Updated Long-Term Results of a Randomized Comparison of Prophylactic and Pre-Emptive Imatinib Following Allogeneic Stem Cell Transplantation for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)

• Published in: Blood 2011-11, Vol.118 (21), p.247-247
• Main Authors: Pfeifer, Heike, Wassmann, B., Bethge, Wolfgang A., Dengler, Jolanta, Bornhäuser, Martin, Stadler, Michael, Beelen, Dietrich, Günther, Andreas, Vucinic, Vladan, Burmeister, Thomas, Stelljes, Matthias, Schwerdtfeger, Rainer, Schaefer-Eckhart, Kerstin, Bader, Peter, Kreyenberg, Hermann, Schuld, Peter, Serve, Hubert, Hoelzer, Dieter, Goekbuget, Nicola, Ottmann, Oliver G.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.247.247

Abstract 247 The presence of minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ ALL is highly predictive of eventual relapse. Imatinib (IM) has very limited efficacy in hematologic relapse of Ph+ALL, but may prevent leukemia recurrence if started when the leukemia burden is still very low and detectable only by molecular techniques. The optimal time for starting IM post transplant and the prognostic relevance of different bcr-abl transcript levels in relation to time after SCT have not been established. To determine the impact of post-transplant IM, given either prophylactically or after detection of bcr-abl transcripts (pre-emptively), on the overall incidence of MRD, remission duration, long-term treatment outcome and tolerability in pts. who underwent SCT for Ph+ALL in complete remission. In a prospective, randomized multicenter trial, previously transplanted Ph+ ALL pts. (n=55) were assigned to receive imatinib prophylactically (n=26) or pre-emptively (n=29). SCT was performed in CR1 in 23 pts. and 27 pts. in the two groups, respectively. Five pts.were transplanted in CR2. Serial assessment of bcr-abl transcripts was performed by quantitative RT-PCR and additionally by nested-RT-PCR if the sensitivity of the qRT-PCR was below the quantitative range. Confirmatory testing of a second independent sample was not required, to reduce the risk of treatment delays. Samples were considered PCR negative only if the ABL copy number exceeded 104. Imatinib administration was scheduled for one year of continuous PCR negativity. IM was started in 24/26 pts. allocated to prophylactic IM and in 14/29 pts. in the pre-emptive arm. The majority of pts. received IM 400 mg/d (26/38 pts.), the other 12 pts. 600 mg IM daily. IM was started a median of 48 d after SCT in the prophylactic arm and 70 d after SCT with pre-emptive therapy. After a median follow-up of 30 mos. and 32 mos., respectively, 82% and 78% of pts. are alive in ongoing CR, 4 pts. died in CR. Five pts. transplanted in CR1 and 2/5 pts. transplanted in CR2 have relapsed (median follow-up 9 mos. and 10.5 mos., respectively). The frequency of MRD positivity was significantly lower in pts. assigned to prophylactic imatinib (10/26; 40%) than those in the pre-emptive treatment arm (20/29; 69%) (p=0.046 by chi2 test). Only 9 of 29 pts. assigned to pre-emptive imatinib remained continuously PCR negative after SCT, with a median follow-up of 32 months (18–46 months) after SCT. The me