PMID- 20587785
OWN - NLM
STAT- MEDLINE
DCOM- 20101129
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 116
IP  - 16
DP  - 2010 Oct 21
TI  - Impact of in vivo alemtuzumab dose before reduced intensity conditioning and 
      HLA-identical sibling stem cell transplantation: pharmacokinetics, GVHD, and 
      immune reconstitution.
PG  - 3080-8
LID - 10.1182/blood-2010-05-286856 [doi]
AB  - In vivo alemtuzumab reduces the risk of graft-versus-host disease (GVHD) and 
      nonrelapse mortality after reduced intensity allogeneic transplantation. However, 
      it also delays immune reconstitution, leading to frequent infections and 
      potential loss of graft-versus-tumor responses. Here, we tested the feasibility 
      of alemtuzumab dose deescalation in the context of fludarabine-melphalan 
      conditioning and human leukocyte antigen (HLA)-identical sibling transplantation. 
      Alemtuzumab was given 1-2 days before graft infusion, and dose reduced from 60 mg 
      to 20 mg in 4 sequential cohorts (total n = 106). Pharmacokinetic studies were 
      fitted to a linear, 2-compartment model in which dose reduction led to incomplete 
      saturation of CD52 binding sites and greater antibody clearance. Increased 
      elimination was particularly evident in the 20-mg group in patients who had 
      CD52-expressing tumors at time of transplantation. The 20-mg dose was also 
      associated with greater risk of severe GVHD (acute grade III-IV or chronic 
      extensive) compared with > 20 mg (hazard ratio, 6.7; 95% CI, 2.5-18.3). In 
      contrast, dose reduction to 30 mg on day -1 was associated with equivalent 
      clinical outcomes to higher doses but better lymphocyte recovery at 12 months. In 
      conclusion, alemtuzumab dose reduction to 30 mg is safe in the context of reduced 
      intensity conditioning and HLA-identical sibling transplantation. This trial was 
      registered at http://www.ncrn.org.uk as UKCRN study 1415.
FAU - Chakraverty, Ronjon
AU  - Chakraverty R
AD  - Royal Free Hampstead National Health Service (NHS) Trust, London, United Kingdom. 
      r.chakraverty@medsch.ucl.ac.uk
FAU - Orti, Guillermo
AU  - Orti G
FAU - Roughton, Michael
AU  - Roughton M
FAU - Shen, Jun
AU  - Shen J
FAU - Fielding, Adele
AU  - Fielding A
FAU - Kottaridis, Panagiotis
AU  - Kottaridis P
FAU - Milligan, Donald
AU  - Milligan D
FAU - Collin, Matthew
AU  - Collin M
FAU - Crawley, Charles
AU  - Crawley C
FAU - Johnson, Peter
AU  - Johnson P
FAU - Clark, Andrew
AU  - Clark A
FAU - Parker, Anne
AU  - Parker A
FAU - Bloor, Adrian
AU  - Bloor A
FAU - Pettengell, Ruth
AU  - Pettengell R
FAU - Snowden, John
AU  - Snowden J
FAU - Pettitt, Andrew
AU  - Pettitt A
FAU - Clark, Richard
AU  - Clark R
FAU - Hale, Geoff
AU  - Hale G
FAU - Peggs, Karl
AU  - Peggs K
FAU - Thomson, Kirsty
AU  - Thomson K
FAU - Morris, Emma
AU  - Morris E
FAU - Mackinnon, Stephen
AU  - Mackinnon S
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20100629
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CD52 Antigen)
RN  - 0 (CD52 protein, human)
RN  - 0 (Glycoproteins)
RN  - 0 (HLA Antigens)
RN  - 3A189DH42V (Alemtuzumab)
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
RN  - Q41OR9510P (Melphalan)
SB  - IM
MH  - Adult
MH  - Alemtuzumab
MH  - Antibodies, Monoclonal/administration & 
      dosage/immunology/pharmacokinetics/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antibodies, Neoplasm/administration & dosage/immunology/*therapeutic use
MH  - Antigens, CD/immunology
MH  - Antigens, Neoplasm/immunology
MH  - Antineoplastic Agents/administration & 
      dosage/immunology/pharmacokinetics/*therapeutic use
MH  - CD52 Antigen
MH  - Female
MH  - Glycoproteins/immunology
MH  - Graft vs Host Disease/immunology/pathology/*prevention & control
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Male
MH  - Melphalan/administration & dosage/therapeutic use
MH  - Middle Aged
MH  - Siblings
MH  - *Stem Cell Transplantation/methods
MH  - *Transplantation Conditioning
MH  - Vidarabine/administration & dosage/analogs & derivatives/therapeutic use
EDAT- 2010/07/01 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/07/01 06:00
PHST- 2010/07/01 06:00 [entrez]
PHST- 2010/07/01 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0006-4971(20)31237-4 [pii]
AID - 10.1182/blood-2010-05-286856 [doi]
PST - ppublish
SO  - Blood. 2010 Oct 21;116(16):3080-8. doi: 10.1182/blood-2010-05-286856. Epub 2010 
      Jun 29.