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The role of chemotherapy additional to high‐dose methotrexate for treatment of patients with primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a malignant disease of the lymphatic system that accounts for about 2% to 5% of all primary intracranial tumours in immunocompetent patients. It is a form of extranodal non‐Hodgkin lymphoma (NHL) and appears at a median age of 62 years. PCNSL is a rare disease with an incidence of 2.7 cases per million population per year, but since the 1990s the occurrence of it has increased in immunocompetent as well as immunocompromised (mostly human immunodeficiency virus (HIV)‐infection related) populations. Symptoms of PCNSL can present manifold though the usual signs are neurological deficits, neuropsychiatric symptoms and raised intracranial pressure. Despite improved treatment strategies, overall survival is still poor and a standard of care for PCNSL patients has not been defined yet. However, high‐dose methotrexate (HD‐MTX) with additional chemotherapy is considered to increase overall survival although the value of additional chemotherapy remains unclear, as there is evidence of a higher risk of adverse events. In this systematic review we summarised and analysed the evidence from randomised controlled trials (RCTs) on efficacy and safety of methotrexate combined with additional chemotherapy in the treatment of adult, immunocompetent PCNSL patients regarding overall survival, progression‐free survival, response rate, adverse events, treatment‐related mortality and quality of life. We searched several important medical databases such as CENTRAL and MEDLINE and found one RCT with 79 patients that fulfilled our inclusion criteria. As a result, this review shows that patients treated with methotrexate plus cytarabine compared to high‐dose methotrexate alone have a statistically significant improvement in progression‐free survival and response rate. No statistically significant difference is shown for overall survival. Adverse events, especially infections, hepatotoxicity and haematological toxicities are more common in patients undergoing therapy with methotrexate plus cytarabine, although there are no differences in terms of treatment‐related mortality. Owing to the small number of included trials and patients, the findings in this review remain uncertain and more RCTs with enlarged numbers of patients and longer follow‐up periods are needed. However, the one analysed study demonstrated that RCTs are feasible on patients with this rare disease and should concentrate on overall survival.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

The role of brain radiotherapy (X‐rays) in the treatment of lymphoma in the brain

Background: Primary central nervous system lymphoma (PCNSL) is a type of cancer that occurs in the brain or spinal cord. It is a rare and aggressive type of lymphoma. People who develop PCNSL survive for only four months on average, if they do not receive treatment. For a long time the only treatment showing any benefit was whole brain radiotherapy (WBR), in which X‐rays are used to destroy cancerous cells in the brain. However, several studies suggest that this treatment method also produces signs of damage to healthy brain tissue. Since the introduction of methotrexate, a powerful chemotherapy drug showing great beneficial effects, experts have debated the role of radiotherapy in the treatment of people with PCNSL. Radiotherapy could be combined with chemotherapy, or not used at all, especially considering its potentially harmful effects.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

Idarubicin for treatment of newly diagnosed acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a type of cancer that mainly affects bone marrow and peripheral blood. Although 40% to 45% of AML patients enjoy long‐term disease‐free survival, most patients will die of the disease. Induction therapy is the first phase of treatment of newly diagnosed AML which is essential for prolonging survival. An anthracycline (a class of chemotherapy drugs derived from the Streptomyces bacterium Streptomyces peucetius var. caesius) combined with cytarabine (a chemotherapy drug used mainly in treatment of haematological malignancies) has remained the standard of induction therapy for several decades. Nowadays there are several kinds of anthracyclines available, among which idarubicin (IDA) draws more attention because of its theoretical advantages in improving efficacy and reducing side effects. However, clinical trials comparing IDA with other anthracyclines have conflicting results.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

High‐dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma

Hodgkin lymphoma (HL) is a malignancy of single lymph nodes, the lymphatic system, and might affect other additional organs. It is a relatively rare disease, accounting for two or three people per 100,000 every year in Western countries, but it is one of the most common cancers in young adults between 20 and 30 years of age. The second peak of the disease is after the age of 60 years. Treatment options for HL have improved since the 1980s, so that even patients in advanced stages may be cured with adequate therapy. Treatment approaches include chemotherapy, radiotherapy or chemotherapy combined with radiotherapy (combined‐modality treatment), of which the combined‐modality treatment is standard for most patients nowadays. Nevertheless, 15% to 20% of patients do not reach complete remission and have refractory disease or relapse. For these patients high‐dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) has become the optimal treatment option. However, the impact of this regimen on overall survival is still unclear. Therefore, we conducted a Cochrane Review on efficacy and safety of HDCT followed by ASCT in patients with primary refractory or relapsed HL. We searched several important medical databases (the Cochrane Central Register of Controlled Trials and MEDLINE) and summarised and analysed evidence from randomised controlled trials (RCTs). We identified three RCTs corresponding to our pre‐defined inclusion criteria treating 398 patients. We included two trials that compared HDCT followed by ASCT versus conventional chemotherapy alone, and one trial evaluating additional sequential HDCT (SHDCT) followed by ASCT against HDCT followed by ASCT.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2013

Late Effects of Treatment for Childhood Cancer (PDQ®): Patient Version

Expert-reviewed information summary about the health problems that continue or appear after cancer treatment has ended.

PDQ Cancer Information Summaries [Internet] - National Cancer Institute (US).

Version: August 11, 2016

Langerhans Cell Histiocytosis Treatment (PDQ®): Patient Version

Expert-reviewed information summary about the treatment of childhood Langerhans Cell Histiocytosis.

PDQ Cancer Information Summaries [Internet] - National Cancer Institute (US).

Version: October 3, 2016

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