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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
Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0002-0283-4418
Department of Haematology, University Hospital of Linko ̈ ping, Linko ̈ ping, Sweden.
Department of Haematology and Coagulation, Sahlgrenska University Hospital, Go ̈ teborg, Sweden.
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2015 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, 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, 135
Keyword [en]
Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-44342DOI: 10.1007/s12032-015-0582-2ISI: 000351474100049PubMedID: 25796502OAI: oai:DiVA.org:oru-44342DiVA: diva2:806420
Note

Funding Agency:

Lions Cancer Research Foundation, Uppsala

Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Prognostic factors, treatment and outcome in adult acute lymphoblastic leukemia: Population-based studies in Sweden
Open this publication in new window or tab >>Prognostic factors, treatment and outcome in adult acute lymphoblastic leukemia: Population-based studies in Sweden
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Acute lymphoblastic leukemia (ALL) has poor prognosis in older/elderly adults and in high-risk/relapsed disease. Recommended treatment of ALL was evaluated (study I-IV). Data was obtained from the Swedish Acute Leukemia registries and from patient records.

I. We assessed ALL relapse treatment and outcome in 76 patients aged 15-65 years (y). Complete remission (CR) was achieved in 50/71 patients (70%). Of them, 29 underwent allogeneic hematopoietic stem cell transplantation (hSCT). Five year overall survival (OS) was 15%, but close to 50% in 19 patients <35y after hSCT.

II. We studied outcome of treatment with the Hyper-CVAD protocol in 19 of 24 patients with T-ALL aged 18-72y. CR was reached in 89%, but 5y leukemia-free survival was only 29%, and 20% in 15 patients not transplanted in CR1. Six patients received hSCT in CR2. Finally, 5y OS in all 19 patients was 47%. The only negative prognostic factor found was age ≥35y.

III. We evaluated minimal residual disease (MRD) monitoring in 35 patients with Philadelphia (Ph) negative B-ALL aged 46-79y and treated with the ABCDV protocol. The CR rate was 91%. MRD was measured by flow cytometry in 73% in CR1 (MRD1) and omitted in those >70y or with high-risk ALL. Five patients received hSCT (only one due to MRD). Five year OS in the whole cohort was 47%. Continuous CR but not OS was improved in patients with MRD1 <0.1 %.

IV. We studied 155 patients with ALL (Ph+ in 35%) aged 55-85y and treated with remission induction/palliation (124/31). Both, intensive, and palliative treatment resulted in the CR rates of 70/83/16% and 3y OS of 26/32/3%. OS was negatively influenced by age and platelet count ≤35×109/L (but not Ph+). OS was not enhanced by introduction of an age-adapted protocol.

We concluded that intensive treatment with subsequent allogeneic hSCT is the most reasonable option in younger patients with ALL recurrence (I). Hyper-CVAD has low relapse-preventing efficacy (II). MRD guided intensification is probably feasible in only a minority of older patients (III). Prognosis in elderly ALL is poor, but no longer impaired by Ph+ (IV).

Place, publisher, year, edition, pages
Örebro: Örebro university, 2016. 56 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 134
Keyword
Acute Lymphoblastic Leukemia, adult, chemotherapy, prognosis, population-based
National Category
Cancer and Oncology Hematology Family Medicine
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-47424 (URN)978-91-7529-121-5 (ISBN)
Public defence
2016-03-18, Universitetssjukhuset, hörsal C2, Södra Grev Rosengatan, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2016-01-15 Created: 2016-01-15 Last updated: 2017-10-17Bibliographically approved

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