Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers.

BACKGROUND In recipients of allogeneic hematopoietic-cell transplants, peripheral-blood cells mobilized with the use of filgrastim (recombinant granulocyte colony-stimulating factor) engraft more rapidly than bone marrow. However, the relative effects of these techniques on the rates of acute and chronic graft-versus-host disease, overall survival, and disease-free survival have not been determined in randomized studies. METHODS Between March 1996 and July 1999, 172 patients (12 to 55 years of age) with hematologic cancer were randomly assigned to receive either bone marrow or filgrastim-mobilized peripheral-blood cells from HLA-identical relatives for hematopoietic rescue after the treatment of hematologic cancer with high doses of chemotherapy, with or without radiation. RESULTS The recovery of both neutrophils and platelets was faster with peripheral-blood cells than with marrow (P<0.001 for both comparisons). The cumulative incidence of grade II, III, or IV acute graft-versus-host disease at 100 days was 64 percent with peripheral-blood cells and 57 percent with marrow (hazard ratio, 1.21; 95 percent confidence interval, 0.81 to 1.81; P=0.35). The cumulative incidence of chronic graft-versus-host disease was 46 percent with peripheral-blood cells and 35 percent with marrow (hazard ratio, 1.16; 95 percent confidence interval, 0.71 to 1.90; P=0.54). The estimated overall probability of survival at two years was 66 percent with peripheral-blood cells and 54 percent with marrow (hazard ratio for death, 0.62; 95 percent confidence interval, 0.38 to 1.02; P=0.06). The rate of disease-free survival at two years was 65 percent with peripheral-blood cells and 45 percent with marrow (hazard ratio for relapse or death, 0.60; 95 percent confidence interval, 0.38 to 0.95; P=0.03). CONCLUSIONS In patients given high-dose chemotherapy, with or without radiation, for the treatment of hematologic cancer, allogeneic peripheral-blood cells used for hematopoietic rescue restore blood counts faster than allogeneic bone marrow, without increasing the risk of graft-versus-host disease.

[1]  J. Jackson,et al.  Immunologic attributes of cytokine mobilized peripheral blood stem cells and recovery following transplantation. , 1996, Bone marrow transplantation.

[2]  R. Storb,et al.  Haemopoietic reconstitution by donor‐derived myelodysplastic progenitor cells after haemopoietic stem cell transplantation , 1999, British journal of haematology.

[3]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[4]  S. Singhal,et al.  Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial , 2000, The Lancet.

[5]  R. Storb,et al.  Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor , 2000, Bone Marrow Transplantation.

[6]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[7]  K. Sullivan,et al.  Chronic graft-versus-host disease and other late complications of bone marrow transplantation. , 1991, Seminars in hematology.

[8]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[9]  I. Benet,et al.  Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases. allo-PBPCT Spanish Group. , 1996, Bone marrow transplantation.

[10]  A. Santoro,et al.  High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies. , 1996, Bone marrow transplantation.

[11]  N. Schmitz,et al.  Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). , 2000, Blood.

[12]  R. Storb,et al.  Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation. , 1996, Blood.

[13]  P. Thall,et al.  Allogeneic blood stem cell transplantation in advanced hematologic cancers , 1997, Bone Marrow Transplantation.

[14]  N. Schmitz,et al.  Transplantation of peripheral blood progenitor cells from HLA‐identical sibling donors , 1996, British journal of haematology.

[15]  G. Morgan,et al.  Allogeneic peripheral blood stem cell transplantation for haematological malignancies – an analysis of kinetics of engraftment and GVHD risk , 1997, Bone Marrow Transplantation.

[16]  R. Storb,et al.  Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor , 1995 .

[17]  N. Schmitz,et al.  Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation , 1998, Bone Marrow Transplantation.

[18]  A. Deisseroth,et al.  Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: Potential advantage of blood over marrow allografts , 1995 .

[19]  J. Ferrara,et al.  Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease. , 1995, Blood.

[20]  R. Storb,et al.  Factors that influence collection and engraftment of autologous peripheral-blood stem cells. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  J. Bourhis,et al.  Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  M. Mielcarek,et al.  CD14+ cells in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells induce secretion of interleukin-6 and G-CSF by marrow stroma. , 1996, Blood.

[23]  S. Heimfeld,et al.  Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. , 2000, Blood.

[24]  F. Aranha,et al.  A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies , 1998, Bone Marrow Transplantation.

[25]  K. Sullivan,et al.  Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease. , 1997, Blood.

[26]  The Risk of Residual Molecular and Cytogenetic Disease in Patients With Philadelphia-Chromosome Positive First Chronic Phase Chronic Myelogenous Leukemia Is Reduced After Transplantation of Allogeneic Peripheral Blood Stem Cells Compared With Bone Marrow , 1999 .

[27]  R. Vij,et al.  Long-term follow-up of high-risk allogeneic peripheral-blood stem-cell transplant recipients: graft-versus-host disease and transplant-related mortality. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  H. Deeg,et al.  Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. , 1992, Blood.

[29]  J. Garcia-conde,et al.  Chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation from matched related donors. A case-control study , 1998, Bone Marrow Transplantation.