study of low-intensity conditioning for allogeneic stem cell transplant

Conditions: Multiple Myeloma; Lymphocytic Leukemia, Chronic; Lymphoma, Low-Grade

Summary: the purpose of this study is to determine whether a reduced intensity conditioning regimen for stem cell transplant with donor cells will allow the donor cells to be effective without causing health problems.

in this research study patients will receive dosages of chemotherapy that are lower than the usual dosages. the study will determine whether a shorter duration of immunosuppression will permit the donor cells to be effective against the cancer without causing more severe gvhd (graft versus host disease). also to be determined is whether the patient's cancer can be prevented from relapsing after blood stem cell transplant by using prophylactic treatment, giving a donor leukocyte infusion before a relapse happens. in this research study samples of blood and bone marrow will be analyzed. these samples will be examined to study the cellular production of inflammatory cytokine levels in attempt to be able to predict which patients will have complications like gvhd or relapse.

Eligibility criteria:
patient inclusion criteria: to be eligible a patient must meet at least one of the next 4 criteria * any patient aged 55 years or older with a hematological malignancy for which allogeneic transplant is considered an appropriate treatment, and/or * any patient, regardless of age, with a hematologic malignancy for which allogeneic transplant is considered an appropriate treatment and the patient is not eligible for a conventional myeloablative transplant because of organ dysfunction and/or * any patient, regardless of age, who has relapsed following prior autologous or allogeneic transplant for a hematologic malignancy and/or * any patient, regardless of age, with one of the following hematological malignancies: 1. multiple myeloma 1. refractory to or failure following conventional chemotherapy such as vad (vincristine, adriamycin and dexamethasone), pulse decadron, or alkylating agents, or 2. chromosomal abnormality associated with poor prognosis by cytogenetics or fish probe. 2. chronic lymphocytic leukemia patients, rai stage 3 or 4 and relapsed following/refractory to alkylating agents or nucleoside analog therapy 3. low grade lymphoma (small lymphocytic, follicular small cleaved cell, or follicular mixed small cleaved and large cell) that is either relapsed or refractory provided the disease is not rapidly progressive, not bulky, and no mass exceeds 5 cm in greatest dimension. to be eligible a patient must meet all of the following criteria * in addition to the above criteria all patients must meet the following minimum organ function: 1. cardiac: ejection fraction at least 30%. 2. renal: adequate renal function as defined by creatinine \ 40 mg/min by 24-hour urine collection or gfr (glomerular filtration rate. (gender and age-adjusted creatinine clearance \>40ml/min by gault-cockroft 55 is acceptable for adults: (140 - age) x weight/72 x scr \[x 0.85 if female\]). 3. pulmonary: fev1 and fvc \>60%. 4. hepatic: total bilirubin \<2.0 and ast (aspartate aminotransferase)/alt (alanine transaminase) \< 3x institutional normal for age. 5. performance (adults): karnofsky score must be at least 60; for pts. under 16, lansky score must be at least 60. * availability of a 5/6 or 6/6 hla a, b, and dr identical relative who is willing and able to donate allogeneic stem cells. serological, low resolution or mid resolution molecular typing will determine the degree of match for hla (human leukocyte antigen) class i regardless of high resolution dna typing results. high resolution typing will be used to determine the degree of match for hla-dr. * no untreated or uncontrolled invasive infections. patients still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic and/or culture) that the infection is well controlled. patients under treatment for infection will be enrolled only after clearance from the principal investigator. * not pregnant patient exclusion criteria: * acute leukemia * hiv positive patients not eligible * any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient * pregnant donor inclusion criteria: * 5/6 or 6/6 hla match for hla-a, b, and dr * age 3-70 years, good general health * no contraindication to g-csf (granulocyte colony-stimulating factor)stimulation * no contraindication to leukapheresis of peripheral blood stem cells * good general health donor exclusion criteria: * hiv positive or history of hiv risk factors * presence of other diseases transmissible by blood that pose unacceptable risk to the study subject. * pregnant * medical or psychological conditions that would make the donor unlikely to tolerate g-csf - injections or leukapheresis