Donor Lymphocyte Infusion in Treating Patients With Recurrent or Persistent Hematologic Cancer After Donor Stem Cell Transplant

OBJECTIVES:

Primary

• Determine if the complete response rate exceeds 10% in patients with recurrent or persistent hematologic malignancies treated with donor lymphocyte infusion.

Secondary

• Estimate the complete response rate in these patients.
• Assess the toxicity of donor lymphocyte infusion in these patients.

OUTLINE: Patients receive up to four donor lymphocyte infusions at least 1 month apart in the absence of disease progression, unacceptable toxicity, or uncontrolled graft-versus-host disease.

DISEASE CHARACTERISTICS:

• Has undergone allogeneic stem cell transplantation (ASCT) for hematologic malignancy at least 30 days ago

• No failure to engraft following transplant
• No active acute or chronic graft-versus-host disease (GVHD)

• Minimal GVHD allowed
• Persistent or relapsed disease after ASCT, including 1 of the following:

• Chronic myelogenous leukemia (CML), meeting any of the following criteria:

• Molecular relapse (may be treated with imatinib mesylate after transplant), as defined by any of the following:

• ASCT was non-T-cell depleted, a negative bcr/abl was documented by PCR post-transplant, and bcr/abl is now detectable by 2 consecutive PCR determinations > 30 days apart
• ASCT was non-T-cell depleted and bcr/abl is detectable by PCR at any time after day 180 post-transplant
• Cytogenetic relapse after 3-6 months of imatinib mesylate
• Relapsed chronic phase, accelerated phase, or blastic phase CML after 3-6 months of imatinib mesylate

• Must currently be in chronic phase or accelerated phase CML only
• Patients with blastic phase CML must attain a second chronic phase
• Acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes, meeting any of the following criteria:

• Molecular relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific molecular abnormality detectable by PCR
• Cytogenetic relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific chromosome abnormality detectable by standard cytogenetics at any time after day 60 post-transplant
• Hematologic relapse, as evidenced by > 20% blasts in bone marrow or soft tissue recurrence

• Must be treated with chemotherapy after transplant, but before study donor lymphocyte infusion (DLI)
• Multiple myeloma

• Relapsed disease or recurrence of M-protein after thalidomide or other salvage treatment

• Prior post-transplant documentation of disappearance of M-protein by immunofixation
• Residual or progressive disease
• Rising M-protein level at any time post-transplant (measured at 3-month intervals)
• Original M-protein detectable at 6 months post-transplant
• Immune protein electrophoresis (IPEP) is required to show that M-component is the same on day 60 post-transplant as pre-transplant
• Residual (> 5%) plasma cells in bone marrow
• Relapsed non-Hodgkin lymphoma or Hodgkin lymphoma

• Relapse or progression of disease must be evidenced within 3 months prior to donor lymphocyte infusion by physical exam, radiographic studies, or molecular studies

• Tumor should be re-biopsied to determine histology
• If Epstein-Barr virus (EBV) lymphoma is suspected, peripheral blood must be assayed for EBV genome (i.e., EBV DNA testing by PCR) within the past 30 days
• EBV infection with associated pancytopenia

• Persistent or refractory pancytopenia with EBV genome detected by PCR in the peripheral blood

• Refractory pancytopenia is defined as pancytopenia that is poorly responsive to growth factors and/or transfusions
• EBV lymphoproliferative disorder

• Clonal lymphadenopathy that is refractory to standard therapy with acyclovir and immunoglobulin (DLI may be given with rituximab)
• Not a candidate for repeat ASCT

• Chimerism status is not required for determining eligibility for DLI
• Patients eligible for allogeneic ASCT, but for whom DLI is offered as the first option, should have full donor chimerism at relapse or after therapy for relapsed disease
• Patients with relapsed underlying disease after transplant who achieved remission after chemotherapy are allowed
• No CNS recurrence that is not cleared by standard chemotherapy

• CNS remission status must be maintained for 2 weeks
• Original hematopoietic progenitor stem cell donor must be available for cell donation

• No syngeneic donors

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy ≥ 8 weeks
• Creatinine < 3 mg/dL
• ABO/Rh and CMV IgG/IgM status known
• No HIV1 and HIV2 antibody
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months (males) or 6 months (females) after completion of study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics