Bone Marrow Transplantation in Treating Patients With Hematologic Cancer

OBJECTIVES:

• Compare the incidence of graft-versus-host disease (GVHD) grades III and IV in patients with hematologic malignancies treated with bone marrow transplantation (BMT) using donors with 1 HLA-A or B non-cross-reactive group mismatch vs control patients previously treated with BMT using donors with 1 HLA-A or B cross-reactive group (CREG) mismatch.
• Compare the incidence of GVHD grades III and IV in patients with hematologic malignancies treated with BMT using donors with 1 HLA-A or B CREG mismatch vs control patients previously treated with BMT using matched donors.
• Determine the relevance of HLA-DRB1 or DQB1 allele mismatching in BMT using donors matched for HLA-A, B, and C.

OUTLINE: Beginning at least 3 weeks after completion of cytoreductive combination chemotherapy, patients under age 18 undergo total body irradiation (TBI) twice a day on days -7 to -4. Patients age 18 and over undergo TBI twice a day on days -6 to -4. All patients then receive cyclophosphamide IV daily on days -3 and -2. Males with acute lymphocytic leukemia, high-grade lymphoma, intermediate-grade lymphoma, or marrow or CNS involvement receive radiotherapy boost to the testes. On day 0, patients receive infusion of bone marrow from unrelated donors with 1 of the following: 1 HLA-A or B non-cross-reactive group mismatch; 1 HLA-A or B cross-reactive group mismatch; or an HLA-A, B, and C match with an HLA-DRB1 or DQB1 mismatch.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• Histologically proven hematologic malignancy of 1 of the following types:

• Chronic myelogenous leukemia (CML) in chronic, accelerated, or blast* phase
• Acute leukemia with high-risk features at diagnosis such as:

• Philadelphia chromosome-positive acute lymphocytic leukemia**
• Acute myeloid leukemia with high-risk cytogenetics such as inv (3), t(3;3) del(5q), -5, del(7q), -7, +8, +11, abnormal 12p, del(20q), -20, or complex abnormalities**
• Acute leukemia with failure after one course of induction chemotherapy
• Acute leukemia in first relapse* or second remission
• High-risk lymphoblastic lymphoma in first remission
• Non-Hodgkin's lymphoma, Hodgkin's disease, or other malignant lymphoproliferative disease after first remission, if an autologous transplantation is not indicated
• Myelodysplastic or myeloproliferative syndromes ineligible for Protocol FHCRC-179 NOTE: * For patients with acute leukemia in relapse or CML in blast crisis, the search for an unrelated donor begins only if: High probability that the patient's medical condition will remain stable for the 3 to 6-month period needed to find a donorAn attempt at remission induction has been undertaken Referring physician and patient accept possibility that search for donor will be canceled if patient's condition worsens

NOTE: ** For newly diagnosed patients with high-risk acute leukemia, early referral is encouraged so that an unrelated donor search may begin immediately

• Availability of an unrelated donor with:

• 1 HLA-A or B non-cross-reactive group (non-CREG) mismatch (except in CML in chronic phase or myelodysplastic syndrome) OR
• 1 HLA-A or B CREG mismatch OR
• An HLA-A, B, and C match with an HLA-DRB1 or DQB1 mismatch (no double mismatch) if 1 of the above 2 donor types unavailable

• No more than 1 HLA-A, B, and C mismatch
• No availability of an HLA-identical sibling or haploidentical relative incompatible for 0 or 1 HLA-A or B locus of the nonshared haplotypes

• For patients with diagnosis other than CML in chronic phase, 1 HLA-DR locus-incompatible related donor has priority over an HLA compatible or class IA or B CREG locus antigen-incompatible unrelated donor
• No severe aplastic anemia
• No leukoencephalopathy

PATIENT CHARACTERISTICS:

Age:

• Under 51
• Eligible for transplantation until age 52 if the donor is identified prior to patient's 51st birthday

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• No severe hepatic disease, including acute hepatitis

Renal:

• Creatinine less than 2 times normal

Cardiovascular:

• No cardiac insufficiency requiring treatment
• No symptomatic coronary artery disease

Pulmonary:

• No severe hypoxemia (i.e., PO2 less than 70 mm Hg) with decreased DLCO (i.e., DLCO less than 70% predicted) OR
• No mild hypoxemia (i.e., PO2 less than 80 mm Hg) with severely decreased DLCO (i.e., DLCO less than 60% predicted)
• No pulmonary fibrosis

Other:

• No other nonmalignant disease that would severely limit life expectancy
• HIV negative
• No contraindication to total body irradiation (TBI)
• Patients excluded from this study because of contraindication to TBI may be treated on protocol FHCRC-739

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy greater than 3,000 cGy to whole brain
• At least 6 months since prior involved-field radiotherapy greater than 1,500 cGy to chest or abdomen

Surgery:

• Not specified