Intensive induction/consolidation therapy without maintenance in adult acute lymphoblastic leukaemia: a pilot assessment

Abstract

Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphoblastic leukaemia (ALL) achieving complete remission. We questioned the value of such maintenance therapy in adult patients treated with intensive induction/consolidation. In a phase II study (SAKK 33/86) 63 patients between 17 and 72 years of age (median 27 years) with newly diagnosed ALL were treated with three intensive cycles of marrow-ablative chemotherapy. All subtypes were included. No maintenance phase was added. 53 patients (84%) entered a complete remission (CR) and 21 (33%) continue to be in unmaintained remission for 11-69 months (median 21 months). The disease-free survival of patients achieving CR and completing all three cycles is 40% at 3 years, with a 95% confidence interval of +/- 19%. These findings are comparable to the results of conventional studies. We conclude that maintenance therapy might not be needed in all adult ALL patients. Its value should be tested in a randomized trial. For patients failing, novel approaches are needed to improve outcome in adult ALL.

Metronomic chemotherapy: An attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance

“…Similarly, treatment protocols for ALL include a period of high-intensity induction, followed by a milder dose consolidation, followed by 2–3 years of lower-dose, higher-frequency maintenance therapy [88]. This strategy gives 90–95% survival rates, and any attempts to omit the maintenance therapy yield inferior results [23, 73, 93]. Choi et al [18] reported encouraging results for a small group of children with tumors of central nervous system treated with upfront high-dose chemotherapy, followed by metronomic maintenance therapy.…”

Recent approaches in acute lymphoblastic leukemia in adults

“…Maintenance therapy, usually consisting of 6‐mercaptopurine and methotrexate, and in some studies augmented by pulses of vincristine and prednisone, is generally administered for a total treatment duration of 2–3 years. Earlier attempts to omit maintenance therapy after intensive induction and consolidation treatment clearly led to inferior results unless patients were transplanted (43, 70, 71). On the other hand, no large or randomized trial has demonstrated a clear advantage for patients treated with intensive maintenance therapy compared to those with conventional maintenance.…”

High hyperdiploid acute lymphoblastic leukemia in adults shows clonal heterogeneity and chromosomal instability at diagnosis and during the course of the disease

“…Patients were referred between 1995 and 2009 from the university hospitals of Basel, Zurich, Bern, Lausanne and cantonal/regional hospitals of St-Gallen, Aarau, Mendrisio, Bellinzona, and Genolier Clinic. Two patients were enrolled in the SAKK ALL 33-86/90 [6] and GRAALL 2005 clinical trials, respectively. Ethical approval for this project was obtained in accordance with the guidelines of the local Ethical Review Board.…”

“…Approaches used and cutoff levels were reported in detail previously [4,7]. Table 1 Clones involving chromosomes 4, 6, 10, and 17 at presentation and/or during the course of disease in ten patients with high hyperdiploid acute lymphoblastic leukemia, expressed as percentages (13) 29 (13) 24 (15) 13 (8) 18 (15) 44 (34) 6 (3) 8 (5) 19 (16) 40 (25) 7 (7) 3 (3) 20 (13) 56 (43) 12 (9) 2 (1) 8 (5) 7 (6) Values in parentheses are numbers of very small abnormal clones (<1%). Clones already present in the previous analysis (<1%) are italicized.…”