Transplantation Of Peripheral Blood Progenitor Cells (PBPC) As Compared To Bone Marrow (BM) From Unrelated Related Donors For Hematologic Cancers Using Fludarabine-Alkylating Agent Based Reduced Intensity Conditioning Regimens

Abstract

Abstract We explored whether there are differences in graft-versus-host disease (GVHD) or mortality risks after transplantation of PBPC and BM from unrelated donors in the setting of reduced intensity conditioning. Included are 219 BM and 887 PBPC recipients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or non-Hodgkin lymphoma (NHL). Patients received an alkylating agent and fludarabine as their conditioning regimen and for GVHD prophylaxis, calcineurin inhibitor (CNI) with methotrexate (MTX) or mycophenolate (MMF). Recipients of low dose total body irradiation regimen were excluded, as PBPC was the sole graft used with this regimen. Transplantations occurred in the U.S. between 2000 and 2008. The median ages of BM and PBPC recipients were 57 years. The characteristics of the treatment groups were similar except that BM recipients were more likely to have NHL, receive melphalan + fludarabine, in vivo T-cell depletion and, tacrolimus + MTX GVHD prophylaxis. The median follow-up of BM and PBPC recipients were 6 and 5 years, respectively. Preliminary analysis suggested an interaction between graft type and GVHD prophylaxis. Therefore, the effect of graft type was tested as follows: PBPC, CNI + MTX, PBPC, CNI + MMF, BM, CNI + MTX and BM, CNI + MMF. Results are shown in Tables 1 and 2. After adjusting for age, performance score, disease / disease status and HLA-match, mortality risks were higher after transplantation of PBPC or BM when GVHD prophylaxis included MMF compared to MTX (Table 1). There were no significant differences in mortality risks after transplantation of PBPC relative to BM with CNI + MTX GVHD prophylaxis (Table 2). But mortality risks were higher after transplantation of BM compared to PBPC with CNI + MMF (Table 2). Risks of grade 2-4 acute and chronic GVHD were higher after transplantation of PBPC or BM when GVHD prophylaxis included MMF compared to MTX (Table 1). Relapse risks were higher after transplantation of BM compared to PBPC with CNI + MMF (HR 1.55, p=0.02) but not with CNI + MTX GVHD prophylaxis (HR 1.13, p=0.38). Independent of graft type and GVHD prophylaxis regimens, in vivo T cell depletion was associated with lower risks of acute (HR 0.69, p<0.001) and chronic (HR 0.52, p<0.0001) GVHD but relapse risks were higher (HR 1.24, p=0.02). The data support BM and PBPC are suitable for unrelated donor transplantation when using fludarabine-alkylating agent based reduced intensity conditioning regimens and CNI + MTX GVHD prophylaxis. The data support avoiding CNI + MMF GVHD prophylaxis in this setting. Table 1 Overall Mortality Non-relapse Mortality Acute GVHD Chronic GVHD BM Hazard ratio Hazard ratio Hazard ratio Hazard ratio CNI+MMF vs. CNI+MTX* 2.06 p<0.0001 2.85 p<0.0001 3.30 p<0.0001 1.75 p=0.02 PBPC CNI+MMF vs. CNI+MTX* 1.27 p=0.004 1.56 p=0.001 2.04, p<0.0001 1.29, p=0.007 Table 2 Overall Mortality Non-relapse Mortality Acute GVHD Chronic GVHD Comparison of BM vs. PBPC Hazard ratio Hazard ratio Hazard ratio Hazard ratio BM, CNI + MTX vs. PBPC CNI + MTX* 0.73 p=0.14 0.73 p=0.14 0.88 p=0.54 0.78 p=0.09 BM, CNI + MMF vs. PBPC CNI + MMF* 1.47 p=0.008 1.34 p=0.17 1.43 p=0.05 1.06 p=0.78 * reference group Disclosures: No relevant conflicts of interest to declare.