Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes
Condition: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: Cyclosporine; Methotrexate; Photopheresis; Mycofenolate mofetil; Pentostatin; allogeneic bone marrow; peripheral blood stem cell; Total body irradiation
Intervention description: 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
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Methotrexate; Pentostatin; Methoxsalen; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; refractory anemia; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  One of the following cytologically proven myelodysplastic syndromes

               -  Refractory anemia (RA)

               -  RA with ringed sideroblasts

               -  RA with excess blasts

               -  Chronic myelomonocytic leukemia

          -  International Prognosis Scoring System (IPSS) score of at least 0.5 OR red cell
             transfusion dependence for at least 6 months (2 units per month)

               -  Patients with an IPSS score less than 0.5 may be eligible provided they
                  previously had a higher IPSS score and received chemotherapy at that time

          -  Suitable human leukocyte antigen (HLA)-matched donor (related or unrelated) available

               -  No cord blood donors

               -  Related donors must be genotypically matched (HLA A, B and DR) at 5/6 or 6/6 loci
                  and may be a sibling, parent, or child

               -  Unrelated donors must have high resolution typing done at A, B, C and DR, and
                  must be matched at all or may have a single antigen or allele mismatch at no more
                  than one of these loci

          -  Patients must have < 20% blasts on bone marrow study within 1 month of study entry

          -  Age of 18 to 70 years

          -  Eastern Cooperative Oncology Group performance status 0-1

          -  Life expectancy at least 6 months

          -  At least 90 days since prior autologous bone marrow transplantation

          -  Serum erythropoietin level greater than 100 for patients who have not received a prior
             course of epoetin alfa

          -  No iron deficiency

               -  Iron deficiency anemia treated with iron replacement therapy allowed

          -  Bilirubin less than 2.0 mg/dL

          -  Alkaline phosphatase less than 2 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times
             ULN

          -  Creatinine less than 2.0 mg/dL OR creatinine clearance greater than 50 mL/min

          -  Left ventricular ejection fraction (LVEF) at least 45% by Multigated Acquisition scan
             (MUGA) or echocardiogram

          -  Carbon Monoxide Diffusing Capacity (DLCO) at least 50% of predicted (corrected for
             hemoglobin)

          -  Forced expiratory volume in 1 second (FEV_1) at least 50% of predicted

          -  Recovered from prior chemotherapy

          -  Physically and psychologically capable of undergoing study regimen

          -  Able to receive 600 cGy of total body irradiation

          -  HIV negative

          -  Negative pregnancy test

        Exclusion Criteria:

          -  Pregnant or nursing

          -  Having other medical condition that would reduce life expectancy

          -  Active ongoing infection

          -  Prior myeloablative or nonmyeloablative allogeneic transplantation for Myelodysplastic
             syndrome or acute myeloid leukemia