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Cancer. 2019 Apr 23. doi: 10.1002/cncr.32156. [Epub ahead of print]

Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group.

Author information

1
Department of Clinical Hematology, ICO Badalona-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
2
Department of Hematology, Hospital of the Virgen de la Victoria, Malaga, Spain.
3
Department of Hematology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.
4
Department of Hematology, Hospital of Sant Pau, Barcelona, Spain.
5
Department of Hematology, ICO-Hospital Duran i Reynals, L'Hospitalet de Llobregat, Catalonia, Spain.
6
Department of Hematology, Le Fe University and Polytechnic Hospital, Valencia, Spain.
7
Department of Hematology, Carlos Haya Hospital, Malaga, Spain.
8
Department of Hematology, Virgen del Rocio University Hospital, Seville, Spain.
9
Department of Hematology, Central Hospital of Asturias, Oviedo, Spain.
10
Department of Hematology, General University Hospital of Alicante, Alicante, Spain.
11
Department of Hematology, Son Espases Hospital, Palma de Mallorca, Spain.
12
Department of Hematology, ICO-Hospital Joan XXIII, Tarragona, Spain.
13
Department of Hematology, Reina Sofia Hospital, Cordoba, Spain.
14
Department of Hematology, Lucus Augusti Hospital, Lugo, Spain.
15
Department of Hematology, del Mar Hospital, Barcelona, Spain.
16
Department of Hematology, Clinical Hospital, Valencia, Spain.
17
Department of Hematology, Morales Meseguer University General Hospital, Murcia, Spain.
18
Department of Hematology, Donostia University Hospital, San Sebastian, Spain.
19
Department of Hematology, Fuenlabrada University Hospital, Madrid, Spain.
20
Department of Hematology, La Zarzuela Hospital, Madrid, Spain.
21
Department of Hematology, Arnau de Vilanova Hospital, Lleida, Spain.
22
Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.

Abstract

BACKGROUND:

Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763).

METHODS:

Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard-dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes.

RESULTS:

Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo-HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease-free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months [P = .05] and 28.7 months vs 11.5 months [P = .05] for DFS and OS, respectively).

CONCLUSIONS:

Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.

KEYWORDS:

Philadelphia chromosome-positive acute lymphoblastic leukemia; clinical disease recurrence; molecular disease recurrence; outcome

PMID:
31012967
DOI:
10.1002/cncr.32156

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