Allogeneic HCT With HLA-matched Donors : a Phase II Randomized Study Comparing 2 Nonmyeloablative Conditionings

Inclusion Criteria:

PATIENT

1. Diseases

   Hematological malignancies confirmed histologically and not rapidly progressing:

   • AML in CR (defined as ≤ 5% marrow blasts and absence of blasts in the peripheral blood);
   • MDS with ≤ 5% marrow blasts and absence of blasts in the peripheral blood;
   • CML in CP;
   • MPS not in blast crisis and not with extensive marrow fibrosis,
   • ALL in CR;
   • Multiple myeloma not rapidly progressing;
   • CLL;
   • Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
   • Hodgkin's disease with chemosensitive disease.

2. Clinical situations

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

     • Age > 50 yrs;
     • Unacceptable end organ performance;
     • Patient's refusal.
   • Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.

3. Other inclusion criteria

   • Male or female; fertile patients must use a reliable contraception method;
   • Age < 75 yrs;
   • Informed consent given by patient or his/her guardian if of minor age.

DONOR

• Related to the recipient (sibling, parent or child) or unrelated;
• Male or female;
• Any age;
• 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA allele matched;
• Weight > 15 Kg (because of leukapheresis);
• Fulfills criteria for allogeneic PBSC donation according to standard procedures;
• Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.

Exclusion Criteria:

PATIENT

• Any condition not fulfilling inclusion criteria;
• HIV positive;
• Non-hematological malignancy(ies) (except non-melanoma skin cancer) < 3 years before nonmyeloablative HCT.
• Life expectancy severely limited by disease other than malignancy;
• Administration of cytotoxic agent(s) for "cytoreduction" within three weeks prior to initiating the nonmyeloablative transplant conditioning (Exceptions are hydroxyurea and imatinib mesylate);
• CNS involvement with disease refractory to intrathecal chemotherapy.
• Terminal organ failure, except for renal failure (dialysis acceptable)
• Uncontrolled infection;
• Karnofsky Performance Score <70%;
• Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment;
• Patient is a female who is pregnant or breastfeeding;
• Previous radiation therapy precluding the use of 2 Gy TBI or 8 Gy TLI;

DONOR

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