Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies.
Fifty-two children with symptomatic sickle cell disease sickle cell disease (SCD) (N = 43) or transfusion-dependent thalassemia (N = 9) received matched sibling donor marrow (46), marrow and cord product (5), or cord blood (1) allografts following reduced intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan between March 2003 and May 2014*. The Kaplan-Meier probabilities of overall and event-free survival at a median of 3.42 (range, 0.75-11.83) years were 94.2% and 92.3% for the group, 93% and 90.7% for SCD, and 100% and 100% for thalassemia, respectively. Treatment-related mortality (all related to graft versus host disease, GVHD) was noted in three (5.7%) recipients, all 17-18 years of age. Acute and chronic GVHD was noted in 23% and 13%, respectively, with 81% of recipients off immunosuppression by 1 year. Graft rejection was limited to the single umbilical cord blood recipient who had prompt autologous hematopoietic recovery. Fourteen (27%) had mixed chimerism at 1 year and beyond; all had discontinued immunosuppression between 4 and 12 months from transplant with no subsequent consequence on GVHD or rejection. Infectious complications included predominantly bacteremia (48% were staphylococcus) and CMV reactivation (43%) necessitating preemptive therapy. Lymphocyte recovery beyond 6 months was associated with subsidence of infectious complications. All patients who engrafted were transfusion independent; no strokes or pulmonary complications of SCD were noted, and pain symptoms subsided within 6 months posttransplant. These findings support using RIC for patients with hemoglobinopathy undergoing matched sibling marrow transplantation (*www.Clinical Trials.gov: NCT00920972, NCT01050855, NCT02435901).
Department of Pediatric, Washington University School of Medicine, St. Louis, Missouri.
Allison A
AA
King
Department of Pediatrics, Children's National Medical Center, Washington, District of Columbia.
Naynesh
N
Kamani
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Nancy
N
Bunin
Department of Pediatrics, Cohen Children's Medical Center of New York, New Hyde Park, New York.
Indira
I
Sahdev
Department of Pediatrics, Cohen Children's Medical Center of New York, New Hyde Park, New York.
Joel
J
Brochstein
Department of Pediatric, Washington University School of Medicine, St. Louis, Missouri.
Robert J
RJ
Hayashi
Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio.
Michael
M
Grimley
Department of Pediatrics, Children's National Medical Center, Washington, District of Columbia.
Allistair
A
Abraham
Department of Pediatrics, Children's National Medical Center, Washington, District of Columbia.
Jacqueline
J
Dioguardi
Department of Pediatrics, Methodist Children's Hospital of South Texas, San Antonio, Texas.
Ka Wah
KW
Chan
Department of Pediatrics, Phoenix Children's Hospital, Phoenix, Arizona.
Dorothea
D
Douglas
Department of Pediatrics, Phoenix Children's Hospital, Phoenix, Arizona.
Roberta
R
Adams
Department of Pediatrics, University of Miami Health System, Miami, Florida.
Martin
M
Andreansky
Rady Children's Hospital, San Diego, California.
Eric
E
Anderson
Department of Pediatrics, Levine Children's Hospital, Charlotte, North Carolina.
Andrew
A
Gilman
Department of Pediatrics, Lurie Children's Hospital, Chicago, Illinois.
Sonali
S
Chaudhury
Department of Pediatrics, Louisiana State University Medical Center, New Orleans, Louisiana.
Lolie
L
Yu
Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
Jignesh
J
Dalal
Department of Pediatrics, All Children's Hospital, St. Petersburg, Florida.
Gregory
G
Hale
Department of Pediatrics, CancerCare Manitoba, CAN, Manitoba, Canada.
Geoff
G
Cuvelier
Department of Pediatrics, Cohen Children's Medical Center of New York, New Hyde Park, New York.
Akshat
A
Jain
Department of Pediatrics, Joseph M. Sanzari Children's Hospital, Hackensack, New Jersey.
Jennifer
J
Krajewski
Department of Pediatrics, Joseph M. Sanzari Children's Hospital, Hackensack, New Jersey.
Alfred
A
Gillio
Department of Pediatrics, University of Chapel Hill, Chapel Hill, North Carolina.
Kimberly A
KA
Kasow
Department of Pediatrics, Riley Hospital for Children, Indianapolis, Indiana.
David
D
Delgado
Department of Pediatric, Washington University School of Medicine, St. Louis, Missouri.
Eric
E
Hanson
Department of Pediatric, Washington University School of Medicine, St. Louis, Missouri.
Lisa
L
Murray
Department of Pediatric, Washington University School of Medicine, St. Louis, Missouri.
Shalini
S
Shenoy
D016026:Bone Marrow Transplantation / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006453:Hemoglobinopathies / Q000601:surgery* / Q000628:therapy*; D006801:Humans; D008297:Male; D035781:Siblings; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*