PMID- 31493539
OWN - NLM
STAT- MEDLINE
DCOM- 20210121
LR  - 20240327
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Print)
IS  - 1083-8791 (Linking)
VI  - 26
IP  - 1
DP  - 2020 Jan
TI  - Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow 
      Transplantation Platform for Primary Immunodeficiency Diseases.
PG  - 94-106
LID - S1083-8791(19)30558-0 [pii]
LID - 10.1016/j.bbmt.2019.08.018 [doi]
AB  - Allogeneic blood or marrow transplantation (BMT) is a potentially curative 
      therapy for patients with primary immunodeficiency (PID). Safe and effective 
      reduced-intensity conditioning (RIC) approaches that are associated with low 
      toxicity, use alternative donors, and afford good immune reconstitution are 
      needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 
      years, were treated on a prospective clinical trial of a novel, radiation-free 
      and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose 
      cyclophosphamide, and busulfan for conditioning with post-transplantation 
      cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a 
      high-risk cohort with a median hematopoietic cell transplantation comorbidity 
      index of 3. With median follow-up of survivors of 1.9 years, 1-year overall 
      survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival 
      was 80% at day +180. Graft failure incidence was 10%. Split chimerism was 
      frequently observed at early post-BMT timepoints, with a lower percentage of 
      donor T cells, which gradually increased by day +60. The cumulative incidences of 
      grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, 
      respectively. All aGVHD was steroid responsive. No patients developed chronic 
      GVHD. Few significant organ toxicities were observed. Evidence of phenotype 
      reversal was observed for all engrafted patients, even those with significantly 
      mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 
      patients with pre-BMT malignancies or lymphoproliferative disorders remain in 
      remission. Most patients have discontinued immunoglobulin replacement. All 
      survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel 
      RIC BMT approach for patients with PID has yielded promising results, even for 
      high-risk patients.
CI  - Published by Elsevier Inc.
FAU - Dimitrova, Dimana
AU  - Dimitrova D
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Gea-Banacloche, Juan
AU  - Gea-Banacloche J
AD  - Mayo Clinic, Phoenix, Arizona.
FAU - Steinberg, Seth M
AU  - Steinberg SM
AD  - Biostatistics and Data Management Section, National Cancer Institute, Center for 
      Cancer Research, National Institutes of Health, Bethesda, Maryland.
FAU - Sadler, Jennifer L
AU  - Sadler JL
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Hicks, Stephanie N
AU  - Hicks SN
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Carroll, Ellen
AU  - Carroll E
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Wilder, Jennifer S
AU  - Wilder JS
AD  - Clinical Research Directorate/Clinical Monitoring Research Program, Frederick 
      National Laboratory for Cancer Research sponsored by the National Cancer 
      Institute, Bethesda, Maryland.
FAU - Parta, Mark
AU  - Parta M
AD  - Clinical Research Directorate/Clinical Monitoring Research Program, Frederick 
      National Laboratory for Cancer Research sponsored by the National Cancer 
      Institute, Bethesda, Maryland.
FAU - Skeffington, Lauren
AU  - Skeffington L
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Hughes, Thomas E
AU  - Hughes TE
AD  - National Institutes of Health Clinical Center, Bethesda, Maryland.
FAU - Blau, Jenny E
AU  - Blau JE
AD  - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
FAU - Broadney, Miranda M
AU  - Broadney MM
AD  - Section on Growth and Obesity, Program in Endocrinology, Metabolism and Genetics, 
      Division of Intramural Research, Eunice Kennedy Shriver National Institute of 
      Child Health and Human Development, National Institutes of Health, Bethesda, 
      Maryland.
FAU - Rose, Jeremy J
AU  - Rose JJ
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Hsu, Amy P
AU  - Hsu AP
AD  - Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy 
      and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
FAU - Fletcher, Rochelle
AU  - Fletcher R
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Nunes, Natalia S
AU  - Nunes NS
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Yan, Xiao-Yi
AU  - Yan XY
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Telford, William G
AU  - Telford WG
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Kapoor, Veena
AU  - Kapoor V
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Cohen, Jeffrey I
AU  - Cohen JI
AD  - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, Maryland.
FAU - Freeman, Alexandra F
AU  - Freeman AF
AD  - Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy 
      and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
FAU - Garabedian, Elizabeth
AU  - Garabedian E
AD  - Genetics and Molecular Biology Branch, National Human Genome Research Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Holland, Steven M
AU  - Holland SM
AD  - Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy 
      and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
FAU - Lisco, Andrea
AU  - Lisco A
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, Maryland.
FAU - Malech, Harry L
AU  - Malech HL
AD  - Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy 
      and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
FAU - Notarangelo, Luigi D
AU  - Notarangelo LD
AD  - Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy 
      and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
FAU - Sereti, Irini
AU  - Sereti I
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, Maryland.
FAU - Shah, Nirali N
AU  - Shah NN
AD  - Pediatric Oncology Branch, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland.
FAU - Uzel, Gulbu
AU  - Uzel G
AD  - Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy 
      and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
FAU - Zerbe, Christa S
AU  - Zerbe CS
AD  - Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy 
      and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
FAU - Fowler, Daniel H
AU  - Fowler DH
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Gress, Ronald E
AU  - Gress RE
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Kanakry, Christopher G
AU  - Kanakry CG
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Kanakry, Jennifer A
AU  - Kanakry JA
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland. Electronic address: 
      jennifer.kanakry@nih.gov.
LA  - eng
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - Z99 CA999999/ImNIH/Intramural NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190904
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 395575MZO7 (Pentostatin)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - G1LN9045DK (Busulfan)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Bone Marrow Transplantation
MH  - Busulfan/*administration & dosage/adverse effects
MH  - Child
MH  - Child, Preschool
MH  - Cyclophosphamide/*administration & dosage/adverse effects
MH  - Disease-Free Survival
MH  - Female
MH  - Follow-Up Studies
MH  - *Graft vs Host Disease/mortality/prevention & control
MH  - Humans
MH  - Lymphocyte Transfusion
MH  - Male
MH  - Middle Aged
MH  - Pentostatin/*administration & dosage/adverse effects
MH  - Primary Immunodeficiency Diseases/mortality/therapy
MH  - Prospective Studies
MH  - Survival Rate
MH  - *Transplantation Conditioning
PMC - PMC6942248
MID - NIHMS1539130
OTO - NOTNLM
OT  - Bone marrow transplantation
OT  - Post-transplantation cyclophosphamide
OT  - Primary immunodeficiency
OT  - Reduced-intensity conditioning
COIS- Conflict of interest statement: None of the authors have any conflicts of 
      interest. CONFLICTS OF INTEREST DISCLOSURE: The authors declare no competing 
      financial interests.
EDAT- 2019/09/08 06:00
MHDA- 2021/01/22 06:00
PMCR- 2021/01/01
CRDT- 2019/09/08 06:00
PHST- 2019/06/11 00:00 [received]
PHST- 2019/08/28 00:00 [revised]
PHST- 2019/08/28 00:00 [accepted]
PHST- 2019/09/08 06:00 [pubmed]
PHST- 2021/01/22 06:00 [medline]
PHST- 2019/09/08 06:00 [entrez]
PHST- 2021/01/01 00:00 [pmc-release]
AID - S1083-8791(19)30558-0 [pii]
AID - 10.1016/j.bbmt.2019.08.018 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2020 Jan;26(1):94-106. doi: 
      10.1016/j.bbmt.2019.08.018. Epub 2019 Sep 4.