CENTRAL and MEDLINE were appraised for quality and summarized in evidence tables. Based on these tables and trials, guideline authors generated high quality clinical recommendation in an intensive collaboration with the methodological experts clinical experts from different multi-interdisciplinary working-groups. During the final consensus conference, a total of 160 evidence-based recommendations were consented. Results:There is a strong consensus that all patients should be treated within a clinical trial. Chemotherapy is the mainstay of treatment for all stages of HL. The histological diagnosis should be confirmed by a reference pathologist. For early favorable stages, two cycles of ABVD followed by involved-field radiotherapy (IF-RT) at 20 Gy are strongly recommended; early unfavorable stages should be treated with 2 cycles of BEACOPP escalated followed by 2 cycles of ABVD and IF-RT of 30 Gy; for advanced stages six cycles of BEACOPP escalated followed by 30 Gy radiotherapy on PET-positive residual mass ≥ 2cm is strongly recommended. It is also recommended that patients with relapses or refractory disease, and without severe co-morbidities, receive autologous stem cell transplantation, but not myeloablative allogeneic stem cell transplantation. Additionally, treatment options of subgroups, such as nodular lymphocyte predominant HL, elderly patients or those with co-morbidities such as HIV, are specified in this guideline. The additional benefit of PET remains uncertain as of the lack of high-quality evidence, therefore different recommendations have been provided for staging, interim and follow-up evaluations. It is highly important that health care professionals discuss aspects of fertility protection with female and male patients before starting any treatment. Options for preserving fertility in women have to be adopted to treatment intensity. For male patients, it is recommended to cyropreserve sperm cells before starting the therapy, independently of treatment intensity. There is strong consensus that patients have to prevent to conceive a child during treatment. Health-care professionals should encourage patients to exercise and should discuss potential harms of complementary medicine with the patient. Due to their immunomudulating effect, it is not recommended to take mistletoes at any time. It is strongly recommended to motivate patients to give up smoking, due to the strong associated increased risk of secondary tumors, especially bronchial carcinoma. Structured follow-up care should be provided and should in particular detect relapses, long-term organ toxicities and secondary malignancies. Summary/Conclusions:The first evidence-based guideline on the treatment of patients with HL translates scientific evidence and expert knowledge into precise recommendations for these patients into clinical practice. In addition to this clinical value, the guideline will enable healthcare professionals to improve patient information and quality management. Disclosures:Engert:Takeda, Millennium: Honoraria, Research Funding. Borchmann:Millenium The Takeda Oncology Company: Research Funding, Travel Grants Other. von Tresckow:Millenium The Takeda Oncology Company: Honoraria, Travel Grants Other.

Twelfth Biannual Report of the Cochrane Haematological Malignancies Group--Focus on Tyrosine Kinase Inhibitors

This 12th biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials in the field of hemato-oncology, covering the publication period from September 1, 2009, through June 30, 2010. Implication for clinical practice and methodological aspects are the main principles used to select trials for this report. Studies on tyrosine kinase inhibitors for patients with chronic myeloid leukemia were identified through electronic search of MEDLINE with a broad search filter that covered all topics in hemato-oncology combined with a highly sensitive search filter for randomized studies as described in the Cochrane Handbook for Systematic Reviews of Interventions.

Eleventh Biannual Report of the Cochrane Haematological Malignancies Group: Focus on Hodgkin Lymphoma

The 11th biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials in the field of hemato-oncology that were identified through the continuous systematic search of MEDLINE. For this electronic search, a broad search filter covering all topics in hemato-oncology was combined with a highly sensitive search filter for randomized studies. This report covers publications from February 1, 2009, through August 31, 2009 (including electronic publications). For this 7-month period, 6344 potentially interesting articles were screened to identify 121 controlled clinical trials (randomized controlled trials or quasi-randomized clinical trials) of therapeutic interventions in hematologic malignancies.

Tenth Biannual Report of the Cochrane Haematological Malignancies Group—Focus on Acute Myeloid Leukemia

Tenth Biannual Report of the Cochrane Haematological Malignancies Group—Focus on Acute Myeloid Leukemia

Corticosteroids for preventing graft-versus-host disease after allogeneic myeloablative stem cell transplantation

Despite ongoing progress, acute and chronic GvHD still represent major drawbacks in the context of allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) due to their high morbidity and mortality. Corticosteroids are used as first-line treatment of acute and chronic GvHD. However, their role for preventing GvHD is unclear as the published study results are controversial. To determine the effectiveness of corticosteroids used for the prophylaxis of GvHD in adults following allogeneic myeloablative HSCT. in improving overall survival, disease-free survival, relapse incidence, non-relapse mortality, acute GvHD grade I to IV, II to IV and III to IV, chronic GvHD, incidence of infectious complications, other adverse effects and cause of deaths. We searched the Cochrane Haematological Malignancies Group trials register, CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (January 1999 to February 2006), EMBASE (January 1999 to 2004), LILACS covering publications until 2004, as well as handsearched conference proceedings, including citations until 2005. Randomised controlled trials (RCT) comparing the addition of corticosteroids to a GvHD prophylaxis regimen in adult patients having undergone allogeneic myeloablative HSCT were included into the review. All types and stages of the underlying disease as well as all types of possible HLA-matching were considered. Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Five RCTs involving 604 people were included. The pooled results revealed that the addition of corticosteroids reduces statistically significant the risk for acute GvHD grade I to IV (HR 0.58; 95% CI 0.45 to 0.76) and II to IV (HR 0.69; 95% CI 0.51 to 0.92). No evidence was found that it has any clinical relevance on overall survival (HR 0.99; 95% CI 0.79 to 1.25) or disease-free survival (HR 0.95; 95% CI 0.74 to 1.23). As well, no statistically significant influence was found for acute GvHD grade III to IV (HR 0.78; 95% CI 0.52 to 1.15), chronic GvHD (HR 1.21;95% CI 0.89 to 1.65]), relapse incidence (HR 0.82; 95% CI 0.57 to 1.18) or non-relapse mortality (HR 0.88;95% CI 0.61 to 1.26). No clear evidence was found that the rate of infectious complications (under the concomitant use of antiviral or antibacterial medication or both) increases with the addition of corticosteroids. With respect to the other outcomes no significant differences could be detected. The addition of corticosteroids reduces the incidences of acute GvHD grade I to IV and II to IV. This reduction, however, did not show any effect on overall survival and disease-free survival. Further randomised controlled studies are needed to evaluate if the timing of steroid administration has a significant influence on the outcome; data on quality of life should be assessed systematically.

Sixth Biannual Report of the Cochrane Haematological Malignancies Group Focus on Non-Hodgkin Lymphoma

Sixth Biannual Report of the Cochrane Haematological Malignancies Group Focus on Non-Hodgkin Lymphoma

Fourth Biannual Report of the Cochrane Haematological Malignancies Group

Fourth Biannual Report of the Cochrane Haematological Malignancies Group

Third Biannual Report of the Cochrane Haematological Malignancies Group

Third Biannual Report of the Cochrane Haematological Malignancies Group

Second Biannual Report of the Cochrane Haematological Malignancies Group

Second Biannual Report of the Cochrane Haematological Malignancies Group

Biannual report of the Cochrane Haematological Malignancies Group.

Biannual report of the Cochrane Haematological Malignancies Group.