Plasma protein biomarker profiling reveals major differences between acute leukaemia, lymphoma patients and controls.

Aiming to accommodate the unmet need for easily accessible biomarkers with a focus on biological differences between haematological diseases, the diagnostic value of plasma proteins in acute leukaemias and lymphomas was investigated. A multiplex proximity extension assay (PEA) was used to analyze 183 proteins in diagnostic plasma samples from 251 acute leukaemia and lymphoma patients and compared with samples from 60 healthy controls. Multivariate modelling using partial least square discriminant analysis revealed highly significant differences between distinct disease subgroups and controls. The model allowed explicit distinction between leukaemia and lymphoma, with few patients misclassified. Acute leukaemia samples had higher levels of proteins associated with haemostasis, inflammation, cell differentiation and cell-matrix integration, whereas lymphoma samples demonstrated higher levels of proteins known to be associated with tumour microenvironment and lymphoma dissemination. PEA technology can be used to screen for large number of plasma protein biomarkers in low µL sample volumes, enabling the distinction between controls, acute leukaemias and lymphomas. Plasma protein profiling could help gain insights into the pathophysiology of acute leukaemia and lymphoma and the technique may be a valuable tool in the diagnosis of these diseases.

Cytogenetic aberrations in adult acute lymphoblastic leukemia-A population-based study.

Cytogenetic aberrations are recognized as important prognostic factors in adult acute lymphoblastic leukemia (ALL), but studies seldom include elderly patients. From the population-based Swedish ALL Registry, we identified 728 patients aged 18-95 years, who were diagnosed with ALL 1997-2015 and had cytogenetic information. Registry data were complemented with original cytogenetic reports. BCR-ABL1 was the most recurrent aberration, with a frequency of 26%, with additional cytogenetic alterations in 64%. KTM2A rearrangement was the second most frequent aberration found in 7%. Low hypodiploidy-near triploidy and complex karyotype had negative impact, while t(1;19);TCF3-PBX1 showed positive impact on overall survival. However, after correction for age only complex karyotype remained significant.

Introducing patient-reported outcome in the acute leukemia quality registries in Sweden.

OBJECTIVES: The use of patient-reported outcome (PRO) measured outside clinical trials is not well defined. We report the first analysis of the prospective PRO study within the Swedish acute myeloid leukemia (AML) and the acute lymphoblastic leukemia (ALL) registries. METHODS: PRO was requested 6 months after diagnosis. The EORTC Quality of life Questionnaire Core 30-item, the Patient Health Questionnaire-8 (PHQ-8), and questions from a Swedish National Cancer Questionnaire were used. RESULTS: An invitation letter was sent to 398 patients; 255 (64%) responded, 60% web-based, and 40% on paper. The ALL cohort had lower physical, role and social functioning, higher symptom burden, and more financial difficulties compared to the AML cohort. A PHQ-8 score ≥ 10p, which indicates depression, was reported in 18% of the patients; 33% of these patients reported being prescribed antidepressants. The patients' overall experience of care was satisfying, but more psychological and practical support was desired. There was no difference in survival between patients who reported their PRO and those who did not. Follow-up at 2 and 4 years is ongoing. CONCLUSIONS: PRO collected in a registry-based setting is feasible, but the selection of time points and questionnaires are delicate in a diverse patient population.

Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry.

OBJECTIVES: As new, effective therapies emerge for acute lymphoblastic leukaemia (ALL), the results of clinical trials need to relate to standard of care. METHODS: We used the population-based Swedish ALL Registry to evaluate characteristics, treatment and long-term outcome in 933 patients with diagnosis between 1997 and 2015. RESULTS: The median age was 53 years. The frequency of Philadelphia (Ph)-positive leukaemia was 34% of examined B-ALL with a peak incidence at 50-59 years. Five-year overall survival (OS) improved between 1997-2006 and 2007-2015; in patients 18-45 years from 50% (95% CI 43-57) to 65% (95% CI 58-72), 46-65 years from 25% (95% CI 18-32) to 46% (95% CI 37-55) and >65 years from 7% (95% CI 2.6-11) to 11% (95% CI 5.9-16) (P < 0.05). Men with Ph-neg B-ALL 46-65 years had inferior OS compared with women (P < 0.01). Standardised mortality ratio was 5.7 (95% CI 5.0-6.3) for patients who survived 5 years from diagnosis. In multivariable analysis, Ph-positive disease was not associated with impaired prognosis but with lower risk of death in 2007-2015. CONCLUSIONS: In a population-based cohort, OS has improved in adult ALL, especially for Ph-positive disease but for middle-aged men with Ph-negative B-ALL outcome was poor. Cure without late toxicity or relapse is still desired.

Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden.

OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T-ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status ≥2 influenced the choice of palliation. Intensive, palliative, and both approaches resulted in complete remission rate 83/16/70% and 3-year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count ≤35×109 /L and age ≥75 years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year age-group. CONCLUSIONS: We report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph-negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment.