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Credit: Chad McNeeley
Combining a couple of “promising” treatment approaches can prevent graft-vs-host disease (GVHD) as well as conventional therapy, researchers have reported in the Journal of Clinical Oncology.
They combined a 4-day myeloablative conditioning regimen of busulfan and fludarabine with 2 days of high-dose cyclophosphamide after transplant.
Typically, patients receive 6 months of immunosuppressive therapy to reduce their risk of GVHD.
The conditioning regimen and post-transplant cyclophosphamide have been tested separately in other studies and have good track records in controlling cancer and preventing severe GVHD.
Those successes led Leo Luznik, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues to combine the 2 therapies.
The team tested the combination in 92 patients with high-risk hematologic malignancies. Diagnoses included acute and chronic leukemias, multiple myeloma, non-Hodgkin lymphoma, and myelodysplastic syndromes. Patients had a median age of 49 (range, 21-65).
All patients received 40 mg/m2/day of intravenous (IV) fludarabine immediately before busulfan on all 4 days of conditioning. The busulfan dose of 130 mg/m2 IV daily was adjusted based on pharmacokinetics.
One or 2 days of rest were allowed before patients received a T-cell-replete bone marrow allograft. Forty-five patients had a matched, related donor, and 47 had a matched, unrelated donor.
Patients received 50 mg/kg/day of IV cyclophosphamide for 2 days, with the first dose starting 62 to 72 hours after the start of allograft infusion.
At 100 days after transplant, 51% of patients had developed grade 2-4 acute GVHD, and 15% had grade 3-4 acute GVHD. Fourteen percent of patients developed chronic GVHD.
The 2-year overall survival rate was 67%, and 2-year event-free survival was 62%.
Dr Luznik said he was encouraged by the low rate of chronic GVHD with the regimen. And he noted that percentages of acute GVHD are similar to those seen with the standard 6-month regimen of immunosuppressive drugs.
Reducing the post-transplant treatment to 2 days with cyclophosphamide, he said, “also allows for the earlier integration of other treatments.”
For example, immunotherapies used to eradicate any remaining cancer could be started much sooner with this regimen, said study author Christopher Kanakry, MD, of the Sidney Kimmel Cancer Center at Johns Hopkins.
“If you give patients immune cells to eradicate any remaining cancer cells that might be present,” he said, “those immune cells would not be prevented from doing their job by ongoing immune suppression drugs that are being used in patients treated with conventional transplant approaches.”
Dr Luznik said the researchers’ next step will be a phase 3 trial comparing this regimen to another experimental approach to prevent GVHD or to the more traditional 6-month immunosuppressive therapy.
Funding for this study was provided by Otsuka Pharmaceutical Co., Ltd. and the National Institutes of Health. 
Credit: Chad McNeeley
Combining a couple of “promising” treatment approaches can prevent graft-vs-host disease (GVHD) as well as conventional therapy, researchers have reported in the Journal of Clinical Oncology.
They combined a 4-day myeloablative conditioning regimen of busulfan and fludarabine with 2 days of high-dose cyclophosphamide after transplant.
Typically, patients receive 6 months of immunosuppressive therapy to reduce their risk of GVHD.
The conditioning regimen and post-transplant cyclophosphamide have been tested separately in other studies and have good track records in controlling cancer and preventing severe GVHD.
Those successes led Leo Luznik, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues to combine the 2 therapies.
The team tested the combination in 92 patients with high-risk hematologic malignancies. Diagnoses included acute and chronic leukemias, multiple myeloma, non-Hodgkin lymphoma, and myelodysplastic syndromes. Patients had a median age of 49 (range, 21-65).
All patients received 40 mg/m2/day of intravenous (IV) fludarabine immediately before busulfan on all 4 days of conditioning. The busulfan dose of 130 mg/m2 IV daily was adjusted based on pharmacokinetics.
One or 2 days of rest were allowed before patients received a T-cell-replete bone marrow allograft. Forty-five patients had a matched, related donor, and 47 had a matched, unrelated donor.
Patients received 50 mg/kg/day of IV cyclophosphamide for 2 days, with the first dose starting 62 to 72 hours after the start of allograft infusion.
At 100 days after transplant, 51% of patients had developed grade 2-4 acute GVHD, and 15% had grade 3-4 acute GVHD. Fourteen percent of patients developed chronic GVHD.
The 2-year overall survival rate was 67%, and 2-year event-free survival was 62%.
Dr Luznik said he was encouraged by the low rate of chronic GVHD with the regimen. And he noted that percentages of acute GVHD are similar to those seen with the standard 6-month regimen of immunosuppressive drugs.
Reducing the post-transplant treatment to 2 days with cyclophosphamide, he said, “also allows for the earlier integration of other treatments.”
For example, immunotherapies used to eradicate any remaining cancer could be started much sooner with this regimen, said study author Christopher Kanakry, MD, of the Sidney Kimmel Cancer Center at Johns Hopkins.
“If you give patients immune cells to eradicate any remaining cancer cells that might be present,” he said, “those immune cells would not be prevented from doing their job by ongoing immune suppression drugs that are being used in patients treated with conventional transplant approaches.”
Dr Luznik said the researchers’ next step will be a phase 3 trial comparing this regimen to another experimental approach to prevent GVHD or to the more traditional 6-month immunosuppressive therapy.
Funding for this study was provided by Otsuka Pharmaceutical Co., Ltd. and the National Institutes of Health.
Credit: Chad McNeeley
Combining a couple of “promising” treatment approaches can prevent graft-vs-host disease (GVHD) as well as conventional therapy, researchers have reported in the Journal of Clinical Oncology.
They combined a 4-day myeloablative conditioning regimen of busulfan and fludarabine with 2 days of high-dose cyclophosphamide after transplant.
Typically, patients receive 6 months of immunosuppressive therapy to reduce their risk of GVHD.
The conditioning regimen and post-transplant cyclophosphamide have been tested separately in other studies and have good track records in controlling cancer and preventing severe GVHD.
Those successes led Leo Luznik, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues to combine the 2 therapies.
The team tested the combination in 92 patients with high-risk hematologic malignancies. Diagnoses included acute and chronic leukemias, multiple myeloma, non-Hodgkin lymphoma, and myelodysplastic syndromes. Patients had a median age of 49 (range, 21-65).
All patients received 40 mg/m2/day of intravenous (IV) fludarabine immediately before busulfan on all 4 days of conditioning. The busulfan dose of 130 mg/m2 IV daily was adjusted based on pharmacokinetics.
One or 2 days of rest were allowed before patients received a T-cell-replete bone marrow allograft. Forty-five patients had a matched, related donor, and 47 had a matched, unrelated donor.
Patients received 50 mg/kg/day of IV cyclophosphamide for 2 days, with the first dose starting 62 to 72 hours after the start of allograft infusion.
At 100 days after transplant, 51% of patients had developed grade 2-4 acute GVHD, and 15% had grade 3-4 acute GVHD. Fourteen percent of patients developed chronic GVHD.
The 2-year overall survival rate was 67%, and 2-year event-free survival was 62%.
Dr Luznik said he was encouraged by the low rate of chronic GVHD with the regimen. And he noted that percentages of acute GVHD are similar to those seen with the standard 6-month regimen of immunosuppressive drugs.
Reducing the post-transplant treatment to 2 days with cyclophosphamide, he said, “also allows for the earlier integration of other treatments.”
For example, immunotherapies used to eradicate any remaining cancer could be started much sooner with this regimen, said study author Christopher Kanakry, MD, of the Sidney Kimmel Cancer Center at Johns Hopkins.
“If you give patients immune cells to eradicate any remaining cancer cells that might be present,” he said, “those immune cells would not be prevented from doing their job by ongoing immune suppression drugs that are being used in patients treated with conventional transplant approaches.”
Dr Luznik said the researchers’ next step will be a phase 3 trial comparing this regimen to another experimental approach to prevent GVHD or to the more traditional 6-month immunosuppressive therapy.
Funding for this study was provided by Otsuka Pharmaceutical Co., Ltd. and the National Institutes of Health.