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High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden
Örebro University Hospital. Hematology Section, Department of Medicine, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0002-0283-4418
Örebro University Hospital. Hematology Section, Department of Medicine, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0002-3384-4387
Department of Hematology, University Hospital of Linköping, Linköping, Sweden.
Karolinska University Hospital, Stockholm, Sweden.
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2014 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, no 5, p. 377-381Article in journal (Refereed) Published
Abstract [en]

Background: Hyper-CVAD is widely used to treat acute lymphoblastic leukemia (ALL) and aggressive lymphomas. This multicenter, population-based study assessed the efficacy of Hyper-CVAD as first-line therapy in patients with T-cell ALL (T-ALL).

Patients and methods: Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol.

Results: The median age was 32 yr (range 18-72 yr). Complete remission (CR) was obtained in 17 of 19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two- and 5-yr leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95% CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age ≥35 yr influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7).

Conclusions: Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 92, no 5, p. 377-381
Keywords [en]
antineoplastic combined chemotherapy protocols; treatment outcome; precursor T-cell lymphoblastic leukemia-lymphoma; stem cell transplantation
National Category
Hematology General Practice
Identifiers
URN: urn:nbn:se:oru:diva-48486DOI: 10.1111/ejh.12269ISI: 000334267500002PubMedID: 24443846Scopus ID: 2-s2.0-84898801134OAI: oai:DiVA.org:oru-48486DiVA, id: diva2:905824
Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2018-06-18Bibliographically 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. p. 56
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 134
Keywords
Acute Lymphoblastic Leukemia, adult, chemotherapy, prognosis, population-based
National Category
Cancer and Oncology Hematology General Practice
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)
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Available from: 2016-01-15 Created: 2016-01-15 Last updated: 2018-01-10Bibliographically approved

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Kozlowski, PiotrÅström, Maria

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