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Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
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2015 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, article id 135Article in journal (Refereed) Published
Abstract [en]

The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

Place, publisher, year, edition, pages
2015. Vol. 32, no 4, article id 135
Keywords [en]
Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-258836DOI: 10.1007/s12032-015-0582-2ISI: 000351474100049PubMedID: 25796502OAI: oai:DiVA.org:uu-258836DiVA, id: diva2:842911
Available from: 2015-07-23 Created: 2015-07-20 Last updated: 2020-01-15Bibliographically approved
In thesis
1. Registry-Based Studies in Adult Acute Lymphoblastic Leukemia in Sweden: Survival and Quality of Life
Open this publication in new window or tab >>Registry-Based Studies in Adult Acute Lymphoblastic Leukemia in Sweden: Survival and Quality of Life
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Acute lymphoblastic leukemia (ALL), a common child malignancy, also constitutes a minor fraction of adult cancer with approximately 50 new cases per year in Sweden. While the five-year overall survival (OS) in pediatric ALL is more than 90%, the prognosis in adults is dismal. Using the Swedish ALL quality registry, this thesis investigates treatment and outcome of adult ALL according to national guidelines. In addition, the introduction of patient-reported outcome in the ALL and Acute Myeloid Leukemia registries is evaluated. 

In Paper I, measurement of minimal residual disease by flow cytometry was found to be feasible but not consistently applied in the 35 patients with Philadelphia (Ph)-negative B-ALL investigated. In Paper II, treatment, toxicity and outcome of 155 patients, 55-85 years (y) with ALL diagnosis between 2005 and 2012 were studied in detail by patient charts review. An age-adopted protocol recommended from 2009 did not result in better outcome. In Paper III, disease recurrence in the same cohort as Paper II was studied. The median overall survival (OS) after ALL relapse was 3.6 months. In Paper IV, the whole ALL registry was studied and OS was estimated in 930 adult patients diagnosed in the periods 1997-2006 and 2007-2015. Five year OS improved in patients 18-45y from 50% to 65%, in patients 46-65y from 25% to 46%, and in patients >65y from 7% to 11%. This demonstrates that young patients have the best prognosis, in part due to the introduction of a dose-intense “pediatric-like” chemotherapy protocol. Compared to women, middle-aged men were found to have a worse outcome.

Historically, Philadelphia-positive (Ph-pos) ALL has a poor prognosis compared to Ph-negative ALL. In this material, the frequency of Ph-pos ALL was 34% of examined B-ALL. Analysis of the whole registry revealed that in 2007-2015, i.e. after the introduction of the tyrosine kinase inhibitor imatinib, Ph-pos ALL was no longer associated with inferior OS. In Paper V, ALL and Acute Myeloid Leukemia patients, six months after diagnosis, completed a web or paper questionnaire regarding quality of life, symptoms and experience with care. The response rate was 64%. Depression symptoms were frequent (18%), especially in young women who reported worrying about fertility.

In summary, although OS in adult ALL has improved, more effective and less toxic therapies in upfront treatment are highly warranted. Collection of patient-reported outcome in a national quality registry is feasible and can add important aspects of cancer care that are not usually addressed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 69
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1630
Keywords
Acute Lymphoblastic Leukemia, Philadelphia Chromosome, Overall Survival, Population-based, Quality Registry, Relapse, Patient-Reported Outcome, Health-Related Quality of Life, Depression
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-401431 (URN)978-91-513-0853-1 (ISBN)
Public defence
2020-03-06, H:son-Holmdahlsalen, Akademiska sjukhuset, ing 100, Uppsala, 09:00 (English)
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Available from: 2020-02-13 Created: 2020-01-15 Last updated: 2020-02-13

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Bergfelt, EmmaHagglund, HansAmini, Rose-MarieHallböök, Hélene
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