The impact of cytogenetic risk on the outcomes of allogeneic hematopoietic cell transplantation in patients with relapsed/refractory acute myeloid leukemia: On behalf of the acute leukemia working party ( ALWP ) of the European group for blood and marrow transplantation (EBMT)

An International Working Group met to revise the diagnostic and response criteria for acute myelogenous leukemia originally published in 1990, as well as to provide definitions of outcomes and reporting standards to improve interpretability of data and comparisons among trials. Since the original publication, there have been major advances in our understanding of the biology and molecular genetics of acute leukemia that are clinically relevant and warrant incorporation into response definitions. Differences from the 1990 recommendations included a category of leukemia-free state, new criteria for complete remission, including cytogenetic and molecular remissions and remission duration. Storage of viable blasts for correlative studies is important for future progress in the therapy of these disorders.

Diagnostic karyotype provides the framework for risk-stratification schemes in acute myeloid leukemia (AML); however, the prognostic significance of many rare recurring cytogenetic abnormalities remains uncertain. We studied the outcomes of 5876 patients (16-59 years of age) who were classified into 54 cytogenetic subgroups and treated in the Medical Research Council trials. In multivariable analysis, t(15;17)(q22;q21), t(8;21)(q22;q22), and inv(16)(p13q22)/t(16;16)(p13;q22) were the only abnormalities found to predict a relatively favorable prognosis (P < .001). In patients with t(15;17) treated with extended all-trans retinoic acid and anthracycline-based chemotherapy, additional cytogenetic changes did not have an impact on prognosis. Similarly, additional abnormalities did not have a significant adverse effect in t(8;21) AML; whereas in patients with inv(16), the presence of additional changes, particularly +22, predicted a better outcome (P = .004). In multivariable analyses, various abnormalities predicted a significantly poorer outcome, namely abn(3q) (excluding t(3;5)(q25;q34)), inv(3)(q21q26)/t(3;3)(q21;q26), add(5q)/del(5q), -5, -7, add(7q)/del(7q), t(6;11)(q27;q23), t(10;11)(p11 approximately 13;q23), other t(11q23) (excluding t(9;11)(p21 approximately 22;q23) and t(11;19)(q23;p13)), t(9;22)(q34;q11), -17, and abn(17p). Patients lacking the aforementioned favorable or adverse aberrations but with 4 or more unrelated abnormalities also exhibited a significantly poorer prognosis (designated "complex" karyotype group). These data allow more reliable prediction of outcome for patients with rarer abnormalities and may facilitate the development of consensus in reporting of karyotypic information in clinical trials involving younger adults with AML. This study is registered at http://www.isrctn.org as ISRCTN55678797 and ISRCTN17161961.