RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.
OBJECTIVES: * Determine the complete response rate in patients with myelodysplastic syndromes treated with reduced-intensity allogeneic bone marrow transplantation, including photopheresis, total body irradiation, and pentostatin. * Determine the disease-free and overall survival of patients treated with this regimen. * Determine the engraftment rate of donor cells in patients treated with this regimen. * Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen. * Determine the toxicity of this regimen in these patients. OUTLINE: This is a single-arm, two-stage, multicenter phase II study. * Preparative Regimen: Patients undergo photopheresis using methoxsalen on days -7 and -6 and receive pentostatin intravenously (IV )continuously on days -5 and -4. Total body irradiation is administered on days -3 and -2 for a total of 3 doses. * Transplantation: Allogeneic bone marrow or peripheral blood stem cells are infused on day 0. * Acute graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV on days -1 to 30 and then orally every 12 hours. Cyclosporine dose is then tapered beginning after day 50 and continuing for 6 months in the absence of GVHD. Once cyclosporine dose is significantly decreased, oral mycophenolate mofetil (MMF) is then administered twice a day. MMF dose is then tapered for 12 months in the absence of GVHD. Patients also receive methotrexate IV on days 1 and 3. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 33 patients would be accrued for this study within 2.1 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Immunosuppressant
Antimetabolite
Psoralens
an antibiotic with immunosuppressamt properties isolated from Penicillium spp
Purine analogue
Unmanipulated allogeneic bone marrow
G-CSF mobilized peripheral blood stem cell
a total of 600 cGy given in 3 200 cGy fractionated doses
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States
Tufts-NEMC Cancer Center
Boston, Massachusetts, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
Jewish Hospital Cancer Center
Cincinnati, Ohio, United States
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Complete Response Rate
Completed response is defined as: Bone marrow evaluation: Repeat bone marrow showing \< 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia (see dysplasia qualifier under peripheral blood evaluation). Peripheral blood evaluation \[absolute values must last at least 2 months\] Hemoglobin \>11 g/dl (untransfused, not on erythropoietin) Neutrophils (1500/mm3 (not on a myeloid growth factor)) Platelets (100,000/mm3 (not on a thrombopoetic agent)) Blasts - 0% No dysplasia. No detectable cytogenetic abnormality, if preexisting abnormality was present
Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.
Number of Patients Who Developed Disease Progression After Achieving Complete Response
Disease free survival (DFS) was listed as a secondary endpoint in the study protocol, which would be assessed in patients who achieved complete response (CR). It was defined to be time from CR to documented progression or to death without progression. Patients without documented progression or death reported were censored at the time of last disease evaluation. However, due to the small number of patients with CR, the number of patients who developed disease progression was reported here.
Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.
Overall Survival
Overall survival (OS) is defined to be the time from registration to death from any cause, with follow-up censored at the date of last contact. Kaplan-Meier method was used to estimate the distribution of OS.
Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.
Proportion of Graft Versus Host Disease
Proportion of Graft versus Host Disease is calculated as number of patients with Graft versus Host Disease divided by all eligible and treated patients
Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.
Time to Engraftment for Neutrophil
Time to neutrophil engraftment is defined from date of infusion to date of neutrophil engraftment. Neutrophil engraftment is defined as ANC \> 500/mm3 on two consecutive measurements. The date of engraftment is the date of the first ANC \> 500/mm3.
Time frame: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.
Time to Engraftment for Platelet
Time to platelet engraftment is defined from date of infusion to date of platelet engraftment. The platelet engraftment is defined as platelets \> 20,000 on two consecutive measurements, at least seven days apart, without platelet transfusions in between and for at least three days before the first measurement that is over 20,000. The date of engraftment is the date of the first measurement that is over 20,000.
Time frame: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.
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