title: Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.
abstract: We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplantation morbidity in this population.
authors.affiliation: Department of Pediatric Stem Cell Transplant, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Duncan
authors.affiliation: Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio. Electronic address: majhain@ccf.org.
authors.forename: Navneet S
authors.initials: NS
authors.lastname: Majhail
authors.affiliation: Center of International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin; Divison of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Ruta
authors.initials: R
authors.lastname: Brazauskas
authors.affiliation: Center of International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hematology, University Hospital, Grenoble, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Haydar A
authors.initials: HA
authors.lastname: Frangoul
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hayashi
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Shands HealthCare and University of Florida, Gainesville, Florida.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Hsu
authors.affiliation: Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
authors.forename: Rammurti T
authors.initials: RT
authors.lastname: Kamble
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kasow
authors.affiliation: Department of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona.
authors.forename: Nandita
authors.initials: N
authors.lastname: Khera
authors.affiliation: Division of Hematology and Oncology, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Alison W
authors.initials: AW
authors.lastname: Loren
authors.affiliation: Department of Pediatric Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: Center for Hematologic Malignancies, Oregon Health and Science University, Portland, Oregon.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.affiliation: Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Paulette
authors.initials: P
authors.lastname: Mehta
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Kasiani C
authors.initials: KC
authors.lastname: Myers
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Shands HealthCare and University of Florida, Gainesville, Florida.
authors.forename: Maxim
authors.initials: M
authors.lastname: Norkin
authors.affiliation: Department of Blood and Marrow Transplant, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Pidala
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David L
authors.initials: DL
authors.lastname: Porter
authors.affiliation: Department of Internal Medicine, University of Central Florida, College of Medicine, Orlando, Florida.
authors.forename: Vijay
authors.initials: V
authors.lastname: Reddy
authors.affiliation: Center of International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Department of Hematology, Academische Ziekenhuis, Maastricht, Netherlands.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.affiliation: Department of Hematology-Oncology, Mount Sinai Hospital, New York, New York.
authors.forename: Amir
authors.initials: A
authors.lastname: Steinberg
authors.affiliation: Cellular Therapy Laboratory, CancerCare Manitoba, Winnipeg, MB, Canada; Department of Pediatrics and Child Health and Immunology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Donna A
authors.initials: DA
authors.lastname: Wall
authors.affiliation: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Warwick
authors.affiliation: Division of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: William A
authors.initials: WA
authors.lastname: Wood
authors.affiliation: Division of Hematology/Oncology, The Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University Medical Center, New Orleans, Louisiana.
authors.forename: Lolie C
authors.initials: LC
authors.lastname: Yu
authors.affiliation: Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children's National Health Systems, Washington, District of Columbia.
authors.forename: David A
authors.initials: DA
authors.lastname: Jacobsohn
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002386:Cataract / Q000209:etiology / Q000276:immunology / Q000473:pathology; D002648:Child; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010020:Osteonecrosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D012008:Recurrence; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists
keywords: Allogeneic transplantation; Hematopoietic cell transplantation; Late effects; Long-term survival; Second transplantation