Allo-hematopoietic cell transplantation for Ph chromosome-positive ALL: impact of imatinib on relapse and survival

Abstract

The utility of imatinib in either the pre-or post-transplant period for Ph chromosome-positive (Ph þ ) ALL is uncertain. In addition, there have been recent concerns regarding imatinib and cardiac toxicity. We investigated the outcome of 32 patients with Ph þ ALL who received an allo-hematopoietic cell transplant (HCT) at the University of Minnesota between 1999 and 2006. The median age at HCT was 21.9 years (range: 2.8-55.2). All patients were conditioned with CY and TBI. GVHD prophylaxis was CsA based. Of the 32 patients, 15 received imatinib therapy pre-or post-HCT (imatinib group) and 17 patients received either no imatinib (n ¼ 11) or only after relapse (n ¼ 6) (non-imatinib group). Overall survival, relapse-free survival and relapse at 2 years was 61, 67 and 13% for the imatinib group as compared with 41, 35 and 35% for the non-imatinib group (P ¼ 0.19, 0.12 and 0.20, respectively). Cardiac toxicity and TRM at 2 years were similar between groups. Thus, patients treated with imatinib in either the pre-or post-transplant setting had trends toward improved outcomes and no increase in cardiac toxicity. We suggest that imatinib be included in the peri-transplant management of all patients with Ph þ ALL.

Current Treatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

“…In contrast, most patients who started imatinib after the detection of BCR-ABL had a prompt suppression of BCR-ABL in response to the drug, and to date there is no difference in outcome between the groups. A small, nonrandomized, single-center study from the University of Minnesota 23 showed a trend toward improved outcome in patients who could be treated with imatinib in the pre-and posttransplantation period after cyclophosphamide and TBI myeloablative conditioning. Similarly, Ram et al 24 reported that imatinib given for a median duration of 11.5 months after RIC with fludarabine and 2 Gy of TBI (which was relatively well tolerated after transplantation, with only 3 of 18 patients needing to stop the drug) was associated with significantly reduced mortality on univariate analysis, although the effect on relapse was not statistically significant.…”

Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT

“…[8][9][10][11][12] Therefore, increasing attention has been paid to MRD status at allo-HCT. 13,14 Post-transplant TKI administration is another issue that has received increasing attention, 13,15,16 since relapse after allo-HCT is still one of the main problems of this disease. 1,16 Although there have been several small-scale studies on post-transplant TKI administration, [17][18][19] the utility of post-transplant TKI administration for long-term survival of Ph+ALL patients is controversial.…”

Evidence-Based Guidelines for the Use of Tyrosine Kinase Inhibitors in Adults with Philadelphia Chromosome–Positive or Bcr-Abl–Positive Acute Lymphoblastic Leukemia: A Canadian Consensus

“…Twenty studies gave a tki during consolidation or for maintenance (or both) in addition to during induction. Three studies gave imatinib before allogeneic transplantation 17,29,42 .…”

“…Evidence: Ten studies in 376 patients gave a tki in the post-transplantation period: eight studies administered imatinib, and two studies administered dasatinib 37,42,49,50,53,56,62,63,70,84 . Seven studies gave a tki only in the post-transplantation period.…”

“…Twenty-four observational studies (twenty prospective, four retrospective) have examined the efficacy of a tki for the treatment of relapsed patients with Ph+ all. Of those studies, fourteen gave imatinib [13][14][15][16]23,29,32,37,42,49,55,56,61,63,75 , five gave dasatinib 44,50,71,83,88 , two gave nilotinib 50,75 , two gave bosutinib 72,85 , and one gave ponatinib 86 . The tkis were given with or without chemotherapy.…”