Prospective randomized study of allogeneic minitransplantation from HLA-identical family or unrelated donors comparing unmanipulated or CD8-depleted PBSC. The conditioning regimen will be 2 Gy TBI alone (related donor with low-risk of transplant rejection) or 2 Gy TBI and 3 x 30 mg/m2 fludarabine (unrelated donor or high risk of transplant rejection). Patients will receive a short but intensive immunosuppressive treatment (cyclosporine and mycophenolate mofetil) to ensure both graft-versus-host and host-versus-graft tolerance. The rationale for using PBSC instead of marrow transplant is to avoid general anesthesia of the donor and to minimize the risk of rejection. The rationale for CD8+ depletion is to diminish the risk of GVHD after PBSC transplantation or DLI.

1. Patients

   1.1. Diseases

   Malignant diseases confirmed histologically and not rapidly progressing:

   • Hematologic malignancies
   • AML;
   • ALL;
   • CML and other myeloproliferative disorders;
   • MDS;
   • Multiple myeloma;
   • CLL;
   • Non-Hodgkin's lymphoma;
   • Hodgkin's disease.
   • Non-hematologic malignancies
   • Renal cell carcinoma (metastatic).

   1.2. Inclusion criteria

   • Male or female; female patients must use a reliable contraception method;
   • Age lower than 70 yrs (family donor) or lower than 65 yrs (unrelated donor);
   • HIV negative;
   • No terminal organ failure;
   • No uncontrolled infection, arrhythmia or hypertension;
   • Family donor (HLA-identical) or unrelated donor (matched for A-B by low resolution typing and for DRB1-DQB1 by high resolution typing);
   • No previous radiation therapy precluding the use of 2 Gy TBI
   • Informed consent given by patient or his/her guardian if of minor age.

   1.3. Clinical situations

   • Theoretical disease indication for a standard allo-transplant, but not feasible because:

   • Age > 55 yrs;

   • Unacceptable end organ performance;

   • Patient's refusal.

   • Indication for a standard auto-transplant:

     • perform mini-allotransplantation 2-6 months after standard autotransplant.

   • Not an indication for intensification but a potential candidate for cellular immunotherapy.

2. Donors

2.1. Inclusion criteria

• Related to the recipient (sibling, parent or child) or unrelated;
• Male or female;
• Weight > 15 Kg (because of leukapheresis);
• HIV negative;
• No major contraindication for allogeneic PBSC donation by generally accepted criteria;
• Informed consent given by donor or his/her guardian if of minor age.

2.2. Exclusion criteria

• Any condition not fulfilling inclusion criteria;
• Unable to undergo leukapheresis because of poor vein access or other reasons.