busulfan, fludarabine, and total-body irradiation in treating patients who are undergoing a donor stem cell transplant for hematologic cancer

Conditions: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Precancerous Condition

Summary: rationale: giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. it also stops 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). giving an infusion of the donor's t cells (donor lymphocyte infusion) after the transplant may help increase this effect. sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. purpose: this phase i/ii trial is studying the side effects of giving busulfan and fludarabine together with total-body irradiation and to see how well they work in treating patients who are undergoing a donor stem cell transplant for hematologic cancer.

objectives: primary * to assess safety and toxicity of the addition of busulfan added to an established fludarabine and low-dose total-body irradiation (tbi) conditioning regimen for non-myeloablative allogeneic transplantation in patients with hematologic malignancies. (phase i) * to assess the non-relapse mortality 1-year after conditioning with busulfan and fludarabine/tbi in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease. (phase ii) secondary * to assess overall survival 1-year survival. (phase ii) * to assess the incidence of graft rejection. (phase ii) * to assess the incidence of grade ii-iv acute graft-vs-host disease (gvhd) and chronic extensive gvhd. (phase ii) * to assess rates of disease progression and/or relapse-related mortality. (phase ii) * to determine non-hematologic grade iii-iv organ specific toxicity. (phase ii) outline: * nonmyeloablative-conditioning regimen: patients receive busulfan iv on day -5 and fludarabine iv over 30 minutes on days -4 to -2. patients undergo total body irradiation on day 0. * allogeneic peripheral blood stem cell transplantation (pbsc): patients undergo donor pbsc infusion on day 0. * graft-versus-host disease prophylaxis: patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180. patients with a related stem cell donor receive oral mycophenolate mofetil twice daily on days 0-28. patients with an unrelated stem cell donor receive oral mycophenolate mofetil 3 times daily on days 0-28 followed by a taper twice daily to day 56. patients with evidence of relapse or persistent disease may also receive up to 3 donor lymphocyte infusions. projected accrual: a total of 225 patients will be accrued for this study; 25 patients accrued into the phase i and 200 patients into phase ii.

Eligibility criteria:
disease characteristics: * diagnosis of a hematologic malignancy of 1 of the following high-risk types: * acute lymphoblastic leukemia * acute myeloid leukemia * chronic myelogenous leukemia * chronic lymphocytic leukemia * myelodysplastic syndromes * myeloproliferative disorder * multiple myeloma * plasma cell dyscrasias * non-hodgkin lymphoma * hodgkin disease patient characteristics: performance status * karnofsky 50-100% life expectancy * not specified hematopoietic * not specified hepatic * no liver failure * no cirrhosis with evidence of portal hypertension * no alcoholic hepatitis * no esophageal varices * no chronic hepatitis * no other liver disease renal * not specified cardiovascular * left ventricular ejection fraction (lvef) \> 35% * no symptomatic coronary artery disease or cardiac failure requiring therapy pulmonary * diffusing capacity of lung for carbon monoxide (dlco) \> 30% * total lung capacity \> 30% * forced expiratory volume in 1 second (fev_1) \> 30% * no supplementary continuous oxygen other * hiv negative * no active nonhematologic malignancy except localized skin cancer * no overt organ dysfunction prior concurrent therapy: * not specified

Keywords: recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes atypical chronic myeloid leukemia, breakpoint cluster region-abelson (bcr-abl) negative refractory chronic lymphocytic leukemia stage iii chronic lymphocytic leukemia stage iv chronic lymphocytic leukemia accelerated phase chronic myelogenous leukemia blastic phase chronic myelogenous leukemia chronic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia stage ii multiple myeloma stage iii multiple myeloma primary systemic amyloidosis refractory multiple myeloma myelodysplastic/myeloproliferative neoplasm, unclassifiable chronic eosinophilic leukemia primary myelofibrosis chronic neutrophilic leukemia essential thrombocythemia polycythemia vera chronic myelomonocytic leukemia acute undifferentiated leukemia extramedullary plasmacytoma isolated plasmacytoma of bone monoclonal gammopathy of undetermined significance stage i multiple myeloma secondary acute myeloid leukemia adult acute myeloid leukemia with 11q23 (mll) abnormalities adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with t(15;17)(q22;q12) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with t(8;21)(q22;q22) nodal marginal zone b-cell lymphoma noncontiguous stage ii adult burkitt lymphoma noncontiguous stage ii adult diffuse large cell lymphoma noncontiguous stage ii adult diffuse mixed cell lymphoma noncontiguous stage ii adult diffuse small cleaved cell lymphoma noncontiguous stage ii adult immunoblastic large cell lymphoma noncontiguous stage ii adult lymphoblastic lymphoma noncontiguous stage ii grade 1 follicular lymphoma noncontiguous stage ii grade 2 follicular lymphoma noncontiguous stage ii grade 3 follicular lymphoma noncontiguous stage ii mantle cell lymphoma noncontiguous stage ii marginal zone lymphoma noncontiguous stage ii small lymphocytic lymphoma recurrent adult burkitt lymphoma recurrent adult hodgkin lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent cutaneous t-cell non-hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma splenic marginal zone lymphoma stage iii adult burkitt lymphoma stage iii adult hodgkin lymphoma stage iii adult diffuse large cell lymphoma stage iii adult diffuse mixed cell lymphoma stage iii adult diffuse small cleaved cell lymphoma stage iii adult immunoblastic large cell lymphoma stage iii adult lymphoblastic lymphoma stage iii grade 1 follicular lymphoma stage iii grade 2 follicular lymphoma stage iii grade 3 follicular lymphoma stage iii mantle cell lymphoma stage iii marginal zone lymphoma stage iii small lymphocytic lymphoma stage iv adult burkitt lymphoma stage iv adult hodgkin lymphoma stage iv adult diffuse large cell lymphoma stage iv adult diffuse mixed cell lymphoma stage iv adult diffuse small cleaved cell lymphoma stage iv adult immunoblastic large cell lymphoma stage iv adult lymphoblastic lymphoma stage iv grade 1 follicular lymphoma stage iv grade 2 follicular lymphoma stage iv grade 3 follicular lymphoma stage iv mantle cell lymphoma stage iv marginal zone lymphoma stage iv small lymphocytic lymphoma extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue