A Retrospective Study of Patients Treated with Imatinib Mesylate Prior to Allogeneic Hematopoietic Stem Cell Transplant.

A retrospective study of CML allogeneic hematopoietic stem cell transplants (HSCT) at the FHCRC from January 2001 to April 2004 was conducted to address the impact of pre-transplant imatinib mesylate (IM) therapy on early treatment toxicity, non-relapse mortality (NRM), overall survival (OS), and relapse. Forty-eight patients, median age 40 years (range, 20–64), received IM prior to transplantation for a median duration of 9.5 months (range, 3–30). Twenty-nine patients received unrelated or mismatched donor HSCT and 19 patients received matched related donor (MRD) HSCT. Forty-four patients were in chronic phase (CP) and 4 patients in accelerated phase (AP) at the time of diagnosis and IM initiation. At transplantation 28 patients were in CP, 14 in AP, 3 in blast crisis (BC) remission, and 3 in BC. Patients were conditioned with busulfan and cytoxan (35) and cytoxan and total body irradiation (13). The median time to neutrophil engraftment for all patients was 16 days (range, 11–33). Median average bilirubin to day 20 and median maximum bilirubin to day 20 were used as an indicator of early transplant hepatotoxicity. These values were 1.0 (range 0.4–5.4) and 1.6 (range 0.6–11.4) for all patients, respectively. Among 48 patients 8 deaths occurred due to poor engraftment (1), diffuse alveolar hemorrhage (1), pneumonia (1), acute GVHD (2), myocardial infarction (1), refractory ITP (1), and fungal infection (1). Only one relapse occurred on day 553 in a CP patient who had no response to IM after 6 months of therapy prior to HSCT. For all patients 100-day survival was 92% (95%CI, 84–99%), one-year survival 85% (95% CI, 74–97%), and 1.5-year survival 73% (95%CI, 54–92%) with a median follow-up of 333 days (range 97–912 days). One of 19 MRD recipients died (at day 440) with a median follow-up among survivors of 291 days. One-year survival for unrelated or mismatched donor recipients was 77% (95% CI, 60–94%). One-year survival was 93% (median follow-up 345 days) for 28 CP patients and 70% (median follow-up 308 days) for 14 AP and 3 BC remission patients. All three patients transplanted in blast crisis are alive (follow-up 115–465 days). There was a suggestive association between time from diagnosis to transplant and mortality (P=0.10) for all patients. To assess the impact of IM response at transplant, patients were assigned to 1 of 5 response groups. One of 13 patients transplanted in complete cytogenetic response (CCyR) died (median follow-up 291 days). None of 9 patients (7 CP and 2 AP) with a major cytogenetic response (MCyR) to IM died (median follow-up 344 days). Three of 10 patients (2/8 CP and 1/2 AP) with no response to IM or with evidence of cytogenetic or hematologic relapse died (median follow-up 467 days). Two of 10 patients with evidence of clonal evolution on IM (median follow-up 354 days) and 2/6 patients who progressed to BC on IM (median follow-up 341 days) died.

CONCLUSION: For all patients acute hepatotoxicity, one-year OS, and NRM appear similar to our Center’s historical data. Patients achieving a CCyR or MCyR after IM therapy did particularly well, perhaps due to CP disease at HSCT and the shorter time to transplant (9 mo, range 3–29 mo). Poor IM response may serve as an indicator of poorer transplant outcome; however, more advanced disease at and longer time to transplantation (32 months, range 4–118 months) alone may explain the more adverse outcome.