By David P. Steensma, MD

2008-12-07

There have been improvements in outcomes for adults with acute lymphocytic leukemia (ALL) over the last four decades,” stated Dr. Adele Fielding, of Royal Free and University College Medical School, London, in the ALL education session yesterday afternoon. (This session is also being offered today at 9:30 a.m. in Room 2001-2003-2005 – West.) However, Dr. Fielding also pointed out that survival for adults with ALL remains poor, especially when compared to outcomes for children — and even for pediatric patients, there is still much room for improvement. This afternoon at 4:30 p.m. in the Yerba Buena Ballroom Salon 9 of the Marriott, a dynamic oral session will highlight non-transplant trials for ALL, primarily presenting results in children. Notably, five of the six presentations in this session will focus on the best method of administration of drugs that have been used in ALL for more than 40 years — corticosteroids, vincristine, and methotrexate — where there are still questions about the optimal dose and schedule.

Dr. Martin Schrappe of Kiel, Germany, will present the results of the large ALL 2000 intergroup trial for pediatric ALL (abstract #7), on behalf of the BFM (German, Austrian, and Swiss) and AEIOP (Italian) cooperative networks. The ALL 2000 investigators randomized 3,655 patients between one and 17 years old to receive either dexamethasone at 10 mg/m2/d, or prednisone at 60 mg/m2/d, from days 8 to 29 of induction. Dexamethasone proved more toxic than prednisone but led to a 5 percent improvement in 6-year event-free survival (84.1% vs. 79.1%), with improvements seen across all disease categories. However, the specific dose of dexamethasone may be important; Dr. Yves Bertrand, of Lyon, France, will note this during his presentation of an interim analysis of EORTC Trial 58951 (abstract #8). The EORTC 58951 study compared 6 mg/m2/d of dexamethasone to 60 mg/m2/d of prednisone, but unlike ALL 2000 where the dexamethasone dose was 10 mg/m2/d, no differences were observed in event-free survival between treated groups in EORTC 58951. As for ALL 2000, EORTC investigators also noted a higher infection rate with dexamethasone. Later in the oral session, Dr. Barbara De Moerloose, of Ghent University Hospital in Belgium, will focus on a different question asked by EORTC 58951 study: the ability of 6 pulses of vincristine and a corticosteroid administered during continuation therapy to prolong event-free survival (abstract #11).

After discussing corticosteroids, session participants will turn their attention to a pair of studies examining various ways of administering methotrexate in childhood ALL. Dr. Yousif Matloub will present the results of the Children’s Oncology Group Study 1991, in which escalating doses of intravenous methotrexate proved superior to oral methotrexate as part of interim maintenance therapy for patients with standard-risk B-cell ALL who had achieved a rapid induction response (abstract #9). These results will then be qualified by Dr. Thierry Leblanc (Hôpital Saint Louis, Paris), representing the FRALLE French ALL co-operative network (abstract #10).

Patients with Philadelphia-chromosome-positive ALL (Ph+-ALL) continue to do very poorly with existing therapies. Still, there are encouraging data that BCR-ABL kinase inhibitors add some benefit. In the final presentation, Dr. Yves Chalandon (Genève, Switzerland) will describe preliminary results from a 118-patient study that added imatinib to pre-transplant therapy for younger adults with Ph+-ALL, confirming the benefit of BCR-ABL inhibitors in that patient population (abstract #12).

Attendees interested in ALL will be pleased to learn that this afternoon’s session is not the only one focused on ALL treatment at this year’s annual meeting. On Monday at 11:00 a.m. in the Yerba Buena Ballroom Salon 9, a session titled “Acute Lymphoblastic Leukemia Therapy: New Trends” will discuss emerging clinical approaches to ALL treatment, including the addition of rookie and journeyman drugs to the therapeutic lineup, to complement the long-established treatment veterans discussed this afternoon.

Dr. Steensma indicated no relevant conflicts of interest.

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