Allogeneic stem-cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH (+/- fludarabine) conditioning combined with post-transplant donor-lymphocyte infusion.
BACKGROUND
We report our updated experience of allogeneic transplantation in lympho-proliferative disorders using a reduced-intensity conditioning regimen combining BEAM (plus fludarabine in three cases) with pre-transplant CAMPATH. Post-transplant donor lymphocytes have been infused for persisting disease or relapse, and both chimerism and minimal residual disease have been monitored utilizing molecular techniques.


METHODS
Thirty patients with median age 47.6 years underwent allogeneic transplantation for relapsed or high-risk lymphoproliferative disease using HLA-identical (sibling n = 25, unrelated n = 2) or one antigen mismatched sibling donors (n = 3). Twenty-one had NHL, three had HD and six had CLL/PLL. Stem-cell source was PBSC (n = 24), BM (n = 5) or both (n = 1) with a median CD34 dose of 4.5 x 10(6)/kg. GvHD prophylaxis was with CYA and MTX.


RESULTS
Engraftment was prompt in the majority of patients, with a median of 15 days to both ANC > 0.5 and platelets > 20. There have been three transplant-related deaths secondary to viral pneumonitis or bacterial pneumonia. Seven patients developed Grade I-II acute GvHD post-transplant. Of 28 evaluable patients, 18 achieved a CR at assessment 2-3 months post-transplant and a further patient converted from PR to CR following DLI, to give an overall CR rate of 68%. Three patients had early progressive disease and six have relapsed from CR or progressed from PR (two of whom have achieved CR following DLI therapy). Overall survival is 67% and event-free survival 48% at 3 years. With a median follow-up of 1.3 years 57% of patients are currently alive and lymphoma-free. A molecular remission has been achieved in nine of 12 informative patients.


CONCLUSIONS
These encouraging results show that this reduced-intensity conditioning regimen is effective, with a low-toxicity profile compared with conventional TBI-based conditioning, and certainly merits further evaluation in this setting.
Lush
R J
RJ
Department of Haematology, Nottingham City Hospital, UK.
Haynes
A P
AP
Byrne
J
J
Cull
G M
GM
Carter
G I
GI
Pagliuca
A
A
Parker
J E
JE
Mufti
G
G
Mahendra
P
P
Craddock
C F
CF
Lui Yin
J A
JA
Garg
M
M
Prentice
H G
HG
Potter
M N
MN
Russell
N H
NH
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D001782:Blood Donors; D002330:Carmustine / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D018450:Disease Progression; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods* / Q000639:trends; D017710:Lymphocyte Transfusion / Q000379:methods / Q000639:trends; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D008875:Middle Aged; D008991:Monitoring, Physiologic; D055502:Secondary Prevention; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D015996:Survival Rate; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods* / Q000639:trends; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D003561:Cytarabine; D000074323:Alemtuzumab; D005047:Etoposide; D008558:Melphalan; D002330:Carmustine