Favorable Outcome of Chronic Myeloid Leukemia Patients Treated with Imatinib Vs Early Allogeneic Stem Cell Transplantation.
Authors: Hasford Joerg , Lauseker Michael , Gathmann Insa , Pfirrmann Markus , Larson Richard A. , Guilhot François , O’Brien Stephen G , Druker Brian J. , Hehlmann Ruediger , Hochhaus Andreas ,   For the IRIS Study Group,   For the German CML Study Group
Published: April 2020

Abstract
Background: Early allogeneic stem cell transplantation has been considered the only curative treatment for CML. The advent of imatinib provided a new chance to suppress long-lastingly the disease without risk of early deaths. As there is no randomized trial comparing transplantation with imatinib therapy, we compared the outcome between transplanted and imatinib-treated patients of two randomized trials.
Data base: We used the survival data of patients randomly allocated to imatinib in the IRIS trial (Druker et al. N Engl J Med2006;355:2408) and compared them with the genetically randomized transplanted (matched related donors) patients of the German CML III and IIIA studies (Hehlmann et al. Blood;109:4686).
Methods: Applying uniform inclusion criteria for age (18–55 yrs at diagnosis) to generate comparable samples, survival time was determined according to the intention-to-treat principle and after stratification for the Euro and EBMT scores using Kaplan-Meier curves. Information about Sokal and Euro score was missing for 123 and 128 patients from the IRIS trial and for 4 resp. 6 patients from the German CML III/IIIA studies.
Results: 377 CML patients in chronic phase treated with imatinib and 285 patients with early allogeneic stem cell transplantation were analyzed. In the imatinib arm of the IRIS trial, 42 patients had been transplanted and 12 patients have died subsequently. Five-year-survival in this subgroup of 377 younger patients of the IRIS trial was 94.7%. The patients’ characteristics of the two groups were comparable (CML III/IIIA vs IRIS), median age: 38 vs 44 yrs., female sex: 40% vs 39%, Sokal Score low 49.8% vs 58.3%, intermediate 30.2% vs 25.2%, high risk 19.9% vs 16.5%; Euro Score low 62.7% vs 58.6%, intermediate 31.5% vs 34.9%, high risk 5.7% vs 6.4%. Median observation time was 75 months for transplanted patients and 61 months for imatinib-treated patients. Patients of both groups have not yet reached median survival times. Five-year survival rates were 94.7 % (all imatinib treated patients) and 71.1 % (all transplanted patients). In all prognostic strata, irrespective of the prognostic score used, five-year-survival with imatinib was evidently superior compared to transplantation: Euro score: low risk 97.8% vs 78.3%, intermediate risk 93.6% vs 58.9%, EBMT score 0–2: 94.7% vs 78.8%, EBMT score 3–4: 94.7% vs 52.2%. There were just 5 transplanted patients with an EBMT score &gt;4. Neither the censoring of the 42 transplanted patients of the IRIS trial affected the results nor the in- or exclusion of the 12 subsequent deaths.
Conclusions: We could not identify any subgroup of patients with CML who clearly showed a benefit from early transplantation compared to treatment with imatinib, given an observation time of 5–6 years.