Page 170 - Haematologica May 2020

A. Lazaryan et al.
Hematology/Oncology, Isala Clinic, Zwolle, the Netherlands; 36Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY, USA; 37Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA; 38The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; 39The Children's Hospital at TriStar Centennial and Sarah Cannon Research Institute, Nashville, TN, USA; 40Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA; 41Section of Hematology/Oncology, Department of Internal Medicine, Louisiana State University Health Shreveport, Shreveport, LA, USA; 42Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA; 43Department of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA; 44Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA; 45Translational Cell Therapy Group, CLINTEC ( Clinical Science, Intervention and Technology), Karolinska Institutet, Stockholm Sweden; 46Academische Ziekenhuis Maastricht, Maastricht, the Netherlands; 47Mayo Clinic Florida, Jacksonville, FL, USA; 48University of Chicago Medicine, Chicago, IL, USA; 49Blood & Marrow Transplant Center, Florida Hospital Medical Group, Orlando, FL, USA; 50UCLA Medical Center, Los Angeles, CA, USA; 51The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA; 52QE II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada; 53Hospital Vall d’Hebron, Barcelona, Spain; 54Rush University Medical Center, Chicago, IL, USA; 55Christian Medical College, Vellore, India; 56Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI, USA; 57Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA; 58Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, IN, USA; 59National Cancer Institute (NCI), Rockville, MD, USA; 60New York Presbyterian Hospital/Columbia University Medical Center, New York, NY, USA; 61UF Health Shands Children's Hospital, Gainesville, FL, USA; 62Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; 63Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan; 64Division of Hematology/Oncology/Cell Therapy, Rush University, Chicago, IL, USA; 65Memorial Sloan Kettering Cancer Center, New York, NY, USA; 66Case Western Reserve University, Cleveland, OH, USA; 67Division of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 68Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA; 69Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN, USA; 70Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA and 71Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN, USA.
ABSTRACT
Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non- myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a 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 (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 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 in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose sig- nificant risks and yield inferior outcomes.
Introduction
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with acute lym- phoblastic leukemia (ALL). Risk stratification of ALL varies across studies and generally includes a spectrum of demographic (e.g., age), clinical (e.g., white blood cell count, minimal residual disease, steroid sensitivity), phe- notypic (B- versus T-cell origin), and cytogenetic character- istics. Several cytogenetic risk stratification schemes have been developed and are used as prognostic tools at diag-
nosis of ALL to guide treatment decisions. However, most prior studies focusing on the prognostic significance of cytogenetics in ALL were influenced by inclusion of patients with Philadelphia chromosome-positive (Ph+) B- ALL and defined for patients who received conventional chemotherapies.
Pivotal Medical Research Council–Eastern Cooperative Oncology Group (MRC-ECOG) and Southwest Oncology Group (SWOG) clinical trials identified commonly recog- nized Ph-negative (Ph–) cytogenetic risks, including KMT2A (MLL) translocations at 11q23 associated with
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