Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution.
OBJECTIVE
Allogeneic transplantation is typically limited to younger patients having a matched donor. To allow a donor to be found for nearly all patients, we have used a nonmyeloablative conditioning regimen in conjunction with stem cells from a related donor with one fully mismatched HLA haplotype.


METHODS
Fludarabine, cyclophosphamide, and alemtuzumab were used as the preparatory regimen. Additional graft-versus-host disease (GVHD) prophylaxis included mycophenolate with or without cyclosporine. Patients with persistence of disease had a donor lymphocyte boost planned. Toxicities, engraftment, response, survival, and immune recovery are reported.


RESULTS
Forty-nine patients with hematologic malignancies or marrow failure and no other available donors were enrolled. Ninety-four percent of patients had successful engraftment, and 8% had secondary graft failure. The treatment-related mortality rate was 10.2%, and 8% of patients had severe GVHD. Encouraging evidence of quantitative lymphocyte recovery through expansion of transplanted T cells was noted by 3 to 6 months. Seventy-five percent of patients attained a complete remission, and 1-year survival rate was 31% (95% CI, 18% to 44%). A standard-risk group of 19 patients with aplasia or in remission at transplantation demonstrated a 63% 1-year survival rate (95% CI, 38% to 80%) and 2.9-year median overall survival time (95% CI, 6.2 to 48 months).


CONCLUSIONS
Nonmyeloablative therapy using haploidentical family member donors is feasible because the main obstacles of GVHD and graft rejection are manageable, allowing readily available stem-cell donors to be found for nearly all patients. Further qualitative and quantitative improvement in immune recovery is needed to address the high rate of relapse and risk of severe infections.
Rizzieri
David A
DA
Department of Medicine, Division of Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA. rizzi003@mc.duke.edu
Koh
Liang Piu
LP
Long
Gwynn D
GD
Gasparetto
Cristina
C
Sullivan
Keith M
KM
Horwitz
Mitchell
M
Chute
John
J
Smith
Clayton
C
Gong
Jerald Z
JZ
Lagoo
Anand
A
Niedzwiecki
Donna
D
Dowell
Jeannette M
JM
Waters-Pick
Barbara
B
Liu
CongXiao
C
Marshall
Dawn
D
Vredenburgh
James J
JJ
Gockerman
Jon
J
Decastro
Carlos
C
Moore
Joseph
J
Chao
Nelson J
NJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D019653:Myeloablative Agonists