Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease.
Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely performed in adult patients with sickle cell disease (SCD). We utilized the chemotherapy-free, alemtuzumab/total body irradiation 300 cGy regimen with sirolimus as post-transplantation immunosuppression in 13 high-risk SCD adult patients between November 2011 and June 2014. Patients received matched related donor (MRD) granulocyte colony-stimulating factor-mobilized peripheral blood stem cells, including 2 cases that were ABO incompatible. Quality-of-life (QoL) measurements were performed at different time points after HSCT. All 13 patients initially engrafted. A stable mixed donor/recipient chimerism was maintained in 12 patients (92%), whereas 1 patient not compliant with sirolimus experienced secondary graft failure. With a median follow-up of 22 months (range, 12 to 44 months) there was no mortality, no acute or chronic graft-versus-host disease (GVHD), and no grades 3 or 4 extramedullary toxicities. At 1 year after transplantation, patients with stable donor chimerism have normalized hemoglobin concentrations and improved cardiopulmonary and QoL parameters including bodily pain, general health, and vitality. In 4 patients, sirolimus was stopped without rejection or SCD-related complications. These results underscore the successful use of a chemotherapy-free regimen in MRD HSCT for high-risk adult SCD patients and demonstrates a high cure rate, absence of GVHD or mortality, and improvement in QoL including the applicability of this regimen in ABO mismatched cases (NCT number 01499888).
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Sickle Cell Center, Department of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois. Electronic address: ssaraf@uic.edu.
Santosh L
SL
Saraf
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
Annie L
AL
Oh
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
Pritesh R
PR
Patel
College of Pharmacy, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
Yash
Y
Jalundhwala
College of Pharmacy, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
Karen
K
Sweiss
University of Illinois Cancer Center, Chicago, Illinois; Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
Matthew
M
Koshy
Institute for Transfusion Medicine & Department of Pathology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
Sally
S
Campbell-Lee
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Sickle Cell Center, Department of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, Illinois.
Michel
M
Gowhari
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Sickle Cell Center, Department of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, Illinois.
Johara
J
Hassan
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
David
D
Peace
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
John G
JG
Quigley
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
Irum
I
Khan
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Sickle Cell Center, Department of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, Illinois.
Robert E
RE
Molokie
University of Illinois Sickle Cell Center, Department of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, Illinois; Division of Pediatric Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
Lewis L
LL
Hsu
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois.
Nadim
N
Mahmud
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
Dennis J
DJ
Levinson
College of Pharmacy, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
A Simon
AS
Pickard
Arizona Respiratory Center and Department of Medicine, University of Arizona, Tucson, Arizona.
Joe G N
JG
Garcia
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Sickle Cell Center, Department of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, Illinois.
Victor R
VR
Gordeuk
Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois; University of Illinois Center for Global Health, Chicago, Illinois. Electronic address: drond@uic.edu.
Damiano
D
Rondelli
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D064591:Allografts; D000755:Anemia, Sickle Cell / Q000628:therapy*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D019172:Transplantation Conditioning; D014916:Whole-Body Irradiation
D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab
ABO mismatch; Adult; Alemtuzumab; Allogeneic transplantation; Quality of life; Sickle cell disease