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.

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Image source: Greaves, M.

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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.

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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

Racial disparity lies at intersection of HIV & Hodgkin lymphoma

A new study finds a significant racial disparity within a doubly troubled population of patients: those with HIV and Hodgkin lymphoma. In such cases, blacks are at significantly higher risk than whites of not receiving treatment for the cancer that in many cases would be effective.

 

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Image source: Dr. Adam Olszewski/Brown University

The study ostensibly showed that HIV-negative people had an 80 percent Hodgkin lymphoma survival rate five years after diagnosis, but HIV-positive people survived at a rate of only 66 percent over the same timeframe. But among HIV-positive patients, 16 percent went untreated. Among people in the study who did get lymphoma treatment, HIV-positive people were statistically just as likely to survive as HIV-negative people. The results apply to the majority of cases in which the subtype of Hodgkin lymphoma is determined.

Importantly, further statistical analysis showed that one of the main risk factors for an HIV-positive person going untreated was being black. Statistically adjusting for possibly confounding factors, HIV-positive blacks were 67 percent more likely than HIV-positive whites to go untreated for the lymphoma. Other risk factors, which are often related to race, were low income and lacking health insurance. Another was being over 60 years of age.

Read the full commentary via ScienceDaily

Read the article abstract here

Timing of end-of-life discussions for patients with blood cancers

A majority of hematologic oncologists report that end-of-life (EOL) discussions happen with patients with blood cancers too late, according to an article published online by JAMA Internal Medicine.

Oreofe O. Odejide, M.D., of the Dana-Farber Cancer Institute, Boston, and coauthors examined the timing of EOL discussions through a survey completed by 349 hematologic oncologists (57.3 percent response rate).

About 56 percent of hematologic oncologists (based on a slightly smaller number who answered a survey question about timing) reported EOL discussions happened “too late.” Oncologists in tertiary centers were more likely to report late EOL discussions with patients than those in community centers.

Read the original research article abstract here

Read the full commentary via ScienceDaily

 

Patients with relapsed/refractory chronic lymphocytic leukaemia may benefit from inclusion in clinical trials irrespective of the therapy received: a case-control retrospective analsysis

Blood Cancer Journal (2015) 5, e356

Treatment for patients with chronic lymphocytic leukaemia (CLL) keeps changing at an incredible pace, perhaps more than in any other haematological malignancy. Indeed, the outlook of patients with CLL is improving with the advent of targeted therapies, including second-generation monoclonal antibodies, immune modulators, BTK inhibitors, PI3K inhibitors and BCL2 antagonists. After decades of randomized trials showing no benefit in overall survival (OS), recent trials have changed this trend and shown a true OS benefit for patients receiving novel agents. Moreover, retrospective analyses from our and other institutions have found a significant improvement in survival over the years, suggesting that new treatments are truly changing the prognosis of the disease.

Carry on reading via Blood Cancer Journal – Patients with relapsed/refractory chronic lymphocytic leukaemia may benefit from inclusion in clinical trials irrespective of the therapy received: a case-control retrospective analsysis.

Leukemia tumor suppressor identified

A protein-coding gene called hnRNP K has been identified as a tumor suppressor for acute myeloid leukemia (AML), a finding that could be important for investigating how best to target treatment of a blood cancer striking mostly older individuals.

Study results were published in the Sept. 24 issue of Cancer Cell:  Post, S  et al. hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies. Cancer Cell, September 2015


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Variation in guideline adherence in non-Hodgkin’s lymphoma care: impact of patient and hospital characteristics

BMC Cancer 2015, 15:578

Background
The objective of this observational study was to assess the influence of patient, tumor, professional and hospital related characteristics on hospital variation concerning guideline adherence in non-Hodgkin’s lymphoma (NHL) care.

Methods
Validated, guideline-based quality indicators (QIs) were used as a tool to assess guideline adherence for NHL care. Multilevel logistic regression analyses were used to calculate variation between hospitals and to identify characteristics explaining this variation. Data for the QIs regarding diagnostics, therapy, follow-up and organization of care, together with patient, tumor and professional related characteristics were retrospectively collected from medical records; hospital characteristics were derived from questionnaires and publically available data.

Results
Data of 423 patients diagnosed with NHL between October 2010 and December 2011 were analyzed. Guideline adherence, as measured with the QIs, varied considerably between the 19 hospitals: >20 % variation was identified in all 20 QIs and high variation between the hospitals (>50 %) was seen in 12 QIs, most frequently in the treatment and follow-up domain.

Hospital variation in NHL care was associated more than once with the characteristics age, extranodal involvement, multidisciplinary consultation, tumor type, tumor aggressiveness, LDH level, therapy used, hospital region and availability of a PET-scanner.

Conclusion
Fifteen characteristics identified at the patient level and at the hospital level could partly explain hospital variation in guideline adherence for NHL care. Particularly age was an important determinant: elderly were less likely to receive care as measured in the QIs. The identification of determinants can be used to improve the quality of NHL care, for example, for standardizing multidisciplinary consultations in daily practice.

via BMC Cancer | Abstract | Variation in guideline adherence in non-Hodgkin’s lymphoma care: impact of patient and hospital characteristics.

Parental Age at Birth and Risk of Hematological Malignancies in Older Adults

Study links father’s age, baby’s risk of blood cancer as an adult

via ScienceDaily.

A new study links a father’s age at birth to the risk that his child will develop blood and immune system cancers as an adult, particularly for only children. The study, which appears in the American Journal of Epidemiology, found no association between having an older mother and these cancers.

The proportion of parents who delay having children until age 35 or older continues to increase, but the long-term health consequences for these children are still emerging. Studies suggest higher risk of several conditions including several childhood and adult-onset cancers in the offspring of older parents. A recent prospective study of more than 100,000 adult women in the California Teacher’s Study showed an association between paternal–but not maternal–age at birth and the risk of hematologic cancer, the 4th most common cancer in the U.S.

Reference: Lauren R. Teras, Mia M. Gaudet, Jennifer L. Blase and Susan M. Gapstur. Parental Age at Birth and Risk of Hematological Malignancies in Older Adults. American Journal of Epidemiology, May 2015

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