The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood

Alice Bertaina, Luciana Vinti, Luisa Strocchio, Stefania Gaspari, Roberta Caruso, Mattia Algeri, Valentina Coletti, Carmelo Gurnari, Mariateresa Romano, Maria Giuseppina Cefalo, Katia Girardi, Valentina Trevisan, Valentina Bertaina, Pietro Merli, Franco Locatelli

Research output: Contribution to journalArticle

Abstract

Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has in vitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2–3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively. Bortezomib (1·3 mg/m2/dose) was administered intravenously on days 1, 4, 8, and 11. Chemotherapy agents were the same as those used in the TACL trial, consisting of dexamethasone, doxorubicin, vincristine and pegylated asparaginase. Three patients (8·1%) died due to infections. Twenty-seven patients (72·9%) achieved CR or CR with incomplete platelet recovery (CRp). Fourteen had minimal residual disease (MRD) lower than 0·1%. Twenty-two of 30 BCP-ALL patients (73·3%) and 5/7 patients (71%) with T-cell ALL achieved CR/CRp. The 2-year overall survival (OS) is 31·3%; CR/CRp patients with an MRD response had a remarkable 2-year OS of 68·4%. These data confirm that the combination of bortezomib with chemotherapy is a suitable/effective option for childhood relapsed/refractory ALL.

Original languageEnglish
Pages (from-to)629-636
Number of pages8
JournalBritish Journal of Haematology
Volume176
Issue number4
DOIs
Publication statusPublished - Feb 1 2017

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Lymphoma
Leukemia
Asparaginase
Proteasome Inhibitors
B-Lymphoid Precursor Cells
Survival
Vincristine
Combination Drug Therapy
Doxorubicin
Dexamethasone
Bortezomib
B-Lymphocytes
Blood Platelets
Therapeutics
Infection

Keywords

  • acute lymphoblastic leukaemia
  • bortezomib
  • childhood leukaemia
  • minimal residual disease
  • relapsed/refractory disease

ASJC Scopus subject areas

  • Hematology

Cite this

The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood. / Bertaina, Alice; Vinti, Luciana; Strocchio, Luisa; Gaspari, Stefania; Caruso, Roberta; Algeri, Mattia; Coletti, Valentina; Gurnari, Carmelo; Romano, Mariateresa; Cefalo, Maria Giuseppina; Girardi, Katia; Trevisan, Valentina; Bertaina, Valentina; Merli, Pietro; Locatelli, Franco.

In: British Journal of Haematology, Vol. 176, No. 4, 01.02.2017, p. 629-636.

Research output: Contribution to journalArticle

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AU - Caruso, Roberta

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