PBSC Transplants from Unrelated Donors Show No Survival Advantage

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.