The Analysis Of The Causes Of Death In The Treatment Of Hematological Malignacies With Allogeneic Stem Cell Transplantation From Sibling Donor

Objective To analyse the causes of death in the treatmeant of hematological malignacies with allogeneic hematopoietic stem cell transplantation(allo-HSCT) from sibling donor,explore the ways to improve the clinical effect.Methods Retrospective analysis was made on clinical data of 140 patients in our hospital between July 2001and July 2008 , which with hematological malignacies (median age 34 years,range 10-57 years), received allo-HSCT from HLA-identical 127 cases and 1-antigen mismatched sibling donors 13 cases . OF them,74 were acute leukemia (AL)(49 in CR1 , 9 in CR 2 or greater, 16 in relapse,refractory or NR) . 45 were chronic myeloid leukemia( CML)(CP 36 ,AP 6 , BC 3 );7 were Myelodysplastic syndrome( MDS )(RA 2 ,RAEB 1, RAEB-t 1, AL secondary to MDS 5). 10 were Non-Hodgkin's lymphoma (NHL) (3 in CR 1, 7 in relapse or NR), 2 were Multiple myeloma (MM). 91 patients were standard-risk group,49 patients were high-risk group.The conditioning regimens was based on TBI+CY or modified BU/CY.A combination of cyclosporine and short course of methotrexate(MTX) and mycophenolate mofetil( MMF) was administered for graft-versus-host disease (GVHD) prophylaxis .Result 138 out of 140 were engrafted(98.6%). The median time (range) to neutrophil >0.5×109 /L and platelet >20×109/L was 12 (9～19)and 20(8～60)days post-transplant,respectively. 22 patients developed acute graft-versus-host disease (aGVHD), the cumulative incidence rate was 15.7 percent.The chronic GVHD was diagnosed in 48 of 140 patients(34.3%). The median follow-up duration was 36( 1～89) months ,48 patients died:27 died of relapse(19 in high-risk group and 8 in standard-risk group) ,21 died of transplant-related mortality (TRM) (10 in high-risk group and 11 in standard-risk group). The cumulative incidence of TRM at 100 days was 5.7%.The estimated probabilies of disease-free survival at 3 years in standard and high-risk patients were 76.5 and 29.6%,respectively(p<0.01). The estimated probabilies of overall survival at 3 years in standard and high-risk patients were 77.4 and 34.5% ,respectively(p<0.01).The relapse related mortality rate in high-risk group was higher than the standard-risk group(p<0.01). The relapse related mortality was the mayjor couse of death in standard-risk group.The transplant-related mortality was the mayjor couse of death in standard-risk group. Of the 21 cases TRM:11 (52.4%)died of mutiple organ failure and infection due to GvHD,5(23.8%)died of severe pulmonary infection, 2(9.5%) died of early complications after hematopoietic stem cell transplantation (1 Veno-occlusive dease of the liver,1Transplant-related microangiopathy, respectively), 2 (9.5%)died of Hepatitis B,1(4.8%)died of infectious shock.Conclusion Relapse was the major cause of death after allogeneic hematopoietic stem cell transplantation.The major causes of transplant-related mortality were GvHD,severe pulmonary infection and the early complications after hematopoietic stem cell transplantation .The key to improve the outcome of allo-HSCT from sibling dornor is to decrease the relase rate,reduce the incidence and severity of GVHD,control infection and prevent the early complications after hematopoietic stem cell transplantation etc.