Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies

Inclusion Criteria:

Patients must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy; patients with hematologic malignancies treatable with hematopoietic stem cell transplant (HSCT) or with a B cell malignancy except those treatable with autologous transplant will be included

Aggressive non-Hodgkin lymphomas (NHLs) and Other Histologies Such as Diffuse large B cell NHL

Patients with primary refractory or relapsed disease not eligible for an autologous transplant
Patients are eligible following an autologous transplant in remission or in relapse
Planned tandem transplant is allowed for patients at high risk of relapse
Low grade NHL with < 6 months duration of complete remission (CR) between courses of conventional therapy
Mantle Cell NHL may be treated in first CR
Chronic lymphocytic leukemia (CLL) - Must have failed 2 lines of conventional therapy and be refractory to fludarabine
Hodgkin disease (HD) - Must have received and failed frontline therapy; patients must have had a prior autologous transplant or were not eligible for autologous transplant; planned tandem transplants are allowed for patients at high risk of relapse
Multiple myeloma (MM) - Must have received prior chemotherapy and a prior autologous transplant, unless autologous transplant was not possible; planned tandem transplants are allowed for patients at high risk of relapse
Acute myeloid leukemia (AML) - Must have < 5% marrow blasts at the time of transplant
Acute lymphocytic leukemia (ALL) - Must have < 5% blasts at the time of transplant
Chronic myeloid leukemia (CML) - Patients will be accepted beyond chronic phase 1 (CP1) if they have received previous myelosuppressive chemotherapy or HSCT, and have < 5% marrow blasts at time of transplant
Myelodysplastic (MDS)/Myeloproliferative disorders - Must have failed previous myelosuppressive chemotherapy or HSCT, and have < 5% marrow blasts at time of transplant
Waldenstrom's Macroglobulinemia - Must have failed 2 courses of therapy
Patients < 12 years old must be approved by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI)
Patients who refuse to be treated on a conventional transplant protocol; for this inclusion, criteria transplants must be approved by both the participating institution´s patient review committee such as the Patient Care Conference (PCC) at the FHCRC and the FHCRC principal investigator

Patients with related or unrelated donors for whom

The best available match is a HLA class II DRB1 and DQB1 matched donor incompatible for any single serologically detectable class I HLA-A, -B, -C mismatch; one additional allele level class I mismatch is allowed OR any combination of 2 allele level mismatches (if typed at the molecular level)
There is a likelihood of rapid disease progression while HLA typing and results of a preliminary search and the donor pool suggests that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found
There is no HLA-A, -B or -C one locus allelic mismatched related donor available
There is no indication for an autologous transplantation as a treatment option

DONOR: Related or unrelated donors who are matched for HLA-DRB1 and DQB1 alleles (must be defined by high resolution typing), and who are mismatched for:

Any single serologically detectable HLA-A or B or C antigen +/- 1 allele or
Any combination of two HLA-A, -B, or -C alleles (if prospectively typed at molecular level)

Exclusion Criteria:

Patients who are homozygous at the mismatched major histocompatibility complex (MHC) class I locus
A positive cross-match exists between the donor and recipient
Patients with rapidly progressive intermediate or high grade NHL
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
Life expectancy severely limited by diseases other than malignancy
Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment
Female patients who are pregnant or breast-feeding
Human immunodeficiency virus (HIV) positive patients
Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
Patients with active bacterial or fungal infections unresponsive to medical therapy

Patients with the following organ dysfunction symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy; ejection fraction is required if the patient is > 50 years of age, or history of cardiac disease or anthracycline exposure

Diffusion capacity of carbon monoxide (DLCO) < 35%; total lung capacity (TLC) < 35%; or forced expiratory volume in one second (FEV1) < 35% and/or receiving supplementary continuous oxygen
Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure; cirrhosis of the liver with evidence of portal hypertension; alcoholic hepatitis; esophageal varices; a history of bleeding esophageal varices; hepatic encephalopathy; uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time; ascites related to portal hypertension; bacterial or fungal liver abscess; biliary obstruction; chronic viral hepatitis with total serum bilirubin >3 mg/dL; or symptomatic biliary disease
Patients with poorly controlled hypertension on multiple antihypertensives
Karnofsky score < 70 for adult patients
Lansky-Play Performance Score < 50 for pediatric patients
DONOR: Bone marrow (BM) donors
DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for granulocyte colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem cell (PBSC)
DONOR: Donors < 12 years of age