PMID- 11458521
OWN - NLM
STAT- MEDLINE
DCOM- 20010809
LR  - 20161124
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 938
DP  - 2001 Jun
TI  - Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose 
      cytotoxic therapy by the graft-versus-tumor effect.
PG  - 328-37; discussion 337-9
AB  - Conventional allografting produces considerable regimen-related toxicities that 
      generally limit this treatment to patients younger than 55 years and in otherwise 
      good medical condition. T cell-mediated graft-versus-tumor (GVT) effects are 
      known to play an important role in the elimination of malignant disease after 
      allotransplants. A minimally myelosuppressive regimen that relies on 
      immunosuppression for allogeneic engraftment was developed to reduce toxicities 
      while optimizing GVT effects. Pre-transplant total-body irradiation (200 cGy) 
      followed by post-transplant immunosuppression with cyclosporine (CSP) and 
      mycophenolate mofetil (MMF) permitted human leukocyte antigen (HLA)-matched 
      sibling donor hematopoietic cell engraftment in 82% of patients (n = 55) without 
      prior high-dose therapy. The addition of fludarabine (90 mg/m2) facilitated 
      engraftment in all 28 subsequent patients. Overall, fatal progression of 
      underlying disease occurred in 20% of patients after transplant. Non-relapse 
      mortality occurred in 11% of patients. Toxicities were low. Grade 2-4 acute 
      graft-versus-host disease (GVHD) associated with primary engraftment developed in 
      47% of patients, and was readily controlled in all but two patients. Donor 
      lymphocyte infusions (DLI) were not very effective at converting a low degree of 
      mixed donor/host chimerism to full donor chimerism; however, the addition of 
      fludarabine reduced the need for DLI. With a median follow-up of 244 days, 68% of 
      patients were alive, with 42% of patients in complete remission, including 
      molecular remissions. Remissions occurred gradually over periods of weeks to a 
      year. If long-term efficacy is demonstrated, such a strategy would expand 
      treatment options for patients who would otherwise be excluded from conventional 
      allografting.
FAU - Feinstein, L
AU  - Feinstein L
AD  - Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., D1-100, P.O. Box 
      19024, Seattle, Washington 98109-1024, USA. lfeinste@fhcrc.org
FAU - Sandmaier, B
AU  - Sandmaier B
FAU - Maloney, D
AU  - Maloney D
FAU - McSweeney, P A
AU  - McSweeney PA
FAU - Maris, M
AU  - Maris M
FAU - Flowers, C
AU  - Flowers C
FAU - Radich, J
AU  - Radich J
FAU - Little, M T
AU  - Little MT
FAU - Nash, R A
AU  - Nash RA
FAU - Chauncey, T
AU  - Chauncey T
FAU - Woolfrey, A
AU  - Woolfrey A
FAU - Georges, G
AU  - Georges G
FAU - Kiem, H P
AU  - Kiem HP
FAU - Zaucha, J M
AU  - Zaucha JM
FAU - Blume, K G
AU  - Blume KG
FAU - Shizuru, J
AU  - Shizuru J
FAU - Niederwieser, D
AU  - Niederwieser D
FAU - Storb, R
AU  - Storb R
LA  - eng
GR  - CA 15704/CA/NCI NIH HHS/United States
GR  - CA 18221/CA/NCI NIH HHS/United States
GR  - HL 36444/HL/NHLBI NIH HHS/United States
GR  - CA 78902/CA/NCI NIH HHS/United States
GR  - P01 CA078902/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - FA2DM6879K (Vidarabine)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - P2K93U8740 (fludarabine)
RN  - VB0R961HZT (Prednisone)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
MH  - Cyclosporine/therapeutic use
MH  - Disease Progression
MH  - Dogs
MH  - Forecasting
MH  - Graft Enhancement, Immunologic/adverse effects/methods
MH  - Graft Survival
MH  - Graft vs Host Disease/drug therapy/etiology
MH  - Graft vs Tumor Effect/*immunology
MH  - Hematopoietic Stem Cell Transplantation/adverse effects/*methods
MH  - Histocompatibility
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Lymphocyte Transfusion
MH  - Methotrexate/therapeutic use
MH  - Middle Aged
MH  - Mycophenolic Acid/analogs & derivatives/therapeutic use
MH  - Neoplasms/therapy
MH  - Prednisone/therapeutic use
MH  - Radiation Chimera
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Tissue Donors
MH  - Transplantation Conditioning/adverse effects/*methods
MH  - Transplantation, Homologous
MH  - Treatment Outcome
MH  - Vidarabine/analogs & derivatives/therapeutic use
MH  - Whole-Body Irradiation
RF  - 51
EDAT- 2001/07/19 10:00
MHDA- 2001/08/10 10:01
CRDT- 2001/07/19 10:00
PHST- 2001/07/19 10:00 [pubmed]
PHST- 2001/08/10 10:01 [medline]
PHST- 2001/07/19 10:00 [entrez]
PST - ppublish
SO  - Ann N Y Acad Sci. 2001 Jun;938:328-37; discussion 337-9.