Recipients Of Peripheral Blood Progenitor Cells Research Articles

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

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 1Overall MortalityNon-relapse MortalityAcute GVHDChronic GVHDBMHazard ratioHazard ratioHazard ratioHazard ratioCNI+MMF vs. CNI+MTX*2.06 p<0.00012.85 p<0.00013.30 p<0.00011.75 p=0.02PBPCCNI+MMF vs. CNI+MTX*1.27 p=0.0041.56 p=0.0012.04, p<0.00011.29, p=0.007 Disclosures:No relevant conflicts of interest to declare.

Effect of Stem Cell Source From Unrelated Donors on Transplant Outcomes In Severe Aplastic Anemia (SAA): a Comparison of Unrelated Bone Marrow (BM) and Peripheral Blood Progenitor Cells (PBPC)

AbstractAbstract 531Unrelated donor HSCT has been considered a therapy of last choice in SAA, because of poor overall survival reported prior to 1998 (32% @ 5-years). This is due in large measure to low resolution donor-recipient HLA typing and the selection of patients. Survival after unrelated donor BM HSCT for SAA has improved in recent years with survival rates of approximately 75% @ 5-years when the donor and recipient are matched at HLA-A, -B, -C and –DRB1. Furthermore, improvements in conditioning regimen may also have reduced the rate of graft rejection. In recent years PBPC instead of BM are increasingly used and PBPC grafts now account for 25% of unrelated donor HSCT for SAA. An earlier report from the CIBMTR and the EBMT identified higher chronic graft-versus-host disease (GVHD) incidence and mortality after transplantation of PBPC from HLA-matched siblings compared to BM in patients with SAA aged ≤20 years. GVHD rates are higher after unrelated adult donor HSCT regardless of graft type, but the effects of PBPC on survival in patients with SAA are not known. Two hundred and forty nine patients transplanted in 2000–2007 received either BM (n=186) or PBPC (n=63) from unrelated adult donors matched at HLA-A, -B, -C, -DRB1. Median follow up was 3 years. Compared with recipients of BM, PBPC recipients were older (median age: 19 vs. 35 years), transplanted in 2006–2007 (37% vs. 46%), more likely to be male (47% vs. 65%), receive non-TBI containing transplant conditioning (fludarabine + cyclophosphamide or busulfan or melphalan ± anti-thymocyte globulin; 34% vs. 55%) and tacrolimus-containing GVHD prophylaxis (29% vs. 57%). Among patients who received TBI-containing regimens, approximately 90% of BM and PB recipients received TBI 200 cGy. There were no differences in patient performance score at HSCT, immunosuppressive treatment prior to HSCT and interval from diagnosis to HSCT (median time to HSCT was 13 months in BM recipients and 11 months, in PBPC recipients). As shown after HLA-matched sibling transplantation, the cumulative incidence of neutrophil recovery (30.5 × 109/L at day-28) and platelet recovery (≥20 × 109/L) was similar in recipients of BM (92% and 83%, respectively) and PBPC (95% and 90%, respectively). The day-100 probability of grades 2–4 acute GVHD was higher after PBPC than after BM (51% vs. 33%, p=0.01). The 3-year probability of chronic GVHD was higher after PBPC than after BM, in patients older than 20 years at HCT (60% vs. 41%, p=0.001) but not in younger patients (23% vs. 26%, p=NS). In multivariate analysis, the risk of mortality was higher after PBPC than after BM (HR 1.79, p=0.02). Other factors that predicted mortality included poor performance score (HR 1.95, p=0.009) and non-TBI transplant conditioning regimens (HR 1.96, p=0.006). Although patient age (>20 vs. ≤20 years) was significantly associated with chronic GVHD there was no significant effect of age on mortality (HR 1.21, p=0.47). The 3-year probability of overall survival adjusted for performance score and transplant conditioning regimen was 76% for BM and 60% for PBPC recipients (p=0.02). These data suggest that: 1) outcomes after URD HSCT for SAA are now similar to outcomes observed in MRD HSCT, 2) BM is the preferred graft source when considering unrelated donor HCT in patients with SAA and 3) the data also support low dose TBI in the preparative regimen for transplant conditioning. Disclosures:No relevant conflicts of interest to declare.

Comparison of Outcomes after Transplantation of G-CSF–Stimulated Bone Marrow Grafts versus Bone Marrow or Peripheral Blood Grafts from HLA-Matched Sibling Donors for Patients with Severe Aplastic Anemia

We compared outcomes of patients with severe aplastic anemia (SAA) who received granulocyte-colony stimulating factor (G-CSF)-stimulated bone marrow (G-BM) (n = 78), unstimulated bone marrow (BM) (n= 547), or peripheral blood progenitor cells (PBPC) (n = 134) from an HLA-matched sibling. Transplantations occurred in 1997 to 2003. Rates of neutrophil and platelet recovery were not different among the 3 treatment groups. Grade 2-4 acute graft-versus-host disease (aGVHD) (relative risk [RR] = 0.82, P = .539), grade 3-4 aGVHD (RR = 0.74, P = .535), and chronic GVHD (cGVHD) (RR = 1.56, P = .229) were similar after G-BM and BM transplants. Grade 2-4 aGVHD (RR = 2.37, P = .012) but not grade 3-4 aGVHD (RR = 1.66, P = .323) and cGVHD (RR = 5.09, P < .001) were higher after PBPC transplants compared to G-BM. Grade 2-4 (RR = 2.90, P < .001), grade 3-4 (RR = 2.24, P = .009) aGVHD and cGVHD (RR = 3.26, P < .001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR = 0.63, P = .05). These data suggest no advantage to using G-BM and the observed higher rates of aGVHD and cGVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA-matched sibling transplants for SAA.

Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis

Umbilical-cord blood (UCB) is increasingly considered as an alternative to peripheral blood progenitor cells (PBPCs) or bone marrow, especially when an HLA-matched adult unrelated donor is not available. We aimed to determine the optimal role of UCB grafts in transplantation for adults with acute leukaemia, and to establish whether current graft-selection practices are appropriate. We used Cox regression to retrospectively compare leukaemia-free survival and other outcomes for UCB, PBPC, and bone marrow transplantation in patients aged 16 years or over who underwent a transplant for acute leukaemia. Data were available on 1525 patients transplanted between 2002 and 2006. 165 received UCB, 888 received PBPCs, and 472 received bone marrow. UCB units were matched at HLA-A and HLA-B at antigen level, and HLA-DRB1 at allele level (n=10), or mismatched at one (n=40) or two (n=115) antigens. PBPCs and bone-marrow grafts from unrelated adult donors were matched for allele-level HLA-A, HLA-B, HLA-C, and HLA-DRB1 (n=632 and n=332, respectively), or mismatched at one locus (n=256 and n=140, respectively). Leukaemia-free survival in patients after UCB transplantation was comparable with that after 8/8 and 7/8 allele-matched PBPC or bone-marrow transplantation. However, transplant-related mortality was higher after UCB transplantation than after 8/8 allele-matched PBPC recipients (HR 1.62, 95% CI 1.18-2.23; p=0.003) or bone-marrow transplantation (HR 1.69, 95% CI 1.19-2.39; p=0.003). Grades 2-4 acute and chronic graft-versus-host disease (GvHD) were lower in UCB recipients compared with allele-matched PBPC (HR 0.57, 95% 0.42-0.77; p=0.002 and HR 0.38, 0.27-0.53; p=0.003, respectively), while the incidence of chronic, but not acute GvHD, was lower after UCB than after 8/8 allele-matched bone-marrow transplantation (HR 0.63, 0.44-0.90; p=0.01). These data support the use of UCB for adults with acute leukaemia when there is no HLA-matched unrelated adult donor available, and when a transplant is needed urgently.

A comparison of postengraftment infectious morbidity and mortality after allogeneic partially T cell–depleted peripheral blood progenitor cell transplantation versus T cell–depleted bone marrow transplantation

Postengraftment infections are a major cause of transplant-related morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-SCT). Allogeneic peripheral blood progenitor cell transplantation (PBPCT) is associated with faster hematopoietic recovery compared to bone marrow transplantation (BMT) and unmanipulated PBPCT may be associated with fewer postengraftment infections. We set out to evaluate and compare the incidence, cause, and outcome of postengraftment infections following HLA-identical sibling T cell-depleted PBPCT vs T cell-depleted BMT between days 30 and 365 posttransplant. Forty recipients of peripheral blood progenitor cells (PBPC) and 47 recipients of bone marrow (BM) were included. The two groups of patients were comparable with respect to their baseline characteristics. PBPC grafts contained significantly more CD34+ cells and PBPCT was associated with significantly faster neutrophil and lymphocyte recovery as compared to BMT. PBPC recipients experienced more chronic graft-vs-host disease (GVHD; 55% vs 34%; p=0.02). The number of definite and clinical infections per 100 patient days was comparable between recipients of PBPC and BM with similar contribution of causative microorganisms. At one year post SCT, 68% of PBPC recipients had experienced at least one CTC grade 3-4 infection vs 65% of BM recipients. Treatment-related mortality at one year from transplantation was 34% after PBPCT vs 30% after BMT, and no difference in infection-related mortality was observed. Postengraftment infectious morbidity and mortality were comparable between recipients of PBPC and BM despite a higher CD34+ cell content of PBPC grafts and faster lymphocyte recovery after PBPCT, which may in part be explained by the higher incidence of chronic GVHD.

A randomized multicenter comparison of CD34 +-selected progenitor cells from blood vs from bone marrow in recipients of HLA-identical allogeneic transplants for hematological malignancies

Objective. Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone marrow transplantation (BMT) vs PBPC transplantation (PBPCT) using CD34 + selection for T-cell depletion (TCD) in both study arms. Patients and Methods. Between January 1996 and October 2000, 120 patients with a diagnosis of acute leukemia, myelodysplasia, multiple myeloma, or lymphoma were randomized to receive either filgrastim-mobilized PBPC or BM from HLA-identical sibling donors after standard high-dose chemoradiotherapy. Patient characteristics did not differ between study arms. Results. Recipients of PBPC received more CD3 + T cells (median: 3.0 vs 2.0×10 5/kg, p<0.0001) and more CD34 + cells (median: 3.6 vs 0.9×10 6/kg, p<0.0001). Neutrophil and platelet recoveries occurred significantly faster after PBPCT. The cumulative incidence of acute GVHD grades II–IV was 37% after BMT vs 52% after PBPCT and was most significantly ( p = 0.007) affected by the number of CD3 + T cells in the graft. Acute GVHD appeared strongly associated with increased treatment-related mortality (TRM) in a time-dependent analysis. Higher numbers of CD34 + cells were associated with less TRM. With a median follow-up of 37 months (range: 12–75), overall survival at 4 years from transplantation was 60% after BMT and 34% for recipients of PBPCT ( p = 0.04), which difference was largely due to increased GVHD and TRM in PBPC recipients receiving T-cell dosages greater than 2×10 5/kg. Conclusion. Outcome following T cell–depleted PBPCT critically depends on the number of CD3 + T cells, whereby high T-cell numbers may blunt a favorable effect of higher CD34 + cell numbers.

TRANSPLANTATION OF PERIPHERAL BLOOD PROGENITOR CELLS FROM UNRELATED DONORS

TRANSPLANTATION OF PERIPHERAL BLOOD PROGENITOR CELLS FROM UNRELATED DONORS

CD34 Positive Blood Cells for Allogeneic Progenitor and Stem Cell Transplantation

The transplantation of allogeneic peripheral blood progenitor cells (PBPC) provides complete and sustained hematopoietic and lymphopoietic engraftment. In healthy donors, large amounts of PBPC can be mobilized with hematopoietic growth factors. However, the high content of immunocompetent T-cells in apheresis products may expose recipients of allogeneic PBPC to an elevated risk of acute and chronic graft-versus-host disease. Thus, the use of appropriate T-cell reduction, but not depletion might reduce this risk. The hazards of graft rejection and a higher relapse rate can be avoided by maintaining a portion of the T-cells in the graft. The positive selection of CD34+ cells from peripheral blood preparations simultaneously provides an approximately 1000-fold reduction of T-cells. These purified CD34+ cells containing committed and pluripotent stem cells are suitable for allogeneic transplantation and can be used in the following instances: 1. As hematopoietic stem and progenitor cell transplantation instead of bone marrow cells, from HLA-identical family donors; 2. for increasing the stem cell numbers from HLA-mismatched or three HLA-loci different family donors in order to reduce the incidence of rejection but without increasing the T-cell number; 3. boosting of poor marrow graft function with stem cells from the same family donors; 4. transplantation from volunteer matched unrelated donors; 5. split transplantation of CD34+ and T-cells; 6. addition of ex vivo expanded CD34+ cells to blood cell or bone marrow transplantation; 7. generation of antigen specific immune effector cells and antigen presenting cells for cell therapy.

Granulocyte Colony-Stimulating Factor “Mobilized” Peripheral Blood Progenitor Cells Accelerate Granulocyte and Platelet Recovery After High-Dose Chemotherapy

Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to "mobilize" peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with "nonmobilized" PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with "nonmobilized" recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving "mobilized" PBPC.

Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy

Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to “mobilize” peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P &lt; .01) when compared with “nonmobilized” PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P &lt; .001) when compared with “nonmobilized” recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving “mobilized” PBPC.