Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning.
We previously reported data from 103 patients with hematologic malignancies (median age 54 years) who received peripheral blood stem cell (PBSC) grafts from HLA-matched unrelated donors after nonmyeloablative conditioning and were given postgrafting immunosuppression consisting of mycophenolate mofetil (MMF; administered from day 0 until day +40 with taper through day +96) and cyclosporine (CSP; given from day -3 to day +100, with taper through day 180) (historical patients). The incidences of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 52% and 49%, respectively, and the 1-year probabilities of relapse, nonrelapse mortality (NRM), and progression-free survival (PFS) were 26%, 18%, and 56%, respectively. Here, we treated 71 patients with hematologic malignancies (median age 56 years) with unrelated PBSC grafts and investigated whether postgrafting immunosuppression with an extended course of MMF, given at full dosing until day +150 and then tapered through day +180, and a shortened course of CSP, through day +80, would promote tolerance induction and reduce the incidence of GVHD (current patients). We observed 77% grade II-IV aGVHD and 45% extensive cGVHD (P=.03, and P=.43, respectively, in current compared to historical patients). The 1-year probabilities of relapse, NRM, and PFS were 23%, 29%, and 47%, respectively (P=.89, P=.02, and P=.08 compared to the historical patients). We conclude that postgrafting immunosuppression with extended MMF and shortened CSP failed to decrease the incidence of GVHD among unrelated PBSC recipients given nonmyeloablative conditioning.
Baron
Frédéric
F
University of Liège, Liège, Belgium.
Sandmaier
Brenda M
BM
Storer
Barry E
BE
Maris
Michael B
MB
Langston
Amelia A
AA
Lange
Thoralf
T
Petersdorf
Effie
E
Bethge
Wolfgang
W
Maziarz
Richard T
RT
McSweeney
Peter A
PA
Pulsipher
Michael A
MA
Wade
James C
JC
Chauncey
Thomas R
TR
Shizuru
Judith A
JA
Sorror
Mohamed L
ML
Woolfrey
Ann E
AE
Maloney
David G
DG
Storb
Rainer
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019172:Transplantation Conditioning / Q000379:methods*; D017211:Treatment Failure
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid
Br J Haematol. 2005 May;129(3):381-91
15842663
Biol Blood Marrow Transplant. 2005 Apr;11(4):272-9
15812392
Blood. 2005 Jun 1;105(11):4532-9
15731182
Blood. 2005 Oct 15;106(8):2912-9
15994282
Curr Opin Hematol. 2005 Nov;12(6):435-43
16217159
Cancer. 2005 Nov 1;104(9):1931-8
16178004
Biol Blood Marrow Transplant. 2006 Apr;12(4):454-65
16545729
Transplantation. 2006 Mar 27;81(6):818-25
16570002
J Clin Oncol. 2006 Sep 1;24(25):4150-7
16896000
Leukemia. 2006 Oct;20(10):1690-700
16871276
Nat Med. 1999 Nov;5(11):1298-302
10545997
Nat Med. 2000 Jul;6(7):762-8
10888924
Transplantation. 2001 Jan 15;71(1):118-25
11211176
Exp Hematol. 2001 Mar;29(3):362-70
11274765
Blood. 2001 Jun 1;97(11):3390-400
11369628
Clin Cancer Res. 2001 Aug;7(8):2254-62
11489799
Blood. 2001 Dec 15;98(13):3868-70
11739201
Blood. 2002 Feb 1;99(3):1071-8
11807015
Blood. 2002 Jul 1;100(1):48-51
12070007
Biol Blood Marrow Transplant. 2002;8(9):512-20
12374456
Blood. 2003 Feb 15;101(4):1620-9
12393457
Blood. 2003 Apr 1;101(7):2886-93
12433677
Blood. 2003 Jul 15;102(2):756-62
12663454
Blood. 2003 Sep 15;102(6):2021-30
12791654
Blood. 2003 Oct 15;102(8):3052-9
12842990
Biol Blood Marrow Transplant. 2004 May;10(5):310-9
15111930
Blood. 2004 Aug 1;104(3):865-72
15090449
Blood. 2004 Oct 15;104(8):2254-62
15226174
Nature. 1989 Jun 22;339(6226):625-6
2786609
Blood. 1997 Apr 15;89(8):3048-54
9108426
Blood. 1997 Jun 15;89(12):4531-6
9192777
Blood. 1998 Feb 1;91(3):756-63
9446633
Nat Med. 1999 Jun;5(6):686-93
10371508
Blood. 2005 Mar 15;105(6):2300-6
15572597
J Clin Oncol. 2005 Mar 20;23(9):1993-2003
15774790
Leukemia. 2005 May;19(5):822-8
15772701