India’s childhood leukaemia survival rate leaps to 80%, thanks to Manchester scheme

University of Manchester |June 2019 | India’s childhood leukaemia survival rate leaps to 80%, thanks to Manchester scheme

A paediatrician from the University of Manchester, Professor Vaskar Saha has helped cure children diagnosed with acute lymphoblastic leukaemia (ALL) by 15% during the five years he has led the ICICLE (Indian Childhood Collaborative Leukaemia Group) clinical project, in partnership with Tata Medical Centre, Kolkata.

Survival rates of most cancers in India are usually 15-25% lower than the United Kingdom. However, with Professor Saha’s work challenging the stereotype that cancer cure is a prerogative of affluent nations, his research has increased survival rates in Kolkata from 65% in 2014 to 80% in 2019.

Vaskar Saha, Professor of Paediatric Oncology at The University of Manchester and Senior Paediatric Consultant and Director of Translational Cancer Research at the Tata Medical Centre, Kolkata, said: “In the UK, 450 children are diagnosed annually with ALL, of which 400 will survive. In India, 9,000 of the 15,000 children diagnosed annually will survive.

“Not so long ago, four in ten Indian children would die because of poor treatment and relapse. The former was mainly due to the absence of standardisation in testing and treatment.

“If we can improve outcomes in India by 10%, then an additional 1,500 children a year grow up to lead normal lives.”

Professor Saha divides his time between Manchester and Tata Medical Centre

Before the ICICLE project launched, excellent medical centres across India were common and most children with acute lymphoblastic leukaemia were able to get the drugs they needed.

Historically, hospitals in India often work in isolation without exposure to the international research community. Travel costs to faraway hospitals were also difficult for poor families or those on low incomes.

Once clinicians started sharing their knowledge and standardised systems were put in place, change began to take root. (Source: University of Manchester)

Read the full story from the University of Manchester India’s childhood leukaemia survival rate leaps to 80%, thanks to Manchester scheme

 

Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years Technology appraisal guidance [TA554]

NICE | December 2018 | Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years | Technology appraisal guidance [TA554]

 

Evidence-based recommendations on tisagenlecleucel therapy (Kymriah) for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years.

 

Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years

 

See also: NICE recommends another revolutionary CAR T-cell therapy for adults with lymphoma

From eyedrops to potential leukaemia treatment

University of Nottingham | December 2018 | From eye drops to potential leukaemia treatment

Scientists at the University of Nottingham have found eye drops  have the potential to be used in treatment for an aggressive form of  blood cancer: acute myeloid leukaemia (AML).  Nottingham staff collaborated on research led by experts at the Wellcome Sanger Institute, University of Cambridge, and other scientists which led to the discovery that a compound identified in eye drops, being developed  to treat a form of eye disease, has shown promise for treating AML.The active ingredient in eye drops has the potential to treat AML, as it targets leukaemic blood cells without harming non-leukemic  blood cells. 

Full details of the research are available from:

University of Nottingham [press release]

Wellcome Sanger Institute [press release]

Abstract 

We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL-rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24. We focus on BRD4 as its main isoforms have distinct molecular properties and find that SRPK1 inhibition produces a significant switch from the short to the long isoform at the mRNA and protein levels. This was associated with BRD4 eviction from genomic loci involved in leukemogenesis including BCL2 and MYC. We go on to show that this switch mediates at least part of the anti-leukemic effects of SRPK1 inhibition. Our findings reveal that SRPK1 represents a plausible new therapeutic target against AML.

The full article is available to read from Nature Communications

Trial to test new treatment combination for children and adults with Leukemia

University of Birmingham | June 2018 | Trial to test new treatment combination for children and adults with Leukaemia

A clinical trial testing a new treatment combination in patients with leukaemia launches through the Combinations Alliance, a joint initiative between Cancer Research UK and the Experimental Cancer Medicine Centres (ECMC) Network based at University of Birmingham.

Researchers want to discover whether pharmaceutical companies AstraZeneca and MSD’s experimental medicine, selumetinib (AZD6244, ARRY-142886), can be effective in combination with a treatment, dexamethasone, already used for several conditions including leukaemia.

This clinical trial, the first of its kind to include both adults and children is based at the  Cancer Research UK Clinical Trials Unit at the University of Birmingham. This trial is planned to open in 23 centres throughout the UK and in 11 additional centres in 6 European countries, to help recruit 42 patients.

Professor Josef Vormoor, international clinical lead for the trial, said: ‘Although there are effective treatments for leukaemia, for some patients, the disease can return after they have been treated. If this combination is successful, it could give us an urgently needed new way to treat patients who have relapsed and have few treatment options left.’ (Source:University of Birmingham)

The full press release can be read at the University of Birmingham’s website 
Further details on the clinical trial are available from Cancer Research 

Health Care Use by Older Adults With Acute Myeloid Leukemia at the End of Life

Little is known about the patterns and predictors of the use of end-of-life health care among patients with acute myeloid leukemia (AML) | Journal of Clinical Oncology

End-of-life care is particularly relevant for older adults with AML because of their poor prognosis.

We performed a population-based, retrospective cohort study of patients with AML who were ≥ 66 years of age at diagnosis and diagnosed during the period from 1999 to 2011 and died before December 31, 2012. Medicare claims were used to assess patterns of hospice care and use of aggressive treatment. Predictors of these end points were evaluated using multivariable logistic regression analyses.

In the overall cohort (N = 13,156), hospice care after AML diagnosis increased from 31.3% in 1999 to 56.4% in 2012, but the increase was primarily driven by late hospice enrollment that occurred in the last 7 days of life. Among the 5,847 patients who enrolled in hospice, 47.4% and 28.8% started their first hospice enrollment in the last 7 and 3 days of life, respectively. Among patients who transferred in and out of hospice care, 62% received transfusions outside hospice. Additionally, the use of chemotherapy within the last 14 days of life increased from 7.7% in 1999 to 18.8% in 2012. Patients who were male and nonwhite were less likely to enroll in hospice and more likely to receive chemotherapy or be admitted to intensive care units at the end of life. Conversely, older patients were less likely to receive chemotherapy or have intensive care unit admission at the end of life, and were more likely to enroll in hospice.

End-of-life care for older patients with AML is suboptimal. Additional research is warranted to identify reasons for their low use of hospice services and strategies to enhance end-of-life care for these patients.

Full reference: Wang, R. et al. (2017) Health Care Use by Older Adults With Acute Myeloid Leukemia at the End of Life. Journal of Clinical Oncology. Published online: 7th August 2017

How big data is being mobilised in the fight against leukaemia

In a project funded by Bloodwise and the Scottish Cancer Foundation, we have created LEUKomics. This online data portal brings together a wealth of CML gene expression data from specialised laboratories across the globe | Lorna Jackson & Lisa Hopcroft for The Conversation

Image source: Paulo Henrique Orlandi Mourao – Wikimedia // CC BY-SA 3.0

Our intention is to eliminate the bottleneck surrounding big data analysis in CML. Each dataset is subjected to manual quality checks, and all the necessary computational processing to extract information on gene expression. This enables immediate access to and interpretation of data that previously would not have been easily accessible to academics or clinicians without training in specialised computational approaches.

Consolidating these data into a single resource also allows large-scale, computationally-intensive research efforts by bioinformaticians (specialists in the analysis of big data in biology). From a computational perspective, the fact that CML is caused by a single mutation makes it an attractive disease model for cancer stem cells. However, existing datasets tend to have small sample numbers, which can limit their potential.

Read the full blog post here

New treatment for Chronic Lymphatic Leukemia could replace chemotherapy

Medical University of Vienna. ScienceDaily, 15 March 2016.

Image source: Wellcome Photo Library // CC BY-NC-ND 4.0

Image shows photomicrograph of bone marrow acid phosphatase in acute T-cell lymphocytic leukaemia

Studies conducted at the Comprehensive Cancer Center at MedUni Vienna and Vienna General Hospital show that the drugs ibrutinib and idelalisib used in the targeted treatment of chronic lymphatic leukemia can significantly prolong the survival time of high-risk patients. The average survival time of these patients is between one and two years when they receive standard treatment, whereas 80% of patients receiving the new treatment were still alive after two years. These results give us reason to hope that, in future, these two drugs could not only replace chemotherapy but even stem cell transplantation.

Both drugs are so-called “small molecules” and belong to the class of substances known as kinase inhibitors. They are used in targeted cancer treatment, where they interrupt the signalling pathways of the cancer cells. Both substances inhibit cell growth and idelalisib additionally affects the cells’ ability to metastasize. Over the course of the last two years, they have been separately tested in studies at MedUni Vienna and are now routinely available to patients.

Read the full commentary here

Leukaemia ‘firsts’ in cancer research and treatment

Greaves, M. Nature Reviews Cancer. 16, 163–172 (2016)

Our understanding of cancer biology has been radically transformed over recent years with a more realistic grasp of its multilayered cellular and genetic complexity. These advances are being translated into more selective and effective treatment of cancers and, although there are still considerable challenges, particularly with drug resistance and metastatic disease, many patients with otherwise lethal malignancies now enjoy protracted remissions or cure.

One largely unheralded theme of this story is the extent to which new biological insights and novel clinical applications have their origins with leukaemia and related blood cell cancers, including lymphoma. In this Timeline article, I review the remarkable and ground-breaking role that studies in leukaemia have had at the forefront of this progress.

Image source: Greaves, M.

Read the abstract here

Predictive staircase to leukemia revealed by researchers

Researchers detail in a new article how they have been able to fingerprint myelodysplastic syndromes, a state for blood cells that turns into acute myeloid leukemia cancer in approximately 30 percent of patients.

Image source: Flickr

In the paper published by the scientific journal Cancer Cell, the researchers detail how they have been able to fingerprint myelodysplastic syndromes (MDS), a state for blood cells that turns into acute myeloid leukemia (AML) cancer in approximately 30% of patients. The study demonstrates that early and accurate prediction of this aggressive cancer is possible.

AML is the most common type of leukemia in adults, and about 1,300 Canadians are expected to develop the disease each year.

Bhatia’s research team found when they deleted one version of the important GSK-3 gene, the other version of the gene became active but remained non-cancerous. However, when the second version of the gene was also deleted, AML cancer began.

To test this, Bhatia’s team collaborated with Italian researchers at the University of Bologna to apply these initial findings to human blood samples that had been previously collected from patients with MDS, some of whom eventually developed AML. McMaster researchers did a retroactive study, and demonstrated that gene expression analysis of patient blood samples was accurate in predicting which patients would develop AML and which would not.

Read the full commentary via ScienceDaily

Read the article abstract here

Ibrutinib superior to traditional chemotherapy in untreated chronic leukemia patients

Burger, J. et al. New England Journal of Medicine, 2015.

A multi-center, international, randomized, Phase III study of older untreated patients with chronic lymphocytic leukemia (CLL) demonstrated that ibrutinib, a kinase inhibitor, is significantly more effective than traditional chemotherapy with chlorambucil.

The study, which followed 269 patients, revealed a 24-month overall survival rate of 97.8 percent for patients taking ibrutinib versus 85.3 percent for those on chlorambucil. Minor adverse effects were reported.

Carry on reading commentary via ScienceDaily

View the full article via NEJM