Impact of Cytogenetic Abnormalities on Outcomes of Adult Philadelphia-Negative Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia. To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative acute lymphoblastic leukemia in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. Patients with abnormal cytogenetics had 40% leukemia-free survival and 42% overall survival at 5-years post-transplant, which was similar to those with normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (p=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse (hazard ratio=2.11; 95% confidence interval, 1.04-4.27) and treatment failure (hazard ratio=1.97; 1.20-3.24). Complex karyotype was prognostic for relapse (hazard ratio=1.69; 1.06-2.69), whereas t(8;14) predicted treatment failure (hazard ratio=2.85; 1.35-6.02) and overall mortality (hazard ratio=3.03; 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse (monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy), intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (p=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities of acute lymphoblastic leukemia can be overcome by transplant, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
Lazaryan, A., Dolan, M., Zhang, M., Wang, H., Kharfan-Dabaja, M., Marks, D., Bejanyan, N., Copelan, E., Majhail, N., Waller, E., Cairo, M., & Acute Leukemia Committee of the CIBMTR. (2019). Impact of Cytogenetic Abnormalities on Outcomes of Adult Philadelphia-Negative Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research. Haematologica. https://doi.org/10.3324/haematol.2019.220756