[Quadruple therapy with CsA, MTX, MMF and ATG for preventing graft-versus-host disease in unrelated donor hematopoietic stem cell transplantation].
OBJECTIVE
To evaluate the efficacy of quadruple therapy with cyclosporine (CsA), methotrexate (MTX), mycophenolate mofetil (MMF) and low-dose antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis in unrelated donor hematopoietic stem cell transplantation (URD-HSCT).


METHODS
Thirteen patients with leukemia received URD-HSCT, of whom 11 had HLA genotypes and 2 had mismatch for 1 genetic locus. Another 11 leukemia patients all serologically matched underwent related donor (RD)-HSCT. Total body irradiation (TBI) plus cyclophosphamide (CTX) was adopted in 19 cases and modified BuCY conditioning regimen (hydroxyurea, busulfan, Ara-C, Cyclophosphamide ) in the other 5 cases. All the patients received CsA+MTX protocal for GVHD prophylaxis, and in those undergoing URD-HSCT, additional MMF and low-dose ATG were used.


RESULTS
The incidence and severity of regimen-related toxicity differed little between unrelated and related transplantation. Acute GVHD (aGVHD) occurred in 46.2% of the patients undergoing URD- HSCT and in 55.6% of those with RD-HSCT, respectively. Four patients had chronic GVHD (cGVHD), in the 7 ones who could be followed up after URD-HSCT; 6 of the 9 patients with RD-HSCT developed cGVHD postoperatively. One patient with URD-HSCT died of hemorrhagic cystitis and another with RD-HSCT died of cytomegalovirus (CMV) pneumonia. The at one-year disease-free survival rate was 87.5% and 90.9% in patients with unrelated and related transplantation respectively. Significant difference was not noted in the positivity rate of CMV antigen between the patients receiving URD-HSCT or RD-HSCT.


CONCLUSIONS
CsA+MTX in combination with MMF and low-dose ATG may decrease the incidence and severity of aGVHD without increasing transplant-related mortality or CMV infection.
Liu
Qi-fa
QF
Department of Hematology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China. liuqifa@fimmu.com
Sun
Jing
J
Zhang
Yu
Y
Xu
Dan
D
Liu
Xiao-li
XL
Xu
Bing
B
Meng
Fan-yi
FY
Zhou
Shu-yun
SY
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D003586:Cytomegalovirus Infections / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D008727:Methotrexate