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RALLE Pilot: Response-guided Therapy for Marrow Relapse in Acute Lymphoblastic Leukemia in Children

Saarinen-Pihkala, Ulla M. MD, PhD*; Parto, Katriina MD, PhD; Riikonen, Pekka MD, PhD; Lähteenmäki, Päivi M. MD, PhD§; Békàssy, Albert N. MD, PhD; Glomstein, Anders MD; Möttönen, Merja MD, PhD#

Journal of Pediatric Hematology/Oncology: May 2012 - Volume 34 - Issue 4 - p 263–270
doi: 10.1097/MPH.0b013e3182352da9
Original Articles

Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10−3, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10−3, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses.

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*Children’s Hospital and Helsinki University Central Hospital, Helsinki

Department of Pediatrics, Tampere University Central Hospital, Tampere

Department of Pediatrics, Kuopio University Central Hospital, Kuopio

§Department of Pediatrics, Turku University Central Hospital, Turku

University Children’s Hospital, Lund, Sweden

Rikshospitalet, Oslo, Norway

#Department of Pediatrics, Oulu University Central Hospital, Oulu, Finland

This study was supported by Research Funding of the Helsinki University Hospitals, Helsinki, Finland, and the Foundation for Pediatric Research, Helsinki, Finland.

The authors declare no conflicts of interest.

Reprints: Ulla M. Saarinen-Pihkala, MD, PhD, Division of Hematology-Oncology and SCT, Children’s Hospital, University of Helsinki, P.O. box 281, 00029 HUS, Helsinki, Finland (e-mail:

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website,

Received April 9, 2011

Accepted August 29, 2011

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.