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High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007
1Hematology Section, Department of Medicine, Örebro University Hospital, Örebro.ORCID iD: 0000-0002-0283-4418
Hematology Section, Department of Medicine, Örebro University Hospital, Örebro.
Department of Hematology, University Hospital of Linköping, Linköping.
Karolinska University Hospital, Stockholm.
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2012 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 9, 1414-1421 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission.

DESIGN AND METHODS: Between 2003-2007, 76 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt's leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated.

RESULTS: Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13-32) and 15% (95% CI: 7-24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2-8.3) after relapse, whereas all patients over 35 years old at diagnosis have died.

CONCLUSIONS: Allogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis.

Place, publisher, year, edition, pages
Ferrata Storti Foundation, 2012. Vol. 97, no 9, 1414-1421 p.
Keyword [en]
Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
National Category
Hematology Family Medicine
Identifiers
URN: urn:nbn:se:oru:diva-48485DOI: 10.3324/haematol.2011.057851ISI: 000308908300022PubMedID: 22511497Scopus ID: 2-s2.0-84865851061OAI: oai:DiVA.org:oru-48485DiVA: diva2:905760
Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2016-12-07Bibliographically 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: 2016-12-07Bibliographically approved

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